bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug-eluting stents: new era and new concerns
Authors: Bhatia V , Bhatia R , Dhindsa M 
Published: February 2004

Abstract
At present there is much excitement about drug-eluting stents, which hold promise for the treatment of coronary artery disease. This ingenious therapy involves coating the outside of a standard coronary stent with a thin polymer containing medication that can prevent scarring at the site of coronary intervention. Early trials with sirolimus coated stents showed that they might prevent coronary artery restenosis, but later studies, involving more complex coronary lesions, did not show a complete absence of restenosis. Recent studies have demonstrated the long term cost effectiveness of drug-eluting stents as they have reduced the need for revascularisation procedures. At present there are few data on the safety and effectiveness of stents over follow up periods exceeding two years, and data obtained from animal models of stenting might not be completely applicable to humans. There are concerns that drug-eluting stents might delay, rather than inhibit, restenosis. Also there is concern regarding the inflammation caused by the polymer substrate. This article reviews the present data on drug-eluting stents and their benefits, shortcomings, and concerns.
Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia
Authors: Jiang Xiaoyan , Zhao Yun , Chan Wing-Yiu , Vercauteren Suzanne , Pang Emily , Kennedy Sean , Nicolini Frank , Eaves Allen , Eaves Connie 
Published: February 2004

Abstract
Ahi-1/AHI-1 (Abelson helper integration site-1) encodes a family of protein isoforms containing one Src homology 3 (SH3) domain and multiple tryptophan-aspartic acid 40 (WD40)–repeat domains. The function of these proteins is unknown, but involvement in leukemogenesis has been suggested by the high frequency of Ahi-1 mutations seen in certain virus-induced murine leukemias. Here we show that in both mice and humans, Ahi-1/AHI-1 expression is highest in the most primitive hematopoietic cells with specific patterns of down-regulation in different lineages. Cells from patients with chronic myeloid leukemia (CML; n = 28) show elevated AHI-1 transcripts in all disease phases and, in chronic phase, in the leukemic cells at all stages of differentiation, including quiescent (G0) CD34+ cells as well as terminally differentiating cells. In the most primitive lin–CD34+CD38– CML cells, transcripts for the 2 shorter isoforms of AHI-1 are also increased. Although 15 of 16 human lymphoid and myeloid leukemic cell lines showed aberrant control of AHI-1 expression, this was not seen in blasts obtained directly from patients with acute Philadelphia chromosome–negative (Ph–) leukemia (n = 15). Taken together, our results suggest that down-regulation of AHI-1 expression is an important conserved step in primitive normal hematopoietic cell differentiation and that perturbations in AHI-1 expression may contribute to the development of specific types of human leukemia.
Modeled Microgravity Inhibits Osteogenic Differentiation of Human Mesenchymal Stem Cells and Increases Adipogenesis
Authors: Zayzafoon Majd , Gathings William E. , McDonald Jay M. 
Published: February 2004

Abstract
Space flight-induced bone loss has been attributed to a decrease in osteoblast function, without a significant change in bone resorption. To determine the effect of microgravity (MG) on bone, we used the Rotary Cell Culture System [developed by the National Aeronautics and Space Administration (NASA)] to model MG. Cultured mouse calvariae demonstrated a 3-fold decrease in alkaline phosphatase (ALP) activity and failed to mineralize after 7 d of MG. ALP and osteocalcin gene expression were also decreased. To determine the effects of MG on osteoblastogenesis, we cultured human mesenchymal stem cells (hMSC) on plastic microcarriers, and osteogenic differentiation was induced immediately before the initiation of modeled MG. A marked suppression of hMSC differentiation into osteoblasts was observed because the cells failed to express ALP, collagen 1, and osteonectin. The expression of runt-related transcription factor 2 was also inhibited. Interestingly, we found that peroxisome proliferator-activated receptor γ (PPARγ2), which is known to be important for adipocyte differentiation, adipsin, leptin, and glucose transporter-4 are highly expressed in response to MG. These changes were not corrected after 35 d of readaptation to normal gravity. In addition, MG decreased ERK- and increased p38-phosphorylation. These pathways are known to regulate the activity of runt-related transcription factor 2 and PPARγ2, respectively. Taken together, our findings indicate that modeled MG inhibits the osteoblastic differentiation of hMSC and induces the development of an adipocytic lineage phenotype. This work will increase understanding and aid in the prevention of bone loss, not only in MG but also potentially in age-and disuse-related osteoporosis.
Insulin-Like Growth Factor-I Augments Chondrocyte Hypertrophy and Reverses Glucocorticoid-Mediated Growth Retardation in Fetal Mice Metatarsal Cultures
Authors: Mushtaq T. , Bijman P. , Ahmed S. F. , Farquharson C. 
Published: February 2004

