bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation of the McKusick-Kaufman Gene and Studies of Relationships with Common Forms of Obesity
Authors: Andersen Kirstine L. , Echwald Søren M. , Larsen Lesli H. , Hamid Yasmin H. , Glümer Charlotte , Jørgensen Torben , Borch-Johnsen Knut , Andersen Teis , Sørensen Thorkild I. A. , Hansen Torben , Pedersen Oluf 
Published: January 2005

Abstract
Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro39Pro and Ile178Ile) and three nonsynonymous variants (Ala242Ser, Arg517Cys, and Gly532Val). Furthermore, the rare Ala242Ser was identified in two families and showed partial cosegregation with obesity. The Pro39Pro, Ile178Ile, and Arg517Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg517Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7–13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9–10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9–11.4) among 523 obese men and 12.2% (CI, 10.8–13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.
The Increase of Leukocytes as a New Putative Marker of Low-Grade Chronic Inflammation and Early Cardiovascular Risk in Polycystic Ovary Syndrome
Authors: Orio Francesco , Palomba Stefano , Cascella Teresa , Di Biase Sebastiano , Manguso Francesco , Tauchmanovà Libuse , Nardo Luciano G. , Labella Donato , Savastano Silvia , Russo Tiziana , Zullo Fulvio , Colao Annamaria , Lombardi Gaetano 
Published: January 2005

Abstract
White blood cell (WBC) count is a known risk factor for atherosclerotic vascular disease in adult women. Polycystic ovary syndrome (PCOS) is potentially a risk factor for atherosclerosis and cardiovascular disease. The aim of the present study was to investigate leukocyte count in PCOS. One hundred and fifty PCOS women matched for age and body mass index with 150 healthy women were enrolled. WBC count, C-reactive protein, and a complete anthropometrical, metabolic, and hormonal evaluation were performed in both groups. Serum insulin, glucose level, and lipid profile were also measured in each subject. WBC count was significantly higher (P &lt; 0.0001) in PCOS with (interquartile range in parentheses) 7260 (393) cells/mm3, compared with controls with 5220 (210) cells/mm3. C-reactive protein levels were significantly increased (P &lt; 0.0001) in PCOS with 2 (1) mg/liter compared with healthy women with 0.7 (0.8) mg/liter. In both groups, there was a significant (P &lt; 0.0001) linear correlation between WBC count and homeostasis model assessment score (PCOS, r = 0.94; controls, r = 0.91). Multiple linear regression analysis showed that other hormone levels are not predictors of leukocyte count both in PCOS and control women. In conclusion, our data demonstrate that PCOS women have an increased WBC count that correlates with homeostasis model assessment values.
Coexistence of Intracellular and Membrane-Bound Progesterone Receptors in Human Testis
Authors: Shah Chirag , Modi Deepak , Sachdeva Geetanjali , Gadkar Sushama , Puri Chander 
Published: January 2005

