bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues
Authors: Kempaiah Prakasha , Chand Hitendra S , Kisiel Walter 
Published: March 2007

Abstract

Background
Previous studies have shown that the expression of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated Kunitz-type serine proteinase inhibitor, is markedly down-regulated in several tumor cells through hypermethylation of the TFPI-2 gene promoter. In the present study, RT-PCR analysis of total RNA from both human normal and tumor cells revealed a novel 289 nucleotide splice variant of the TFPI-2 transcript designated as aberrantly-spliced TFPI-2 (asTFPI-2).

Results
Nucleotide sequence analyses indicated that asTFPI-2 consists of complete exons II and V, fused with several nucleotides derived from exons III and IV, as well as six nucleotides derived from intron C. 5'- and 3'-RACE analyses of total RNA amplified exclusively the wild-type TFPI-2 transcript, indicating that asTFPI-2 lacks either a 5'-untranslated region (UTR) or a 3'-poly (A)+ tail. Quantitative real-time RT-PCR analyses revealed that several human tumor cells contain 4 to 50-fold more copies of asTFPI-2 in comparison to normal cells. In spite of the absence of a 5'-UTR or poly (A)+ tail, the asTFPI-2 variant exhibited a half-life of ~16 h in tumor cells.

Conclusion
Our studies reveal the existence of a novel, aberrantly-spliced TFPI-2 transcript predominantly expressed in tumor cells and provides suggestive evidence for an additional mechanism for tumor cells to down-regulate TFPI-2 protein expression enhancing their ability to degrade the extracellular matrix.
Feeding oxidized fat during pregnancy up-regulates expression of PPARα-responsive genes in the liver of rat fetuses
Authors: Ringseis Robert , Gutgesell Anke , Dathe Corinna , Brandsch Corinna , Eder Klaus 
Published: March 2007

Abstract

Background
Feeding oxidized fats causes activation of peroxisome proliferator-activated receptor α (PPARα) in the liver of rats. However, whether feeding oxidized fat during pregnancy also results in activation of PPARα in fetal liver is unknown. Thus, this study aimed to explore whether feeding oxidized fat during pregnancy causes a PPARα response in fetal liver. Two experiments with pregnant rats which were administered three different diets (control; oxidized fat; clofibrate as positive control) in a controlled feeding regimen during either late pregnancy (first experiment) or whole pregnancy (second experiment) were performed.

Results
In both experiments pregnant rats treated with oxidized fat or clofibrate had higher relative mRNA concentrations of the PPARα-responsive genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 (CYP4A1), L-type carnitin-palmitoyl transferase I (L-CPT I), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in the liver than control rats (P < 0.05). In addition, in both experiments fetuses of the oxidized fat group and the clofibrate group also had markedly higher relative mRNA concentrations of ACO, CYP4A1, CPT I, MCAD, and LCAD in the liver than those of the control group (P < 0.05), whereas the relative mRNA concentrations of PPARα, SREBP-1c, and FAS did not differ between treatment groups. In the second experiment treatment with oxidized fat also reduced triacylglycerol concentrations in the livers of pregnant rats and fetuses (P < 0.05).

Conclusion
The present study demonstrates for the first time that components of oxidized fat with PPARα activating potential are able to induce a PPARα response in the liver of fetuses. Moreover, the present study shows that feeding oxidized fat during whole pregnancy, but not during late pregnancy, lowers triacylglycerol concentrations in fetal livers.
New genes in the evolution of the neural crest differentiation program
Authors: Martinez-Morales Juan-Ramon , Henrich Thorsten , Ramialison Mirana , Wittbrodt Joachim 
Published: March 2007

Abstract
Background
Development of the vertebrate head depends on the multipotency and migratory behavior of neural crest derivatives. This cell population is considered a vertebrate innovation and, accordingly, chordate ancestors lacked neural crest counterparts. The identification of neural crest specification genes expressed in the neural plate of basal chordates, in addition to the discovery of pigmented migratory cells in ascidians, has challenged this hypothesis. These new findings revive the debate on what is new and what is ancient in the genetic program that controls neural crest formation.

