bluuebunny/crossref_metadata_2025 huggingface dataset:
Down-Regulation of Placenta Growth Factor by Promoter Hypermethylation in Human Lung and Colon Carcinoma
Authors: Xu Lei , Jain Rakesh K.
Published: August 2007

Two recent clinical trials have shown that the placenta growth factor (PlGF) is up-regulated after bevacizumab treatment in colorectal cancer and after SU11248 treatment in metastatic renal cell carcinoma. The regulation of expression for the vascular endothelial growth factor (VEGF) has been well documented in human tumors; however, the data for PlGF are lacking. We investigated the epigenetic regulation of PlGF and correlated the results with clinicopathologic features. We used plgf promoter analysis, cDNA microarray, immunohistochemistry, and Northern blot analysis to determine the expression level of PlGF in 22 human lung carcinoma and 11 colorectal tumors and in 12 cell lines. Sodium bisulfite modification of genomic DNA followed by methylation-specific PCR (MSP) and sequencing were used to determine the methylation status of the PlGF promoter. Treatments with 5-aza-2′-deoxycytidine and trichostatin A (TSA) were used to reactivate PlGF expression. Significance analysis showed that PlGF expression level was low in human lung and colorectal tumor tissues and in cell lines. PlGF gene promoter was hypermethylated. Treatment with the demethylating agent 5-Aza-dC restored PlGF transcript expression in the lung and colon carcinoma cell lines. By combining the results from cDNA microarray, immunohistochemistry, and MSP, we report, for the first time, that the PlGF gene promoter is methylated, and methylation may be one of the mechanisms that contributes to the low PlGF expression level in human lung and colorectal tumor tissues and cell lines. (Mol Cancer Res 2007;5(9):873–80)
Wwox Suppresses Prostate Cancer Cell Growth through Modulation of ErbB2-Mediated Androgen Receptor Signaling
Authors: Qin Haiyan R. , Iliopoulos Dimitrios , Nakamura Tatsuya , Costinean Stefan , Volinia Stefano , Druck Teresa , Sun Jin , Okumura Hiroshi , Huebner Kay
Published: August 2007

The expression of the WWOX tumor suppressor gene is lost or reduced in a large fraction of various cancers, including prostate cancer. We previously reported that Wwox overexpression induced apoptosis and suppressed prostate cancer growth in vitro and in vivo. In this study, pathways through which Wwox contributes to control of prostate cancer cell growth have been investigated. We found that Wwox interacts with Ap2γ and prevents it from entering the nucleus to bind the ERBB2 promoter region to activate transcription of ERBB2, a mediator of androgen receptor activity and prostate cancer cell growth at limiting androgen concentration. Ectopic expression of Wwox reduced ErbB2 protein expression in vitro and expression of Wwox protein inversely correlated with expression of ErbB2 protein in prostate cancer tissues. Furthermore, Wwox suppressed Ap2γ/ErbB2–induced prostate cancer cell growth and suppressed prostate-specific antigen secretion through interaction with Ap2γ and down-modulation of ErbB2, an effect that required functional androgen receptor. (Mol Cancer Res 2007;5(9):957–65)
Beta-Adrenergic Receptor Blockade Attenuates the Exercise-Induced Suppression of TNF-Alpha in Response to Lipopolysaccharide in Rats
Authors: Kitamura Hiromi , Shiva Daisuke , Woods Jeffrey A. , Yano Hiromi
Published: August 2007

Stressful exercise has been found to reduce the proinflammatory cytokine response to lipopolysaccharide (LPS). In this study, we aimed to determine whether receptor antagonists for corticosterone or catecholamines would increase the LPS-induced tumor necrosis factor-α (TNF-α) response after exhaustive exercise. Female F344 rats were randomly assigned to one of five groups: control (vehicle), RU-486 (glucocorticoid receptor antagonist, 30 mg/kg)-, propranolol [nonselective β-adrenergic receptor (AR) blockade, 30 mg/kg]-, atenolol (β1-AR blockade, 30 mg/kg)-, or ICI 118551 (β2-AR blockade, 30 mg/kg)-treated groups. Each antagonist was given intraperitoneally 30 min prior to exercise or control period. Exercised rats ran until exhaustion on a treadmill at gradually increasing speeds, from 10 to 36 m/min at 15% grade. Immediately postexercise or control period all rats were injected with LPS (1 mg/kg, i.v.). Plasma TNF-α was reduced by prior exercise to approximately 10% of that of sedentary controls (p < 0.01). Plasma TNF-α concentration in exercised RU-486-treated rats was significantly different than that of nonexercised rats (19.2%, p < 0.01) and not different from exercised rats. However, pretreatment of rats with the nonselective β-AR blocker propranolol almost completely reversed the exercise-induced suppression of plasma TNF-α in response to LPS. β1-AR pretreatment almost completely attenuated the exercise-induced suppression of LPS-induced plasma TNF-α while β2-antagonism had a partial effect. These results indicate that exercise-induced catecholamines, acting through β-ARs (especially the β1-AR), are responsible for the exercise-induced suppression of plasma TNF-α after LPS administration.
Differential Regulation of Homocysteine Transport in Vascular Endothelial and Smooth Muscle Cells
Authors: Jiang Xiaohua , Yang Fan , Brailoiu Eugen , Jakubowski Hieronim , Dun Nae J. , Schafer Andrew I. , Yang Xiaofeng , Durante William , Wang Hong
Published: August 2007

Objective—

We previously reported that homocysteine (Hcy) inhibits endothelial cell (EC) growth and promotes vascular smooth muscle cell (VSMC) proliferation. This study characterized and directly compared Hcy transport in cultured human aortic ECs (HAECs) and smooth muscle cells (HASMCs).