AbstractProgesterone and progesterone receptors (PR) play a crucial role in female reproduction, but their roles in male reproductive physiology are largely unknown. Our previous studies demonstrated the presence of a specific membrane-bound PR in mature human spermatozoa that is known to regulate important sperm functions. The present study was undertaken to determine whether there exist PR in human testis and to investigate their molecular characteristics and expression profiles. PR mRNA and protein were detected in the spermatogenic cells, Sertoli cells, and occasionally the Leydig cells. PR protein was localized in nucleus and cytoplasm of spermatogonia, primary and secondary spermatocytes, and round spermatids in a stage-specific manner. Intense PR localization was observed in stages IV and V, whereas it was low at stages I, II, and III of spermatogenesis. RT-PCR studies revealed the presence of transcripts for PR in human testis and spermatogenic cells. In accordance with the reported molecular sizes of the known isoforms of PR, two mRNA transcripts of 3.8 and 2.8 kb for PR in adult human testis and spermatogenic cell RNA were detected by Northern blot hybridization. Western blot analysis of testicular and spermatogenic cell lysates revealed two bands of 120 and 90 kDa, corresponding to the conventional PR. In these tissue lysates, an additional band of approximately 55 kDa was detected that was also observed as a single band in sperm lysates, indicating that this smaller protein may correspond to the membrane-bound PR. The membrane-bound PR protein was demonstrated on the spermatogenic cells when probed with progesterone-bound fluorescein conjugate. The results of the present study demonstrate the existence of both intracellular PR-B and PR-A mRNA and protein in the spermatogenic cells of the human testis. A membrane-bound PR was also localized in these cells. The varying levels of intracellular PR during different stages of spermatogenesis and the presence of the membrane-bound PR imply the significance of progesterone in male reproductive events such as regulation of spermatogenesis.
Cytochrome P450 Oxidoreductase Gene Mutations and Antley-Bixler Syndrome with Abnormal Genitalia and/or Impaired Steroidogenesis: Molecular and Clinical Studies in 10 Patients
Authors: Fukami Maki , Horikawa Reiko , Nagai Toshiro , Tanaka Toshiaki , Naiki Yasuhiro , Sato Naoko , Okuyama Torayuki , Nakai Hideo , Soneda Shun , Tachibana Katsuhiko , Matsuo Nobutake , Sato Seiji , Homma Keiko , Nishimura Gen , Hasegawa Tomonobu , Ogata Tsutomu 
Published: January 2005

AbstractWe report on molecular and clinical findings in 10 Japanese patients (four males and six females) from eight families (two pairs of siblings and six isolated cases) with Antley-Bixler syndrome accompanied by abnormal genitalia and/or impaired steroidogenesis. Direct sequencing was performed for all the 15 exons of cytochrome P450 oxidoreductase gene (POR), showing two missense mutations (R457H and Y578C), a 24-bp deletion mutation resulting in loss of nine amino acids and creation of one amino acid (L612_W620delinsR), a single bp insertion mutation leading to frameshift (I444fsX449), and a silent mutation (G5G). R457H has previously been shown to be a pathologic mutation, and computerized modeling analyses indicated that the 15A&gt;G for G5G could disturb an exonic splicing enhancer motif, and the remaining three mutations should affect protein conformations. Six patients were compound heterozygotes, and three patients were R457H homozygotes; no mutation was identified on one allele of the remaining one patient. Clinical findings included various degrees of skeletal features, such as brachycephaly, radiohumeral synostosis, and digital joint contractures in patients of both sexes, normal-to-poor masculinization during fetal and pubertal periods in male patients, virilization during fetal life and poor pubertal development without worsening of virilization in female patients, and relatively large height gain and delayed bone age from the pubertal period in patients of both sexes, together with maternal virilization during pregnancy. Blood cholesterol was grossly normal, and endocrine studies revealed defective CYP17A1 and CYP21A2 activities. The results suggest that Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis is caused by POR mutations, and that clinical features are variable and primarily explained by impaired activities of POR-dependent CYP51A1, CYP17A1, CYP21A2, and CYP19A1.
Localization and Quantification of Cyclic Changes in the Expression of Endocrine Gland Vascular Endothelial Growth Factor in the Human Corpus Luteum
Authors: Fraser Hamish M. , Bell Julie , Wilson Helen , Taylor Paul D. , Morgan Kevin , Anderson Richard A. , Duncan W. Colin 
Published: January 2005