Results
To determine the origin of neural crest genes, we analyzed Phenotype Ontology annotations to select genes that control the development of this tissue. Using a sequential blast pipeline, we phylogenetically classified these genes, as well as those associated with other tissues, in order to define tissue-specific profiles of gene emergence. Of neural crest genes, 9% are vertebrate innovations. Our comparative analyses show that, among different tissues, the neural crest exhibits a particularly high rate of gene emergence during vertebrate evolution. A remarkable proportion of the new neural crest genes encode soluble ligands that control neural crest precursor specification into each cell lineage, including pigmented, neural, glial, and skeletal derivatives.

Conclusion
We propose that the evolution of the neural crest is linked not only to the recruitment of ancestral regulatory genes but also to the emergence of signaling peptides that control the increasingly complex lineage diversification of this plastic cell population.
Bortezomib Is Active in Patients With Untreated or Relapsed Waldenström's Macroglobulinemia: A Phase II Study of the National Cancer Institute of Canada Clinical Trials Group
Authors: Chen Christine I. , Kouroukis C. Tom , White Darrell , Voralia Michael , Stadtmauer Edward , Stewart A. Keith , Wright John J. , Powers Jean , Walsh Wendy , Eisenhauer Elizabeth 
Published: March 2007

Purpose To evaluate the efficacy and toxicity of single-agent bortezomib in Waldenström's macroglobulinemia (WM). Patients and Methods Symptomatic WM patients, untreated or previously treated, received bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, and 11 on a 21-day cycle until two cycles past complete response (CR), stable disease (SD) attained, progression (PD), or unacceptable toxicity. Responses were based on both paraprotein levels and bidimensional disease measurements. Results Twenty-seven patients were enrolled. A median of six cycles (range, two to 39) of bortezomib were administered. Twenty-one patients had a decrease in immunoglobulin M (IgM) of at least 25%, with 12 patients (44%) reaching at least 50% IgM reduction. Using both IgM and bidimensional criteria, responses included seven partial responses (PRs; 26%), 19 SDs (70%), and one PD (4%). Total response rate was 26%. IgM reductions were prompt, with nodal responses lagging. Hemoglobin levels increased by at least 10 g/L in 18 patients (66%). Most nonhematologic toxicities were grade 1 to 2, but 20 patients (74%) developed new or worsening peripheral neuropathy (five patients with grade 3, no grade 4), a common cause for dose reduction. Onset of neuropathy was within two to four cycles and reversible in the majority. Hematologic toxicities included grade 3 to 4 thrombocytopenia in eight patients (29.6%) and neutropenia in five (19%). Toxicity led to treatment discontinuation in 12 patients (44%), most commonly because of neuropathy. Conclusion Bortezomib has efficacy in WM, but neurotoxicity can be dose limiting. The slower response in nodal disease may require prolonged therapy, perhaps with a less intensive dosing schedule to avoid early discontinuation because of toxicity. Future studies of bortezomib in combination with other agents are warranted.
Abdominal Computed Tomography Predicts Progression in Patients With Rai Stage 0 Chronic Lymphocytic Leukemia
Authors: Muntañola Ana , Bosch Francesc , Arguis Pedro , Arellano-Rodrigo Eduardo , Ayuso Carmen , Giné Eva , Crespo Marta , Abrisqueta Pau , Moreno Carol , Cobo Francesc , López-Guillermo Armando , Montserrat Emili 
Published: March 2007

Purpose Whether computed tomography (CT) should be routinely included in the diagnostic work-up in patients with chronic lymphocytic leukemia (CLL) has not yet been determined. The aim of this study was to analyze the prognostic significance of abdominal CT in patients with CLL in Rai clinical stage 0. Patients and Methods Abdominal CT was performed at diagnosis in 140 patients consecutively diagnosed with CLL in Rai stage 0 disease. Results An abnormal abdominal CT was found in 38 patients (27%). Abnormal CT correlated with increased bone marrow infiltration (P = .024), high lymphocyte count (P = .001), increased ZAP-70 expression (P = .003), and short lymphocyte doubling time (LDT; P = .007). Patients with abnormal CT progressed more frequently and had a shorter time to progression than those with normal CT (median, 3.5 years v not reached, respectively; P < .001) and required earlier treatment intervention. In a multivariate analysis, only high ZAP-70 expression (relative risk = 3.60) and an abnormal abdominal CT (RR = 2.71) correlated with disease progression. Conclusion In this series, an abnormal abdominal CT was a strong predictor of progression in patients with early-stage CLL. The inclusion of CT scans in the initial work-up of patients with early clinical stage on clinical grounds can, therefore, provide relevant clinical information.
Reclassification of 300 Primary Cutaneous B-Cell Lymphomas According to the New WHO–EORTC Classification for Cutaneous Lymphomas: Comparison With Previous Classifications and Identification of Prognostic Markers
Authors: Senff Nancy J. , Hoefnagel Juliette J. , Jansen Patty M. , Vermeer Maarten H. , van Baarlen Joop , Blokx Willeke A. , Canninga-van Dijk Marijke R. , Geerts Marie-Louise , Hebeda Konnie M. , Kluin Philip M. , Lam King H. , Meijer Chris J.L.M. , Willemze Rein 
Published: March 2007

