bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Lactate Dehydrogenase Is a Novel Marker for the Evaluation of Disease Severity in the Early Stage of Toxic Epidermal Necrolysis
Authors: Yun Sook Jung , Choi Myoung-Soon , Piao Mei Shan , Lee Jee-Bum , Kim Seong-Jin , Won Young Ho , Lee Seung-Chul
Published: August 2008

Objective: To evaluate serum lactate dehydrogenase (LDH) and its correlation with skin manifestations in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: Serum LDH levels were measured in 33 patients (17 SJS and 16 TEN), from initial hospital admission to remission stage. Results: The mean LDH level was 920.82 ± 655.50 U/l in TEN and 595.35 ± 182.03 U/l in SJS (normal range: 218–472). We arbitrarily divided these patients into 2 groups, the first were admitted within 3 days of onset (early stage) and the second after 4 days of onset (late stage). The ratio of early- to late-stage patients was 7:9 in TEN and 7:10 in SJS. The mean LDH level for 7 TEN patients in the early stage was 1,319.14 ± 843.10 U/l, which was significantly higher than that of the SJS group (686.71 ± 171.81 U/l; p = 0.024). In the late-stage patients, the mean levels of TEN and SJS patients were 611.0 ± 160.33 and 531.4 ± 167.89 U/l, respectively; these differences between TEN and SJS were not significant. Conclusion: Serum LDH levels can be used as a marker of disease severity in the early stage of TEN.
Superoxide Anion Stress Attenuates the Contractile Response of the Guinea Pig Vas Deferens to ATP and Diadenosine Tetraphosphate
Authors: Al-Rawi Mahmood B. , Aleisa Abdulaziz M. , Khattab Mahmoud M.
Published: August 2008

Induction of endogenous superoxide anion stress by the use of the superoxide dismutase inhibitor diethylthiocarbamate (DETCA; 10 mmol/l) produced a potent inhibition of the ATP (0.3–10 mmol/l) and diadenosine tetraphosphate (AP4A) contractile activity in the isolated vas deferens by 29–92 and 24–90%, respectively. Pyrogallol (0.1 mmol/l), the exogenous superoxide anion generator, produced a significant inhibition on the contractile activity of the vas deferens induced by ATP and AP4A by 33–89 and 25–82%, respectively. DETCA (10 mmol/l) and pyrogallol (0.1 mmol/l) attenuated the contractile response of isolated guinea pig vas deferens strips to the selective P2X agonist α,β-methyleneATP (α,β-meATP; 50 µmol/l) by 25 and 47%, respectively. In Ca2+-free high-K+ (80 mmol/l) Krebs solution, pyrogallol and DETCA produced inhibition of the contractile response to α,β-meATP (50 µmol/l) in similar way to that in normal Krebs solution. The further addition of CaCl2 (1 mmol/l) abolished the inhibitory effects exerted by pyrogallol and DETCA. The control contractile response to α,β-meATP (50 µmol/l) was not affected in Ca2+-free high-K+ (80 mmol/l) Krebs solution. It may be concluded that superoxide anion stress produces a significant inhibitory effect on both mono- and di-nucleotide purinergic contraction of the vas deferens. Superoxide anion appears to interrupt the P2X1-mediated transduction cascade at some step(s) of intracellular calcium handling.
Long-Term Efficacy and Safety Profile of Lanthanum Carbonate: Results for up to 6 Years of Treatment
Authors: Hutchison Alastair J. , Barnett M. Edwina , Krause Rolfdieter , Kwan Jonathan T.C. , Siami Ghodrat A.
Published: August 2008

Background/Aims: Lanthanum carbonate (LC, FOSRENOL®) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy. Methods: Patients from four previous trials entered this study. Results: Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium × phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system. Conclusions: LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.
Effect of Cervical Spine Manipulation on a Pre-Existing Vascular Lesion within the Canine Vertebral Artery
Authors: Wynd Shari , Anderson Todd , Kawchuk Greg
Published: August 2008

Background: Serious adverse events such as cervical artery dissection (CAD) have been reported to occur following cervical spine manipulation therapy (cSMT). To investigate the relation between these events, we utilized an animal model to determine if vertebral arteries with a suspected susceptibility factor (wall lesion) could be injured further by cSMT. Methods: Lesions to the vertebral artery wall were created by angioplasty in 10 anesthetized canines. Resulting injury dimensions were quantified using intravascular ultrasound before and after cSMT. Student’s t were performed to assess the significance of changes in arterial dimension. Results: Statistical analysis demonstrated that the pre-cSMT and post-cSMT lesions did not differ significantly in their length, area or volume (p > 0.05). Conclusions: In this animal model, cSMT did not alter the dimensions of pre-existing vertebral artery lesions.
The Contributions of Paul Ehrlich to Pharmacology: A Tribute on the Occasion of the Centenary of His Nobel Prize
Authors: Bosch Fèlix , Rosich Laia
Published: August 2008