Abstract
Angiogenesis is essential for normal growth and function of the corpus luteum. The roles of various angiogenic factors in these events are being elucidated. Endocrine gland vascular endothelial growth factor (EG-VEGF) has recently been described in the human ovary. To define the localization of EG-VEGF mRNA in the corpus luteum and determine changes in its expression, dated human corpora lutea were studied at the early, mid-, and late luteal phases. Quantitative RT-PCR was employed to determine changes in EG-VEGF mRNA and compare expression to its related factor prokineticin-2 and the established angiogenic factor, VEGF. In situ hybridization was used to localize sites of production of EG-VEGF. To investigate whether expression of EG-VEGF was under the influence of LH or progesterone, luteinized granulosa cells were stimulated with human chorionic gonadotropin in the presence or absence of a progesterone synthesis inhibitor. EG-VEGF mRNA increased throughout the luteal phase, whereas there was no change in VEGF mRNA. The relative abundance of RNAs based upon PCR signal intensity showed that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2 was low. EG-VEGF mRNA was localized predominantly to granulosa-derived cells of the corpus luteum. Human chorionic gonadotropin stimulated both VEGF and EG-VEGF mRNA in vitro, but the level of expression was not influenced by progesterone. These results establish that in the human corpus luteum EG-VEGF is principally derived from granulosa lutein cells and that its synthesis is highest during the mid- to late luteal phase.
Homozygous Disruption of P450 Side-Chain Cleavage (CYP11A1) Is Associated with Prematurity, Complete 46,XY Sex Reversal, and Severe Adrenal Failure
Authors: Hiort Olaf , Holterhus Paul-Martin , Werner Ralf , Marschke Christine , Hoppe Ute , Partsch Carl-Joachim , Riepe Felix G. , Achermann John C. , Struve Dagmar 
Published: January 2005

AbstractDisruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations of the CYP11A1 gene is thought to be incompatible with fetal survival because of impaired progesterone production by the fetoplacental unit. We present a 46,XY patient with a homozygous disruption of CYP11A1.The child was born prematurely with complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis of the CYP11A1 gene revealed a homozygous single nucleotide deletion leading to a premature termination at codon position 288. This mutation will delete highly conserved regions of the P450scc enzyme and thus is predicted to lead to a nonfunctional protein. Both healthy parents were heterozygous for this mutation.Our report demonstrates that severe disruption of P450scc can be compatible with survival in rare instances. Furthermore, defects in this enzyme are inherited in an autosomal-recessive fashion, and heterozygote carriers can be healthy and fertile. The possibility of P450scc-independent pathways of steroid synthesis in addition to the current concept of luteoplacental shift of progesterone synthesis in humans has to be questioned.
Adenoviral Gene Transfer Allows Smad-Responsive Gene Promoter Analyses and Delineation of Type I Receptor Usage of Transforming Growth Factor-β Family Ligands in Cultured Human Granulosa Luteal Cells
Authors: Kaivo-Oja Noora , Mottershead David G. , Mazerbourg Sabine , Myllymaa Samu , Duprat Sébastien , Gilchrist Robert B. , Groome Nigel P. , Hsueh Aaron J. , Ritvos Olli 
Published: January 2005

AbstractIn the human ovary, cell growth and differentiation are regulated by members of the TGF-β superfamily, including growth differentiation factor-9 (GDF9), TGF-β, and activin. TGF-β and activin are known to signal via Smad3 activation, and we have recently shown the involvement of Smad3 in cellular responses to GDF9. Recent studies with Smad3-deficient mice have also indicated a key role for this signaling mediator in ovarian folliculogenesis. We now demonstrate the use of a Smad3 reporter (CAGA-luciferase) adenovirus in primary cultures of human granulosa-luteal (hGL) cells to detect GDF9, TGF-β, and activin responses. In rodent granulosa cells, TGF-β and GDF9 signal through the TGF-β type I receptor or activin receptor-like kinase 5 (Alk5), whereas the effect of activin is mediated though the activin type IB receptor, also known as Alk4. We now show that the GDF9 response in hGL cells is markedly potentiated upon overexpression of Alk5 by adenoviral gene transduction, as measured by the CAGA-luciferase reporter activity. A similar response to Alk5 overexpression was observed for TGF-β, but not for activin. Adenoviral overexpression of the activin type IB receptor Alk4 in hGL cells specifically potentiated activin signaling, but not GDF9 or TGF-β signaling. Alk5 overexpression in hGL cells also potentiated the GDF9 response when inhibin B production was used as the read-out. These results indicate that the CAGA-luciferase adenovirus can be used to study Smad3 signaling in primary cultures of human cells, and that adenoviral overexpression of wild-type receptors of the TGF-β superfamily can be used to amplify the cellular response to ligands such as GDF9, TGF-β, and activin. Furthermore, these studies indicate the involvement of Alk5 in GDF9 signaling in human cells and therefore, along with other recent studies, highlight how a limited number of type I and II receptors cooperate to generate specificity of action within the TGF-β superfamily.
Growth Hormone (GH) Responses to GH-Releasing Hormone-Arginine Testing in Human Immunodeficiency Virus Lipodystrophy
Authors: Koutkia Polyxeni , Canavan Bridget , Breu Jeff , Grinspoon Steven 
Published: January 2005