Purpose In the new WHO–European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas three major groups of primary cutaneous B-cell lymphoma (CBCL) are distinguished: primary cutaneous marginal zone B-cell lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) with a good prognosis, and primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT), with an intermediate-level prognosis. This study aimed to assess the clinical significance of the new classification compared with previous classification schemes (EORTC 1997; WHO 2001) and to define prognostic factors within the newly defined categories. Patients and Methods In the present study clinical data and histologic sections of 300 patients with CBCL, formerly classified according to the EORTC classification, were reviewed and reclassified according to the WHO and the new WHO-EORTC classification schemes. Results After reclassification, the study comprised 71 patients with PCMZL, 171 patients with PCFCL, and 58 patients with PCLBCL-LT, showing 5-year disease-specific survivals of 98%, 95%, and 50%, respectively. When compared with the EORTC and WHO schemes, 5.3% and 36.3% of patients with CBCL were reclassified into another prognostic category. Multivariate analysis of PCFCL revealed localization on the leg and expression of FOXP1 as independent parameters associated with a poor prognosis. Expression of Bcl-2 or MUM-1 had no significant effect on survival in this group. In PCLBCL-LT, no independent prognostic parameters were found. Conclusion These results emphasize the clinical significance of the WHO-EORTC classification, but suggest that within the group of PCFCL, distinction should be made between lymphomas presenting on the legs and lymphomas presenting at other sites.
Measuring Quality of Care in the Treatment of Colorectal Cancer: The Moffitt Quality Practice Initiative
Authors: Jacobsen Paul B. , Shibata David , Siegel Erin M. , Druta Mihaela , Lee Ji-Hyun , Marshburn Jan , Davenport Linda , Cruse Hugh , Levine Richard , Gondi Avantica , Brown Richard , Malafa Mokenge 
Published: March 2007

Purpose The Moffitt Quality Practice Initiative (MQPI) is a practice-based system of quality self-assessment, the ultimate goal of which is to improve the quality of cancer care at a statewide level. The initial phase of this project focused on developing procedures, determining feasibility, and evaluating utility for assessing quality of care for colorectal cancer within an existing affiliate network. Patients and Methods Representatives from four oncology groups selected quality measures consistent with evidence-, consensus-, and safety-based guidelines that could be abstracted from medical records. Trained abstractors then reviewed records of all eligible colorectal patients seen by each practice in 2004. Frequencies of responses for each indicator were tabulated for overall and practice-specific level of adherence and were compared among practices. Results Adherence was uniformly high for several indicators, including confirmatory pathology report, staging information, and chemotherapy discussion or recommendation. Lower adherence was evident across practices for performance of carcinoembryonic tests and complete colonoscopic evaluations. Significant variation among practices was evident only for consent for chemotherapy. Conclusion The initial phase of MQPI demonstrated the feasibility and utility of assessing quality indicators for colorectal cancer among members of an existing affiliate network. Findings identified areas where adherence to care was uniformly high, but also identified areas where both overall and practice-specific adherence were less than optimal. These efforts lay the groundwork for expanding MQPI in several directions that have in common the potential to improve the quality of cancer care on a statewide basis.
Future Supply and Demand for Oncologists : Challenges to Assuring Access to Oncology Services
Authors: Erikson Clese , Salsberg Edward , Forte Gaetano , Bruinooge Suanna , Goldstein Michael 
Published: March 2007

