bluuebunny/crossref_metadata_2025 huggingface dataset:
Aldose Reductase Regulates Growth Factor-Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Colon Cancer Cells
Authors: Tammali Ravinder , Ramana Kota V. , Singhal Sharad S. , Awasthi Sanjay , Srivastava Satish K.
Published: October 2006

Inhibition of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2 by nonsteroidal anti-inflammatory drugs reduces the progression of colon cancer. Inhibition of aldose reductase (AR; EC. 1.1.1.21.) by sorbinil or by antisense ablation prevented fibroblast growth factor–induced and platelet-derived growth factor–induced up-regulation of PGE2 synthesis in human colon cancer cells, Caco-2. AR besides reducing aldo-sugars efficiently reduces toxic lipid aldehydes and their conjugates with glutathione. Inhibition of AR prevented growth factor-induced COX-2 activity, protein, and mRNA and significantly decreased activation of nuclear factor-κB and protein kinase C (PKC) and phosphorylation of PKC-β2 as well as progression of Caco-2 cell growth but had no effect on COX-1 activity. Cell cycle analysis suggests that inhibition of AR prevents growth factor-induced proliferation of Caco-2 cells at S phase. Treatment of Caco-2 cells with the most abundant and toxic lipid aldehyde 4-hydroxy-trans-2-nonenal (HNE) or its glutathione-conjugate [glutathionyl-HNE (GS-HNE)] or AR-catalyzed product of GS-HNE, glutathionyl-1,4-dihydroxynonane (GS-DHN), resulted in increased COX-2 expression and PGE2 production. Inhibition of AR prevented HNE- or GS-HNE-induced but not GS-DHN-induced up-regulation of COX-2 and PGE2. More importantly, in vivo studies showed that administration of AR-small interfering RNA (siRNA), but not control siRNA, to nude mice bearing SW480 human colon adenocarcinoma cells completely arrested tumor progression. Collectively, these observations suggest that AR is an obligatory mediator of growth factor-induced up-regulation of COX-2, PGE2, and growth of Caco-2 cells, indicating that inhibition of AR may be a novel therapeutic approach in preventing the progression of colon cancer. (Cancer Res 2006; 66(19): 9705-13)
Enhancer of Zeste 2 as a Marker of Preneoplastic Progression in the Breast
Authors: Ding Lei , Kleer Celina G.
Published: October 2006

Amplification of the Polycomb group transcriptional repressor Enhancer of Zeste 2 (EZH2) occurs in various malignancies including breast cancer, where its overexpression is associated with poor outcome. We found that EZH2 is up-regulated in ductal carcinoma in situ, atypical ductal hyperplasia, and even morphologically normal breast epithelial cells from women who have an increased risk of breast cancer. This review discusses how EZH2 may promote neoplastic conversion and it surveys the evidence suggesting that EZH2 may offer a clinical tool to help identify patients at risk for developing breast cancer before precursor lesions are histologically evident. (Cancer Res 2006; 66(19): 9352-5)
Targeted Disruption of Protein Kinase Cε Reduces Cell Invasion and Motility through Inactivation of RhoA and RhoC GTPases in Head and Neck Squamous Cell Carcinoma
Authors: Pan Quintin , Bao Li Wei , Teknos Theodoros N. , Merajver Sofia D.
Published: October 2006

Over 70% of patients with head and neck squamous cell carcinoma (HNSCC) present with locoregionally advanced stage III and IV disease. In spite of aggressive therapy, locoregional disease recurs in 60% and metastatic disease develops in 15% to 25% of patients causing a major decline in quality and length of life. Therefore, there is a need to identify and understand genes that are responsible for inducing an aggressive HNSCC phenotype. Evidence has shown that protein kinase C (PKC) ε is a transforming oncogene and may play a role in HNSCC progression. In this study, we determine the downstream signaling pathway mediated by PKCε to promote an aggressive HNSCC phenotype. RNA interference knockdown of PKCε in UMSCC11A and UMSCC36, two highly invasive and motile HNSCC cell lines with elevated endogenous PKCε levels, resulted in cells that were significantly less invasive and motile than the small interfering RNA–scrambled control transfectants; 51 ± 5% (P < 0.006) and 49 ± 3% (P < 0.010) inhibition in invasion and 69 ± 1% (P < 0.0005) and 66 ± 3% (P < 0.0001) inhibition in motility, respectively. PKCε-deficient UMSCC11A clones had reduced levels of active and serine-phosphorylated RhoA and RhoC. Moreover, constitutive active RhoA completely rescued the invasion and motility defect, whereas constitutive active RhoC completely rescued the invasion and partially rescued the motility defect of PKCε-deficient UMSCC11A clones. These results indicate that RhoA and RhoC are downstream of PKCε and critical for PKCε-mediated cell invasion and motility. Our study shows, for the first time, that PKCε is involved in a coordinated regulation of RhoA and RhoC activation, possibly through direct post-translational phosphorylation. (Cancer Res 2006; 66(19): 9379-84)
High Serum C-Reactive Protein Level Is Not an Independent Predictor for Stroke
Authors: Bos Michiel J. , Schipper C. Maarten A. , Koudstaal Peter J. , Witteman Jacqueline C.M. , Hofman Albert , Breteler Monique M.B.
Published: October 2006

Background—

Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke.

