bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐operative signalling mechanisms required for erythroid precursor expansion in response to erythropoietin and stem cell factor
Authors: Arcasoy Murat O. , Jiang Xiaohong 
Published: June 2005

SummaryThe regeneration of circulating red blood cells in response to anaemia associated with blood loss or haemolysis involves an increased rate of erythropoiesis and expansion of proerythroblasts, the bone marrow precursor cells that terminally differentiate into mature erythrocytes. This study investigated the mechanisms by which erythropoietin (Epo) and stem cell factor (Scf) modulate the expansion of proerythroblasts. Homogenous populations of primary human proerythroblasts were generated in liquid cultures of CD34+ cells. In serum‐free cultures, proerythroblasts failed to survive in the presence of Epo or Scf alone, but exhibited synergistic proliferation in response to combined Epo and Scf treatment, exhibiting one‐log expansion in 5 d. Intracellular signal transduction in response to Epo and Scf revealed that tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 5, a downstream target for the non‐receptor tyrosine kinase, Janus kinase 2 (Jak2), was mediated by Epo but not Scf. The mitogen‐activated protein kinases (MAPKs) extracellular regulated kinase (Erk) 1–2 were phosphorylated in response to either Epo or Scf. Phosphorylation of Akt, a signalling molecule downstream of phosphatidylinositol 3‐kinase (PI3K), was observed following Scf but not Epo treatment. To determine the contribution of specific signalling pathways to synergistic expansion of proerythroblasts in response to co‐operative effects of Epo and Scf, cells were treated with kinase inhibitors targeting Jak2, PI3K and MAPK kinase. There was a significant, dose‐dependent inhibition of proerythroblast expansion in response to all three kinase inhibitors. In conclusion, Epo‐ and Scf‐mediated co‐operative, synergistic expansion of primary erythroid precursors requires selective activation of multiple signalling pathways, including the Jak‐Stat, PI3K and MAPK pathways.
Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study
Authors: Ljungman Per , Nahi Hareth , Linde Annika 
Published: June 2005

SummaryAn open, randomised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies. The responses were not improved by two doses compared with one (influenza A virus serotypes H1/N1 18% vs. 22% and H3/N2 26% vs. 14%; influenza B 25% vs. 22%). The results were similar in patients with ongoing and discontinued therapy. Patients treated with monoclonal antibodies for lymphoma had very poor responses. We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies.
The measurement of urinary hydroxyurea in sickle cell anaemia
Authors: Neil Dalton R , Turner Charles , Dick Moira , Height Susan E , Awogbade Moji , Inusa Baba , Okpala Iheanyi , O'Driscoll Sandra , Thein Swee Lay , Rees David C 
Published: June 2005

SummaryHydroxyurea is increasingly used in the treatment of sickle cell disease (SCD) although there is little evidence on how best to monitor treatment and compliance. It is also not known why 10–50% patients do not benefit from the drug and whether some of this resistance is because of pharmacokinetic factors. We have developed an assay using mass spectrometry (MS) to measure urinary concentrations of hydroxyurea. We have used this assay to study 12 children and six adults with SCD taking hydroxyurea and found that urinary hydroxyurea was present for at least 12 h following tablet ingestion. Thirty‐five urine samples were analysed that were expected to contain hydroxyurea, based on the reported timing of the last dose and hydroxyurea was detected in 29 (83%) of these. There were also marked differences in urinary hydroxyurea concentrations, suggesting pharmacokinetic variability may explain some of the differences in response to hydroxyurea. Urine samples were also analysed by MS for penicillin metabolites and 43 of the 57 (75%) contained phenoxyacetate, suggesting the ingestion of penicillin within the last 12 h. These assays are potentially useful to study hydroxyurea metabolism further, develop optimal dosing regimes and monitor compliance with treatment.
A novel classification of tumour budding in colorectal cancer based on the presence of cytoplasmic pseudo‐fragments around budding foci
Authors: Shinto E , Mochizuki H , Ueno H , Matsubara O , Jass J R 
Published: June 2005

