bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Induction of the Nicotinamide Adenine Dinucleotide-Linked 15-Hydroxyprostaglandin Dehydrogenase by an Androgen and Interleukin-6 or Forskolin in Human Prostate Cancer Cells
Authors: Tong Min , Tai Hsin-Hsiung 
Published: February 2004

AbstractThe nicotinamide adenine dinucleotide-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of 15 (S)-hydroxyl group of prostaglandins and lipoxins and participates along with cyclooxygenases and lipoxygenases in controlling the cellular levels of prostaglandins and lipoxins. 15-PGDH could be induced by IL-6 and forskolin in addition to androgens in a time- and dose-dependent manner but not by other cytokines and growth factors in LNCaP cells. Concurrent addition of IL-6 and forskolin showed additive effect in the induction of 15-PGDH activity. However, combined addition of dihydrotestosterone (DHT) and IL-6 or DHT plus forskolin exhibited synergistic induction of 15-PGDH activity. The increase in enzyme activity was correlated with the expression of the enzyme protein as shown by Western blot analysis. The induction by DHT or IL-6 or forskolin or their combinations was inhibited by antiandrogen, casodex, in a dose-dependent manner, indicating that a functional androgen receptor was required for the action of any of these three agents. The induction by forskolin plus DHT or by either agent or by IL-6 alone was greatly inhibited by H-89, indicating the involvement of protein kinase A in the actions of forskolin, DHT, and IL-6. The induction of 15-PGDH by IL-6 was also blocked by some other protein kinase inhibitors, indicating the participation of MAPK, MAPK/ERK kinase, and STAT3 in the signaling pathway of IL-6. These results indicate that the induction of 15-PGDH by DHT, IL-6, and forskolin in LNCaP cells may involve a functional androgen receptor and phosphorylation-dependent multiple signaling pathways.
Genetic Analysis of Adenohypophysis Formation in Zebrafish
Authors: Herzog Wiebke , Sonntag Carmen , Walderich Brigitte , Odenthal Jörg , Maischein Hans-Martin , Hammerschmidt Matthias 
Published: February 2004

AbstractThe adenohypophysis consists of at least six different cell types, somatotropes, lactotropes, thyrotropes, melanotropes, corticotropes, and gonadotropes. In mouse, cloning of spontaneous mutations and gene targeting has revealed multiple genes required for different steps of adenohypophysis development. Here, we report the results of a systematic search for genes required for adenohypophysis formation and patterning in zebrafish. By screening F3 offspring of N-ethyl-N-nitrosourea-mutagenized founder fish, we isolated eleven mutants with absent or reduced expression of GH, the product of somatotropes, but a normally developing hypothalamus. Of such mutants, eight were further analyzed and mapped. They define four genes essential for different steps of adenohypophysis development. Two of them, lia and pia, affect the entire adenohypophysis, whereas the other two are required for a subset of adenohypophyseal cell types only. The third gene is zebrafish pit1 and is required for lactotropes, thyrotropes, and somatotropes, similar to its mouse ortholog, whereas the fourth, aal, is required for corticotropes, melanotropes, thyrotropes, and somatotropes, but not lactotropes. In conclusion, the isolated zebrafish mutants confirm principles of adenohypophysis development revealed in mouse, thereby demonstrating the high degree of molecular and mechanistic conservation among the different vertebrate species. In addition, they point to thus far unknown features of adenohypophysis development, such as the existence of a new lineage of pituitary cells, which partially overlaps with the Pit1 lineage. Positional cloning of the lia, pia, and aal genes might reveal novel regulators of vertebrate pituitary development.
Compounded Versus Proprietary Sincalide for Evaluation of Gallbladder Ejection Fraction
Authors: Guarasci Daniel T , Trinh Le Huyen N , Baeumler George R , Bednarczyk Edward M 
Published: February 2004