Methods and Results—

Hcy (10 μmol/L) was transported into both cell types in a time-dependent fashion but was approximately 4-fold greater in HASMCs, and is nonstereoenantiomer specific. Hcy transport in HAECs had a Michaelis-Menten constant (
Km
) of 39 μmol/L and a maximal transport velocity (
Vmax
) of 873 pmol/mg protein/min. In contrast, Hcy transport in HASMCs had a lower affinity (
Km
=106 μmol/L) but a higher transport capacity (
Vmax
=4192 pmol/mg protein/min). Competition studies revealed that the small neutral amino acids tyrosine, cysteine, glycine, serine, alanine, methionine, and leucine inhibited Hcy uptake in both cell types, but the inhibition was greater for tyrosine, serine, glycine, and alanine in HAECs. Sodium-depletion reduced Hcy transport to 16% in HAECs and 56% in HASMCs. Increases in pH from 6.5 to 8.2 or lysosomal inhibitors blocked Hcy uptake only in HAECs. In addition, Hcy shares carrier systems with cysteine, in a preferable order of alanine-serine-cysteine (ASC)>aspartate and glutamate (X
AG
)=large branched-chain neutral amino acids (L) transporter systems in HAECs and ASC>L>X
AG
in HASMCs. The sodium-dependent system ASC plays a predominant role for Hcy transport in vascular cells.

Conclusions—

Transport system ASC predominantly mediates Hcy transport in EC and is lysosomal dependent.
Coronary Vessel Development Is Dependent on the Type III Transforming Growth Factor β Receptor
Authors: Compton Leigh A. , Potash Dru A. , Brown Christopher B. , Barnett Joey V.
Published: August 2007

Transforming growth factor (TGF)β receptor III (TGFβR3), or β-glycan, binds all 3 TGFβ ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors (TGFβR1, TGFβR2). TGFβR3 facilitates signaling via TGFβR1/TGFβR2 but also has been suggested to play a unique and nonredundant role in TGFβ signaling. Targeted deletion of
Tgfbr3
revealed a requirement for
Tgfbr3
during development of the coronary vessels. Coronary vasculogenesis is significantly impaired in null mice, with few vessels evident and numerous, persistent blood islands found throughout the epicardium.
Tgfbr3
-null mice die at embryonic day 14.5, the time when functional coronary vasculature is required for embryo viability. However, in null mice nascent coronary vessels attach to the aorta, form 2 coronary ostia, and initiate smooth muscle recruitment by embryonic day 14. Analysis of earlier developmental stages revealed defects in the epicardium. At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium.
Tgfbr3
-null mice also displayed other defects in coronary development, including dysmorphic and distended vessels along the atrioventricular groove and subepicardial hemorrhage. In null mice, vessels throughout the yolk sac and embryo form and recruit smooth muscle in a pattern indistinguishable from heterozygous or wild-type littermates. These data demonstrate a requirement for
Tgfbr3
during coronary vessel development that is essential for embryonic viability.
Oxidized Phospholipids Induce Phenotypic Switching of Vascular Smooth Muscle Cells In Vivo and In Vitro
Authors: Pidkovka Nataliya A. , Cherepanova Olga A. , Yoshida Tadashi , Alexander Matthew R. , Deaton Rebecca A. , Thomas James A. , Leitinger Norbert , Owens Gary K.
Published: August 2007

Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) and its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated within atherosclerotic lesions and are known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells (SMCs) plays a critical role in the development, progression, and end-stage clinical consequences of atherosclerosis, yet little is known regarding the effects of specific oxPLs on SMC phenotype. The present studies were focused on determining whether oxPLs regulate expression of SMC differentiation marker genes and the molecular mechanisms involved. Results showed that POVPC and PGPC induced profound suppression of smooth muscle (SM) α-actin and SM myosin heavy chain expression while simultaneously increasing expression of MCP-1, MCP-3, and cytolysin. OxPLs also induced nuclear translocation of Krüppel-like transcription factor 4 (KLF4), a known repressor of SMC marker genes. siRNA targeting of KLF4 nearly blocked POVPC-induced suppression of SMC marker genes, and myocardin. POVPC-induced repression of SMC marker genes was also significantly attenuated in KLF4 knockout SMCs. Taken together, these results suggest a novel role for oxPLs in phenotypic modulation of SMCs and indicate that these effects are dependent on the transcription factor, KLF4. These results may have important novel implications for the mechanisms by which oxPLs contribute to the pathogenesis of atherosclerosis.
Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure
Authors: Tanaka Kazuhiko , Zlochiver Sharon , Vikstrom Karen. L. , Yamazaki Masatoshi , Moreno Javier , Klos Matthew , Zaitsev Alexey. V. , Vaidyanathan Ravi , Auerbach David S. , Landas Steve , Guiraudon Gérard , Jalife José , Berenfeld Omer , Kalifa Jérôme
Published: August 2007