Methods and Results—

The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990–1993) were ≥55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only.

Conclusions—

Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.
Cardiac Troponin I but Not Cardiac Troponin T Induces Severe Autoimmune Inflammation in the Myocardium
Authors: Göser Stefan , Andrassy Martin , Buss Sebastian J. , Leuschner Florian , Volz Christian H. , Öttl; Renate , Zittrich; Stefan , Blaudeck Natascha , Hardt Stefan E. , Pfitzer Gabriele , Rose Noel R. , Katus Hugo A. , Kaya Ziya
Published: October 2006

Background—

Cardiac troponins in blood are the most preferred markers of myocardial damage. The fact that they are normally not found in the circulation provides a high level of clinical sensitivity and specificity even when cardiac lesions are small. After myocardial injury, the troponins enter the circulation, where they can be used for diagnosis of acute coronary syndromes. Thus, the cardiac troponins are paramount for disease classification and risk stratification. However, little is known about the long-term effects of the released troponins on cardiac function.

Methods and Results—

In this study we prepared recombinant murine cardiac troponin I (mc-TnI) and murine cardiac troponin T and used them to immunize mice. We report that A/J mice immunized with mc-TnI developed severe inflammation of the myocardium with increased expression of inflammatory chemokines RANTES (regulated on activation normal T cell expressed and secreted), monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)–1α, MIP-1β, MIP-2, T-cell activation gene 3, and eotaxin and chemokine receptors CCR1, CCR2, and CCR5. The inflammation was followed by cardiomegaly, fibrosis, reduced fractional shortening, and 30% mortality over 270 days. In contrast, mice immunized with murine cardiac troponin T or with the control buffer showed little or no inflammation and no death. Furthermore, we demonstrate that mice preimmunized with mc-TnI before left anterior descending coronary artery ligation showed greater infarct size, more fibrosis, higher inflammation score, and reduced fractional shortening.

Conclusions—

Overall, our results show for the first time that provocation of an autoimmune response to mc-TnI induces severe inflammation in the myocardium followed by fibrosis and heart failure with increased mortality in mice.
Moscow's Proxy? Cuba and Africa 1975–1988
Authors: Gleijeses Piero
Published: October 2006

This article explores the role that Cuba played in Africa after its dispatch of 36,000 soldiers to Angola in late 1975 and the first few months of 1976. The article focuses on the two most important aspects of Cuba's policy in Africa after 1976: its intervention in Ethiopia in 1977–1978; and its continuing presence in Angola, a presence that continued until 1991. The article analyzes Cuba's motivations, the extent to which Fidel Castro's policy was a function of Soviet demands, and the effect of Cuba's policy in Africa on relations with the United States. The concluding section offers an assessment of the costs and benefits of Cuba's policy.
The Predictability of Interdecadal Changes in ENSO Activity and ENSO Teleconnections
Authors: Power Scott , Haylock Malcolm , Colman Rob , Wang Xiangdong
Published: October 2006

El Niño–Southern Oscillation (ENSO) in a century-long integration of a Bureau of Meteorology Research Centre (BMRC) coupled general circulation model (CGCM) drives rainfall and temperature changes over Australia that are generally consistent with documented observational changes: dry/hot conditions occur more frequently during El Niño years and wet/mild conditions occur more frequently during La Niña years. The relationship between ENSO [as measured by Niño-4 or the Southern Oscillation index (SOI), say] and all-Australia rainfall and temperature is found to be nonlinear in the observations and in the CGCM during June–December: a large La Niña sea surface temperature (SST) anomaly is closely linked to a large Australian response (i.e., Australia usually becomes much wetter), whereas the magnitude of an El Niño SST anomaly is a poorer guide to how dry Australia will actually become. Australia tends to dry out during El Niño events, but the degree of drying is not as tightly linked to the magnitude of the El Niño SST anomaly. Nonlinear or asymmetric teleconnections are also evident in the western United States/northern Mexico. The implications of asymmetric teleconnections for prediction services are discussed.

The relationship between ENSO and Australian climate in both the model and the observations is strong in some decades, but weak in others. A series of decadal-long perturbation experiments are used to show that if these interdecadal changes are predictable, then the level of predictability is low. The model’s Interdecadal Pacific Oscillation (IPO), which represents interdecadal ENSO-like SST variability, is statistically linked to interdecadal changes in ENSO’s impact on Australia during June–December when ENSO’s impact on Australia is generally greatest. A simple stochastic model that incorporates the nonlinearity above is used to show that the IPO [or the closely related Pacific Decadal Oscillation (PDO)] can appear to modulate ENSO teleconnections even if the IPO–PDO largely reflect unpredictable random changes in, for example, the relative frequency of El Niño and La Niña events in a given interdecadal period.