OBJECTIVE To report a comparison of compounded and proprietary sincalide in the evaluation of gallbladder ejection fraction during hepatobiliary scintigraphy. CASE SUMMARIES Two patients were referred to nuclear medicine with symptoms consistent with hepatobiliary dysfunction. Both underwent hepatobiliary scintigraphy to evaluate anatomic and physiologic tract patency of the hepatobiliary system. Compounded sincalide, an adjuvant pharmaceutical used to evaluate gallbladder ejection fraction, was infused during hepatobiliary scintigraphy, and gallbladder ejection fractions were 11% and 24%, respectively. Hepatobiliary scintigraphy was repeated on both patients 72 hours later with proprietary sincalide used as the adjuvant pharmaceutical. The gallbladder ejection fractions were 32% and 72%, respectively. DISCUSSION The use of sincalide to evaluate gallbladder ejection fraction in hepatobiliary scintigraphy is widely accepted in the surgical and nuclear medicine community. In late 2001, the sole manufacturer of sincalide announced indefinite unavailability of the product. Following the announcement, several compounding pharmacies began selling extemporaneously compounded sincalide as a replacement. Use of the compounded product has assumed therapeutic equivalence. CONCLUSION Significant differences in gallbladder ejection fraction between compounded sincalide and sincalide in our patients are likely due to the intrinsic variability in response to sincalide. Clinicians should be aware of this variability, as well as the potential effect of concomitant medications.
Pharmacologic Therapy for HIV-Associated Lipodystrophy
Authors: Benavides Sandra , Nahata Milap C 
Published: February 2004

OBJECTIVE To evaluate the efficacy and safety of pharmacologic therapy in the treatment of HIV-associated lipodystrophy, with a focus on the treatment of fat redistribution. Drug therapies that have been shown to be beneficial in other forms of lipodystrophy and are currently being evaluated in HIV-associated lipodystrophy are also discussed. DATA SOURCES A MEDLINE search was conducted from 1996 to February 2003. Bibliographies of all articles were reviewed and pertinent articles were included. Abstracts from major meetings in 2002 and 2003 were also reviewed. STUDY SELECTION AND DATA EXTRACTION All published studies were included in the review. DATA SYNTHESIS Lipodystrophy has become more prevalent in patients with HIV. Lipodystrophy consists of adipose redistribution and metabolic abnormalities including dyslipidemia and insulin resistance. Treatment of lipodystrophy has been directed at either decreasing the amount of visceral adipose tissue (VAT), dorsocervical adipose tissue (commonly known as buffalo hump) and/or increase subcutaneous adipose tissue (SAT). Recombinant human growth hormone (rhGH) decreases VAT and buffalo hump, although it has been associated with a high frequency of adverse effects. Metformin and the thiazolidinediones have favorable metabolic effects, but were not found to be effective in correcting body compositional changes associated with lipodystrophy. Anabolic steroids and L-carnitine are not effective in the treatment of lipodystrophy. CONCLUSION No drug therapy exists to fully ameliorate or correct the cosmetic changes of HIV-associated lipodystrophy. Clinicians must weigh the benefits and risks of each agent and individualize treatment for each patient.
Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion
Authors: Refsum Helga , Smith A David , Ueland Per M , Nexo Ebba , Clarke Robert , McPartlin Joseph , Johnston Carole , Engbaek Frode , Schneede Jørn , McPartlin Catherine , Scott John M 
Published: February 2004

AbstractBackground: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations.Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years.Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.
Pyrosequencing of TPMT Alleles in a General Swedish Population and in Patients with Inflammatory Bowel Disease
Authors: Haglund Sofie , Lindqvist Malin , Almer Sven , Peterson Curt , Taipalensuu Jan 
Published: February 2004