Aims : Tumour budding is an adverse prognostic factor in colorectal cancer (CRC). We have investigated the significance of cytoplasmic fragments occurring in the immediate vicinity of tumour budding foci.Methods and results : Seventy‐three CRCs with high‐grade budding (> 10 budding foci in a × 20 objective field) were classified according to extent of budding (10–19 versus 20+ foci) and by the presence or absence of cytoplasmic fragments identified by immunostaining for cytokeratin. In serial sections, cytoplasmic fragments were shown to be dendritic cell processes in continuity with budding tumour cells and were renamed pseudo‐fragments. Cytoplasmic pseudo‐fragments, but not extent of budding, were associated with aberrant expression of β‐catenin (P = 0.045) and laminin‐5 γ2 (P < 0.0001), and with absent peritumoral lymphocytic infiltration (P = 0.0077). Cytoplasmic pseudo‐fragments had a stronger association with infiltrating growth pattern (P = 0.0014) than extent of tumour budding (P = 0.014). There was no association between extent of budding and cytoplasmic pseudo‐fragments (P = 0.12).Conclusions : Cytoplasmic pseudo‐fragments may be a marker for an activated budding phenotype that is associated with cell motility and increased invasiveness in CRC and is independent of the extent of budding.
Extrafollicular proliferation of B cells in the absence of follicular hyperplasia: a distinct reaction pattern in lymph nodes correlated with primary or recall type responses
Authors: Brighenti A , Andrulis M , Geissinger E , Roth S , Müller‐Hermelink H K , Rüdiger T 
Published: June 2005

Aims : Extrafollicular activation of B cells is rarely observed in human lymph nodes. The aim of this study was to extensively analyse the expression of surface molecules and transcription factors in four such cases, comparing them with follicular B cells and medullary cord plasma cells.Methods and results : Various combinations of B‐cell‐related surface markers and transcription factors were studied by triple immunofluorescence. While in the germinal centre, reactive immunoglobulin production occurred exclusively in non‐proliferating cells, in extrafollicular activation proliferation of B cells and immunoglobulin production coexisted. In two of these cases proliferating cells were mainly IgG+CD27+, i.e. derived from class‐switched postgerminal centre memory B cells. Some of these cells expressed CD30. In the other two cases, immunoglobulin‐forming cells were non‐class‐switched IgM+CD27– B cells, representing a primary expansion of naive B cells.Conclusions : Extrafollicular B‐cell activation is the morphological correlate of rapid B‐cell responses that do not involve the germinal centres. It is pathogenetically heterogeneous, comprising primary responses that occur prior to, or independent of, germinal centre reaction or memory cell activation in recall responses.
Demographic and pathological characteristics of serrated polyps of colorectum
Authors: Higuchi T , Sugihara K , Jass J R 
Published: June 2005

Aims : To characterize a series of colorectal polyps, focusing on the clinicopathological features of serrated adenoma (SA), mixed polyp (MP) and the recently recognized sessile serrated adenoma (SSA).Methods and results : Eight hundred and ninety‐one conventional adenomas (AD), 298 hyperplastic polyps (HP), 27 SSA, 10 MP and 24 traditional SA were obtained from patients during colonoscopic examination. SSA were more likely to be proximally located than other polyps. All SA, MP and SSA and a randomly selected subset of HP (n = 61) and ADs (n = 93) were assessed for expression of mucin, MLH1, MGMT, and Ki67. SSA expressed more MUC5AC than either HP or SA. Loss of MLH1 was not observed in any serrated polyps and in only one AD. Loss of MGMT occurred in 13% of AD, and showed no correlation with histological type, size or location. Loss of MGMT occurred in 24% of SSA, MP and SA (combined), and was more frequent in proximal lesions and larger lesions. SSA had a higher proliferative index than HP. In MP, the proliferative index of the non‐dysplastic component was closer to HP than SSA, while the dysplastic component was intermediate between SA and AD.Conclusions : SSA differ from other serrated polyps of colorectum in terms of location, morphology and immunophenotype.
Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours
Authors: Hoei‐Hansen C E , Almstrup K , Nielsen J E , Brask Sonne S , Graem N , Skakkebaek N E , Leffers H , Rajpert‐De Meyts E 
Published: June 2005