Note, however, that predictability in ENSO-related variability on decadal time scales might be either underestimated by the CGCM, or be too small to be detected by the modest number of perturbation experiments conducted. If there is a small amount of predictability in ENSO indices on decadal time scales, and there may be, then the nonlinearity described above provides a mechanism via which ENSO teleconnections could be modulated on decadal time scales in a partially predictable fashion.
Estimates of Power Consumed by Mixing in the Ocean Interior
Authors: St. Laurent Louis , Simmons Harper
Published: October 2006

Much attention has focused on the power required for driving mixing processes in the ocean interior, the thermohaline circulation, and the related meridional overturning circulation (MOC). Recent estimates range from roughly 0.5 to 2 TW (1 TW = 1 × 1012 W), based on differing arguments for the closure of the MOC mass budget. While these values are both O(1) TW, the thermodynamic implications of the estimates are significantly different. In addition, these numbers represent an integral constraint on the global circulation, and the apparent discrepancy merits careful examination. Through basic thermodynamic considerations on water mass mixing, a mechanical power consumption of 3 ± 1 TW is found to be consistent with a basic knowledge of the distribution and magnitude of oceanic turbulence diffusivities. This estimate is somewhat independent of any specific model for mass closure of the MOC. In addition, this estimate is based on a thermocline diffusivity of only 0.1 cm2 s−1, with enhanced diffusivities acting only in the deep and bottom waters. Adding enhanced diffusivities in the upper ocean, or lowering the mixing efficiency below 20%, will increase the power estimate. Moreover, 3 TW is a reasonable estimate for the power availability to processes acting beneath the oceanic mixed layer.
Two Approaches to Quantifying Uncertainty in Global Temperature Changes
Authors: Lopez Ana , Tebaldi Claudia , New Mark , Stainforth Dave , Allen Myles , Kettleborough Jamie
Published: October 2006

A Bayesian statistical model developed to produce probabilistic projections of regional climate change using observations and ensembles of general circulation models (GCMs) is applied to evaluate the probability distribution of global mean temperature change under different forcing scenarios. The results are compared to probabilistic projections obtained using optimal fingerprinting techniques that constrain GCM projections by observations. It is found that, due to the different assumptions underlying these statistical approaches, the predicted distributions differ significantly in particular in their uncertainty ranges. Results presented herein demonstrate that probabilistic projections of future climate are strongly dependent on the assumptions of the underlying methodologies.
State of the Ground: Climatology and Changes during the Past 69 Years over Northern Eurasia for a Rarely Used Measure of Snow Cover and Frozen Land
Authors: Groisman Pavel Ya , Knight Richard W. , Razuvaev Vyacheslav N. , Bulygina Olga N. , Karl Thomas R.
Published: October 2006

Significant climatic changes over northern Eurasia during the twentieth century are revealed in numerous variables including those affecting and characterizing the state of the cryosphere. In addition to commonly used in situ observations of snow cover such as snow depth and snow courses, synoptic archives in the former Soviet Union contain regular daily and semidaily reports about the state of the ground in the area surrounding the station. Information about frozen, dry, wet, ponded, and snow-covered land, and in the case of snow-covered land, about the characteristics of snow cover, is available in these reports. A new Global Synoptic Data Network (GSDN) consisting of 2100 stations within the boundaries of the former Soviet Union created jointly by the National Climatic Data Center (NCDC) and Russian Institute for Hydrometeorological Information (RIHMI) was used to assess the climatology of snow cover, frozen and unfrozen ground reports, and their temporal variability for the period from 1936 to 2004. Comparison with satellite measurements of snow cover extent is also presented.

During the second half of the twentieth century and over many regions in northern Eurasia, an increase in unfrozen ground conditions (5 days since 1956 over the Russian Federation) was observed. The most prominent changes occurred in the spring season in Siberia and the Far East north of 55°N during April and May by 3 to 5 days, which constitute a 15%–35% change in these regions compared to long-term mean values. Since the beginning of the dataset, surface temperature changes in high latitudes have not been monotonic. As a result, linear trend analyses applied to the entire period of observations can lead to paradoxical conclusions. Specifically, changes in snow cover extent during the 1936–2004 period cannot be linked with “warming” (particularly with the Arctic warming) because in this particular period the Arctic warming was absent.
An Approximate Footprint Model for Flux Measurements in the Convective Boundary Layer
Authors: Wang Weiguo , Davis Kenneth J. , Ricciuto Daniel M. , Butler Martha P.
Published: October 2006