AbstractBackground: Interindividual differences in therapeutic efficacy in patients treated with thiopurines might be explained by the presence of thiopurine S-methyltransferase (TPMT) alleles that encode for reduced TPMT enzymatic activity. It is therefore of value to know an individual’s inherent capacity to express TPMT.Method: We developed a pyrosequencing method to detect 10 single-nucleotide polymorphisms (SNPs) in TPMT. A Swedish population (n = 800) was examined for TPMT*3A, TPMT*3B, TPMT*3C, and TPMT*2. Patients with inflammatory bowel disease (n = 24) and healthy volunteers (n = 6), selected on the basis of TPMT enzymatic activity, were investigated for all 10 SNPs to determine the relationship between TPMT genotype and phenotype.Results: In the general population we identified the following genotypes with nonfunctional alleles: TPMT*1/*3A (*3A allelic frequency, 3.75%), TPMT*1/*3C (*3C allelic frequency, 0.44%), TPMT*1/*3B (*3B allelic frequency, 0.13%), and TPMT*1/*2 (*2 allelic frequency, 0.06%). All nine individuals with normal enzymatic activity were wild-type TPMT*1/*1. Thirteen individuals with intermediate activity were either TPMT*1/*3A (n = 12) or TPMT*1/*2 (n = 1). Eight individuals with low enzymatic activity were TPMT*3A/*3A (n = 4), TPMT*3A/*3C (n = 2), or TPMT*1/*3A (n = 2).Conclusion: Next to wild type, the most frequent alleles in Sweden are TPMT*3A and TPMT*3C. A previously established phenotypic cutoff for distinguishing normal from intermediate metabolizers was confirmed. To identify the majority of cases (90%) with low or intermediate TPMT activity, it was sufficient to analyze individuals for only 3 of the 10 SNPs investigated. Nevertheless, this investigation indicates that other mutations might be of relevance for decreased enzymatic activity.
Factors behind the Increase in Cardiovascular Mortality in Russia: Apolipoprotein AI and B Distribution in the Arkhangelsk Study 2000
Authors: Averina Maria , Nilssen Odd , Brenn Tormod , Brox Jan , Arkhipovsky Vadim L , Kalinin Alexei G 
Published: February 2004

AbstractBackground: Cardiovascular mortality is markedly higher in Russia than in Western Europe and the US. Little is known about indicators of atherosclerotic risk in the Russian population. To our knowledge, this is the first study of apolipoprotein (apo) AI and B in Russia based on the WHO-IFCC standard.Methods: We measured apo AI and B by immunoturbidimetric assay in 3694 men and women from Arkhangelsk, Russia, in 1999–2000.Results: The age-related distribution of apo B was similar to that in other countries, whereas the apo AI profile was different. For men ≥20 years, apo AI was considerably higher than in studies from other countries. Women had also relatively high apo AI concentrations, although the difference was not as pronounced as in men. The apo AI concentration was positively associated with age and lifestyle variables such as alcohol consumption and physical activity, and negatively associated with body mass index and self-reported myocardial infarction. γ-Glutamyltransferase was positively associated with apo AI in both sexes.Conclusions: The apparently favorable apolipoprotein profiles contrast with official death statistics indicating high cardiovascular mortality in Russia. High apo AI might indicate excessive alcohol consumption.
Parallel Detection of Autoantibodies with Microarrays in Rheumatoid Diseases
Authors: Feng Yanfei , Ke Xue , Ma Rongshui , Chen Ying , Hu Gengxi , Liu Feizhou 
Published: February 2004