On the centenary of Paul Ehrlich’s Nobel Prize, this German researcher deserves to be remembered as a pioneer in a large number of scientific disciplines. As a result of his enthusiasm and scientific abilities, dedication, and contacts with other scientists of his time, he was able to make countless contributions in fields as diverse as histology, haematology, immunology, oncology, microbiology and pharmacology, among others. Although the Swedish award was meant to recognize the standardization of the manufacture of antidiphtheria serum, it was the discovery of arsphenamine (Salvarsan) for the treatment of syphilis which won him wider international acclaim. From a pharmacological perspective, Ehrlich’s outstanding contributions include dissemination of the ‘magic bullet’ concept for the synthesis of antibacterials, introduction of concepts such as chemoreceptor and chemotherapy, and linking the chemical structure of compounds to their pharmacological activity. These achievements took place within the framework he established for the transition from experimental pharmacology to therapeutic pharmacology. He introduced a modern research system based on the synthesis of multiple chemical structures for pharmacological screening in animal models of disease states. These contributions were undoubtedly decisive in propitiating the wider development of antibiotics decades later. For these reasons, it is fitting to mark the 100th anniversary of the Nobel Prize awarded to this great scientist by commemorating the importance of his contributions to the advance of pharmacology.
Dissociation Between Sympathetic Nerve Traffic and Sympathetically Mediated Vascular Tone in Normotensive Human Obesity
Authors: Agapitov Alexei Vasilievich , Correia Marcelo Lima de Gusmão , Sinkey Christine Ann , Haynes William Geoffrey
Published: August 2008

Obesity increases the risk of hypertension and its cardiovascular complications. This has been partly attributed to increased sympathetic nerve activity, as assessed by microneurography and catecholamine assays. However, increased vasoconstriction in response to obesity-induced sympathoactivation has not been unequivocally demonstrated in obese subjects without hypertension. We evaluated sympathetic α-adrenergic vascular tone in the forearm by brachial arterial infusion of the α-adrenoreceptor antagonist phentolamine (120 μg/min) in normotensive obese (daytime ambulatory arterial pressure: 123±1/77±1 mm Hg; body mass index: 35±1 kg/m
2
) and lean (daytime ambulatory arterial pressure: 123±2/77±2 mm Hg; body mass index: 22±1 kg/m
2
) subjects (n=25 per group) matched by blood pressure, age, and gender. Microneurographic sympathetic nerve activity to skeletal muscle was significantly higher in obese subjects (30±3 versus 22±1 bursts per minute;
P
=0.02). Surprisingly, complete α-adrenergic receptor blockade by phentolamine (at concentrations sufficient to completely inhibit norepinephrine and phenylephrine-induced vasoconstriction) caused equivalent vasodilatation in obese (−57±2%) and lean subjects (−57±3%;
P
=0.9). In conclusion, sympathetic vascular tone in the forearm circulation is not increased in obese normotensive subjects despite increased sympathetic outflow. Vasodilator factors or mechanisms occurring in obese normotensive subjects could oppose the vasoconstrictor actions of increased sympathoactivation. Our findings may help to explain why some obese subjects are protected from the development of hypertension.
Location of a Reflection Site Is Elusive
Authors: Westerhof Berend E. , van den Wijngaard Jeroen P. , Murgo Joseph P. , Westerhof Nicolaas
Published: August 2008

Aortic pulse wave velocity (PWV), a measure of aortic stiffness, is an important indicator of cardiovascular risk. Derivation of PWV from uncalibrated proximal aortic or carotid pressure alone has practical advantages. However, when the time of return of the reflected wave, Δt, is used to calculate PWV, inaccurate data are obtained. With aging PWV increases but Δt hardly decreases, suggesting that the reflection site moves toward the periphery. We hypothesized that the forward and reflected waves in the distal aorta are not in phase, leading to an undefined reflection site. We derived forward and backward waves, at the entrance and distal end of a uniform tube, with length “L.” With the tube closed at the end, forward and reflected waves are there in phase, and PWV=2L/Δt. When the tube is ended with the input impedance of the lower body, forward and backward waves at its end are not in phase, and Δt is increased, suggesting that the reflection site is further away (tube seems longer), and PWV calculated from 2L/Δt is underestimated. Using an anatomically accurate model of the human arterial system, we show that the forward and backward waves in the distal aorta are not in phase. When aortic PWV increases, Δt changes only little, and the reflection site appears to move to the periphery, similar to what is observed in humans. We conclude that to define the location of a reflection site is elusive and that PWV cannot be calculated from time of return of the reflected wave.
“I Believe They Are Papists!”: Natives, Moravians, and the Politics of Conversion in Eighteenth-Century Connecticut
Authors: Fisher Linford D.
Published: August 2008

In 1743, four Moravians evangelizing Natives in western Connecticut were arrested and tried before colonial officials and ministers. Placing this fascinating episode in the context of imperial warfare and religious revivalism of the early 1740s, the essay illustrates how Indians on the borderlands became key players in times of conflict.
“These Stray Letters of Mine”: Forgery and Self-Creation in the Letters of Cardinal William O'Connell
Authors: O'Toole James M.
Published: August 2008

The essay proves that the published Letters of His Eminence, William Cardinal O'Connell (1915) are forgeries. They are still useful, however, in understanding the process by which individuals create and re-create their own lives and in demonstrating the power we invest in documents thought to be “original.”
Le Logos et l'empereur, nouveaux Orphée « Postérité d'une image entrée dans la littérature avec Clément d'Alexandrie »
Authors: Jourdan Fabienne
Published: August 2008