An explicit footprint model for flux measurements of passive scalars in the lower part of the convective boundary layer (CBL) is introduced. A simple footprint model is derived analytically in an idealized CBL. The simple model can simulate the overall characteristics of the flux footprint. Then a method is proposed to adjust the analytical solutions to those from a Lagrangian stochastic model that considers more realistic atmospheric conditions in the vertical direction. The adjusted footprint model is a function of Monin–Obukhov length (L), roughness length, receptor height, and CBL depth (h). Comparison between the results from the adjusted footprint model and stochastic model suggests that the adjusted footprint model can well simulate the streamwise extent of the footprint within the dimensionless upwind distance X < 1, which accounts for a majority of the footprint. The model applies to stabilities of –L/h between 0.01 and 0.1 and roughness lengths between 10−5 and 2 × 10−3h in the lower part of the mixed layer (from 0.1h to 0.6h).
Loss of imprinting at the Dlk1-Gtl2 locus caused by insertional mutagenesis in the Gtl2 5' region
Authors: Steshina Ekaterina Y , Carr Michael S , Glick Elena A , Yevtodiyenko Aleksey , Appelbe Oliver K , Schmidt Jennifer V
Published: October 2006

Background

TheDlk1andGtl2genes define a region of mouse chromosome 12 that is subject to genomic imprinting, the parental allele-specific expression of a gene. Although imprinted genes play important roles in growth and development, the mechanisms by which imprinting is established and maintained are poorly understood. Differentially methylated regions (DMRs), which carry methylation on only one parental allele, are involved in imprinting control at many loci. TheDlk1-Gtl2region contains three known DMRs, theDlk1DMR in the 3' region ofDlk1, the intergenic DMR 15 kb upstream ofGtl2, and theGtl2DMR at theGtl2promoter. Three mouse models are analyzed here that provide new information about the regulation ofDlk1-Gtl2imprinting.

Results

A previously existing insertional mutation (Gtl2lacZ), and a targeted deletion in which theGtl2upstream region was replaced by aNeocassette (Gtl2Δ5'Neo), display partial lethality and dwarfism upon paternal inheritance. Molecular characterization shows that both mutations cause loss of imprinting and changes in expression of theDlk1,Gtl2andMeg8/Riangenes.Dlk1levels are decreased upon paternal inheritance of either mutation, suggestingDlk1may be causative for the lethality and dwarfism. Loss of imprinting on the paternal chromosome in bothGtl2lacZandGtl2Δ5'Neomice is accompanied by the loss of paternal-specificGtl2DMR methylation, while maternal loss of imprinting suggests a previously unknown regulatory role for the maternalGtl2DMR. Unexpectedly, when theNeogene is excised,Gtl2Δ5'animals are of normal size, imprinting is unchanged and theGtl2DMR is properly methylated. The exogenous DNA sequences integrated upstream ofGtl2are therefore responsible for the growth and imprinting effects.

Conclusion

These data provide further evidence for the coregulation of the imprintedDlk1andGtl2genes, and support a role forDlk1as an important neonatal growth factor. The ability of theGtl2lacZandGtl2Δ5'Neomutations to cause long-range changes in imprinting and gene expression suggest that regional imprinting regulatory elements may lie in proximity to the integration site.
The four serotypes of dengue recognize the same putative receptors in Aedes aegypti midgut and Ae. albopictus cells
Authors: Mercado-Curiel Ricardo F , Esquinca-Avilés Héctor Armando , Tovar Rosalinda , Díaz-Badillo Álvaro , Camacho-Nuez Minerva , Muñoz María de Lourdes
Published: October 2006

Background

Dengue viruses (DENV) attach to the host cell surface and subsequently enter the cell by receptor-mediated endocytosis. Several primary and low affinity co-receptors for this flavivirus have been identified. However, the presence of these binding molecules on the cell surface does not necessarily render the cell susceptible to infection. Determination of which of them serve asbona fidereceptors for this virus in the vector may be relevant to treating DENV infection and in designing control strategies.

Results

(1) Overlay protein binding assay showed two proteins with molecular masses of 80 and 67 kDa (R80 and R67). (2) Specific antibodies against these two proteins inhibited cell binding and infection. (3) Both proteins were bound by all four serotypes of dengue virus. (4) R80 and R67 were purified by affinity chromatography fromAe. aegyptimosquito midguts and fromAe albopictusC6/36 cells. (5) In addition, a protein with molecular mass of 57 kDa was purified by affinity chromatography from the midgut extracts. (6) R80 and R67 from radiolabeled surface membrane proteins of C6/36 cells were immunoprecipitated by antibodies againstAe. aegyptimidgut.

Conclusion

Our results strongly suggest that R67 and R80 are receptors for the four serotypes of dengue virus in the midgut cells ofAe. aegyptiand in C6/36Ae.albopictuscells.
Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease
Authors: Skogen Michael , Roth Jennifer , Yerkes Sarah , Parekh-Olmedo Hetal , Kmiec Eric
Published: October 2006

Background

Huntington's Disease (HD) is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt) is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions.