AbstractThe study aims were to improve our understanding of the mechanisms of glucocorticoid-induced growth retardation at the growth plate and determine whether IGF-I could ameliorate the effects. Fetal mouse metatarsals were cultured for up to 10 d with dexamethasone (Dex; 10–6m) and/or IGF-I and GH (both at 100 ng/ml). Both continuous and alternate-day Dex treatment inhibited bone growth to a similar degree, whereas IGF-I alone or together with Dex caused an increase in bone growth. GH had no effects. These observations may be explained at the cellular level; cell proliferation within the growing bone was decreased by Dex and increased by IGF-I and these effects were more marked in the cells of the perichondrium than those in the growth plate. However, the most prominent observation was noted in the hypertrophic zone where all treatments containing IGF-I significantly increased (3-fold) the length of this zone, whereas Dex alone had no significant effect. In conclusion, Dex impaired longitudinal growth by inhibiting chondrocyte proliferation, whereas IGF-I stimulated chondrocyte hypertrophy and reversed the growth-inhibitory Dex effects. However, the IGF-I-mediated improvement in growth was at the expense of altering the balance between proliferating and hypertrophic chondrocytes within the metatarsal.
Orphan Nuclear Receptor Small Heterodimer Partner, a Novel Corepressor for a Basic Helix-Loop-Helix Transcription Factor BETA2/NeuroD
Authors: Kim Joon-Young , Chu Khoi , Kim Han-Jong , Seong Hyun-A , Park Ki-Cheol , Sanyal Sabyasachi , Takeda Jun , Ha Hyunjung , Shong Minho , Tsai Ming-Jer , Choi Hueng-Sik 
Published: February 2004

AbstractSmall heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA binding domain (DBD) and represses the transcriptional activity of various nuclear receptors. In this study, we examined the novel cross talk between SHP and BETA2/NeuroD, a basic helix-loop-helix transcription factor. In vitro and in vivo protein interaction studies showed that SHP physically interacts with BETA2/NeuroD, but not its heterodimer partner E47. Moreover, confocal microscopic study and immunostaining results demonstrated that SHP colocalized with BETA2 in islets of mouse pancreas. SHP inhibited BETA2/NeuroD-dependent transactivation of an E-box reporter, whereas SHP was unable to repress the E47-mediated transactivation and the E-box mutant reporter activity. In addition, SHP repressed the BETA2-dependent activity of glucokinase and cyclin-dependent kinase inhibitor p21 gene promoters. Gel shift and in vitro protein competition assays indicated that SHP inhibits neither dimerization nor DNA binding of BETA2 and E47. Rather, SHP directly repressed BETA2 transcriptional activity and p300-enhanced BETA2/NeuroD transcriptional activity by inhibiting interaction between BETA2 and coactivator p300. We also showed that C-terminal repression domain within SHP is also required for BETA2 repression. However, inhibition of BETA2 activity was not observed by naturally occurring human SHP mutants that cannot interact with BETA2/NeuroD. Taken together, these results suggest that SHP acts as a novel corepressor for basic helix-loop-helix transcription factor BETA2/NeuroD by competing with coactivator p300 for binding to BETA2/NeuroD and by its direct transcriptional repression function.
Complementary Medicine Prescription Patterns in Germany
Authors: Schneider Berthold , Hanisch Jürgen , Weiser Michael 
Published: February 2004