Heart failure (HF) commonly results in atrial fibrillation (AF) and fibrosis, but how the distribution of fibrosis impacts AF dynamics has not been studied. HF was induced in sheep by ventricular tachypacing (220 bpm, 6 to 7 weeks). Optical mapping (Di-4-ANEPPS, 300 frames/sec) of the posterior left atrial (PLA) endocardium was performed during sustained AF (burst pacing) in Langendorff-perfused HF (n=7, 4 μmol/L acetylcholine; n=3, no acetylcholine) and control (n=6) hearts. PLA breakthroughs were the most frequent activation pattern in both groups (72.0±4.6 and 90.2±2.7%, HF and control, respectively). However, unlike control, HF breakthroughs preferentially occurred at the PLAs periphery near the pulmonary vein ostia, and their beat-to-beat variability was greater than control (1.93±0.14 versus 1.47±0.07 changes/[beats/sec], respectively,
P
<0.05). On histological analysis (picrosirius red), the area of diffuse fibrosis was larger in HF (23.4±0.4%) than control (14.1±0.6%;
P
<0.001, n=4). Also the number and size of fibrous patches were significantly larger and their location was more peripheral in HF than control. Computer simulations using 2-dimensional human atrial models with structural and ionic remodeling as in HF demonstrated that changes in AF activation frequency and dynamics were controlled by the interaction of electrical waves with clusters of fibrotic patches of various sizes and individual pulmonary vein ostia. During AF in failing hearts, heterogeneous spatial distribution of fibrosis at the PLA governs AF dynamics and fractionation.
Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3
Authors: Surapisitchat James , Jeon Kye-Im , Yan Chen , Beavo Joseph A.
Published: August 2007

Endothelial barrier dysfunction leading to increased permeability and vascular leakage is an underlying cause of several pathological conditions, including edema and sepsis. Whereas cAMP has been shown to decrease endothelial permeability, the role of cGMP is controversial. Endothelial cells express cGMP-inhibited phosphodiesterase (PDE)3A and cGMP-stimulated PDE2A. Thus we hypothesized that the effect of cGMP on endothelial permeability is dependent on the concentration of cGMP present and on the relative expression levels of PDE2A and PDE3A. When cAMP synthesis was slightly elevated with a submaximal concentration of 7-deacetyl-7-(
O
-[
N
-methylpiperazino]-γ-butyryl)-dihydrochloride–forskolin (MPB–forskolin), we found that low doses of either atrial natriuretic peptide (ANP) or NO donors potentiated the inhibitory effects of MPB–forskolin on thrombin-induced permeability. However, this inhibitory effect of forskolin was reversed at higher doses of ANP or NO. These data suggest that cGMP at lower concentrations inhibits PDE3A and thereby increases a local pool of cAMP, whereas higher concentrations cGMP activates PDE2A, reversing the effect. Inhibitors of PDE3A mimicked the effect of low-dose ANP on thrombin-induced permeability, and inhibition of PDE2A reversed the stimulation of permeability seen with higher doses of ANP. Finally, increasing PDE2A expression with tumor necrosis factor-α reversed the inhibition of permeability caused by low doses of ANP. As predicted, the effect of tumor necrosis factor-α on permeability was reversed by a PDE2A inhibitor. These findings suggest that the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, which, in large part, is attributable to the relative amounts of PDE2A and PDE3A in endothelial cells.
A New Test of Convergence Theory
Authors: Marsh Robert
Published: August 2007

A classic version of convergence theory was proposed by Marion Levy (1966) as part of his theory of modernization: if and as the level of modernization increases (defined as a higher ratio of reliance upon inanimate energy and tools, relative to animate energy), the level of structural uniformity among relatively modernized societies continually increases. This hypothesis that there is more uniformity among modernized than among non-modernized societies is tested here with cross-national data from 148 non-modernized and 52 modernized societies. Using the coefficient of variation (V) as the measure of convergence, I analyze a wide range of variables: level of economic development, capitalist market economy, demographic variables, technology, the state and political democracy, cognitive modernization, health, income inequality and poverty, gender particularism-universalism, and information and communications. I find that the modernized societies do show more convergence (lower V scores) than the non-modernized societies on 49 of the 51 variables tested. Among the 21 societies that were already modernized in 1965, as they became more modernized during the period from1965 to the present, they also became more convergent on 32 of the 45 variables analyzed. Thus, variation in social structure is greater among less modernized than among more modernized societies, and this has implications for theories of globalization.
Convergence Pressures and Responses: Recent Social Insurance Development in Modern Welfare States
Authors: Nelson Kenneth , Montanari Ingalill , Palme Joakim
Published: August 2007

Pressures from global market forces along with austerity and retrenchment have generated predictions of converging welfare state institutions. The purpose of this paper is to examine the development of social insurance programs among 18 of the economically most advanced democracies during 1980–2000. Have social insurance rights converged and have changes been of such a character that we can discern converging trends of social insurance models? The results indicate convergence in the replacement rates, coverage and employer financing of social insurance benefits up to 1980, after which these signs of convergence tend to disappear or transform into divergence. Rather than countries becoming reclassified, changes implemented in social insurance rights appear to have strengthened the distinctive characteristics of social insurance models identified.
Promoting Democracy: The Challenge of Creating a Civil Society
Authors: Lovell David
Published: August 2007

Perhaps the most notable feature of "democracy" today is its almost universal acceptance as the only legitimate form of government. Most examples of open dissent against this view are so patently self-interested as to command little respect. Yet however attractive it may be, the development of modern democracy has been largely an incremental product of Europe and its colonial diaspora, which embody quite specific cultural and social assumptions. Now these states have become dedicated to democracy's extension around the world. This paper examines the nature and success of these attempts to extend democracy. It asks, in particular, whether the culture of a robust civil society on which democracy relies can be successfully exported and what challenges it faces from more traditional social relationships.
Democracy, Economic Crisis, and Market Oriented Reforms
Authors: Kalinowski Thomas
Published: August 2007