Results

As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG) as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP). Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene.

Conclusion

Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease.
General practitioner practices in requesting laboratory tests for patients with gastroenteritis in the Netherlands, 2001–2002
Authors: van den Brandhof Winette E , Bartelds Aad IM , Koopmans Marion PG , van Duynhoven Yvonne THP
Published: October 2006

Background

The objective of this study was to estimate the (selective) proportion of patients consulting their GP for an episode of gastroenteritis for whom laboratory tests were requested. In addition adherence of GPs to the guidelines for diagnostic test regime was ascertained.

Methods

Data were collected from a GP network in the Netherlands. Information was also collected on the reason for requesting the test, test specifications, and test results.

Results

For 12% of the GP patients with gastroenteritis, a stool sample was requested and tested for enteric pathogens. In most patients, the duration, followed by severity of complaints or a visit to a specific, high-risk country were reported as reasons to request laboratory diagnostics. Tests were requested most often in summer months and in February. Campylobacter (requested for 87% of the tests), Salmonella (84%), Shigella (78%) and Yersinia (56%) were most frequently included in the stool tests. Campylobacter was detected most often in patients.

Conclusion

Test requests did not always comply with existing knowledge of the etiology of gastroenteritis in GP patients and were not always consistent with the Dutch GP guidelines. Therefore, the data of this study can be used to develop educational approaches for GP's as well as for revision of the guidelines.
Targeting of mutant hogg1in mammalian mitochondria and nucleus: effect on cellular survival upon oxidative stress
Authors: Chatterjee Aditi , Mambo Elizabeth , Zhang Yonggang , DeWeese Theodore , Sidransky David
Published: October 2006

Background

Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, aging and cancer. The modified guanine, 7,8-dihydro-8-oxoguanine (also known as 8-hydroxyguanine) is one of the major oxidized bases generated in DNA by reactive oxygen species and has gained most of the attention in recent years as a marker of oxidative DNA injury and its suspected role in the initiation of carcinogenesis. 8-hydroxyguanine is removed by hOgg1, a DNA glycosylase/AP lyase involved in the base excision repair pathway.

Methods

We over-expressed wild type and R229Q mutant hOGG1 in the nucleus and mitochondria of cells lacking mitochondrial hOGG1 expression through an expression vector containing nuclear and mitochondrial targeting sequence respectively. We used quantitative real time PCR to analyze mtDNA integrity after exposure to oxidative damaging agents, in cells transfected with or without mitochondrially-targeted mutant hogg1.

Result

Over-expression of wild type hOgg1 in both nucleus and mitochondria resulted in increased cellular survival when compared to vector or mutant over-expression of hOGG1. Interestingly, mitochondrially-targeted mutant hogg1 resulted in more cell death than nuclear targeted mutant hogg1 upon exposure of cells to oxidative damage. Additional we examined mitochondrial DNA integrity after oxidative damage exposure using real-time quantitative PCR. The presence of mutant hogg1 in the mitochondria resulted in reduced mitochondrial DNA integrity when compared to the wild type. Our work indicates that the R229Q hOGG1 mutation failed to protect cells from oxidative damage and that such mutations in cancer may be more detrimental to cellular survival when present in the mitochondria than in the nucleus.

Conclusion

These findings suggest that deficiencies in hOGG1, especially in the mitochondria may lead to reduced mitochondrial DNA integrity, consequently resulting in decreased cell viability.
Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer
Authors: Taja-Chayeb Lucia , Chavez-Blanco Alma , Martínez-Tlahuel Jorge , González-Fierro Aurora , Candelaria Myrna , Chanona-Vilchis Jose , Robles Elizabeth , Dueñas-Gonzalez Alfonso
Published: October 2006

Background

Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells.

Results

PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRα gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor.

Conclusion

The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.
Characterization of neutralizing epitopes within the major capsid protein of human papillomavirus type 33
Authors: Roth Stefanie D , Sapp Martin , Streeck Rolf E , Selinka Hans-Christoph
Published: October 2006

Background

Infections with papillomaviruses induce type-specific immune responses, mainly directed against the major capsid protein, L1. Based on the propensity of the L1 protein to self-assemble into virus-like particles (VLPs), type-specific vaccines have already been developed. In order to generate vaccines that target a broader spectrum of HPV types, extended knowledge of neutralizing epitopes is required. Despite the association of human papillomavirus type 33 (HPV33) with cervical carcinomas, fine mapping of neutralizing conformational epitopes on HPV33 has not been reported yet. By loop swapping between HPV33 and HPV16 capsid proteins, we have identified amino acid sequences critical for the binding of conformation-dependent type-specific neutralizing antibodies to surface-exposed hyper variable loops of HPV33 capsid protein L1.