Abstract
Prior studies suggest reduced overnight GH secretion in association with excess visceral adiposity among patients with HIV lipodystrophy (LIPO, i.e. with fat redistribution). We now investigate GH responses to standardized GHRH-arginine in LIPO patients (n = 39) in comparison with body mass index- and age-matched control groups [HIV patients without fat distribution (NONLIPO, n = 17)] and healthy subjects (C, n = 16). IGF-I [242 ± 17; 345 ± 38; 291 ± 27 ng/ml (P &lt; 0.05 vs. NONLIPO)] was lowest in the LIPO group. Our data demonstrate failure rates of 18% for the LIPO group vs. 5.9% for the NONLIPO group and 0% for the C group, using a stringent criterion of 3.3 ng/ml for peak GH response to GHRH-arginine (P &lt; 0.05 LIPO vs. C). Using less stringent cutoffs, the failure rate in the LIPO group rises to 38.5% at 7.5 ng/ml. Among the LIPO patients, the peak GH response to GHRH-arginine was significantly predicted by visceral adipose tissue (P = 0.008), free fatty acid (P = 0.04), and insulin level (P = 0.007) in regression modeling controlling for age, body mass index, sc fat area, and triglyceride level. These data demonstrate increased failure rates to standardized stimulation testing with GHRH-arginine in LIPO patients, in association with increased visceral adiposity. The effects of low-dose GH should be assessed in the large subset of LIPO patients with abnormal GH stimulation testing.
Coordinating for service delivery in public-private partnership and private finance initiative construction projects: Early findings from an exploratory study
Authors: Tranfield D , Rowe A , Smart P K , Levene R , Deasley P , Corley J 
Published: January 2005

This paper presents the early findings of an extensive literature review and an exploratory empirical investigation into five UK construction organizations and outlines the management and organization design issues in introducing service delivery based on teamworking practices in construction. In particular, it highlights the challenges facing the industry in transitioning from prioritizing an asset delivery focus to a service delivery focus (SDF), especially when delivering private finance initiative and public private partnership types of project. The paper argues that introducing SDF cultures requires addressing issues commonly encountered in today's dynamic business environment, driven by the need to work collaboratively across organizational boundaries over long complex project cycles. Cultural change in this context is argued to be an emergent phenomenon resulting from the interconnectedness of a web of networks coexisting at the industry, organization, and project levels in a dynamic open system, prone to constant reconfiguration. This paper articulates the preliminary findings of an exploratory study that initiates much-needed understanding of how whole-life serviceability can be leveraged in construction projects. In essence, a network perspective of organizational design is enunciated, which suggests that ‘teamworking’ is the key to coordinating ‘design for service delivery’ across projects, across functions, across organizations, and over time (often 30 years plus). This dominant networked organizational form on which teamworking practices are focused is identified as the ‘special-purpose vehicle’ (SPV), an intermediary organization that is often the fundamental mechanism for project delivery. Further areas of research associated with the operations of SPVs are highlighted.
Synthesis of [2Fe–2S] and [4Fe–4S] Clusters Having Terminal Amide Ligands from an Iron(II) Amide Complex
Authors: Ohki Yasuhiro , Sunada Yusuke , Tatsumi Kazuyuki 
Published: January 2005

