bluuebunny/crossref_metadata_2025 huggingface dataset:
The Absence of Histone H2B Monoubiquitination in theArabidopsis hub1(rdo4) Mutant Reveals a Role for Chromatin Remodeling in Seed Dormancy
Authors: Liu Yongxiu , Koornneef Maarten , Soppe Wim J.J.
Published: March 2007

Seed dormancy is defined as the failure of a viable seed to germinate under favorable conditions. Besides playing an adaptive role in nature by optimizing germination to the most suitable time, a tight control of dormancy is important in crop plants. Extensive genetic and physiological studies have identified the involvement of several factors, but the molecular mechanisms underlying this process are still largely unknown. We cloned the HISTONE MONOUBIQUITINATION1 (HUB1) gene, of which the mutant (previously identified as reduced dormancy4) has reduced seed dormancy and several pleiotropic phenotypes. HUB1 encodes a C3HC4 RING finger protein. The Arabidopsis thaliana genome contains one HUB1 homolog, which we named HUB2. The hub2 mutant also has reduced seed dormancy and is not redundant with hub1. Homologs of HUB1 and HUB2 in other species are required for histone H2B monoubiquitination. In agreement with this, the ubiquitinated form of histone H2B could not be detected in the hub1 and hub2 mutants. In yeast and human cells, histone H2B monoubiquitination is associated with actively transcribed genes. The hub1 mutant showed altered expression levels for several dormancy-related genes. We propose a role for chromatin remodeling in seed dormancy by H2B monoubiquitination through HUB1 and HUB2.
Expression of β‐catenin and p53 are prognostic factors in deep aggressive fibromatosis
Authors: Gebert C , Hardes J , Kersting C , August C , Supper H , Winkelmann W , Buerger H , Gosheger G
Published: March 2007

Aims:  To determine the prognostic significance of β‐catenin in aggressive fibromatosis and to identify potential molecular markers for new targeted therapies.

Methods and results:  A tissue microarray of 37 cases of deep aggressive fibromatosis was constructed and subjected to immunohistochemical analysis for β‐catenin, p53, smooth muscle actin (SMA), desmin, Ki67, c‐erbB2, epidermal growth factor receptor (EGFR), c‐kit, CD34 and S100. Complete clinical follow‐up was available for 23 patients. Nuclear β‐catenin expression was associated with an increased rate of local tumour recurrence (60.0% 1‐year and 0% 5‐year event‐free survival; P < 0.05). Furthermore, p53 expression was associated with an increased risk of tumour recurrence (50% 1‐year event‐free survival rate and 0% 5‐years event‐free survival rate, P < 0.05). The coexpression of p53 and β‐catenin was significantly correlated (P < 0.05). No statistically significant association was seen between MIB1 and p53 or β‐catenin expression, respectively. No expression of EGFR, c‐erbB2 or c‐kit was seen.

Conclusions:  The overexpression of β‐catenin and p53 is associated with a decreased event‐free survival in deep aggressive fibromatosis. Further studies are required to establish whether these findings can lead to an improvement in the treatment of this rare neoplasm.
Prognostic significance of the wnt signalling pathway molecules APC, β‐catenin and E‐cadherin in colorectal cancer—a tissue microarray‐based analysis
Authors: Lugli A , Zlobec I , Minoo P , Baker K , Tornillo L , Terracciano L , Jass J R
Published: March 2007

Aims:  To investigate dysregulation of the wnt signalling pathway by assessing β‐catenin expression/increasing expression and loss of cytoplasmic adenomatous polyposis coli (APC) and membranous E‐cadherin in colorectal cancer (CRC) and determining the prognostic significance of these variables.

Methods and results:  Unselected, non‐consecutive CRC resections (n = 1420) were subdivided into three groups: mismatch repair (MMR)‐proficient, MLH1– and presumed hereditary non‐polyposis colonic cancer (HNPCC). Immunohistochemical analysis of β‐catenin expression (0% versus > 0%) and increasing expression (increasing percentage‐positivity) and loss of APC and E‐cadherin was performed using the tissue microarray technique. In MMR‐proficient CRC, increased nuclear β‐catenin expression and loss of membranous E‐cadherin were independently associated with higher N stage (P = 0.03 and < 0.0001), vascular invasion (P < 0.01 and < 0.001) and worse survival (P < 0.01 and < 0.001). Additionally, there was an association between loss of membranous E‐cadherin and higher T stage (P = 0.03). In MLH1– CRC, loss of membranous E‐cadherin was associated with higher N stage (P = 0.05) and worse survival (P = 0.03). In presumed HNPCC CRC nuclear β‐catenin and membranous E‐cadherin were not associated with tumour progression or worse survival. In all CRC subsets loss of cytoplasmic APC was not associated with clinicopathological features.

Conclusions:  Increasing nuclear β‐catenin expression and loss of membranous E‐cadherin are independent, adverse prognostic factors in MMR‐proficient and MLH1– CRC.
Coeliac disease: a histological follow‐up study
Authors: Bardella M T , Velio P , Cesana B M , Prampolini L , Casella G , Di Bella C , Lanzini A , Gambarotti M , Bassotti G , Villanacci V
Published: March 2007

Aims:  To assess the histological response to a gluten‐free diet (GFD) in a series of coeliac patients in clinical remission, of different ages and with varying degrees of mucosal damage at diagnosis.