Results

Reactivities of monoclonal antibodies (mAbs) H33.B6, H33.E12, H33.J3 and H16.56E with HPV16:33 and HPV33:16 hybrid L1 VLPs revealed the complex structures of their conformational epitopes as well as the major residues contributing to their binding sites. Whereas the epitope of mAb H33.J3 was determined by amino acids (aa) 51–58 in the BC loop of HPV33 L1, sequences of at least two hyper variable loops, DE (aa 132–140) and FGb (aa 282–291), were found to be essential for binding of H33.B6. The epitope of H33.E12 was even more complex, requiring sequences of the FGa loop (aa 260–270), in addition to loops DE and FGb.

Conclusion

These data demonstrate that neutralizing epitopes in HPV33 L1 are mainly located on the tip of the capsomere and that several hyper variable loops contribute to form these conformational epitopes. Knowledge of the antigenic structure of HPV is crucial for designing hybrid particles as a basis for intertypic HPV vaccines.
No association of DRD2, DRD3, and tyrosine hydroxylase gene polymorphisms with personality traits in the Japanese population
Authors: Hibino Hiroyuki , Tochigi Mamoru , Otowa Takeshi , Kato Nobumasa , Sasaki Tsukasa
Published: October 2006

Background

Dopamine D2 receptor (DRD2) and dopamine D3 receptor (DRD3) genes could be candidates for personality-related genes considering their pharmacological profiles or structures. However, a limited number of studies have investigated the association between these genes and personality traits. In the present study, we investigated the DRD2, DRD3, and tyrosine hydroxylase (TH) genes in relation to personality traits in the Japanese population. Epistasis (gene-gene interaction) among the genes was extensively analyzed, in addition to the analysis based on each gene.

Methods

The -241A/G, -141C Ins/Del, and Ser311Cys polymorphisms in the DRD2 gene, the Ser9Gly polymorphism of the DRD3 gene, and the Val81Met and PstI site polymorphisms in the TH gene were genotyped in 257 healthy Japanese subjects. Personality traits were evaluated by using the Revised NEO Personality Inventory (NEO PI-R) and the State-Trait Anxiety Inventory (STAI). The associations between gene polymorphisms and the scores for NEO PI-R or Trait Anxiety of STAI were statistically analyzed by one-way analysis of covariance (ANCOVA) adjusting sex and age. Epistasis was assessed using two-way ANCOVA between the polymorphisms of independent two genes.

Results

In the analysis based on each gene, trends for association were observed between State Anxiety and the DRD2 -141C Ins/Del polymorphism (p = 0.031, uncorrected), and between Trait Anxiety and the DRD2 Ser311Cys or TH PstI site polymorphism (p = 0.048 and 0.041, respectively, uncorrected). In epistatic analysis, a trend for interaction was observed on the scores for Neuroticism and Trait Anxiety between the DRD2 -141C Ins/Del and TH Val81Met polymorphisms (p = 0.015 and 0.010, respectively, uncorrected). However, these differences were insignificant after Bonferroni correction.

Conclusion

The present study did not provide evidence for the association between these dopamine-related genes and personality traits in the Japanese population.
Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus?
Authors: Reefman Esther , de Jong Marcelus CJM , Kuiper Hilde , Jonkman Marcel F , Limburg Pieter C , Kallenberg Cees GM , Bijl Marc
Published: October 2006

Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB). Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages, and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests that these lesions result from an inflammatory clearance of apoptotic cells.
PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53
Authors: You Xin , Boyle David L , Hammaker Deepa , Firestein Gary S
Published: October 2006

PUMA (p53-upregulated modulator of apoptosis) is a pro-apoptotic gene that can induce rapid cell death through a p53-dependent mechanism. However, the efficacy of PUMA gene therapy to induce synovial apoptosis in rheumatoid arthritis might have limited efficacy if p53 expression or function is deficient. To evaluate this issue, studies were performed to determine whether p53 is required for PUMA-mediated apoptosis in fibroblast-like synoviocytes (FLS). p53 protein was depleted or inhibited in human FLS by using p53 siRNA or a dominant-negative p53 protein. Wild-type and p53-/- murine FLS were also examined to evaluate whether p53 is required. p53-deficient or control FLS were transfected with PUMA cDNA or empty vector. p53 and p21 expression were then determined by Western blot analysis. Apoptosis was assayed by ELISA to measure histone release and caspase-3 activation, or by trypan blue dye exclusion to measure cell viability. Initial studies showed that p53 siRNA decreased p53 expression by more than 98% in human FLS. Loss of p53 increased the growth rate of cells and suppressed p21 expression. However, PUMA still induced apoptosis in control and p53-deficient FLS after PUMA cDNA transfection. Similar results were observed in p53-/- murine FLS or in human FLS transfected with a dominant-negative mutant p53 gene. These data suggest that PUMA-induced apoptosis in FLS does not require p53. Therefore, approaches to gene therapy that involve increasing PUMA expression could be an effective inducer of synoviocyte cell death in rheumatoid arthritis regardless of the p53 status in the synovium.
Population‐based Triage Management in Response to Surge‐capacity Requirements during a Large‐scale Bioevent Disaster
Authors: Burkle Frederick M.
Published: October 2006