In this paper I analyze the nexus between economic crises, market oriented reforms, and democratization in Indonesia and Korea since the 1997/98 Asian financial crisis. I provide some support for the hypothesis that democracies are better able to survive economic crises than authoritarian regimes. In both countries democratization facilitated a crisis resolution strategy based on market oriented reforms. However, I assert that in the long run the social consequences of market-oriented reforms tend to undermine democratization partly because both are so closely linked and the majority of the population sees them as one. This process does not necessarily destroy democracies but it leaves them more vulnerable to possible external shocks in the future.
A Forgotten Minority: The Afro-Sri Lankans
Authors: de Silva Jayasuriya Shihan
Published: August 2007

This paper seeks to understand why people of African descent in Sri Lanka have a low profile. Drawing attention to cultural retentions and transformations, it examines the process of their assimilation within post-independent Sri Lanka. It argues that the fate of today's Afro-Sri Lankans was shaped during the British era. The prestige of Afro-Sri Lankans rested on their military abilities. Turning to their contemporary status, it appears that their considerable talents as musicians and dancers have not been adequately recognised and nurtured. These internationally marketable assets need to be supported through aid.
Service to God, Service to Master/Client: African Indian Military Contribution in Karnataka
Authors: Obeng Pashington
Published: August 2007

This essay examines how African Indians (Abyssinians, Habshis, Siddis) from medieval times to the present have played significant political and military roles to forge sovereignties in the land area currently covered by the State of Karnataka, South India. I provide a brief history of the military activities of African Indians in the Indian subcontinent to foreground how the Africans deployed the unstable political climate in the Deccan, ethnicization of military culture, religious filiation, and force of personality to assert influence over communities that settled in areas bounded by present-day Karnataka.
African Bedouin in Palestine
Authors: Beckerleg Susan
Published: August 2007

The changing ethnic identity and origins of people of Bedouin and African origin living in southern Israel and the Gaza Strip are explored in this paper. For thousands of years, and into the twentieth century, slaves were captured in Africa and transported to Arabia. Negev Bedouin in Palestine owned slaves, many of whom were of African origin. When Israel was created in 1948 some of these people of African origin became refugees in Gaza, while others remained in the Negev and became Israeli citizens. With ethnic identity a key factor in claims and counter claims to land in Palestine/Israel, African slave origins are not stressed. The terminology of ethnicity and identity used by people of African origin and other Palestinians is explored, and reveals a consciousness of difference and rejection of the label abed or slave/black person.
Dynamics of Ethnic Identity Among the Siddis of Hyderabad
Authors: Minda Yimene Ababu
Published: August 2007

The existing commercial contact between India and Africa since prehistoric times grew substantially since the rise of Islam in the 7th century, leaped to its climax during the middle ages and continued until the second half of the 20th century. This commercial relationship involved the trade in humans from Africa to Asia. Many African war captives were sold as slaves in India to serve as domestics and infantries among the aristocracy of rising Islamic kingdoms while some emigrated by free will and settled in India engaging in various occupations. Descendants of African slaves and immigrants, who are locally known as Siddis, presently live in various geographical pockets of India forming their own ethnic enclaves amidst their host societies. The main Siddi communities in India are located in Gujarat, Hyderabad, Karnataka, in the Bombay region and along the western coast, including Goa. The Siddis of Hyderabad, like the other Siddi communities are changing fast, yielding to modern demands and trends. National and global pressures strongly militate against their tradition and change in their identity has been inevitable. As a result of their intermarriage with other ethnic communities and adoption of either Indian or Arab identities, today's Siddis have little resemblance to their predecessors. This study shows that the Siddis are moving in divergent directions of assimilation. Many Moslem Siddis are assimilating into the Yemeni Arab community of Hyderabad while Christian Siddis identify themselves with the Indian Christian population. Moslem and Christian Siddis are accused by each other as being pro-Pakistan Islamic radicals and 'Hindu nationalism' adherents respectively. The Siddis, although historically constituted a single ethnic community, are in the process of a significant identity change by joining two ideologically differing groups.
Introduction Out Of Africa? 2
Authors: Palmié Stephan
Published: August 2007

The introduction to this second special issue aims to probe the epistemological conditions of possibility of African Americanist anthropology. In particular, it highlights the problematic of definitions of units of analysis in the comparative logic on which this particular field of inquiry has long been based. Given the conceptual instability of the categories 'Africa' and 'America' discussed in the previous number of this special double issue, attention is given to how scholars variously became implicated in the creation of 'African horizons', and to potential ways in which past approaches might not only be opened up to 'symmetrical analyses', but in fact transcended.
Treating Medieval Plague: The Wonderful Virtues of Theriac
Authors: Fabbri Christiane Nockels
Published: August 2007

This paper examines one of the most popular remedies in medieval plague medicine, namely theriac, and explores possible reasons for its remarkable continuity in the late medieval and early modern medical tradition. Theriac, reputed as a universal antidote since ancient times, was a complex compound, composed of multiple ingredients, difficult to prepare, and subject to strict manufacturing and commercial controls. The paper centers on the therapeutic applications of theriac and on its relative pharmacologic efficacy in treating the symptoms of plague. The consistent use of theriac in plague medicine attests not only to the conservatism of medieval medical practice, but also to an underlying solidly founded rationale that combined humoral doctrine, empiric observation, and pharmacologic effect.
Philosophers and Physicians on the Scientific Validity of Latin Physiognomy, 1200-1500
Authors: Ziegler Joseph
Published: August 2007