Methods and results:  Biopsy samples from 249 coeliac patients (F 165, M 84) were analysed basally and after clinical and biochemical remission following a GFD. All patients showed an improvement in mucosal findings after starting a GFD, but complete histological normalization was observed in 74.1% of paediatric cases (diagnosed before 14 years of age) and in only 17.5% of adults. Statistical analysis showed that sex, the clinical picture at diagnosis and the length of time between biopsy at the time of diagnosis and on a GFD were not related to histological normalization. In contrast, the age at diagnosis was statistically significantly related to it (P < 0.0001). In addition, the presence/absence of Helicobacter pylori was independent of the normalization of the duodenal mucosa.

Conclusions:  In clinical practice the criteria for diagnosis of coeliac disease are sufficiently standardized, whereas for follow‐up they are less well defined. We suggest that in order to compare the results from different studies, it should be stated whether remission after treatment is based on clinical or histological criteria or both.
Mammary and extramammary Paget's disease: an immunohistochemical study of 83 cases
Authors: Liegl B , Leibl S , Gogg‐Kamerer M , Tessaro B , Horn L‐C , Moinfar F
Published: March 2007

Aim:  Mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) are rare neoplasms. The aim of this study was, by the use of immunohistochemistry, to derive further information about the cell(s) of origin, find a diagnostically useful immunohistochemical panel and investigate candidates for possible targeted therapy.

Material and results:  Sixty MPD and 23 EMPD cases were studied using antibodies to cytokeratin (CK) 34βE12, CK8/18, CK7, CK5/6, CK20, gross cyctic disease fluid protein (GCDFP)‐15, MUC1‐8, epidermal growth factor receptor (EGFR) (HER1), HER3 and HER4. In all MPD cases CK7 and MUC1 were positive. CK8/18 was positive in 59/60 cases. GCDFP‐15, MUC2, MUC3, MUC4, MUC7, MUC8 were positive in 29/60, 3/60, 35/47, 4/40, 3/43 and 2/45 cases, respectively. In all EMPD cases CK8/18 and CK7 were positive. MUC1, GCDFP‐15, MUC5AC, MUC3, MUC8 and CK20 were positive in 22/23, 19/23, 8/19, 3/19, 1/19 and 3/23 cases, respectively. With the remaining antibodies no immunoreactivity was observed.

Conclusion:  MUC1 and low‐molecular‐weight CKs in conjunction with immunonegativity for high‐molecular‐weight CKs are the most diagnostically useful markers. MPD is caused by the epidermotropic spread of underlying tumour cells, whereas EMPD probably arises from intraepithelial cells of sweat gland origin. Targeted therapy with antibodies against EGFR (HER1), HER3 or HER4 is unlikely to prove of clinical value.
Prognostic significance of Id‐1 and its association with EGFR in renal cell cancer
Authors: Li X , Zhang Z , Xin D , Chua C W , Wong Y C , Leung S C L , Na Y , Wang X
Published: March 2007

Aims:  Epidermal growth factor receptor (EGFR) is suggested as one of the positive regulators in the invasive progression of renal cell cancer (RCC). Recently, Id‐1 (inhibitor of differentiation or DNA binding), a helix‐loop‐helix transcription factor, has been identified as one of the key factors in the EGFR signalling pathway. The aim of this study was to investigate the significance of Id‐1 expression in renal cell cancer and to study its relationship with EGFR.

Methods and results:  Id‐1 and EGFR expression was examined in tissue microarray (TMA) samples of 107 RCC and 32 normal kidney specimens by immunohistochemistry. Relative Id‐1 and EGFR protein expression was quantified by estimating the staining intensity on a four‐grade scale. We found that while negative to weak expression of Id‐1 and EGFR was observed in non‐malignant kidney tissues, most RCCs showed significant positive Id‐1 and EGFR expression in tumour cells. In addition, Id‐1 immunostaining intensity was positively associated with increased tumour staging, grading and EGFR expression.

Conclusion:  Overexpression of Id‐1 is a novel marker for advanced RCC which is positively correlated with EGFR expression. Our results suggest that Id‐1 may play an important role in the development of RCC and indicate that Id‐1 is a potential marker of patients with a poor prognosis.
Breast carcinoma with basal differentiation: a proposal for pathology definition based on basal cytokeratin expression
Authors: Rakha E A , El‐Sayed M E , Green A R , Paish E C , Lee A H S , Ellis I O
Published: March 2007

Aim:  To assess the expression and coexpression of a range of different biomarkers that have been used to define breast carcinomas with a basal phenotype (BP) and their relationship with prognosis in an attempt to refine the definition of BP and to evaluate the reliability of using a single biomarker to identify these tumours.

Methods and results:  The expression pattern of basal cytokeratins (CK5/6 and CK14), oestrogen, progesterone and androgen receptors, epidermal growth factor receptor, HER2, BRCA1, P‐cadherin and myoepithelial markers (smooth muscle actin and p63) were studied in a well‐characterized series of invasive breast carcinoma (1872 cases) with long‐term follow‐up using immunohistochemistry and tissue microarray. Although the additional markers were associated with basal CK expression, they did not serve to improve recognition of cases with differing outcome when compared with basal CKs alone and, if used to define cases, reduced considerably the proportion of cases allocated to this poor prognostic type of breast cancer.