Abstract
Background: Clinical needs often dictate testing for several autoantibodies in a single patient with evidence of autoimmune disease. We developed a microarray containing 15 autoantigens for the detection of autoantibodies in rheumatoid autoimmune diseases.
Methods: We synthesized recombinant centromere protein B, cytokeratin 19, SSA 52-kDa antigen, SSA 60-kDa antigen, SSB antigen, and Jo-1 antigen and prepared anti-nuclear antibody antigens. Cyclic citrullinated peptide, histone, goat IgG for detection of rheumatoid factor, double-stranded DNA, and single-stranded DNA were purchased, as were recombinant small nuclear ribonucleoprotein U1, topoisomerase I, and Smith antigen (Sm). All 15 antigens were of human origin except calf thymus Sm. Proteins were printed on polystyrene. The arrays were incubated with serum samples and then with horseradish peroxidase-conjugated secondary antibodies and chemiluminescent substrates, and light signals were captured by a charge-coupled device camera-based chip reader. Antibodies were quantified by use of calibration curves. Positive samples were confirmed by commercially available methods.
Results: The detection limit of the microarray system was 20 pg of IgG printed on the polystyrene support. More than 85% of the confirmed positive sera were detected as positive with the microarray system based on cutoff values established with the microarray system. The imprecision (CV) of the microarrays was &lt;15% for all 15 autoantibody assays, with the exception of single-stranded DNA (18% and 23%) within and between batches. Characteristic autoantibody patterns were seen in patients with clinical diagnoses of rheumatoid arthritis (n = 83), systemic lupus erythematosus (n = 71), systemic sclerosis (n = 36), polymyositis (n = 38), and Sjogren syndrome (n = 20).
Conclusions: This microarray system provides results similar to those by conventional methods. Assessment of the diagnostic accuracy of the system remains to be done.
IFCC Reference System for Measurement of Hemoglobin A1c in Human Blood and the National Standardization Schemes in the United States, Japan, and Sweden: A Method-Comparison Study
Authors: Hoelzel Wieland , Weykamp Cas , Jeppsson Jan-Olof , Miedema Kor , Barr John R , Goodall Ian , Hoshino Tadao , John W Garry , Kobold Uwe , Little Randie , Mosca Andrea , Mauri Pierluigi , Paroni Rita , Susanto Fransiscus , Takei Izumu , Thienpont Linda , Umemoto Masao , Wiedmeyer Hsiao-Mei ,   the IFCC Working Group on HbA1c Standardization
Published: February 2004

AbstractBackground: The national programs for the harmonization of hemoglobin (Hb)A1c measurements in the US [National Glycohemoglobin Standardization Program (NGSP)], Japan [Japanese Diabetes Society (JDS)/Japanese Society of Clinical Chemistry (JSCC)], and Sweden are based on different designated comparison methods (DCMs). The future basis for international standardization will be the reference system developed by the IFCC Working Group on HbA1c Standardization. The aim of the present study was to determine the relationships between the IFCC Reference Method (RM) and the DCMs.Methods: Four method-comparison studies were performed in 2001–2003. In each study five to eight pooled blood samples were measured by 11 reference laboratories of the IFCC Network of Reference Laboratories, 9 Secondary Reference Laboratories of the NGSP, 3 reference laboratories of the JDS/JSCC program, and a Swedish reference laboratory. Regression equations were determined for the relationship between the IFCC RM and each of the DCMs.Results: Significant differences were observed between the HbA1c results of the IFCC RM and those of the DCMs. Significant differences were also demonstrated between the three DCMs. However, in all cases the relationship of the DCMs with the RM were linear. There were no statistically significant differences between the regression equations calculated for each of the four studies; therefore, the results could be combined. The relationship is described by the following regression equations: NGSP-HbA1c = 0.915(IFCC-HbA1c) + 2.15% (r2 = 0.998); JDS/JSCC-HbA1c = 0.927(IFCC-HbA1c) + 1.73% (r2 = 0.997); Swedish-HbA1c = 0.989(IFCC-HbA1c) + 0.88% (r2 = 0.996).Conclusion: There is a firm and reproducible link between the IFCC RM and DCM HbA1c values.
Sensitivity of Whole-Blood T Lymphocytes in Individual Patients to Tacrolimus (FK 506): Impact of Interleukin-2 mRNA Expression as Surrogate Measure of Immunosuppressive Effect
Authors: Härtel Christoph , Schumacher Nina , Fricke Lutz , Ebel Brigitte , Kirchner Holger , Müller-Steinhardt Michael 
Published: February 2004