Aims : NANOG is a key regulator of embryonic stem cell (ESC) self‐renewal and pluripotency. Our recent genome‐wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens.Methods and results : We detected abundant expression of NANOG in CIS and in CIS‐derived testicular tumours with marked differences; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down‐regulation occurring earlier than for OCT‐4. We detected no expression at the protein level in normal testis.Conclusions : NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT‐4 are determinants of the stem cell‐like pluripotency of the preinvasive CIS cell. Timing of NANOG down‐regulation in fetal gonocytes suggests that NANOG may act as a regulatory factor up‐stream to OCT‐4.
Primary frontal sinus aspergillosis: an uncommon occurrence
Authors: Panda Naresh Kumar , Ekambar Eshwara Reddy C. 
Published: June 2005

SummaryPrimary frontal sinus aspergillosis is extremely uncommon with only few cases reported in the English literature. Isolated frontal sinus aspergillosis is usually asymptomatic and produces symptoms due to orbital or intracranial involvement. We report two cases of primary frontal sinus aspergillosis, presenting as frontoethmoidal mucocele and mimicking a ‘Pott's puffy tumor,’ respectively. Forehead swelling produced by frontal sinus aspergillosis will be the first to be reported in the English literature.
Two cases of cutaneous cryptococcosis
Authors: Xiujiao Xia , Ai'e Xu 
Published: June 2005

SummaryWe report two cases of cutaneous cryptococcosis in male patients without underlying disease. Case 1 had a granulomatous mass on his right neck, gradually enlarging for 3 months. After the mass was debrided surgically in a hospital, the incision wound gradually developed into a severe ulceration. Mycological examination revealed Cryptococcus neoformans infection. It was significant that histopathology of both pre‐surgery granuloma and post‐surgery ulceration revealed thick‐walled spores with thick capsule. Chest X‐ray revealed a shadow in the left lower lung. After treatment with amphotec for 21 days, the lesion healed. Case 2 had an approximately 2 × 2 cm solitary dull nodule on his right thigh, which had been present for 8 months. Mycological examination confirmed that the lesion was caused by C. neoformans. The patient's ratio of peripheral blood CD4+ cell was slightly reduced. After 14 days of treatment with oral fluconazole, followed by oral itraconazole for 2 months, mycological and clinical cure were achieved. The two isolates were identified as C. neoformans var. gattii serotype C and C. neoformans var. grubii serotype A.
Identification of Malassezia species from Tunisian patients with pityriasis versicolor and normal subjects
Authors: Salah S. Ben , Makni F. , Marrakchi S. , Sellami H. , Cheikhrouhou F. , Bouassida S. , Zahaf A. , Ayadi A. 
Published: June 2005

SummaryBackground: The genus Malassezia (Pityrosporum), recognized as a member of microbiological flora of the skin in humans and warm‐blooded animals, has been recently revised to include 10 Malassezia species. The aim of the study was the isolation, identification and analysis of Malassezia species distribution in skin of healthy volunteers and lesions of pityriasis versicolor (PV). Material and methods: Specimens were taken from 100 patients with PV and 30 healthy volunteers. Cultures were made in modified Dixon agar medium and the isolates were identified by morphological and physiological methods: macroscopy, microscopy, catalase, β‐glucosidase and lipid assimilation tests. Results: Malassezia globosa was the predominant species in lesional skin of PV (65%). It was isolated alone in 47% of cases and associated in 18% with M. furfur (13%) or M. sympodialis (5%). In healthy skin M. globosa was found alone in 7.77% and associated in 15.54%, respectively, with M. furfur (4.44%), M. sympodialis (4.44%), M. restricta (3.33%) and M. slooffiae (1.11%). Conclusion: From these findings it was suggested that M. globosa presents the main species implicated in the pathogenicity of PV and M. furfur as the second agent of importance.
Pharmacological properties and clinical efficacy of a recently licensed systemic antifungal, caspofungin
Authors: Maschmeyer Georg , Glasmacher Axel 
Published: June 2005