Purpose To conduct a comprehensive analysis of supply of and demand for oncology services through 2020. This study was commissioned by the Board of Directors of ASCO. Methods New data on physician supply gathered from surveys of practicing oncologists, oncology fellows, and fellowship program directors were analyzed, along with 2005 American Medical Association Masterfile data on practicing medical oncologists, hematologists/oncologists, and gynecologic oncologists, to determine the baseline capacity and to forecast visit capacity through 2020. Demand for visits was calculated by applying age-, sex-, and time-from-diagnosis-visit rate data from the National Cancer Institute's analysis of the 1998 to 2002 Surveillance, Epidemiology and End Results (SEER) database to the National Cancer Institute's cancer incidence and prevalence projections. The cancer incidence and prevalence projections were calculated by applying a 3-year average (2000–2002) of age- and sex-specific cancer rates from SEER to the US Census Bureau population projections released on March 2004. The baseline supply and demand forecasts assume no change in cancer care delivery and physician practice patterns. Alternate scenarios were constructed by changing assumptions in the baseline models. Results Demand for oncology services is expected to rise rapidly, driven by the aging and growth of the population and improvements in cancer survival rates, at the same time the oncology workforce is aging and retiring in increasing numbers. Demand is expected to rise 48% between 2005 and 2020. The supply of services provided by oncologists during this time is expected to grow more slowly, approximately 14%, based on the current age distribution and practice patterns of oncologists and the number of oncology fellowship positions. This translates into a shortage of 9.4 to 15.0 million visits, or 2,550 to 4,080 oncologists—roughly one-quarter to one-third of the 2005 supply. The baseline projections do not include any alterations based on changes in practice patterns, service use, or cancer treatments. Various alternate scenarios were also developed to show how supply and demand might change under different assumptions. Conclusions ASCO, policy makers, and the public have major challenges ahead of them to forestall likely shortages in the capacity to meet future demand for oncology services. A multifaceted strategy will be needed to ensure that Americans have access to oncology services in 2020, as no single action will fill the likely gap between supply and demand. Among the options to consider are increasing the number of oncology fellowship positions, increasing use of nonphysician clinicians, increasing the role of primary care physicians in the care of patients in remission, and redesigning service delivery.
A review of the quality of gastrointestinal investigations performed in UK laboratories
Authors: Duncan Andrew , Hill Peter G 
Published: March 2007

Background: About 10 years ago, a survey showed significant deficiencies in the quality of gastrointestinal investigations performed by UK laboratories. Subsequently, several clinical guidelines have been developed and external quality assessment schemes introduced. This survey was performed to assess whether earlier deficiencies have been addressed. Methods: The repertoire of gastrointestinal investigations in UK departments of clinical biochemistry was obtained by questionnaire. Nominees were sent further questionnaires to assess various aspects of the service. Analytical performance was determined by sending samples for analysis and by reviewing external quality assessment (EQA) programmes. Results: The survey showed that in many instances no internal quality control (IQC) is used, analytical performance is poor, reference ranges are inaccurate, protocols are inappropriate, EQA is not adopted, some useful tests are not widely available and interpretation for some tests is inadequate. Conclusions: Much of the responsibility for this scenario lies with individual laboratories. Although participation in available EQA schemes is mandatory for accreditation, many laboratories are failing to participate in such schemes, and IQC is inadequate for many gastrointestinal tests. One reason for the poor performance is likely to be the low numbers of tests performed: laboratories receiving infrequent requests may be less able to produce reliable results and develop interpretive expertise. The survey highlights areas requiring the development of consensus guidelines by the Association for Clinical Biochemistry and British Society of Gastroenterology, so that appropriate tests are available and a reliable analytical service provided for laboratory-based and point-of-care gastrointestinal investigations in the UK.
Rapid detection of R90H mutations in the human urate transporter 1 gene
Authors: Inazu Tetsuya , Kawahara Tetsuya , Ishikawa Isao 
Published: March 2007