AbstractBackground: To optimize immunosuppressive treatment in individual transplant patients, functional measurements of the effects of tacrolimus (FK 506) are of clinical importance. Previous investigations have demonstrated the occurrence of tacrolimus-resistant production of interleukin-2 (IL-2) in vitro, which may explain in part why rejection episodes are still a frequent problem despite attainment of therapeutic blood concentrations and HLA matching. However, an adequate surrogate marker to define the tacrolimus response in individual patients has not been established.Methods: We investigated the immunosuppressive effects of tacrolimus on anti-CD3/anti-CD28 T-cell costimulation in a human whole-blood assay, analyzing T-cell proliferation, activation marker expression (CD25, CD69), IL-2 protein expression, and cytokine mRNA expression in vitro (n = 11 healthy individuals). We also quantified IL-2 mRNA expression in patients undergoing tacrolimus (n = 4) or cyclosporin A (CsA; n = 4) monotherapy before ex vivo living-donor kidney transplantation.Results: T-cell proliferation; CD25, CD69, and IL-2 concentrations; and IL-4 mRNA were significantly decreased in vitro. In contrast, cytokine mRNA profiles revealed variable tacrolimus sensitivity. Whole-blood samples from 3 of 11 healthy individuals demonstrated marked suppression of IL-2 mRNA expression (&gt;50%) when tacrolimus was administered in vitro. When CsA was added to whole-blood cultures, the influence on IL-2 mRNA expression was comparable to that of tacrolimus in 9 of 11 individuals. Two individuals responded conversely, indicating that differences in the in vitro response to tacrolimus and CsA among individuals may be attributable to potential heterogeneity in the involvement of the CD28 pathway. Kinetic profiles of IL-2 mRNA expression also revealed individually distinct degrees of calcineurin inhibitor sensitivity in patients undergoing tacrolimus or CsA monotherapy before living-donor kidney transplantation.Conclusions: Our results suggest an individual degree of calcineurin inhibitor sensitivity of activated whole-blood lymphocytes based on IL-2 mRNA expression. Our approach is potentially valuable for identifying transplant patients in whom IL-2 mRNA expression is unaffected or even enhanced after initiation of immunosuppressive therapy. Such individuals may be less sensitive to the immunosuppressive agent and therefore at increased risk of transplant rejection. Prospective studies are necessary to determine the correlation of IL-2 mRNA expression with the clinical risk of transplant rejection.
Effect of a Controlled Feedback Intervention on Laboratory Test Ordering by Community Physicians
Authors: Bunting Peter S , van Walraven Carl 
Published: February 2004

Abstract
Background: Most studies of interventions to reduce laboratory test utilization have occurred in academic hospital settings, used historical controls, or have had short postintervention follow-up. Interventions with the greatest impact use multiple approaches, are repeated regularly, include comparisons with physician peers, and have a personal approach. We determined whether laboratory test utilization by community physicians could be reduced by a multifaceted program of education and feedback.
Methods: We identified 200 physicians who ordered the largest number of common laboratory tests during 1 year in a nonhospital, commercial community (reference) laboratory. They were assigned to intervention and control groups (100 each). Intervention physicians were visited individually up to three times by laboratory representatives over a 2-year period. At each visit, educational material and the physician’s personal laboratory test utilization data were presented and discussed briefly in general terms, with the latter compared with utilization data for the physician’s peers. Overall test utilization rates 1 year before, during, and 2 years after the intervention were measured using population-based databases. Time-series analysis was used to determine the effect of the intervention on laboratory test utilization.
Results: The two groups began with similar test utilization: control group, 4.06 × 106 tests in 1.48 × 106 visits (2.73 tests/visit); intervention group, 3.90 × 106 tests in 1.41 × 106 visits (2.77 tests/visit). During the 2-year intervention, intention-to-treat analysis showed that utilization decreased significantly in the intervention group compared with the controls [relative reduction of 7.9% (P &lt;0.0001); absolute reduction of 0.22 tests/visit (95% confidence interval, 0.20–0.24)]. This difference persisted until the end of study observation, or more than 2 years after the intervention ended.
Conclusion: A multifaceted education and feedback strategy can significantly and persistently decrease laboratory utilization by practicing community physicians.