SummaryCaspofungin, a semisynthetic derivative of the pneumocandin B0, is the first licensed compound of a new class of antifungal agents, the echinocandins. It attacks the fungal cell by selective inhibition of the beta‐(1,3)‐d‐glucan synthase, which is not present in mammalian cells. In vitro studies have indicated a potent fungicidal effect on Candida species, and in vivo studies in immunocompromised animals with invasive candidiasis demonstrated a favourable outcome. In randomized clinical trials in patients with oropharyngeal/oesophageal and invasive candidiasis, caspofungin was at least as effective as amphotericin B deoxycholate, yet showed a significantly superior safety profile. Of patients with invasive aspergillosis refractory to or intolerant of other antifungal agents, 45% showed a partial or complete response to caspofungin given as a salvage treatment. Also, it demonstrated comparable clinical efficacy but superior tolerability in the empirical antifungal therapy in neutropenic patients compared with liposomal amphothericin B. Caspofungin has an excellent tolerability and a low potential for drug interactions. Thus, caspofungin represents an interesting and clinically valuable new antifungal drug that broadens the available therapeutic armamentarium for the treatment of invasive fungal infections.
SPEED KILLS: A LONGITUDINAL ANALYSIS OF TRAFFIC FATALITIES AND THE 55 MPH SPEED LIMIT*
Authors: Meier Kenneth J. , Morgan David R. 
Published: June 2005

An interrupted time‐series design is used to analyze the impact of the 55 mph speed limit on U.S. traffic fatalities over the period 1950 to 1980. In addition to speed such potential effects on highway fatalities as safety improvements, decreased speed dispersion, and decreased travel are examined.We conclude that the overwhelming proportion of the decline in traffic fatalities from 1973 to 1974 must be attributed to the change in the speed limit.
COST‐BENEFIT ANALYSIS FOR NON‐ECONOMISTS?
Authors: Crowell Elizabeth 
Published: June 2005

Edward Gramlich, Benefit‐Cost Analysis of Government ProgramsPeter G. Sassone and William A. Schaffer, Cost‐Benefit Analysis: A HandbookRobert Sugden and Alan Williams, The Principles of Practical Cost‐Benefit AnalysisMark S. Thompson, Benefit‐Cost Analysis for Prognm Evaluation
INTERNATIONAL FUTURES AND POLICY
Authors: CLUTE ROBERT E. 
Published: June 2005

Donna Meadows with John Richardson and Gerhart Bruckman. Groping in the Dark: The First Decade of Global Modelling. Brita Schwarz with Uno Svedin and Björn Wittrock. Methods in Future Studies: Problems and Applications. U.S. Congress, Office of Technology Assessment. Global Models, World Futures, and Public Policy: A Critique. Council on Environmental Quality and Department of State. The Global 2000 Report to the President: Entering the Twenty‐First Century Organization for Economic Co‐operation and Development, Interfutures: Facing the Future: Mastering the Probable and Managing the Unpredictable Richard Barnet. The Lean Years: Politics in the Age of Scarcity Lester Brown. Building a Sustainable Society Orio Giarini. Dialogue on Wealth and Welfare: An Alternative View of World Capital Formation Julian Simon. The Ultimate Resource Michael Marien and Lane Jennings (Eds.). Future Survey Annual
ENERGY POLICY: HOW FAILURE WAS SNATCHED FROM THE JAWS OF SUCCESS
Authors: Kashand Don E. , Rycroft Robert W. 
Published: June 2005

Prior to the energy crisis of 1973, the U.S. did not have an energy policy. The failure of the American political system to anticipate and respond to the changing facts of energy was an inevitable outcome of the way policy is made. Consistent with tradition, the search for a consensus was begun from 1973–1980. The U.S. abandoned cheap energy as a high priority and adopted secure, abundant and clean energy. Conservation came to be viewed as a source of energy along with nuclear power and synfuels. Price deregulation was the most important policy tool. The Reagan administration upset this consensus and substituted the market place as the means for maximizing supplies rather than reduce demand.The federal role was limited to bringing publicly‐owned bonds into the marketplace. At the same time, it reduced RED and concern for the environment. Thus, the Reagan administration succeeded in snatching failure from the jaws of success.
PUBLIC BUDGETING: CONCEPTS AND APPLICATIONS
Authors: Kane Thomas J. 
Published: June 2005