In the Protrepticus, Clement of Alexandria suggests Orpheus' song is a prefiguration of the power of the Word. In the fourth century A. D., Eusebius and Themistius will apply this interpretation of Orpheus' song respectively to the Logos and to the Emperor. In the image proposed by Eusebius the Alexandrian's influence is obvious, whereas its transformation in Themistius illustrates its political evolution. An examination of these two different applications shows not only Clement's role in the transfer of a symbolic figure, but also the originality of its first Christian transposition in the Protrepticus.
Shopping Behavior Among Gay Men
Authors: Reilly Andrew , Rudd Nancy A. , Hillery Julie
Published: August 2008

Literature on gay men and body image are examined in relation to shopping behaviors, with hypotheses developed to test whether one's body image affects consumer choices. The researchers studied credit card debt, shopping frequency, amount of time spent shopping, and shopping venue. An online questionnaire was used to collect data from 213 gay men. Results indicate that Appearance Orientation positively affects shopping in a specialty store, shopping in a thrift store, frequency of shopping, and time spent shopping, whereas Appearance Satisfaction negatively affects television shopping. Thus, body image and shopping are linked. For many gay men, shopping may be a means of establishing or reinforcing cultural identity or a way to express individuality and novelty. Findings can be used by academics and practitioners in developing and examining innovative retail environments. Future research is discussed.
Marketing Segmentation Through Machine Learning Models
Authors: Florez-Lopez Raquel , Ramon-Jeronimo Juan Manuel
Published: August 2008

Customer relationship management (CRM) aims to build relations with the most profitable clients by performing customer segmentation and designing appropriate marketing tools. In addition, customer profitability accounting (CPA) recommends evaluating the CRM program through the combination of partial measures in a global cost—benefit function. Several statistical techniques have been applied for market segmentations although the existence of large data sets reduces their effectiveness. As an alternative, decision trees are machine learning models that do not consider a priori hypotheses, achieve a high performance, and generate logical rules clearly understood by managers. In this article, a three-stage methodology is proposed that combines marketing feature selection, customer segmentation through univariate and oblique decision trees, and a new CPA function based on marketing, data warehousing, and opportunity costs linked to the analysis of different scenarios. This proposal is applied to a large insurance marketing data set for alternative cost and price conditions showing the superiority of univariate decision trees over statistical techniques.
Novel Approaches to the Treatment of Sepsis Syndrome
Authors: Clayton Jennifer K. , Starr Jessica A.
Published: August 2008

Sepsis, severe sepsis, and septic shock are common diagnoses in intensive care units worldwide. In the United States, it is estimated that 750 000 cases of sepsis occur annually. This rate is expected to climb, with an additional 1 million cases per year expected by 2020. These infection-induced inflammatory syndromes ultimately lead to organ dysfunction, and a significantly high mortality rate. Recently, advances in knowledge of sepsis syndrome have led to progress in identifying potential treatment options beyond our current standards of care. Many health care facilities have implemented protocols to guide clinicians to use such standards: early goal-directed therapy and activated protein C therapy in qualifying patients. Nonetheless, debate continues to confuse identification of patient populations in whom corticosteroid therapy should be recommended. While the data describing studies of novel treatment approaches has been controversial in some cases, there have been promising results observed in others. Here we review several treatments that have recently gained attention in the medical literature: HMG-CoA reductase inhibitors (statins), selenium therapy, immunoglobulin therapy, and several agents currently in preclinical study.
Current Perspectives on Extended-Spectrum Beta-Lactamase–Producing Gram-Negative Bacilli
Authors: Wright Brad M. , Eiland Edward H.
Published: August 2008

Beta-lactamase enzymes produced by gram-negative bacilli were identified before the first beta-lactam antibiotics were used to treat infections. As these enzymes adapted to available beta-lactam agents, newer beta-lactam agents were developed. Development and widespread use of the oxyimino-cephalosporins led to the emergence of extended-spectrum beta-lactamase enzymes that hydrolyze the penicillins, extended-spectrum cephalosporins, and aztreonam. There are now over 200 recognized ESBLs in a variety of gram-negative bacilli conferring resistance to penicillins, cephalosporins, a monobactam, and even carbapenems. The emergence of these enzymes is associated with poor patient outcomes, increased total health care costs, and more carbapenem use. Carbapenems should be selected judiciously to optimize outcomes while preventing further selection of extended-spectrum beta-lactamase resistance.
Dreams of Control at a Distance: Gender, Surveillance, and Social Control
Authors: Monahan Torin
Published: August 2008

Modern surveillance systems operate upon masculine logics of disembodied control at a distance. As such, they artificially abstract bodies, identities, and interactions from social contexts in ways that both obscure and aggravate gender and other social inequalities. This article explores the gender dimensions of surveillance systems in several public domains: welfare, healthcare, and transportation. By exposing the dominant rationalities of such systems and critiquing the discourses that support them, one can challenge the supposed neutrality of such technologies and question the power relations to which they give rise. The goal of this article, therefore, is to introduce a new line of inquiry into gender and surveillance, one that perceives surveillance as operating on the level of abstraction but with embodied effects for women and men.
NASCAR and the "Southernization" of America: Spectatorship, Subjectivity, and the Confederation of Identity
Authors: Newman Joshua I. , Giardina Michael D.
Published: August 2008