The article surveys and contextualizes the main arguments among philosophers and academic physicians surrounding the status of physiognomy as a valid science from the thirteenth to the early sixteenth centuries. It suggests that despite constant doubts, learned Latin physiognomy in the later Middle Ages was recognized by natural philosophers (William of Spain, Jean Buridan, William of Mirica) and academic physicians (Rolandus Scriptor, Michele Savonarola, Bartolomeo della Rocca [Cocles]) as a body of knowledge rooted in a sound theoretical basis. Physiognomy was characterized by stability and certainty. As a demonstrative science it was expected to provide rational explanation for every bodily sign. In this respect, learned physiognomy in the Middle Ages was dramatically different from its classical sources, from Islamic and possibly from early-modern physiognomy as well.
Toward a General Research Process for Using Dubin's Theory Building Model
Authors: Holton Elwood F. , Lowe Janis S.
Published: August 2007

Dubin developed a widely used methodology for theory building, which describes the components of the theory building process. Unfortunately, he does not define a research process for implementing his theory building model. This article proposes a seven-step general research process for implementing Dubin's theory building model. An example of a theory building process is used to explicate a research process that will aid new theorists and reviewers of theory in conceptualizing a rigorous and systematic process to implement Dubin's model.
A Standardized Approach to Performing the Action Research Arm Test
Authors: Yozbatiran Nuray , Der-Yeghiaian Lucy , Cramer Steven C.
Published: August 2007

The study of stroke and its treatment in human subjects requires accurate measurement of behavioral status. Arm motor deficits are among the most common sequelae after stroke. The Action Research Arm Test (ARAT) is a reliable, valid measure of arm motor status after stroke. This test has established value for characterizing clinical state and for measuring spontaneous and therapy-induced recovery; however, sufficient details have not been previously published to allow for performance of this scale in a standardized manner over time and across sites. Such an approach to ARAT scoring would likely reduce variance between investigators and sites. This report therefore includes a manual that provides a highly detailed and standardized approach for assigning ARAT scores. Intrarater reliability and interrater reliability, as well as validity, with this approach were measured and are excellent. The ARAT, when performed in a standardized manner, is a useful tool for assessment of arm motor deficits after stroke.
The association of ICAM-1 Exon 6 (E469K) but not of ICAM-1 Exon 4 (G241R) and PECAM-1 Exon 3 (L125V) polymorphisms with the development of differentiation syndrome in acute promyelocytic leukemia
Authors: Dore Adriana I , Santana-Lemos Barbara A A , Coser Virginia M , Santos Flávia L S , Dalmazzo Leandro F , Lima Ana S G , Jacomo Rafael H , Elias Jorge , Falcão Roberto Passetto , Pereira Waldir V , Rego Eduardo M
Published: August 2007

The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation. As leukocyte extravasation is a key event in DS pathogenesis, we analyzed the association between the polymorphisms at Exon 4 (G241R) and Exon 6 (E469K) of ICAM-1 and Exon 3 (L125V) of PECAM-1 genes with DS development in APL patients treated with ATRA and anthracyclines. DS was diagnosed in 23/127 (18.1%) APL patients at an average of 11.5 days after the start of ATRA. All patients presented respiratory distress associated with increased ground-glass opacity in chest radiographies. Other accompanying symptoms were: fever not attributable to infection (65.2%), generalized edema (37.5%), weight gain (37.5%), and impairment of renal function (8.6%). We detected an association between development of DS and the AA genotype at Codon 469 of ICAM-1 (odds ratio of 3.5; 95% confidence interval: 1.2–10.2). Conversely, no significant association was detected between G241R or L125V polymorphisms at Exon 4 of ICAM-1 and Exon 3 of PECAM-1, respectively. Our results suggest that susceptibility to DS in APL patients may be influenced by genetic variation in adhesion molecule loci.
A hCXCR1 transgenic mouse model containing a conditional color-switching system for imaging of hCXCL8/IL-8 functions in vivo
Authors: Zheng Lei , Njauw Ching-ni , Martins-Green Manuela
Published: August 2007

To address the functions of human CXCL8 (hCXCL8)/IL-8 through hCXCR1 in vivo, we have developed a humanized, transgenic mouse for hCXCR1. This mouse line is versatile and allows for a variety of functional analyses using bioimaging, including Cre/loxP-mediated, tissue-specific hCXCR1 expression in a spatiotemporal manner; a color-switching mechanism, which uses spectrum-complementary, genetically encoded green and red fluorescence markers to label the hCXCR1-expressing cells [enhanced GFP (eGFP)] against the background [monomeric red fluorescent protein (mRFP)]; a bioluminescent marker, which is present in the hCXCR1-expressing cells; and an exogenous cell surface marker (eGFP moiety) in the hCXCR1-expressing cells, which facilitates identification, isolation, and targeting of these cells. The established, transgenic founder line RCLG3A (TG+) expresses only mRFP and does so ubiquitously. When the RCLG3A mice are crossed with the tamoxifen-inducible, whole-tissue Cre mice (ROSA26-Cre/Esr+/−), administration of tamoxifen induces whole-body hCXCR1 expression and color-switching. When RCLG3A mice are crossed with thymocyte-specific Cre mice (Lck-Cre+/+), the hCXCR1 expression and color-switching are restricted in a lineage-specific manner. This mouse line can be used to understand the functions of hCXCL-8 in vivo. In addition, our approach and vectors can be used to establish other tissue-specific, transgenic mice in conjunction with multifunctional cell markers, which facilitate cell imaging, tracing, and manipulation in vivo.
Inhibition of HIV replication by the plasminogen activator is dependent on vitronectin-mediated cell adhesion
Authors: Elia Chiara , Cassol Edana , Sidenius Nicolai , Blasi Francesco , Castagna Antonella , Poli Guido , Alfano Massimo
Published: August 2007