Conclusion:  BP can be defined based on the expression of basal CKs regardless of the expression of other markers.
A Monoclonal Antibody to Lewis Y/Lewis b Revealing Mimicry of the Histone H1 to Carbohydrate Structures
Authors: Christensen P. A. , Danielczyk A. , Ravn P. , Stahn R. , Karsten U. , Goletz S.
Published: March 2007

Antibodies to either peptide or carbohydrate tumour antigens are established tools for diagnostics and therapy. We here describe an antibody (A70‐A/A9) recognizing a carbohydrate epitope common to the tumour‐associated Lewis Y and Lewis b antigens (Fucα1‐2Galβ1‐4/3[Fucα1‐3/4]GlcNAcβ‐). Its specificity was established without doubt with a panel of 86 synthetic mono‐ and oligosaccharidic structures. This antibody was found to cross‐react with the nuclear protein histone H1. Binding to H1 was specific, periodate‐insensitive (non‐carbohydrate) and saturable. Histone H1 was able to inhibit Lewis Y binding very effectively in a concentration‐dependent manner. We conclude that it represents an example of natural peptide mimicry of a carbohydrate epitope. It may explain the observed occurrence of ‘anti‐histone autoantibodies’ in cancer patients.
Lack of association between serum adiponectin levels and the Pro12Ala polymorphism in Asian Indians
Authors: Radha V. , Vimaleswaran K. S. , Babu S. , Deepa R. , Anjana M. , Ghosh S. , Majumder P. P. , Rao M. R. S. , Mohan V.
Published: March 2007

Aims  The aim of the study was to investigate the association of serum adiponectin levels with the Pro12Ala polymorphism of the peroxisome proliferator activated receptor‐γ (PPARG) gene in Asian Indians.

Methods  We selected 400 diabetic subjects, 200 with the Pro12Pro genotype (100 male and 100 female) and 200 with the Pro12Ala genotype (100 male and 100 female) and 400 age‐ and sex‐matched normal glucose tolerance subjects with similar genotype profiles from the Chennai Urban Rural Epidemiology Study. Fasting serum adiponection levels were measured using radioimmunoassay. The Pro12Ala polymorphism was genotyped by PCR–restriction fragment length polymorphism using BstUI.

Results  All clinical and biochemical parameters were similar in the subjects with the Pro12Pro and Pro12Ala genotypes. There was no significant difference in serum adiponectin values between subjects with the Pro12Pro and Pro12Ala genotypes (males 5.4 vs. 5.8 µg/ml, P = 0.546; females 6.9 vs. 7.2 µg/ml, P = 0.748). Adiponectin values did not differ among these two genotypes even when categorized based on their diabetes status (normal glucose tolerance Pro12Pro 7.9 vs. Pro12Ala 7.7 µg/ml, P = 0.994; diabetes Pro12Pro 4.7 vs. Pro12Ala 5.4 µg/ml, P = 0.622).

Conclusion  The Pro12Ala polymorphism of the PPARG gene is not associated with serum adiponectin levels in Asian Indians.
The Success of Sharing Societies: Lessons from History
Authors: Getz Trevor
Published: March 2007

Global history is often viewed as a competitive battleground in which civilizations, nations, or peoples repeatedly clash over resources or ideology. Correspondingly, victory in the global arena is often seen as belonging to the most inventive or innovative societies. Yet a more complex look at innovation reveals that it is often the result of a gradual and widely collaborative process, often involving the efforts or contributions of citizens of several states or societies. This article suggests that the myths surrounding invention and the reification of innovation as a cultural trait have distracted social scientists and policy makers from recognizing the significance of imported technologies, ideas, strategies, and products in helping societies overcome a wide range of challenges. It illustrates this contention with evidence from several historical episodes that suggest that successful societies are not only open to innovation from among their own populace, but also to contributions from abroad.
America's Forgotten Founder: John Dickinson and the American Revolution
Authors: Calvert Jane
Published: March 2007

Although John Dickinson was one of the central figures in the American Founding, he is virtually unknown by scholars. This article makes a case for his importance and claims that the reason for his absence from the scholarship is the confusion surrounding his political thought and action. Until now, no work has explained the apparent contradiction of his vigorous advocacy of American rights, his refusal to support the Declaration of Independence, and his subsequent military service on the side of the Rebels. The argument here is that the seeming contradictions resolve and Dickinson's position in the Revolution is consistent and comprehendible when situated in the tradition of Quaker political thought.
Venous Obstruction After Pacemaker Implantation
Authors: KORKEILA PETRI , NYMAN KAI , YLITALO ANTTI , KOISTINEN JUHANI , KARJALAINEN PASI , LUND JUHA , AIRAKSINEN K.E. JUHANI
Published: March 2007

Background: Central vein leads are known to predispose to venous obstruction. Although usually asymptomatic, obstruction may render electrode removal difficult. This study aimed at quantifying changes in venous calibers in a prospective fashion by intravenous contrast venography (ICV) before and after pacemaker (PM) or cardioverter‐defibrillator implantation.