BACKGROUND There is growing interest in complementary medicine worldwide and a corresponding need to know how patients and practitioners interact. OBJECTIVE To chart the use of complementary medications compared with conventional treatments among practitioners and patients in Germany. METHODS Comparative analysis of patients' data from a prospective cohort study of 4178 patients presenting with chronic as well as acute symptoms by 218 practitioners at 218 centers in all German federal states between 2001 and 2002. Practices focused on either conventional medicine, complementary medicine, or both. Data were gathered on prescription patterns, treatment satisfaction and adherence, and the degree of patient involvement in treatment decisions. RESULTS Complementary medicine was preferentially prescribed over conventional medicine in patients <18 and >65 years old, in women, and in patients with chronic symptoms. Patients receiving complementary medications had, on average, higher rates of accompanying illnesses, received more preparations, and were more closely involved in the decision process than patients prescribed conventional therapies. The decision to use complementary medicine was based on both the patient's and the practitioner's wishes in 40.8% of the cases compared with 25.8% of the cases of conventional therapies. Tolerability and satisfaction with treatment appeared greater with complementary than with conventional therapies. CONCLUSION Complementary medicine is generally well established in Germany, apparently in a dialogue with conventional medicine. Patients receiving complementary medicine appear to be more closely involved in the decision process and more satisfied with treatments than conventionally treated patients.
Troponin I in Patients without Chest Pain
Authors: Ritter Detlef , Lee Paul A , Taylor James F , Hsu Leo , Cohen Jerome D , Chung Hyung D , Virgo Katherine S 
Published: February 2004

AbstractBackground: Testing for troponin has important clinical value for patients who present with typical symptoms of acute coronary syndromes (ACS) such as chest pain (CP). Much less is known about the value of troponin testing for patients who present with other symptoms of ACS (anginal equivalent symptoms).Methods: The utilization and prognostic value of cardiac troponin I (cTnI) were evaluated at a Veterans Affairs Acute Care Facility. Clinical charts of 1184 predominantly male patients, who submitted specimens for initial cTnI testing by AxSYM, were evaluated for demographic data, cardiovascular risk factors, major diseases, and complaints at the time of testing. The endpoint was defined as all-cause death during a 200-day period after initial testing.Results: Sixty-one percent of cTnI tests were ordered for patients who did not present with CP. Patients presenting with symptoms other than CP did not have significantly lower plasma cTnI than patients with CP. However, patients with symptoms other than CP were rarely diagnosed with ACS unless cTnI was ≥2 μg/L. The mortality during the follow-up period was severalfold higher among patients presenting with symptoms other than CP (CP, 6%; without CP, 22%; P &lt;0.0001, χ2 test). cTnI ≥0.2 μg/L provided significant additional predictive information for patients who presented with anginal equivalent symptoms such as shortness of breath or general weakness.Conclusion: Patients with anginal equivalent symptoms of ACS and low-positive cTnI are less often diagnosed with ACS and have a higher mortality than patients with CP.
Diagnosis of Congenital Disorders of Glycosylation by Capillary Zone Electrophoresis of Serum Transferrin
Authors: Carchon Hubert A , Chevigné Roland , Falmagne Jean-Bernard , Jaeken Jaak 
Published: February 2004

Abstract
Background: Congenital disorders of glycosylation (CDG) are usually diagnosed by isoelectric focusing (IEF) of serum transferrin (Tf). The aim of this study was to evaluate capillary zone electrophoresis (CZE) as a diagnostic alternative to IEF.
Methods: We performed 792 CZE analyses of Tf, using the CEofixTM-CDT (carbohydrate-deficient transferrin) assay. Peak identification was based on relative migration times (RMTs) to reduce migration variability.
Results: Tf profiles comprised three main groups (A–C). Groups A and B were characterized by one or two dominant tetrasialo-Tf peaks, whereas group C showed a widely variable Tf isoform composition. Group A was composed of four subgroups: a major group with a typical Tf profile (considered as reference group), two minor groups with decreased or moderately increased trisialo-Tf isoform, and a group showing the presence of unknown compounds with RMTs similar to mono- and disialo-Tf. However, these compounds were absent on IEF. Group C contained all profiles from patients with confirmed as well as putative CDG. From the reference group, 99% confidence intervals were calculated for the RMTs of the Tf isoforms, and percentiles representing the Tf isoform distributions were defined.
Conclusions: All patients with abnormal IEF results and confirmed CDG were identified by CZE; thus, this method can be used as a diagnostic alternative to IEF in a manner suitable for automation. Because whole serum is analyzed, it should be kept in mind that CZE profiles can show substances other than Tf.
Highly Recurrent RET Mutations and Novel Mutations in Genes of the Receptor Tyrosine Kinase and Endothelin Receptor B Pathways in Chinese Patients with Sporadic Hirschsprung Disease
Authors: Garcia-Barceló Mercè , Sham Mai-Har , Lee Wing-Shan , Lui Vincent Chi-Hang , Chen Benedict Ling-Sze , Wong Kenneth Kak-Yuen , Wong Joyce Suet-Wan , Tam Paul Kwong-Hang 
Published: February 2004