Urokinase-type plasminogen activator (uPA), an inducer of macrophage adhesion, inhibits HIV-1 expression in PMA-stimulated, chronically infected U1 cells. We investigated whether uPA-dependent cell adhesion played a role in uPA-dependent inhibition of HIV-1 replication in these cells. Monocyte-derived macrophages (MDM) were generated from monocytes of HIV-infected individuals or from cells of seronegative donors infected acutely in vitro. U1 cells were stimulated in the presence or absence of uPA in standard tissue culture (TC) plates, allowing firm cell adhesion or ultra-low adhesion (ULA) plates. Moreover, U1 cells were also maintained in the presence or absence of vitronectin (VN)-containing sera or serum from VN−/− mice. Virus production was evaluated by RT activity in culture supernatants, whereas cell adhesion was by crystal violet staining and optical microscopy. uPA inhibited HIV replication in MDM and PMA-stimulated U1 cells in TC plates but not in ULA plates. uPA failed to inhibit HIV expression in U1 cells stimulated with IL-6, which induces virus expression but not cell adhesion in TC plates. VN, known to bind to the uPA/uPA receptor complex, was crucial for these adhesion-dependent, inhibitory effects of uPA on HIV expression, in that they were not observed in TC plates in the presence of VN−/− mouse serum. HIV production in control cell cultures was increased significantly in ULA versus TC plates, indicating that macrophage cell adhesion per se curtails HIV replication. In conclusion, uPA inhibits HIV-1 replication in macrophages via up-regulation of cell adhesion to the substrate mediated by VN.
Hepatitis C virus core protein up-regulates anergy-related genes and a new set of genes, which affects T cell homeostasis
Authors: Domínguez-Villar M , Muñoz-Suano A , Anaya-Baz B , Aguilar S , Novalbos J P , Giron J A , Rodríguez-Iglesias M , Garcia-Cozar F
Published: August 2007

Hepatitis C virus (HCV) infection is the main cause for chronic hepatitis, leading to cirrhosis and hepatic carcinoma. Virally induced immune dysfunction has been called as the cause for viral persistence. Previous results demonstrate that CD4 Jurkat cells stably expressing the HCV core protein show an increased activation of NFAT transcription factor and an impaired IL-2 promoter activity, affecting intracellular signaling pathways in a manner that mimics clonal anergy. We had shown previously that NFAT activates a transcriptional program, ensuing in immunological tolerance. In the present work, we have engineered lentiviral vectors expressing the HCV core to analyze the events, which unfold in the initial phase of HCV core-induced anergy. We show that genes initially described to be up-regulated by ionomycin-induced anergy in mice are also up-regulated in humans, not only by ionomycin but also by HCV core expression. We also show that HCV core is sufficient to cause NFAT nuclear translocation and a slow-down in cell-cycle progression, and using whole genome microarrays, we identify novel genes up-regulated in Jurkat cells expressing HCV core. The relevance of our results is highlighted by the presence of HCV in CD4 T cells from HCV chronically infected patients.
Thyroid Hormone Replacement for Central Hypothyroidism: A Randomized Controlled Trial Comparing Two Doses of Thyroxine (T4) with a Combination of T4 and Triiodothyronine
Authors: Slawik Marc , Klawitter Björn , Meiser Edith , Schories Marcus , Zwermann Oliver , Borm Katrin , Peper Martin , Lubrich Beate , Hug Martin J. , Nauck Markus , Olschewski Manfred , Beuschlein Felix , Reincke Martin
Published: August 2007

Background: Dosage of T4 in central hypothyroidism is primarily guided by the free serum T4 level (fT4). However, the optimum fT4 range is ill defined, and subtle hypothyroidism might be missed using this approach.

Objectives: Our aim was to investigate the effects of a body weight (bw)-adapted T4 treatment, alone or in combination with T3, on metabolism, well-being, and cognitive function in comparison to a regimen leading to normal fT4.

Design: This was a placebo-controlled trial (double-blind, crossover).

Patients: A total of 29 patients (age 52 ± 2 yr; females/males, 8/21) with hypopituitarism, including TSH deficiency, participated in the study.

Interventions: Three regimens were compared (5 wk each): “EMPIRICAL-T4,” empirical T4 dosage (1 ± 0.05 μg/kg bw) leading to normal fT4; BW-ADAPTED-T4 (1.6 μg/kg bw T4); and “BW-ADAPTED-T3T4,” bw-adapted combination of T3 and T4 (ratio of 1:10).