Methods: One hundred and fifty (mean age 67; 61% male) consecutive patients were enrolled, and followed for 6 months. A successful ICV was done at baseline prior to implantation and at 6‐month follow‐up in 136 (91%) patients. Minimum (Dmin) and maximum (Dmax) vessel diameters were obtained from both ICVs. A new stenosis was defined as a 50% diameter reduction in a venous segment when compared to baseline. We implanted a total of 230 electrodes: 47 (34.6%) single lead, 84 (61.8%) 2‐lead, and 5 (3.7%) 3‐lead systems.

Results: At baseline ICV, 10 patients (7%) were found to have venous anomalies, including 8 patients with obstructive lesions, 1 patient with a persistent left superior vena cava, and 1 patient with double axillary vein. At 6 months, a new obstructive venous lesion had developed in a total of 19 (14%) patients, none of whom exhibited any local symptoms. Of these patients 14 (10%) had a stenosis (mean Dmin 4.6 mm and diameter 38% of baseline), and 5 (3.6%) had a complete venous occlusion. In most cases the new stenosis developed in a location where the vessel was narrowest at baseline. Clinical predictors for the development of stenosis were atrial fibrillation at baseline and biventricular PM implantation.

Conclusions: This is the first systematic study to quantify venous changes after PM or ICD implantation. Our study shows that venous anomalies rendering PM implantation difficult are not infrequent. The incidence of new venous obstruction was 14%. Atrial fibrillation and biventricular PM implantation were independent predictors of venous obstruction.
Prediction of Conversion from Paroxysmal to Permanent Atrial Fibrillation
Authors: BUDEUS MARCO , FELIX OLIVER , HENNERSDORF MARCUS , WIENEKE HEINRICH , ERBEL RAIMUND , SACK STEFAN
Published: March 2007

Background: Paroxysmal atrial fibrillation (PAF) transits to permanent atrial fibrillation (PEAF). The current study was to determine whether a P wave‐triggered P wave signal averaged electrocardiogram (P‐SAECG) and chemoreflexsensitivity (CHRS) are useful to predict a conversion to PEAF in patients with PAF.

Methods: The filtered P wave duration (FPD) and the root mean square voltage of the last 20 ms of the P wave (RMS 20) were measured by P‐SAECG. The ratio between the difference of RR intervals in the ECG and venous pO2 before and after 5‐minutes oxygen inhalation is measured (ms/mmHg) for the determination of CHRS.

Results: A total of 180 patients with PAF were enrolled and followed for a mean of 22.5 months. PEAF occurred in 38 patients (21%) and these patients had a significantly larger left atrial size (43.2 ± 4.9 vs. 41.0 ± 5.4 mm, P = 0.021), a significantly longer FPD (158.8 ± 18.2 vs. 136.7 ± 16.6 ms, P < 0.0001), and a significantly lower CHRS (1.96 ± 0.99 vs. 2.44 ± 1.19 ms/mmHg, P = 0.024) than patients with PAF. Patients with PEAF tended to have a lower RMS 20 (2.38 ± 0.65 vs. 2.75 ± 1.18 μV, P = 0.067) than patients with PAF. The χ2 test showed that the combination of FPD ≥ 145 ms, RMS 20 ≤3.0 μV, left atrial size ≥ 41 mm, and CHRS ≤2.0 ms/mmHg had the best predictive power for PEAF. Patients who fulfilled these criteria had a 12‐fold increased risk for a conversion from PAF to PEAF.

Conclusions: Our results show that a P‐SAECG, an analysis of CHRS, and left atrial enlargement are clinical predictors of a progression from PAF to PEAF.
Endocardial Ventricular Pacing Through a Bioprosthetic Tricuspid Valve
Authors: ANTONELLI DANTE , ADAM FREEDBERG NAHUM
Published: March 2007

A patient with bioprosthetic tricuspid valve was treated with ventricular endocardial pacing using a new delivery system consisting of a steerable catheter and a 4.1 F bipolar, fixed‐screw, steroid eluting lead. The functioning of the lead and bioprosthetic tricuspid valve was excellent during the following year.
Successful Placement of Left Ventricular Pacing Lead Despite Coronary Sinus Perforation into the Pericardial Space with an Obstructive Flap
Authors: TAMIN SYAHIDAH SYED , HUSSIN AZLAN , IMRAN ZA , HALMEY NIK , AZMAN WAN
Published: March 2007

Coronary sinus perforation is a relatively uncommon but much feared complication that may occur during the placement of left ventricular pacing lead. Coronary sinus perforation, especially in the presence of an obstructive flap, usually indicates the need to abandon the implantation attempt, as there are difficulties in crossing the obstructive flap as well as uncertainty of whether the lead is in the true lumen or into the pericardial space. We describe our experience in successfully placing the left ventricular lead safely despite the problems arising from these circumstances.
Successful Termination of Atrial Flutter by Ibutilide During Pregnancy
Authors: BURKART THOMAS A. , KRON JORDANA , MILES WILLIAM M. , CONTI JAMIE B. , GONZALEZ MARIO D.
Published: March 2007

Sustained atrial fibrillation and atrial flutter during pregnancy are uncommon arrhythmias that can significantly complicate normal prenatal care. Direct current external cardioversion is the current method of terminating these arrhythmias. In practice, however, this technique is sometimes considered undesirable by both physician and patients due to the need for deep sedation or anesthesia. In the present study, we describe the use of ibutilide to safely terminate symptomatic persistent atrial flutter in a patient during her 24th week of pregnancy.
Area deprivation and oral health in Scottish adults: a multilevel study
Authors: Bower Elizabeth , Gulliford Martin , Steele Jimmy , Newton Tim
Published: March 2007

Abstract –  Objectives:  To explore the association between area deprivation and adult oral health.