Both the naturally occurring and deliberate release of a biological agent in a population can bring catastrophic consequences. Although these bioevents have similarities with other disasters, there also are major differences, especially in the approach to triage management of surge capacity resources. Conventional mass‐casualty events use uniform methods for triage on the basis of severity of presentation and do not consider exposure, duration, or infectiousness, thereby impeding control of transmission and delaying recognition of victims requiring immediate care. Bioevent triage management must be population based, with the goal of preventing secondary transmission, beginning at the point of contact, to control the epidemic outbreak. Whatever triage system is used, it must first recognize the requirements of thoseSusceptible but not exposed, thoseExposed but not yet infectious, thoseInfectious, thoseRemoved by death or recovery, and those protected byVaccination or prophylactic medication (SEIRVmethodology). Everyone in the population falls into one of these five categories. This article addresses a population approach to SEIRV‐based triage in which decision making falls under a two‐phase system with specific measures of effectiveness to increase likelihood of medical success, epidemic control, and conservation of scarce resources.
Kisspeptins Are Novel Potent Vasoconstrictors in Humans, with a Discrete Localization of Their Receptor, G Protein-Coupled Receptor 54, to Atherosclerosis-Prone Vessels
Authors: Mead Emma J. , Maguire Janet J. , Kuc Rhoda E. , Davenport Anthony P.
Published: October 2006

The G protein-coupled receptor GPR54 (also designated KISS1) is activated by cleavage products of the KiSS1 protein, the kisspeptins (KP), to act as a molecular switch for puberty. Additionally, KP are potent inhibitors of tumor metastasis and play a role in placentation, both processes involving angiogenesis. Our aim was to investigate whether GPR54 and KP are expressed within normal and diseased human vasculature and what their functional role may be. RT-PCR screening of human blood vessels revealed a discrete localization of GPR54 mRNA in smooth muscle of vessels with the same developmental origins, aorta, coronary artery, and umbilical vein, a pattern confirmed by immunocytochemistry and radioligand binding. Novel ligand [125I]KP-13 exhibited saturable and high-affinity binding in aorta smooth muscle sections (dissociation constant KD = 0.2 ± 0.03 nm), and using confocal microscopy, we found colocalization of receptor and peptide to vascular endothelial cells and to the atherosclerotic plaque of coronary artery. RIA detected 13.04 ± 2.94 and 20.50 ± 5.00 fmol/g KP in human coronary artery and aorta, respectively. KP-10, KP-13, and KP-54 acted as vasoconstrictors with comparable potency and efficacy in isolated rings of coronary artery (negative logarithm of the EC50 and maximal response, respectively, as follows: KP-10, 7.89 ± 0.24 and 33.7 ± 17.0; KP-13, 8.66 ± 0.88 and 35.1 ± 7.9; KP-54, 8.86 ± 1.11 and 25.7 ± 5.5) and umbilical vein (negative logarithm of the EC50 and maximal response, respectively, as follows: KP-10, 8.44 ± 022 and 24.3 ± 3.7; KP-13, 8.43 ± 0.88 and 28.4 ± 8.6; KP-54, 8.93 ± 0.39 and 36.9 ± 5.2). In conclusion, we have detected expression of both peptide and receptor in aorta, coronary artery, and umbilical vein and have shown for the first time that the KP are vasoconstrictors in humans, suggesting a previously undescribed role for GPR54 and KP in the cardiovascular system.
Procaine penicillin solutions in the treatment of nasal polyposis
Authors: Ruskin Simon L.
Published: October 2006

1. Nasal polyposis is amenable to conservative treatment by the use of solutions of procaine penicillin, 3,000 to 5,000 units per cc., when instilled into the nasal sinuses.

2. Procaine penicillin solutions provide a prolonged acting penicillin effect combined with the antihistaminic effect of procaine in decongesting the nasal mucosa. It is a great advance in nasal therapy.
Acute laryngotracheobronchitis. an analysis of 1,175 cases with 98 tracheotomies
Authors: Everett A. Reginald
Published: October 2006

SUMMARY AND CONCLUSION.
Diagnosis in persistent cerebrospinal fluid fistulas
Authors: Duckert Larry G. , Mathog Robert H.
Published: October 2006

Cerebrospinal fluid (CSF) rhinorrhea and otorrhea have presented difficult problems in both diagnosis and management; moreover, the threat of impending meningitis necessitates early localization of the source of the leak.