Written against the backdrop of the exploding popularity of NASCAR auto racing, the authors argue that the American South's post-Emancipation mediated history-and the signifiers through which it has been mediated-legislate a lingua franca of White privilege, White supremacy, and patriarchal hegemony. Under the auspices of a seemingly natural "heritage culture," the authors surmise that "the South" actively stands for something. The authors use this article to make the case that when it is brought to life by way of public spectacle, such as the spectacles of the neo-Confederate sporting local, this imaginary South resurrects the power structures that have long influenced the lived experiences of the region. They conclude by arguing that under the auspices of a Bush-inspired, post-9/11, anti-affirmative action backlash, a hyper-White, neo-Confederate NASCAR gives license to the resurgent regimes of the most vigilant factions of the ethnocentric American White Right.
Jean-Paul Sartre and the Moral Authority of the Intellectual
Authors: Dimitriadis Greg
Published: August 2008

The work of late philosopher Jean-Paul Sartre offers us a trenchant example of a morally engaged and committed thinker at hard work willing to challenge his own ideas to their core as the moment demanded. In the age of the specific intellectual, Sartre's vision of intellectual work foregrounds existential choice, human freedom, and the imaginary. It is a disposition that allowed him to think through and across a variety of social, personal, and intellectual issues with a broad range of discursive forms and tools. More than anything, Sartre offers us a strategy that forces us outward, into the problems of the world, with the goal of interrupting history.
Theoretical Predictors of Delinquency among Public School Students in a Mid-Southern State
Authors: Lowe Nathan C. , May David C. , Elrod Preston
Published: August 2008

Theoretical predictors of delinquency among a sample of rural and small town youths are examined by testing the impact of numerous theoretical indices both within in-school and out-of-school settings, while also examining gender, through the use of structural equation models. Our findings suggest the impact of theoretical predictors on delinquency varies not only by gender, but by social context as well. Implications for policy and future research are discussed.
Maintenance of a normal thymic microenvironment and T-cell homeostasis require Smad4-mediated signaling in thymic epithelial cells
Authors: Jeker Lukas T. , Barthlott Thomas , Keller Marcel P. , Zuklys Saulius , Hauri-Hohl Mathias , Deng Chu-Xia , Holländer Georg A.
Published: August 2008

Signals mediated by the transforming growth factor-β superfamily of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis, and function, but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical transforming growth factor-β signaling by the loss of Smad4 expression in TECs leads to qualitative changes in TEC function and a progressively disorganized thymic microenvironment. Moreover, the number of thymus resident early T-lineage progenitors is severely reduced in the absence of Smad4 expression in TECs and directly correlates with extensive thymic and peripheral lymphopenia. Our observations hence place Smad4 within the signaling events in TECs that determine total thymus cellularity by controlling the number of early T-lineage progenitors.
Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations
Authors: Tunstall-Pedoe Oliver , Roy Anindita , Karadimitris Anastasios , de la Fuente Josu , Fisk Nicholas M. , Bennett Phillip , Norton Alice , Vyas Paresh , Roberts Irene
Published: August 2008

Down syndrome (DS) children have a high frequency of acute megakaryoblastic leukemia (AMKL) in early childhood. At least 2 in utero genetic events are required, although not sufficient, for DS-AMKL: trisomy 21 (T21) and N-terminal–truncating GATA1 mutations. To investigate the role of T21 in DS-AMKL, we compared second trimester hemopoiesis in DS without GATA1 mutations to gestation-matched normal controls. In all DS fetal livers (FLs), but not marrows, megakaryocyte-erythroid progenitor frequency was increased (55.9% ± 4% vs 17.1% ± 3%, CD34+CD38+ cells; P < .001) with common myeloid progenitors (19.6% ± 2% vs 44.0% ± 7%) and granulocyte-monocyte (GM) progenitors (15.8% ± 4% vs 34.5% ± 9%) commensurately reduced. Clonogenicity of DS-FL versus normal FL CD34+ cells was markedly increased (78% ± 7% vs 15% ± 3%) affecting megakaryocyte-erythroid (∼ 7-fold higher) and GM and colony-forming unit–granulocyte, erythrocyte macrophage, megakaryocyte (CFU-GEMM) progenitors. Replating efficiency of CFU-GEMM was also markedly increased. These data indicate that T21 itself profoundly disturbs FL hemopoiesis and they provide a testable hypothesis to explain the increased susceptibility to GATA1 mutations in DS-AMKL and DS-associated transient myeloproliferative disorder.
Evolutionary conservation of zinc finger transcription factor binding sites in promoters of genes co-expressed with WT1 in prostate cancer
Authors: Eisermann Kurtis , Tandon Sunpreet , Bazarov Anton , Brett Adina , Fraizer Gail , Piontkivska Helen
Published: August 2008

Background

Gene expression analyses have led to a better understanding of growth control of prostate cancer cells. We and others have identified the presence of several zinc finger transcription factors in the neoplastic prostate, suggesting a potential role for these genes in the regulation of the prostate cancer transcriptome. One of the transcription factors (TFs) identified in the prostate cancer epithelial cells was the Wilms tumor gene (WT1). To rapidly identify coordinately expressed prostate cancer growth control genes that may be regulated by WT1, we used anin silicoapproach.