AbstractBackground: Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. HSCR has a complex pattern of inheritance and is sometimes associated with mutations in genes of the receptor tyrosine kinase (RET) and endothelin receptor B (EDNRB) signaling pathways, which are crucial for development of the enteric nervous system.Methods: Using PCR amplification and direct sequencing, we screened for mutations and polymorphisms in the coding regions and intron/exon boundaries of the RET, GDNF, EDNRB, and EDN3 genes of 84 HSCR patients and 96 ethnically matched controls.Results: We identified 10 novel and 2 previously described mutations in RET, and 4 and 2 novel mutations in EDNRB and in EDN3, respectively. Potential disease-causing mutations were detected in 24% of the patients. The overall mutation rate was 41% in females and 19% in males (P = 0.06). RET mutations occurred in 19% of the patients. R114H in RET was the most prevalent mutation, representing 7% of the patients or 37% of the patients with RET mutations. To date, such a high frequency of a single mutation has never been reported in unrelated HSCR patients. Mutations in EDNRB, EDN3, and GDNF were found in four, two, and none of the patients, respectively. Two patients with mutations in genes of the EDNRB pathway also harbored a mutation in RET. Three novel and three reported polymorphisms were found in EDNRB, EDN3, and GDNF.Conclusion: This study identifies additional HSCR disease-causing mutations, some peculiar to the Chinese population, and represents the first comprehensive genetic analysis of sporadic HSCR disease in Chinese.
Detection of the Factor V Leiden Mutation by a Modified Photo-Cross-Linking Oligonucleotide Hybridization Assay
Authors: French Cynthia , Li Conan , Strom Charles , Sun Weimin , Van Atta Reuel , Gonzalez Belen , Wood Michael 
Published: February 2004

Abstract
Background: Our previously developed assay for detection of the factor V Leiden mutation (G1691A) based on a nucleic acid photo-cross-linking technology used two allele-specific capture probes and six fluorescein-modified signal-generating reporter probes. We wished to improve the sensitivity and performance of the method.
Methods: We developed new reporter probes with ∼10-fold more fluorescein molecules than the original probes. The single, cross-linker-modified capture probe was replaced by a three-probe system, separating the probe–target cross-linking function and the allelic differentiation function. The capture probe cross-linked to either or both of two flanking probes through stem structures at the capture-probe/flanking-probe junctions. The flanking probes cross-linked to target DNA through two cross-linking sites each. Genomic DNA was extracted from 0.2 mL of whole blood and restriction-enzyme digested to create a defined 677 bp target sequence. Preliminary genotype ranges were determined for the assay by testing of pretyped samples. We then tested 1054 clinical samples, using an automated sample processor.
Results: The new assay had a 10-fold increase in signal-to-background ratio. Genotype results for 1039 of 1054 clinical samples (98.6%) agreed with those of a PCR-based method. Of the 15 remaining samples, 10 produced an indeterminate result outside the defined genotype ranges, 2 yielded insufficient signal to be genotyped, and 3 gave a discordant result. All 15 samples were genotyped correctly after reextraction of genomic DNA and retesting.
Conclusion: The modified photo-cross-linking assay for factor V Leiden detection is a sensitive non-PCR-based assay with potential for use in high-throughput clinical laboratories.
High-Throughput Mutation Detection Method to Scan BRCA1 and BRCA2 Based on Heteroduplex Analysis by Capillary Array Electrophoresis
Authors: Esteban-Cardeñosa Eva , Duran Mercedes , Infante Mar , Velasco Eladio , Miner Cristina 
Published: February 2004