The most common techniques for evaluation and isolation of CSF rhinorrhea and otorrhea have included X‐ray studies, intrathecal dyes, and radioactive cisternography. These studies, although useful, have not always demonstrated the area of the leak. Roentgenographic evaluations, including tomography, often have not isolated the fracture or defined the area of fluid accumulation. Dyes, consisting of methylene blue, Evans blue and fluorescein, injected intrathecally and recovered on nasal pledgets, have been used by a number of investigators with variable success. Radioactive tracers and cisternography used to isolate CSF fistulas, also on occasion have yielded inaccurate data.

These various difficulties in diagnosis suggested a more recent review of the subject. To evaluate the efficacy of tomography, intrathecal tracers and cisternography, seven patients with persistent CSF otorrhea or rhinorrhea, and one patient with combined otorrhea and rhinorrhea were evaluated from Januaryy, 1970 to 1975. Analysis of the procedures revealed variable and inconsistent results. Problems were related to placement and removal of pledgets, positioning of the patient and different volumes and rates of flow. The difficulties encountered with the conventional diagnostic techniques were exemplified in one particular patient with multiple fistulas requiring one extracranial and several intracranial procedures for correction. A standard protocol applying X‐rays, tomography, intrathecal tracers with intranasal pledgets and cisternography is offered.
Transnasal transsphenoidal approach to the sella
Authors: Roth James A. , Seljeskog Edward L. , Duvall Arndt J. , Long Donlin M.
Published: October 2006

The transnasal transsphenoidal approach to the sella turcica has been refined and perfected through advances in medicine and technology. Originally performed for excision of pituitary adenomas, its present primary use is pituitary ablation in hormonally dependent diseases. Our study of 55 patients who have undergone this procedure during the years 1970‐1975 demonstrates that this microscopic technique gives excellent exposure and visualization of intrasellar contents. Our method with several instrument modifications is discussed. It is technically an easy procedure with a minimum of morbidity and mortality.
Lesions of the vagus nerve: Diagnosis, treatment and rehabilitation
Authors: Rontal Michael , Rontal Eugene
Published: October 2006

Lesions of the vagus nervous system have devastating effects on the vital functions of coughing, swallowing and phonation. A clear understanding of the vagal correlative anatomy and physiology leads to a practical organization of upper respiratory and digestive tract lesions. A reasoned and thoughtful treatment plan evolves that leads the patient to comprehensive treatment and rehabilitation.
Surgical repair of the caudal end of the septum
Authors: Wexler Manuel R.
Published: October 2006

The repair of the caudal end of a severely deviated septum has been a challenge since the beginning of septum surgery. In the time of Freer and Killian, a caudal and dorsal strip was always left. Frequently, the most obvious portion of the septal deformity, the caudal end, was undisturbed and the deformity persisted. Metzenbaum, Fomon and Cottle described procedures designed to correct this problem.

The procedure described in this presentation utilizes the maxilla‐pre‐maxillary approach to the septum. The laporotomy of the rhinoplasty procedure is used to expose the upper lateral cartilages. These cartilages are submucously uncovered and separated from the dorsal margin of the septal cartilage. This provides complete exposure of the line of fracture usually responsible for the extreme deflection of the caudal end of the septal cartilage.

A strip of cartilage including the line of fracture is removed. The caudal end is attached to the mucoperichondrium of the right side and now is completely mobile. The caudal end is placed over the maxillary spine and sutured in position by a chromic cat gut suture from the prespine fascia through the caudal edge of the septal cartilage. The upper lateral cartilages are sutured to the dorsal margin of the septum acting as a splint to hold the sections of cartilage straight and immobile until the tissues heal.
Surgical and nonsurgical management of facial paralysis following closed head injury
Authors: Adour Kelar Karim , Boyajian John A. , Kahn Zev M. , Schneider Glenn S.
Published: October 2006

The outcomes of facial nerve decompression, surgical exploration, and nonsurgical treatment for facial paralysis following closed head injury were analyzed in 30 patients with an intact facial nerve, and complete evaluation. Objective evaluation of outcome was achieved by calculation of a Facial Paralysis Recovery Profile and Recovery Index (Profile minus complications). Twelve of 15 patients with incomplete facial paralysis were treated medically. All followed patients with incomplete paralysis and bilaterally equal facial nerve excitability had a Recovery Index of +10 (complete recovery of function, no complications). Three with partial de‐nervation had a Recovery Profile of +10 with mild contracture and syn‐kinesis.

The average Recovery Profiles for all patients treated by decompression, exploration, or nonsurgically were respectively 4.0, 5.7, and 5.7.

The Recovery Indices were +1.8, +3, and +2.7, respectively. Where nerve excitability had become abnormal, facial nerve decompression was of no benefit in traumatic facial paralysis due to closed head injury. Nerve excitability tests of peripheral branches are of great value for prognosis and selection of patients who do not need surgical intervention. Substitution of facial nerve exploration for facial nerve decompression seems reasonable. Polytomography of the facial canal is invaluable in selection of patients for operation