Robert W. Burchell, James H. Carr, Richard L. Florida and Jarnes Nemeth. The New Reality of Municipal Finance: The Rise and Fall of the Intergovernmental City.Government Finance Officers Association. Capital Budgeting: Blueprints for Change.Edward A. Lehan. Budgetmaking: A Workbook of Public Budgeting Theory and Practice.Thomas D. Lynch. Public Budgeting in America, 2nd Edition.John L. Mikesell. Fiscal Administration: Analysis and Applications for the Public Sector, 2nd Edition.
THE POLITICS OF MANAGEMENT AND TECHNOLOGY IN THE USSR
Authors: Luke Timothy W. 
Published: June 2005

Book reviewed in this article:Nathan Leites, The Soviet Style in Management (New York: Crane Russak, 1985).Bruce Parrott, Politics and Technology in the Soviet Union (Cambridge, MA: M.I.T. Press, 1985).Bruce Parrott, Trade, Technology and Soviet‐American Relations (Bloom‐ington, IN: Indiana University Press, 1985).
A COMPARISON OF THE EFFECTIVENESS OF INCENTIVES AND DIRECTIVES: THE CASE OF DUTCH WATER QUALITY POLICY
Authors: Bressers Hans Th. A. 
Published: June 2005

The use of effluent charges as an instrument o f regulatory policy has been the object of much dispute. The controversy between advocates and opponents of replacing directives by incentive strategies in various fields of public intervention has always been rather heated, though carried on more in terms of theory than of empirical evidence drawn from experience with policy instruments in actual operation. Much like permit trading in the United States, regulatory effluent charges in The Netherlands more or less “sneaked in through the back door.” The Dutch system o f water quality charges had originally been designed to fulfill solely a revenue‐raising function.The unique features of The Netherlands system make it an interesting example of the use of charges. The Dutch system of effluent charges has been in operation since 1970 and, in terms of the level of the charges, is more than twice as large as the more recent German program. Furthermore its use as a regulatory instrument has been “accidental.” It did not replace the official intervention strategy of direct regulation. Given this situation, the Dutch case provides a unique opportunity to examine the effects of these two approaches as they were applied to the same case.Three statistical analyses of the impacts of the policy instrument used, supplemented by two expert assessments of these impacts, show the Dutch effluent charges have had a very remarkable effect on industrial polluters. In Holland, t h e water quality policy i s regarded as one of t h e few examples o f successful governmental intervention. The final section presents some general thoughts on relevance of the Dutch experience with effluent charges for other countries.
LABOR FORCE PARTICIPATION AND POVERTY STATUS AMONG RURAL AND URBAN WOMEN WHO HEAD FAMILIES
Authors: Cautley Eleanor , Slesinger Doris P. 
Published: June 2005

This paper examines differentials in the propensity to be living in poverty among women who head families with minor children. Characteristics of mothers are examined for four subgroups: residents of central cities, suburbs, small towns, and rural areas. Using Public Use Microdata Sample data from the 1980 Census, results are presented using Multiple Classification Analysis. After controlling for the effects of mother's race, marital status, education, work status, and ages of her children, single mothers in central cities and smaIl towns have the highest rates of poverty (48% and 45% respectively), closely followed by those in rural areas (41%). Suburban single mothers are least likely to live in poverty (33%).Results show that employment status is the strongest predictor of poverty, followed by education and marital status. A subanalysis of women who work full‐time reveals major differences in earned income, with suburban women earning the highest incomes, followed by women living in central cities, then rural areas and, finally, small towns. A decomposition of this difference reveals that about two‐thirds of the difference is due to pay scales, and only one‐third due to the structure of occupational opportunity.
THE POLITICAL ECONOMY OF THE NATIONAL DEFENSE STOCKPILE
Authors: Twight Charlotte 
Published: June 2005

It is really a cynical playing of politics with this issue of the strategic stockpile. I don't like being on watch while this kind of nonsense is going on. (Humphrey, 1983, p. 67)
Few government programs display both the political salability and the vulnerability to political manipulation that characterize the National Defense Stockpile. This article analyzes the ways in which changing institutional constraints have shaped the nature and extent of parochial manipulation of the National Defense Stockpile over more than half a century of U.S. stockpiling experience. Focusing on the roles of Congress and the executive branch in establishing the relevant institutional rules and accommodating constituent pressures within the framework of those rules, this article examines the use and perpetuation of the strategic materials stockpile for personal political gain.