Results: BW-ADAPTED-T4 administration increased mean fT4 concentrations to the upper limit of the normal range (peak levels). Compared with EMPIRICAL-T4, BW-ADAPTED-T4 treatment resulted in a lower body mass index (BMI) (29.0 ± 0.7 vs. 29.5 ± 0.7 kg/m2; P < 0.03), lower total cholesterol (198 ± 9 vs. 226 ± 7 mg/dl; P < 0.01), and lower low-density lipoprotein (LDL) cholesterol (116 ± 5 vs. 135 ± 7 mg/dl; P < 0.01). BW-ADAPTED-T3T4 treatment was associated with additional beneficial effects on ankle reflex time and working memory but resulted in supraphysiological free serum T3 (fT3) levels.

Limitations: Long-term side effects may have been missed.

Conclusions: Using a dose of 1.6 μg/kg bw improved markers commonly associated with central hypothyroidism. This suggests that T4 dosage based on bw and aiming at fT4 in the upper reference range is superior to titration of T4 aiming at middle normal fT4 concentrations in those patients.
Diagnostic accuracy of the haemoglobin colour scale in neonates and young infants in resource-poor countries
Authors: van Rheenen P F , de Moor L T T
Published: August 2007

Due to the insidious nature of infant anaemia, this disorder frequently remains undetected and untreated by health-care workers in resource-poor settings. We assessed the accuracy of a low-cost and simple diagnostic tool, the haemoglobin colour scale (HCS), in estimating haemoglobin (Hb) values in infants between zero and four months of age. In a rural hospital in Zambia, blood samples were analysed for Hb concentration by HCS and HemoCue method. Bland-Altman plots were used to express agreement between the two methods. The mean difference between HCS and HemoCue at birth ( n = 94), two months ( n = 87) and four months ( n = 69) was 0.39, 0.20 and 0.11g/dL, respectively. Limits of agreement were 2.39 to 1.51, 1.80 to 2.20 and 1.98 to 1.75 g/dL, respectively. Disagreement with HemoCue measurements of more than 2 g/dL was noted in only 4% of all blood samples. We conclude that the HCS provides Hb estimations in infants aged 0-4 months that are sufficiently accurate to improve timely recognition of anaemia in settings where there is no laboratory.
Mortality due to dapsone hypersensitivity syndrome complicating multi-drug therapy for leprosy in Nepal
Authors: Pandey B , Shrestha K , Lewis J , Hawksworth R A , Walker S L
Published: August 2007

Dapsone is a component of multi-drug therapy (MDT) for the treatment of all types of leprosy. It is known that dapsone hypersensitivity syndrome (DHS) complicates the treatment in a proportion of patients. We performed a retrospective study of patients commenced on MDT between 1990 and 2006; 2% developed DHS and 0.25% died due to DHS.
Outbreak of Coxsackie B4 arthritis among newborns and staff of a neonatal unit
Authors: Bhambhani Vikas , Abraham Jacob , Sahni Mohit , Harit A K , Khare Shashi , Puliyel Jacob M
Published: August 2007

We investigated an outbreak of Coxsackie B4 arthritis in a neonatal unit involving 20 neonates and 12 staff members, over an eight-month period. Laboratory investigations, serology tests, indicate that the outbreak was caused by Coxsackie B4 virus. Contamination of one of the overhead water reservoirs, supplying the nursery, was responsible. After the water tanks were cleaned out, no new cases were reported over five years.
Lymphatic filariasis in the coastal areas of Digha, West Bengal, India
Authors: Chandra G , Chatterjee S N , Das S , Sarkar N
Published: August 2007

The state of West Bengal, India, has a long coastline with the Bay of Bengal. No information exists regarding filarial epidemiology and its vector in these coastal areas. The present study was designed to assess the epidemiology of lymphatic filariasis and the role of available mosquitoes as its vector in eight coastal villages around Digha, West Bengal. Night blood samples of 4016 individuals were collected and each of them was examined clinically for any manifestations of the disease. Overall, microfilaria rate, mean microfilarial density and disease rate were 9.06%, 8.63% and 7.72%, respectively. The causative parasite was identified as Wuchereria bancrofti and Culex quinquefasciatus was incriminated as the vector responsible. Vector infection and infectivity rates were assessed to be 12.5% and 0.73%, respectively. The human blood index of human-house-frequenting vector population was 70%. Vector density, vector infection, infectivity rates and human blood index were higher in the rainy season in the study area. Overall, the filarial situation was bad and, as a measure, single-dose diethylcarbamazine citrate (6 mg/kg body weight) treatment was given to all the microfilariaemic patients. Night blood samples of the treated individuals were tested for microfilariae on days 10 and 365, which revealed interesting results.
Burden of diabetic illness in an urban hospital in Nigeria
Authors: Ogbera O
Published: August 2007

This is a retrospective study that set out to determine the mortality patterns and case fatality rates of people with diabetes mellitus (DM) in a Nigerian hospital. The sources of data were the medical records, ward admissions, deaths register and death certificates. Of a total of 13,797 medical admissions made over a period of 11 years (1990-2000),1423 (10.3%) were DM related and the documented case fatality rate of DM was 22.6%.
Children's surgery cancelled due to malaria and anaemia
Authors: Booker S R , Collins C M , Cover J A , Lavy C B D , Brueton R N
Published: August 2007

At our hospital 461 children were admitted for elective orthopaedic and reconstructivesurgery between January and December 2003; 90 of these (19.5%) were positive for malaria, and 37 (8%) had haemoglobin levels below 8 g/dL. The mean delay between admission and operation was five days for patients without anaemia or malaria, 7.17 days for patients with malaria,11.05 days for patients with anaemia and 13 days for patients with both anaemia and malaria.
Evaluating the use and acceptability of a needle-remover device in India
Authors: Muller Nancy , Steele Matthew , Balaji K A , Krishna Madhu , Berman Adriane P , Robertson Joan , Vail Janet
Published: August 2007

The objective of this study was to assess the effect of the use of a manually operated needle remover on sharps-waste management practices in clinical settings in India - specifically, evaluating its acceptability and performance.