Methods:  Multilevel regression analysis of data taken from the 1998 Adult Dental Health Survey in the UK comprising 632 participants living in 346 households located in 31 postcode sectors in Scotland. Three oral health outcomes were investigated: number of sound (including restored) teeth; has one or more unsound teeth; has periodontal pocketing 4 mm or more in one or more teeth.

Results:  In the most deprived areas, individuals had a mean of 4.6 fewer sound teeth than those in the least deprived areas. The difference in normalised number of sound teeth between least and most deprived areas was −0.707 (95% CI −1.164, −0.250), P = 0.024. After adjusting for age, sex, qualification status, head of household social class and household income, the estimated difference was −0.238 (−0.591 to 0.115) (P = 0.164). Area deprivation was not associated with having one or more unsound teeth or periodontal pocketing 4 mm or more in one or more teeth.

Conclusions:  There is a univariate association of area deprivation with the number of sound teeth. This association is largely explained by household and individual level socioeconomic variables. A small area deprivation effect cannot be excluded in these data. The findings challenge current understanding of the relationship between area deprivation and oral health. Further multilevel research exploring the relationship between area deprivation and oral health is required using a larger sample and a prospective longitudinal design.
Risk indicators for recurrent aphthous ulcers among adults in the US
Authors: Chattopadhyay Amit , Chatterjee Sharmila
Published: March 2007

Abstract –  Background and aims:  Recurrent aphthous ulcers (RAU) in the oral cavity are painful, causing substantial morbidity in the US and elsewhere in the world. Despite this, there is a lack of population‐based studies representative of the US national adult population to describe the epidemiology, and estimate the true disease burden and association with independent risk factors. Although several studies have investigated the role of various factors in RAU etiology, the epidemiology and etiology of RAU remain unclear. This study aims to establish the prevalence and describe the epidemiology of RAU in adults.

Methods:  Data from the Third National Health and Nutrition Examination Survey (NHANES III) were analyzed in SUDAAN using multivariable logistic regression, modeling RAU occurrences.

Results:  Overall, for all Americans regardless of age, prevalence of RAU was 1030 per 100 000 people (95% CI 830–1220). The prevalence of RAU among adults was 850 per 100 000 (95% CI 630–1070). The lower vestibule was the most commonly involved site. Multivariable analyses suggested that adjusted odds of RAU were greatest for those 17–29 years of age (adjusted OR 2.7; 95% CI 1.4–5.5), for men (adjusted OR 1.7; 95% CI 0.9–2.8), and for those with low serum insulin levels (OR 2.0; 95% CI 0.9–4.4). Never smokers had greater risk of RAU (OR 9.2, 95% CI 2.8–30.1) compared with those who smoked more than 10 cigarettes per day.

Conclusion:  This study establishes the prevalence of RAU among adults in the US and demonstrates that whereas cigarette smoking is associated with lesser odds, low insulin levels might be independently associated with greater odds of RAU.
A Regression Model to Estimate Regional Ground Water Recharge
Authors: Lorenz David L. , Delin Geoffrey N.
Published: March 2007

A regional regression model was developed to estimate the spatial distribution of ground water recharge in subhumid regions. The regional regression recharge (RRR) model was based on a regression of basin‐wide estimates of recharge from surface water drainage basins, precipitation, growing degree days (GDD), and average basin specific yield (SY). Decadal average recharge, precipitation, and GDD were used in the RRR model. The RRR estimates were derived from analysis of stream base flow using a computer program that was based on the Rorabaugh method. As expected, there was a strong correlation between recharge and precipitation. The model was applied to statewide data in Minnesota. Where precipitation was least in the western and northwestern parts of the state (50 to 65 cm/year), recharge computed by the RRR model also was lowest (0 to 5 cm/year). A strong correlation also exists between recharge and SY. SY was least in areas where glacial lake clay occurs, primarily in the northwest part of the state; recharge estimates in these areas were in the 0‐ to 5‐cm/year range. In sand‐plain areas where SY is greatest, recharge estimates were in the 15‐ to 29‐cm/year range on the basis of the RRR model. Recharge estimates that were based on the RRR model compared favorably with estimates made on the basis of other methods. The RRR model can be applied in other subhumid regions where region wide data sets of precipitation, streamflow, GDD, and soils data are available.
Liver dysfunction in patients with acute pulmonary embolism
Authors: Aslan Sahin , Meral Mehmet , Akgun Metin , Acemoglu Hamit , Ucar Elif Yilmazel , Gorguner Metin , Mirici Arzu
Published: March 2007

Aim:  Although liver injury due to cardiac, chronic respiratory and circulatory failure has been reported, this has yet to be studied in patients with pulmonary embolism (PE). We investigated liver injury in patients with acute PE.