Results

Evolutionary conserved transcription factor binding sites (TFBS) recognized by WT1, EGR1, SP1, SP2, AP2 and GATA1 were identified in the promoters of 24 differentially expressed prostate cancer genes from eight mammalian species. To test the relationship between sequence conservation and function, chromatin of LNCaP prostate cancer and kidney 293 cells were tested for TF binding using chromatin immunoprecipitation (ChIP). Multiple putative TFBS in gene promoters of placental mammals were found to be shared with those in human gene promoters and some were conserved between genomes that diverged about 170 million years ago (i.e., primates and marsupials), therefore implicating these sites as candidate binding sites. Among those genes coordinately expressed withWT1was the kallikrein-related peptidase 3 (KLK3) gene commonly known as the prostate specific antigen (PSA) gene. This analysis located several potential WT1 TFBS in thePSAgene promoter and led to the rapid identification of a novel putative binding site confirmedin vivoby ChIP. Conversely for two prostate growth control genes, androgen receptor (AR) and vascular endothelial growth factor (VEGF), known to be transcriptionally regulated by WT1, regulatory sequence conservation was observed and TF bindingin vivowas confirmed by ChIP.

Conclusion

Overall, this targeted approach rapidly identified important candidate WT1-binding elements in genes coordinately expressed with WT1 in prostate cancer cells, thus enabling a more focused functional analysis of the most likely target genes in prostate cancer progression. Identifying these genes will help to better understand how gene regulation is altered in these tumor cells.
Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells
Authors: Jorgensen Ellen , Stinson Andy , Shan Lin , Yang Jin , Gietl Diana , Albino Anthony P
Published: August 2008

Background

Although lung cancer is among the few malignancies for which we know the primary etiological agent (i.e., cigarette smoke), a precise understanding of the temporal sequence of events that drive tumor progression remains elusive. In addition to finding that cigarette smoke (CS) impacts the functioning of key pathways with significant roles in redox homeostasis, xenobiotic detoxification, cell cycle control, and endoplasmic reticulum (ER) functioning, our data highlighted a defensive role for the unfolded protein response (UPR) program. The UPR promotes cell survival by reducing the accumulation of aberrantly folded proteins through translation arrest, production of chaperone proteins, and increased degradation. Importance of the UPR in maintaining tissue health is evidenced by the fact that a chronic increase in defective protein structures plays a pathogenic role in diabetes, cardiovascular disease, Alzheimer's and Parkinson's syndromes, and cancer.

Methods

Gene and protein expression changes in CS exposed human cell cultures were monitored by high-density microarrays and Western blot analysis. Tissue arrays containing samples from 110 lung cancers were probed with antibodies to proteins of interest using immunohistochemistry.

Results

We show that: 1) CS induces ER stress and activates components of the UPR; 2) reactive species in CS that promote oxidative stress are primarily responsible for UPR activation; 3) CS exposure results in increased expression of several genes with significant roles in attenuating oxidative stress; and 4) several major UPR regulators are increased either in expression (i.e., BiP and eIF2α) or phosphorylation (i.e., phospho-eIF2α) in a majority of human lung cancers.

Conclusion

These data indicate that chronic ER stress and recruitment of one or more UPR effector arms upon exposure to CS may play a pivotal role in the etiology or progression of lung cancers, and that phospho-eIF2α and BiP may have diagnostic and/or therapeutic potential. Furthermore, we speculate that upregulation of UPR regulators (in particular BiP) may provide a pro-survival advantage by increasing resistance to cytotoxic stresses such as hypoxia and chemotherapeutic drugs, and that UPR induction is a potential mechanism that could be attenuated or reversed resulting in a more efficacious treatment strategy for lung cancer.
Tetratricopeptide repeat domain 9A is an interacting protein for tropomyosin Tm5NM-1
Authors: Cao Shenglan , Ho Gay Hui , Lin Valerie CL
Published: August 2008

Background

Tetratricopeptide repeat domain 9A (TTC9A) protein is a recently identified protein which contains three tetratricopeptide repeats (TPRs) on its C-terminus. In our previous studies, we have shown that TTC9A was a hormonally-regulated gene in breast cancer cells. In this study, we found that TTC9A was over-expressed in breast cancer tissues compared with the adjacent controls (P < 0.00001), suggesting it might be involved in the breast cancer development process. The aim of the current study was to further elucidate the function of TTC9A.

Methods

Breast samples from 25 patients including the malignant breast tissues and the adjacent normal tissues were processed for Southern blot analysis. Yeast-two-hybrid assay, GST pull-down assay and co-immunoprecipitation were used to identify and verify the interaction between TTC9A and other proteins.