Thirty-one Balcan Mini-Destructor needle removers were introduced into seven health facilities in two cities in India - Delhi and Jaipur. One hundred and nineteen health workers, including auxiliary nurse midwives, nurses, and laboratory staff, used the device. Data were prospectively collected by observation and interview on device usage, malfunction and acceptability over a 23-week period. Focus group discussions on current practices were conducted prior to study initiation and, after completion, on device acceptability and performance.

The manual needle remover was well accepted. Devices were seen as easy to use and durable. In total, 88,719 needles were removed.

In conclusion, the needle-remover device was considered an acceptable method of preventing needle reuse and isolating infectious sharps waste in clinical settings.
Neonatal tetanus at the close of the 20th century in Nigeria
Authors: Ogunlesi Tinuade A , Okeniyi John A O , Owa Joshua A , Oyedeji Gabriel A
Published: August 2007

The year 2000 marked another failed World Health Organization deadline for neonatal tetanus (NNT) eradication. Existing preventive strategies can be enhanced by exploring factors involved in the persistence of the scourge. Thus, records of neonates admitted between 1996 and 2000 into the Wesley Guild Hospital, Ilesa, were analysed. Of 3051 total neonatal admissions,162 (5.3%) had NNT. Eighty-nine (54.9%) mothers had clinic-based antenatal care (ANC), but only 59 (36.4%) had tetanus toxoid (TT) vaccines. The majority (66.7%) of them delivered at home or churches and others at either private clinics or primary health centres. Overall, the case fatality rate was 43.8%, though it was significantly higher among babies whose mothers had neither clinic-based ANC (odds ratio [OR] = 2.62; 95% confidence interval [CI] = 1.33-5.18) nor antenatal TT vaccination (OR = 2.41; 95% CI = 1.17-5.03). Thus, improvement on ANC, anti-tetanus immunization and ensuring hygienic deliveries are crucial for eliminating NNT in the 21st century.
Esmarch tourniquet in orthopaedic surgery
Authors: Akinyoola A L , Oginni L M , Orimolade E A , Ogundele O J
Published: August 2007

A bloodless field is important in many orthopaedic operations necessitating the use of a pneumatic tourniquet or Esmarch bandage. The outcome of the use of an Esmarch bandage for exsanguination and as a tourniquet in 112 consecutive patients who had elective orthopaedic operations on 131 limbs was evaluated. The setting was at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, from March 2003 to February 2005. The mean age of the patients was 25.7 + standard deviation years (range 1-70 years). The duration of tourniquet application ranged from 20 min to 2 h 35 min. Four limbs (3.1%) developed acute compartment syndrome; four (3.1%) had tourniquet paralysis with ulnar nerve involvement in three limbs. All limbs regained full neurological function following physiotherapy. There was wound infection in two limbs (1.5%). In spite of its drawbacks, the Esmarch bandage is still useful for exsanguination and as a tourniquet in orthopaedic surgery where there is no pneumatic tourniquet.
Impact of HIV-1infection on survival in patients with haematological malignancies in Yaoundeé, Cameroon
Authors: Mbanya D N , Minkoulou E M , Fezeu L , Kaptue L
Published: August 2007

The impact of HIV-1 infection on the survival of patients with haematological cancers in Yaoundé, Cameroon, was examined. The prevalence of HIV-1was 26.2% among 172 patients, predominantly lymphoid malignancies. At the time of analysis, 75% of patients had died giving an incidence rate of 0.05 deaths per year and a median of survival of 15 (6-27) months. However, the hazard ratio for HIV-infected patients to die was not statistically different from that of uninfected patients (1.3, 95% confidence interval: 0.9-2.0).
Ethnic variations in health-seeking behaviours and attitudes between Fulani herders and Oruba farmers in southwestern Nigeria
Authors: Otusanya Sakiru A , Brieger William R , Titiloye Musibau , Salami Kabiru K , Adesope Azeez
Published: August 2007

Rural Yoruba and Fulani residents of two local governments in Oyo State, Nigeria, were surveyed to determine differences in health-seeking behaviour. Fulani residents were more likely to use private facilities during a recent illness, while Yoruba residents more commonly used government facilities: a fact reflected in the overall attitudes of those surveyed. The need for greater outreach and involvement of minority populations is recommended to enhance public service utilization.
Workers’ factory takeovers and new state policies in Argentina: towards an ‘institutionalisation’ of non-governmental public action?
Authors: Dinerstein Ana Cecilia
Published: August 2007

English

In the last decade many Argentine enterprises became bankrupt, inspiring thousands of workers to take them over and resume production by forming cooperatives. In 2004, the Programme for Self-Managed Work became the instrument by which the government ‘institutionalised’ the takeovers, depoliticising the radical aspects of workers’ actions in exchange for financial and technical assistance in pursuit of workers’ objectives of job preservation and self-managed work. This article presents results from (1) an ongoing ESRC research project on ‘The Movement of the Unemployed in Argentina‘(RES-155-25-0007), NGPA Programme, LSE and (2) previous research on social mobilisation and policy change in Argentina (2002–03).