Abstract
Background: Scanning for mutations in BRCA1 and BRCA2 in a large number of samples is hampered by the large sizes of these genes and the scattering of mutations throughout their coding sequences. Automated capillary electrophoresis has been shown to be a powerful system to detect mutations by either single-strand conformation polymorphism or heteroduplex analysis (HA).
Methods: We investigated the adaptation of gel-based HA of BRCA1 and BRCA2 to a fluorescent multicapillary platform to increase the throughput of this technique. We combined multiplex PCR, three different fluorescent labels, and HA in a 16-capillary DNA sequencer and tested 57 DNA sequence variants (11 insertions/deletions and 46 single-nucleotide changes) of BRCA1 and BRCA2.
Results: We detected all 57 DNA changes in a blinded assay, and 2 additional single-nucleotide substitutions (1186 A&gt;G of BRCA1 and 3624 A&gt;G of BRCA2), previously unresolved by conformation-sensitive gel electrophoresis. Furthermore, different DNA changes in the same PCR fragment could be distinguished by their peak patterns.
Conclusions: Capillary-based HA is a fast, efficient, and sensitive method that considerably reduces the amount of “hands-on” time for each sample. By this approach, the entire coding regions of BRCA1 and BRCA2 from two breast cancer patients can be scanned in a single run of 90 min.
Detection of SARS Coronavirus in Patients with Severe Acute Respiratory Syndrome by Conventional and Real-Time Quantitative Reverse Transcription-PCR Assays
Authors: Poon Leo L M , Chan Kwok Hung , Wong On Kei , Cheung Timothy K W , Ng Iris , Zheng Bojian , Seto Wing Hong , Yuen Kwok Yung , Guan Yi , Peiris Joseph S M 
Published: February 2004

Abstract
Background: A novel coronavirus (CoV) was recently identified as the agent for severe acute respiratory syndrome (SARS). We compared the abilities of conventional and real-time reverse transcription-PCR (RT-PCR) assays to detect SARS CoV in clinical specimens.
Methods: RNA samples isolated from nasopharyngeal aspirate (NPA; n = 170) and stool (n = 44) were reverse-transcribed and tested by our in-house conventional RT-PCR assay. We selected 98 NPA and 37 stool samples collected at different times after the onset of disease and tested them in a real-time quantitative RT-PCR specific for the open reading frame (ORF) 1b region of SARS CoV. Detection rates for the conventional and real-time quantitative RT-PCR assays were compared. To investigate the nature of viral RNA molecules in these clinical samples, we determined copy numbers of ORF 1b and nucleocapsid (N) gene sequences of SARS CoV.
Results: The quantitative real-time RT-PCR assay was more sensitive than the conventional RT-PCR assay for detecting SARS CoV in samples collected early in the course of the disease. Real-time assays targeted at the ORF 1b region and the N gene revealed that copy numbers of ORF 1b and N gene sequences in clinical samples were similar.
Conclusions: NPA and stool samples can be used for early diagnosis of SARS. The real-time quantitative RT-PCR assay for SARS CoV is potentially useful for early detection of SARS CoV. Our results suggest that genomic RNA is the predominant viral RNA species in clinical samples.
Detection of Human Polyomaviruses in Urine from Bone Marrow Transplant Patients: Comparison of Electron Microscopy with PCR
Authors: Biel Stefan S , Nitsche Andreas , Kurth Andreas , Siegert Wolfgang , Özel Muhsin , Gelderblom Hans R 
Published: February 2004

AbstractBackground: We studied electron microscopy (EM) as an appropriate test system for the detection of polyomavirus in urine samples from bone marrow transplant patients.Methods: We evaluated direct EM, ultracentrifugation (UC) before EM, and solid-phase immuno-EM (SPIEM). The diagnostic accuracy of EM was studied by comparison with a real-time PCR assay on 531 clinical samples.Results: The detection rate of EM was increased by UC and SPIEM. On 531 clinical urine samples, the diagnostic sensitivity of EM was 47% (70 of 149) with a specificity of 100%. We observed a linear relationship between viral genome concentration and the proportion of urine samples positive by EM, with a 50% probability for a positive EM result for urine samples with a polyomavirus concentration of 106 genome-equivalents (GE)/mL; the probability of a positive EM result was 0% for urine samples with &lt;103 GE/mL and 100% for urine samples containing 109 GE/mL.Conclusions: UC/EM is rapid and highly specific for polyomavirus in urine. Unlike real-time PCR, EM has low sensitivity and cannot quantify the viral load.