Methods:  We retrospectively reviewed 107 acute PE patients over a two‐year period. Patients were categorized as having: (1) severe (PaO2 < 45 mmHg), moderate (45 mmHg ≤ PaO2≤ 60 mmHg) or mild hypoxemia (60 mmHg < PaO2 < 80 mmHg) groups; (2) massive and non‐massive PE; (3) absence or presence of pre‐existing cardiopulmonary disease; and (4) absence or presence of right ventricle dysfunction. Serum levels of liver enzymes were compared between groups.

Results:  Transaminase levels were higher in severe hypoxemia patients compared mild hypoxemia patients (p=0.045 and p=0.036). Albumin and bilirubin levels were lower and higher, respectively, in patients with severe and moderate hypoxemia compared to mild hypoxemia patients (p < 0.05 and p < 0.01). There was a negative correlation between hepatic markers and PaO2 and %SaO2: r=–0.212, p=0.032 between AST and %SaO2; r=–0.243, p=0.013 and r=–0.241, p=0.014 between ALT and PaO2 and %SaO2; and r=–0.224, p=0.024 and r= –0.283, p=0.004 between direct bilirubin and PaO2 and %SaO2. AST and ALT levels were higher in massive PE than non‐massive PE patients (p=0.0001). Albumin levels were lower in patients with right ventricle dysfunction than in those without (p=0.02). One (0.9%) had a clinical picture of hypoxic hepatitis.

Conclusion:  Abnormal LFTs showed a mixed pattern in patients with acute PE.
Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection
Authors: Ghaziani Tahereh , Alavian Seyed‐Moayed , Zali Mohammad R. , Shahraz Saeid , Agah Mohammdreza , Jensen Kevin P. , Ansari Shahin , Sendi Hossein , Lambrecht Richard W. , Covault Jonathan , Bonkovsky Herbert L.
Published: March 2007

Aim:  We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection.

Methods:  Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls.

Results:  Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0–84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade.

Conclusion:  Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.
Population-Based Sequencing of the V3 Region of
env
for Predicting the Coreceptor Usage of Human Immunodeficiency Virus Type 1 Quasispecies
Authors: Delobel Pierre , Nugeyre Marie-Thérèse , Cazabat Michelle , Pasquier Christophe , Marchou Bruno , Massip Patrice , Barre-Sinoussi Françoise , Israël Nicole , Izopet Jacques
Published: March 2007

Genotypic population-based methods could be faster and less expensive than phenotypic recombinant assays for determining human immunodeficiency virus type 1 (HIV-1) coreceptor usage in patient samples, but their clinical use requires good genotype-phenotype correlation and concordance with clonal analyses. We have assessed these requirements by clonal analysis of the V1 to V3
env
PCR products of 26 patients infected with subtype B HIV-1. We used the resulting set of molecular clones, all sequenced and characterized using a single-cycle recombinant virus phenotypic entry assay, to reevaluate genotype-phenotype correlations. Combining the previously described 11/25 and net charge rules for the V3 genotype improved the prediction of HIV-1 coreceptor usage. We also evaluated the concordance of population-based and clonal analyses for predicting the coreceptor usage of HIV-1 quasispecies. Our population-based recombinant phenotypic assay and direct sequencing of V3 were similarly sensitive for detecting the presence of minor species in the virus population, and both correlated well with clonal analysis. The improved genotype-phenotype correlation obtained by combining two simple genotypic rules and the good concordance with clonal analyses suggest that direct sequencing of V3 is a valuable alternative to population-based recombinant phenotypic assays.
Genome Sequences of Three Koi Herpesvirus Isolates Representing the Expanding Distribution of an Emerging Disease Threatening Koi and Common Carp Worldwide
Authors: Aoki Takashi , Hirono Ikuo , Kurokawa Ken , Fukuda Hideo , Nahary Ronen , Eldar Avi , Davison Andrew J. , Waltzek Thomas B. , Bercovier Herve , Hedrick Ronald P.
Published: March 2007

Since the mid-1990s, lethal infections of koi herpesvirus (KHV) have been spreading, threatening the worldwide production of common carp and koi (both
Cyprinus carpio
). The complete genome sequences of three KHV strains from Japan, the United States, and Israel revealed a 295-kbp genome containing a 22-kbp terminal direct repeat. The finding that 15 KHV genes have clear homologs in the distantly related channel catfish virus (ictalurid herpesvirus 1) confirms the proposed place of KHV in the family
Herpesviridae
, specifically in the branch with fish and amphibian hosts. KHV thus has the largest genome reported to date for this family. The three strains were interpreted as having arisen from a wild-type parent encoding 156 unique protein-coding genes, 8 of which are duplicated in the terminal repeat. In each strain, four to seven genes from among a set of nine are fragmented by frameshifts likely to render the encoded proteins nonfunctional. Six of the affected genes encode predicted membrane glycoproteins. Frameshifts or other mutations close to the 3′ ends of coding sequences were identified in a further six genes. The conclusion that at least some of these mutations occurred in vivo prompts the hypothesis that loss of gene functions might be associated with emergence of the disease and provides a basis for further investigations into the molecular epidemiology of the virus.
Both Linear and Discontinuous Ribosome Scanning Are Used for Translation Initiation from Bicistronic Human Immunodeficiency Virus Type 1
env
mRNAs
Authors: Anderson Jenny L. , Johnson Adam T. , Howard Jane L. , Purcell Damian F. J.
Published: March 2007