Background: Hypouricaemia is a relatively common disorder in the general population. Since the discovery of the human urate transporter 1 (hURAT1) gene, the number of patients diagnosed with renal hypouricaemia caused by hURAT1 gene mutation(s) has increased. A rapid method for detecting such a mutation(s) for diagnostic aid is described herein. Methods: A rapid method for detecting G269A (R90H) mutations by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed. Results: The patient had compound heterozygous mutations in the hURAT1 gene (R90H and W258X), but showed no clinical manifestations such as urolithiasis or exercise-induced acute renal failure. The G269A (R90H) mutation was detected by PCR-RFLP using the Notl restriction enzyme. Conclusions: PCR-RFLP is useful for detecting G269A (R90H) mutations in the hURAT1 gene.
Dehydroepiandrostenedione sulphate interferes in many direct immunoassays for testosterone
Authors: Middle Jonathan G 
Published: March 2007

Background: In response to a report that the Abbott Architect direct testosterone immunoassay was affected by dehydroepiandrostenedione sulphate (DHEAS) cross-reactivity, this study investigated the effect of DHEAS on other testosterone methods using a UK National External Quality Assessment Scheme (UK NEQAS) for steroid hormones special distribution. Methods: Separate male and female matrix pools of normal human serum were prepared and divided into three portions. Two portions from each matrix were spiked with 10.07 and 20.14. μmol/L DHEAS, respectively. Aliquots of these pools were distributed to participants in UK NEQAS for male and female testosterone at distribution 319 (July 2006). Median testosterone results for each method group were examined for an increase in testosterone concentration. Results: In the female matrix, the effect on Abbott Architect was confirmed and shown also for Roche Elecsys, Roche E170 Modular and Beckman Access (includes some Beckman DxI users). In the male matrix, the effect on Abbott Architect, Roche Elecsys and Roche E170 Modular was similar in magnitude to that in the female matrix, but was smaller for Beckman Access/DxI. However, the effect on Immulite 2000 (includes some Immulite 2500 users) was greater in the male matrix. Indications of interference in other methods, used by only a few laboratories (notably Tosoh AIA and Wallac Delfia), were also observed. Conclusions: DHEAS interference in testosterone assays is a feature of many routine testosterone methods, and occurs in both male and female matrices.
Development of a denaturing high-performance liquid chromatography screening method for SMAD4 in juvenile polyposis syndrome
Authors: Hatch Sarah L , Trewick Anne L , Payne Stewart J 
Published: March 2007

Background: Juvenile polyposis syndrome is an inherited condition associated with the development of gastrointestinal polyps and subsequent cancer. An efficient denaturing high-performance liquid chromatography (DHPLC) screening method has been developed to detect mutations in SMAD4, which account for around 20% of reported cases. Methods: The nucleotide sequences of polymerase chain reaction (PCR)amplified SMAD4 exons were examined using WAVEMAKERTM software to determine suitable DHPLC conditions. Multiple wild-type controls were characterized by DHPLC, and known mutations analysed where available. Results: DHPLC elution profiles for wild-type and variant SMAD4 alleles were successfully characterized across a range of column oven temperatures. Conclusions: DHPLC analysis of SMAD4 has been refined to an efficient screening protocol that uses the minimal number of column oven temperatures for reliable mutation detection.
The Avon patellofemoral arthroplasty
Authors: Ackroyd C. E. , Newman J. H. , Evans R. , Eldridge J. D. J. , Joslin C. C. 
Published: March 2007

We report the mid-term results of a new patellofemoral arthroplasty for established isolated patellofemoral arthritis. We have reviewed the experience of 109 consecutive patellofemoral resurfacing arthroplasties in 85 patients who were followed up for at least five years. The five-year survival rate, with revision as the endpoint, was 95.8% (95% confidence interval 91.8% to 99.8%). There were no cases of loosening of the prosthesis. At five years the median Bristol pain score improved from 15 of 40 points (interquartile range 5 to 20) pre-operatively, to 35 (interquartile range 20 to 40), the median Melbourne score from 10 of 30 points (interquartile range 6 to 15) to 25 (interquartile range 20 to 29), and the median Oxford score from 18 of 48 points (interquartile range 13 to 24) to 39 (interquartile range 24 to 45). Successful results, judged on a Bristol pain score of at least 20 at five years, occurred in 80% (66) of knees. The main complication was radiological progression of arthritis, which occurred in 25 patients (28%) and emphasises the importance of the careful selection of patients. These results give increased confidence in the use of patellofemoral arthroplasty.