Abstract
The reaction of iron(II) bis-amide Fe{N(SiMe3)2}2 with elemental sulfur afforded a direct entry to new [Fe2S2] and [Fe4S4] clusters with terminal amide groups, Fe4S4{N(SiMe3)2}4 (1) and Fe2S2{N(SiMe3)2}2(tmtu)2 (2), whose structures have been determined by X-ray crystallography. Tetrameric cubane cluster 1 exhibits one reversible and one quasireversible processes in the cyclic voltammetry, whereas dimeric rhombus complex 2 reveals one irreversible reduction process.
Highly Sensitive Flow Analysis of Trace Level Arsenic in Water Based on Vaporization-collection In-line Preconcentration
Authors: Toda Kei , Ohba Takashi 
Published: January 2005

Abstract
Vaporization-collection in-line preconcentration (VCIP) is proposed for simple and highly sensitive measurement of vaporizable water pollutants. In this work, VCIP has been applied to arsenic analysis to develop an instrument for use in the field. The signal is 200 times higher than with conventional direct injection. Low ppb levels of As can be analyzed automatically in one step. This method is expected to be applicable to the measurement of very low levels of other water vaporizable pollutants as well.
Editorial Notes
Authors: Kemerer Chris F. 
Published: January 2005

This issue marks the end of the third and last year of my term as Editor-in-Chief of ISR. Three years ago I wrote an editorial for the first issue that set the tone and immediate goals for the journal, summarized as follows: “ISR has established itself as one of a small set of top-tier academic journals in the information systems discipline. Editorial policy changes have been designed to strengthen a number of aspects of the journal, particularly the timeliness of the work published, without having a negative impact on the journal's reputation for publishing high-quality work” (ISR website 2002). Looking back at the past three years, these goals have been met—we have decreased turnaround time by more than 50%, and the journal's ratings are as strong as (or stronger than) they were before. In this editorial note I will highlight our current processes and provide some data regarding the journal's progress over the last three years.
Combined Review: Architectural Anthropology and Minaret Building and Apprenticeship in Yemen
Authors: MOORE JERRY D. 
Published: January 2005

Architectural Anthropology. Mari‐José Amerlinck, ed. Westport, CT: Bergin and Garvey, 2001. 232 pp. Minaret Building and Apprenticeship in Yemen. Trevor H. J. Marchand. Richmond, Surrey: Curzon Press, 2001. 304 pp.
Combined Review: Experiencing the New Genetics: Family and Kinship on the Medical Frontier and Born and Bred: Idioms and New Reproductive Technologies in England
Authors: RAGONÉ HELÉNA 
Published: January 2005

Experiencing the New Genetics: Family and Kinship on the Medical Frontier. Kaja Finkler. Philadelphia: University of Pennsylvania Press, 2000. 296 pp. Born and Bred: Idioms and New Reproductive Technologies in England. Jeanette Edwards. New York: Oxford University Press, 2000. 264 pp.
Helmholtz and the shaping of the American physics elite in the Gilded Age
Authors: CAHAN DAVID 
Published: January 2005

ABSTRACT:
This essay concerns Helmholtz's relationships with American physics students and colleagues, and with his general image in Gilded Age America. His person, his teaching style, his views on the nature and function of science and its role within culture at large, and his institutional facilities played an important part in shaping the views of young American scientists and the institutional structures that they developed. The essay samples Helmholtz's reputation among American men of science and letters, and surveys the American physics students and postdocs who studied with him in Berlin or worked in or simply visited him and his institute there. It points to the leadership roles that several of these men played in their own academic institutions and their new emerging discipline. It provides an analysis of Helmholtz as a teacher and mentor of American physics students, and considers the special case of Henry Rowland's relationship with Helmholtz and his Berlin institute. Finally, it suggests that Helmholtz played a role, as inspirer, in the emergence of four key institutions of American physics—The physical review, The astrophysical journal, the American Physical Society, and the National Bureau of Standards. American physics students and postdocs in the Gilded Age idolized and lionized Helmholtz as a hero of pure science and research, as the embodiment of what it meant to be a physicist. As such, he helped shape the professional ideals and reality of the American physics elite that emerged during the late-19th century.