Results

Tropomyosin Tm5NM-1 was identified as one of the TTC9A partner proteins. The interaction between TTC9A and Tm5NM-1 was further confirmed by GST pull-down assay and co-immunoprecipitation in mammalian cells. TTC9A domains required for the interaction were also characterized in this study. The results suggested that the first TPR domain and the linker fragment between the first two TPR domains of TTC9A were important for the interaction with Tm5NM-1 and the second and the third TPR might play an inhibitory role.

Conclusion

Since the primary function of tropomyosin is to stabilize actin filament, its interaction with TTC9A may play a role in cell shape and motility. In our previous results, we have found that progesterone-induced TTC9A expression was associated with increased cell motility and cell spreading. We speculate that TTC9A acts as a chaperone protein to facilitate the function of tropomyosins in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis.
Comparison of the mismatch-specific endonuclease method and denaturing high-performance liquid chromatography for the identification of HBB gene mutations
Authors: Hung Chia-Cheng , Su Yi-Ning , Lin Chia-Yun , Chang Yin-Fei , Chang Chien-Hui , Cheng Wen-Fang , Chen Chi-An , Lee Chien-Nan , Lin Win-Li
Published: August 2008

Background

Beta-thalassemia is a common autosomal recessive hereditary disease in the Meditertanean, Asia and African areas. Over 600 mutations have been described in the beta-globin (HBB), of which more than 200 are associated with a beta-thalassemia phenotype.

Results

We used two highly-specific mutation screening methods, mismatch-specific endonuclease and denaturing high-performance liquid chromatography, to identify mutations in the HBB gene. The sensitivity and specificity of these two methods were compared. We successfully distinguished mutations in the HBB gene by the mismatch-specific endonuclease method without need for further assay. This technique had 100% sensitivity and specificity for the study sample.

Conclusion

Compared to the DHPLC approach, the mismatch-specific endonuclease method allows mutational screening of a large number of samples because of its speed, sensitivity and adaptability to semi-automated systems. These findings demonstrate the feasibility of using the mismatch-specific endonuclease method as a tool for mutation screening.
Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression
Authors: Hansson Frida , Toporski Jacek , Månsson Robert , Johansson Bertil , Norén-Nyström Ulrika , Jacobsen Sten Eirik W , Wiebe Thomas , Larsson Marcus , Sigvardsson Mikael , Castor Anders
Published: August 2008

Background

Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements.

Results

Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage.

Conclusion

The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.
Albuminuria and its correlates in an Iranian type 2 diabetic population
Authors: Nakhjavani Manouchehr , Esteghamati Alireza , Esfahanian Fatemeh , Aghamohammadzadeh Naser , Hamidi Sepehr , Meysamie Alipasha , Abbasi Mehrshad
Published: August 2008

Objective

To study the prevalence and correlates of increased urinary albumin excretion (UAE) in an Iranian type 2 diabetic population.

Methods

Over a one year period since October 2002, 400 consecutive type 2 diabetic patients referred to an outpatient diabetes clinic, were enrolled in a cross sectional study. Subjects had no history of renal impairment or overt proteinuria. Data concerning demographic characteristics and cardiovascular risk factors were recorded and height, weight and blood pressure were measured. Glucose, cholesterol, HDL-C, LDL-C, triglyceride, apoprotein B, lipoprotein a, creatinine, and HbA1c were measured in fasting blood samples. Overnight twelve-hour UAE were assessed by immunoturbidometry method. Regression analyses were employed to determine the correlates of UAE.

Results

Out of 400 patients, 156 (40%) subjects had increased UAE (UAE ≥ 30 mg/24 hour). The UAE was higher in males compared to females (145.5 vs. 72.1 mg/day; p < 0.05); however, the age and HDL adjusted UAE levels were not significantly different between men and women (120.1 vs. and 87.9 mg/day; p = 0.37). Increased UAE was correlated with decreasing HDL-C and a longer duration of diabetes independent of other variables; increased UAE was correlated with HbA1c as well. Age, systolic and diastolic blood pressure, total cholesterol, LDL-C, triglyceride, apoprotein B, lipoprotein a, and GFR did not correlate with increased UAE.

Conclusion

In this study, increased UAE was considerably frequent among type 2 diabetic patients without any significant history of renal dysfunction. Albuminuria was found to be associated with dyslipidemia (low HDL-C), long duration of diabetes, and uncontrolled glycemia revealed by higher HbA1c.
The identification of allergen proteins in sugar beet (Beta vulgaris) pollen causing occupational allergy in greenhouses
Authors: Luoto Susanne , Lambert Wietske , Blomqvist Anna , Emanuelsson Cecilia
Published: August 2008

Background

During production of sugar beet (Beta vulgaris) seeds in greenhouses, workers frequently develop allergic symptoms. The aim of this study was to identify and characterize possible allergens in sugar beet pollen.

Methods

Sera from individuals at a local sugar beet seed producing company, having positive SPT and specific IgE to sugar beet pollen extract, were used for immunoblotting. Proteins in sugar beet pollen extracts were separated by 1- and 2-dimensional electrophoresis, and IgE-reactive proteins analyzed by liquid chromatography tandem mass spectrometry.