Human immunodeficiency virus type 1 (HIV-1) generates 16 alternatively spliced isoforms of
env
mRNA that contain the same overlapping open reading frames for Vpu and Env proteins but differ in their 5′ untranslated regions (UTR). A subset of
env
mRNAs carry the extra upstream Rev initiation codon in the 5′ UTR. We explored the effect of the alternative UTR on the translation of Vpu and Env proteins from authentic
env
mRNAs expressed from cDNA constructs. Vpu expression from the subset of
env
mRNA isoforms with exons containing an upstream Rev AUG codon was minimal. However, every
env
mRNA isoform expressed similar levels of Env protein. Mutations that removed, altered the strength of, or introduced upstream AUG codons dramatically altered Vpu expression but had little impact on the consistent expression of Env. These data show that the different isoforms of
env
mRNA are not redundant but instead regulate Vpu production in HIV-1-infected cells. Furthermore, while the initiation of Vpu translation conforms to the leaky ribosome-scanning model, the consistent Env synthesis infers a novel, discontinuous ribosome-scanning mechanism to translate Env.
Maintenance of Nef-Mediated Modulation of Major Histocompatibility Complex Class I and CD4 after Sexual Transmission of Human Immunodeficiency Virus Type 1
Authors: Noviello C. M. , Pond S. L. Kosakovsky , Lewis M. J. , Richman D. D. , Pillai S. K. , Yang O. O. , Little S. J. , Smith D. M. , Guatelli J. C.
Published: March 2007

Viruses encounter changing selective pressures during transmission between hosts, including host-specific immune responses and potentially varying functional demands on specific proteins. The human immunodeficiency virus type 1 Nef protein performs several functions potentially important for successful infection, including immune escape via down-regulation of class I major histocompatibility complex (MHC-I) and direct enhancement of viral infectivity and replication. Nef is also a major target of the host cytotoxic T-lymphocyte (CTL) response. To examine the impact of changing selective pressures on Nef functions following sexual transmission, we analyzed genetic and functional changes innefclones from six transmission events. Phylogenetic analyses indicated that the diversity ofnefwas similar in both sources and acutely infected recipients, the patterns of selection across transmission were variable, and regions of Nef associated with distinct functions evolved similarly in sources and recipients. These results weighed against the selection of specific Nef functions by transmission or during acute infection. Measurement of Nef function provided no evidence that the down-regulation of either CD4 or MHC-I was optimized by transmission or during acute infection, although rarenefclones from sources that were impaired in these activities were not detected in recipients. Nef-specific CTL activity was detected as early as 3 weeks after infection and appeared to be an evolutionary force driving the diversification ofnef. Despite the change in selective pressure between the source and recipient immune systems and concomitant genetic diversity, the majority of Nef proteins maintained robust abilities to down-regulate MHC-I and CD4. These data suggest that both functions are important for the successful establishment of infection in a new host.
Epitope-Dependent Avidity Thresholds for Cytotoxic T-Lymphocyte Clearance of Virus-Infected Cells
Authors: Bennett Michael S. , Ng Hwee L. , Dagarag Mirabelle , Ali Ayub , Yang Otto O.
Published: March 2007

Cytotoxic T lymphocytes (CTLs) are crucial for immune control of viral infections. “Functional avidity,” defined by the sensitizing dose of exogenously added epitope yielding half-maximal CTL triggering against uninfected target cells (SD
50
), has been utilized extensively as a measure of antiviral efficiency. However, CTLs recognize infected cells via endogenously produced epitopes, and the relationship of SD
50
to antiviral activity has never been directly revealed. We elucidate this relationship by comparing CTL killing of cells infected with panels of epitope-variant viruses to the corresponding SD
50
for the variant epitopes. This reveals a steeply sigmoid relationship between avidity and infected cell killing, with avidity thresholds (defined as the SD
50
required for CTL to achieve 50% efficiency of infected cell killing [KE
50
]), below which infected cell killing rapidly drops to none and above which killing efficiency rapidly plateaus. Three CTL clones recognizing the same viral epitope show the same KE
50
despite differential recognition of individual epitope variants, while CTLs recognizing another epitope show a 10-fold-higher KE
50
, demonstrating epitope dependence of KE
50
. Finally, the ability of CTLs to suppress viral replication depends on the same threshold KE
50
. Thus, defining KE
50
values is required to interpret the significance of functional avidity measurements and predict CTL efficacy against virus-infected cells in pathogenesis and vaccine studies.
Lytic and Latent Antigens of the Human Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Induce T-Cell Responses with Similar Functional Properties and Memory Phenotypes
Authors: Bihl Florian , Narayan Murli , Chisholm John V. , Henry Leah M. , Suscovich Todd J. , Brown Elizabeth E. , Welzel Tania M. , Kaufmann Daniel E. , Zaman Tauheed M. , Dollard Sheila , Martin Jeff N. , Wang Fred , Scadden David T. , Kaye Kenneth M. , Brander Christian
Published: March 2007

The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses.
Molecular Determinants of the Interaction between Coxsackievirus Protein 3A and Guanine Nucleotide Exchange Factor GBF1
Authors: Wessels Els , Duijsings Daniël , Lanke Kjerstin H. W. , Melchers Willem J. G. , Jackson Catherine L. , van Kuppeveld Frank J. M.
Published: March 2007