Results

A 14 kDa protein was identified as an allergen, since IgE-binding was inhibited by the well-characterized allergen Che a 2, profilin, from the related species Chenopodium album. The presence of 17 kDa and 14 kDa protein homologues to both the allergens Che a 1 and Che a 2 were detected in an extract from sugar beet pollen, and partial amino acid sequences were determined, using inclusion lists for tandem mass spectrometry based on homologous sequences.

Conclusion

Two occupational allergens were identified in sugar beet pollen showing sequence similarity with Chenopodium allergens. Sequence data were obtained by mass spectrometry (70 and 25%, respectively for Beta v 1 and Beta v 2), and can be used for cloning and recombinant expression of the allergens. As for treatment of Chenopodium pollinosis, immunotherapy with sugar beet pollen extracts may be feasible.
The prediction of interferon treatment effects based on time series microarray gene expression profiles
Authors: Huang Tao , Tu Kang , Shyr Yu , Wei Chao-Chun , Xie Lu , Li Yi-Xue
Published: August 2008

Background

The status of a disease can be reflected by specific transcriptional profiles resulting from the induction or repression activity of a number of genes. Here, we proposed a time-dependent diagnostic model to predict the treatment effects of interferon and ribavirin to HCV infected patients by using time series microarray gene expression profiles of a published study.

Methods

In the published study, 33 African-American (AA) and 36 Caucasian American (CA) patients with chronic HCV genotype 1 infection received pegylated interferon and ribavirin therapy for 28 days. HG-U133A GeneChip containing 22283 probes was used to analyze the global gene expression in peripheral blood mononuclear cells (PBMC) of all the patients on day 0 (pretreatment), 1, 2, 7, 14, and 28. According to the decrease of HCV RNA levels on day 28, two categories of responses were defined: good and poor. A voting method based on Student's t test, Wilcoxon test, empirical Bayes test and significance analysis of microarray was used to identify differentially expressed genes. A time-dependent diagnostic model based on C4.5 decision tree was constructed to predict the treatment outcome. This model not only utilized the gene expression profiles before the treatment, but also during the treatment. Leave-one-out cross validation was used to evaluate the performance of the model.

Results

The model could correctly predict all Caucasian American patients' treatment effects at very early time point. The prediction accuracy of African-American patients achieved 85.7%. In addition, thirty potential biomarkers which may play important roles in response to interferon and ribavirin were identified.

Conclusion

Our method provides a way of using time series gene expression profiling to predict the treatment effect of pegylated interferon and ribavirin therapy on HCV infected patients. Similar experimental and bioinformatical strategies may be used to improve treatment decisions for other chronic diseases.
TKTL1 is overexpressed in a large portion of non-small cell lung cancer specimens
Authors: Schultz Holger , Kähler Daniel , Branscheid Detlev , Vollmer Ekkehard , Zabel Peter , Goldmann Torsten
Published: August 2008

In several tumors the transketolase activity, controlled inter alia by enzymes of the pentose phosphate pathway which is an alternative, energy generating reaction-cascade to glycolysis, has been correlated with proliferation. The increase of thiamine-dependant transketolase enzyme reactions is induced especially through upregulated transketolase-like enzyme 1 (TKTL1)-activity; that shows TKTL1 to be a causative enzyme for tumors enhanced, anaerobic glucose degradation. We investigated TKTL1-expression in 88 human, formalin-fixed non-small cell lung cancer tissues and 24 carcinomas of the breast by immunohistochemical stainings applying a 0 to 3 staining-score system (3 = strongest expression). For means of validation we additionally stained 40 NSCLC fixed and paraffin-embedded utilizing the HOPE-technique; showing comparable results to the formalin-fixed, paraffin-embedded specimens (not shown). Potential correlations with age, sex, TNM-classification parameters and tumor grading as well as tumor transcription factor 1 (TTF1) and surfactant protein A (SPA) expression were investigated. 40.9% of the analyzed lung tumors expressed TKTL1 weakly (Score 1), 38.6% moderately (score 2) and 17.1% strongly (score 3). 3 tumors were diagnosed TKTL1-negative (3.4%; score 0). All Breast cancer specimen stainings were positive and scored 1: 32%; scored 2: 36%; scored 3: 32%. Alveolar macrophages and Alveolar Epithelial Cells Type II were also found to be TKTL1-positive.

None of the listed clinical parameters could be found to show a significant correlation to TKTL1 signal appearance.

Although we describe the expression of TKTL1 in lung cancers, we need to state that up till now there is no scientific indication for any treatment regimens based upon these findings.
Pancreatic tuberculosis with splenic tuberculosis mimicking advanced pancreatic cancer with splenic metastasizes: a case report
Authors: Rong YF , Lou WH , Jin DY
Published: August 2008

A 60-year-old woman presented with vague abdominal pain for one week was referred to pancreatic tail carcinoma accompanied with splenic metastasizes. She came to our hospital for further treatment. Ultrasonography and abdominal computed tomography (CT) revealed a pancreatic tail tumor with splenic metastasizes. There was no history of tuberculosis. Laparotomy was performed because pancreatic tail carcinoma with splenic metastasizes was highly suspected. Indurated mass in the pancreatic tail and sporadic metastasizes in the spleen had been found during the surgery. The pancreatic tail and the spleen were removed and proved to be tuberculosis on histological examination of a frozen section. The patient was given antituberculosis therapy and is now getting well. Tuberculosis should be considered in the differential diagnosis of pancreatic masses. The response to antituberculosis treatment is very favorable.
Role of fibroblast growth factor 8 (FGF8) in animal models of osteoarthritis
Authors: Uchii Masako , Tamura Tadafumi , Suda Toshio , Kakuni Masakazu , Tanaka Akira , Miki Ichiro
Published: August 2008

Introduction

Fibroblast growth factor 8 (FGF8) is isolated as an androgen-induced growth factor, and has recently been shown to contribute to limb morphogenesis. The aim of the present study was to clarify the role of FGF8 in animal models of osteoarthritis (OA).