The 3A protein of coxsackievirus B3 (CVB3), a small membrane protein that forms homodimers, inhibits endoplasmic reticulum-to-Golgi complex transport. Recently, we described the underlying mechanism by showing that the CVB3 3A protein binds to and inhibits the function of GBF1, a guanine nucleotide exchange factor for ADP-ribosylation factor 1 (Arf1), thereby interfering with Arf1-mediated COP-I recruitment. This study was undertaken to gain more insight into the molecular determinants underlying the interaction between 3A and GBF1. Here we show that 3A mutants that have lost the ability to dimerize are no longer able to bind to GBF1 and trap it on membranes. Moreover, we identify a conserved region in the N terminus of 3A that is crucial for GBF1 binding but not for 3A dimerization. Analysis of the binding domain in GBF1 showed that the extreme N terminus, the dimerization/cyclophilin binding domain, and the homology upstream of Sec7 domain are required for the interaction with 3A. In contrast to that of full-length GBF1, overexpression of a GBF1 mutant lacking its extreme N terminus failed to rescue the effects of 3A. Together, these data provide insight into the molecular requirements of the interaction between 3A and GBF1.
Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and D
Authors: Abbink Peter , Lemckert Angelique A. C. , Ewald Bonnie A. , Lynch Diana M. , Denholtz Matthew , Smits Shirley , Holterman Lennart , Damen Irma , Vogels Ronald , Thorner Anna R. , O'Brien Kara L. , Carville Angela , Mansfield Keith G. , Goudsmit Jaap , Havenga Menzo J. E. , Barouch Dan H.
Published: March 2007

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.
Development of Sindbis Viruses Encoding nsP2/GFP Chimeric Proteins and Their Application for Studying nsP2 Functioning
Authors: Atasheva Svetlana , Gorchakov Rodion , English Robert , Frolov Ilya , Frolova Elena
Published: March 2007

Sindbis virus (SINV) is one of almost 30 currently known alphaviruses. In infected cells, it produces only a few proteins that function in virus replication and interfere with the development of the antiviral response. One of the viral nonstructural proteins, nsP2, not only exhibits protease and RNA helicase activities that are directly involved in viral RNA replication but also plays critical roles in the development of transcriptional and translational shutoffs in the SINV-infected cells. These multiple activities of nsP2 complicate investigations of this protein's functions and further understanding of its structure. Using a transposon-based approach, we generated a cDNA library of SINV genomes with a green fluorescent protein (GFP) gene randomly inserted into nsP2 and identified a number of sites that can be used for GFP cloning without a strong effect on virus replication. Recombinant SIN viruses encoding nsP2/GFP chimeric protein were capable of growth in tissue culture and interfering with cellular functions. SINV, expressing GFP in the nsP2, was used to isolate nsP2-specific protein complexes formed in the cytoplasm of the infected cells. These complexes contained viral nsPs, all of the cellular proteins that we previously coisolated with SINV nsP3, and some additional protein factors that were not found before in detectable concentrations. The random insertion library-based approach, followed by the selection of the viable variants expressing heterologous proteins, can be applied for mapping the domain structure of the viral nonstructural and structural proteins, cloning of peptide tags for isolation of the protein-specific complexes, and studying their formation by using live-cell imaging. This approach may also be applicable to presentation of additional antigens and retargeting of viruses to new receptors.
Metabolic syndrome and its association with morbidity and mortality
Authors: Ardern Chris I. , Janssen Ian
Published: March 2007

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that are associated with increased risk of diabetes, cardiovascular disease (CVD), and all-cause mortality; however, it is clear that considerable variation exists in these relationships. Given that the prevalence of MetS increases with age, is higher in men than in women, and varies with race and ethnicity, a number of questions about the clinical application of MetS in predicting morbidity and mortality in diverse populations remain unanswered. Thus, in this review, we compare the ability of MetS to predict health risk across age, sex, race, and ethnicity, and in primary versus secondary prevention subgroups to explore these relationships. Furthermore, as there is currently no universal MetS criteria, we also discuss differences in the prediction of morbidity and mortality in studies that used different criteria to define MetS. At present, further research is necessary to examine the health risks associated with (i) different combinations of MetS components in diverse populations, (ii) the relative importance of each MetS component in predicting different health outcomes, and (iii) the independent contribution of MetS in predicting risk of morbidity and mortality beyond that incurred by other risk factors.
ON POSITIVE THEORIES OF GROUPS WITH REGULAR FREE LENGTH FUNCTIONS
Authors: KHAN BILAL , MYASNIKOV ALEXEI G. , SERBIN DENIS E.
Published: March 2007

In this paper we discuss a general approach to positive theories of groups. As an application we get a robust description of positive theories of groups with regular free Lyndon length function. Our approach combines techniques of infinite words (see [17, 3]), cancellation diagrams introduced in [14], and Merzlyakov's method [15].
REWRITING SYSTEMS AND ORDERINGS ON ARTIN MONOIDS
Authors: BAHLS PATRICK , SMITH TYLER
Published: March 2007

In this paper we introduce a complete rewriting system on any large-type Artin monoid. The rewriting system stems from a well-ordering defined by Burckel on the related class of braid monoids. As a consequence of our rewriting system's existence we will recover the fact that certain large-type monoids are well-orderable, and we will discern finer detail regarding the structure of this associated ordering.