Methods

The expression of FGF8 in the partial meniscectomy model of OA in the rabbit knee was examined by immunohistochemistry. The effect of intraperitoneal administration of anti-FGF8 antibody was tested in a model of OA that employed injection of monoiodoacetic acid or FGF8 into the knee joint of rats. The effect of FGF8 was also tested using cultured chondrocytes. Rabbit articular chondrocytes were treated with FGF8 for 48 hours, and the production of matrix metalloproteinase and the degradation of sulfated glycosaminoglycan in the extracellular matrix (ECM) were measured.

Results

The expression of FGF8 in hyperplastic synovial cells and fibroblasts was induced in the meniscectomized OA model, whereas little or no expression was detected in normal synovium. Injection of FGF8 into rat knee joints induced the degradation of the ECM, which was suppressed by anti-FGF8 antibody. In the monoiodoacetic acid-induced arthritis model, anti-FGF8 antibody reduced ECM release into the synovial cavity. In cultured chondrocytes, FGF8 induced the release of matrix metalloproteinase 3 and prostaglandin E2, and caused degradation of the ECM. The combination of FGF8 and IL-1α accelerated the degradation of the ECM. Anti-FGF8 antibody suppressed the effects of FGF8 on the cells.

Conclusion

FGF8 is produced by injured synovium and enhances the production of protease and prostaglandin E2 from inflamed synoviocytes. Degradation of the ECM is enhanced by FGF8. FGF8 may therefore participate in the degradation of cartilage and exacerbation of osteoarthritis.
The Role of the Hospital in Psychiatric Research
Authors: Monro A. B.
Published: August 2008

Some time ago one could have said both truly and succinctly that hospitals are the places where patients are, and from this basic premise it would have been fairly easy to work out a presentable picture of the role of hospitals in research. Now, however, epidemiologists tell us that many mentally sick people are not admitted to hospital, and clinicians stress that if admission occurs it is likely to represent a recurrent episode in a long programme of management in which important therapeutic influences are brought to bear on the patient at work or in other places remote from hospital. It therefore seems reasonable to conclude that certain types or phases of research which might once have been carried out in hospital must now be done elsewhere.
Motherhood and Childlessness in Monozygous Twins
Authors: Kaij L. , Malmquist A.
Published: August 2008

Gross somatic illnesses and psychotic reactions associated with pregnancy, parturition and the puerperium are well known, but it is only in recent years that attention has been paid in any systematic way to milder neurotic reactions post partum. During the last decade reports have appeared from several centres on woman's reactions to pregnancy, studied from various viewpoints. As regards psychological reactions it is obvious that the modern Western woman has to a considerable extent an ambivalent attitude to maternity. It is therefore hardly surprising if this attitude, together with the sometimes pronounced somatic strain of pregnancy, results in a high frequency of emotional disturbances during and after pregnancy.
Basic Psychoanalytic Concepts: X. Interpretations and other Interventions
Authors: Sandler J. , Dare C. , Holder A.
Published: August 2008

Previous papers in this series have concentrated on concepts which relate to the communications brought by the patient and to the factors, in both patient and therapist, which either facilitate or hinder the free flow and understanding of these communications. However, in the discussionof working through(Sandler, Dare and Holder, 1970a) reference was made to those interventions of the analyst which aim at bringing about enduring changes in the patient, and to the need for continual elaboration and reinforcement of the analyst's interventions. Whilst the term ‘interpretation’ is often used in a general sense to refer to these interventions (at least, to the extent that they are verbal) it seems appropriate to examine the concept in some detail.
Body-Mind Problems from an Empirical Point of View
Authors: Polonio P.
Published: August 2008

At one time the doctor used to treat both the patient and his illness; with the understanding of aetiology comes the possibility of ignoring the patient, saying only ‘take the pills and you will recover’. Since such treatments have become all too easy, both doctors and patients have turned away from them to personality problems and the symptoms of psychogenic disorders, so much more difficult, more time-consuming and more interesting.
Amniocentesis: A Means of Pre-Natal Diagnosis of Conditions Associated with Severe Mental Subnormality
Authors: Cowie Valerie A.
Published: August 2008

In the past two decades revolutionary scientific advances and social developments have changed our attitude to the management of conditions associated with severe mental subnormality. Therapeutic achievement has admittedly been on a limited scale, and in terms of medical treatment in the conventional medical sense is likely to remain so. Very great hope lies, however, in the use of our newly-gained knowledge and expertise for prevention rather than cure.