bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognition on the ground
Authors: Maynard Douglas W.
Published: February 2006

Suggesting that much of social science is still wedded to the ‘dogma of the ghost in the machine,’ I discuss my ethnomethodological and conversation analytic approach to the assembly of cognitive objects. It is important to reverse the usual social psychological metalanguage of mind causing behavior, and see how practices in interaction operate to display cognitive states of participants. Two examples are given: one in regard to the assembly of gestalts, including social actions in talk, and the other concerning the production of responses as accountable phenomena in the survey interview. While advances are being made in brain imaging, the connections between the neurobiology of the mind and the practices embedded in human conduct are tenuous at best. For the social scientist, approaching cognition through practices puts ghosts and other ephemera in abeyance and allows for analysis of the detail exhibited in behavior when minds are purportedly at work.
Firm and industry influences on the value of growth options
Authors: Tong Tony W. , Reuer Jeffrey J.
Published: February 2006

Strategy research on real options has emphasized the need to understand better the sources of the option value of the firm.We begin to address this issue by assessing the relative importance of firm as opposed to industry influences on the value of firms’ growth options. On the one hand, firms have been viewed as possessing distinct portfolios of real options, and firms vary in how they recognize and manage latent options. On the other hand, shared options arise that represent collective opportunities available to rivals, and their value can be affected by industry factors. Findings from variance decomposition analyses reveal that industry effects are important, yet firm effects always dominate; they are between 1.5 and 2.5 times as large as stable and transient industry effects combined.Thus, while shared options exist and industry conditions are important, it is the heterogeneity in firms’ proprietary options and their differences in managing options that appear to matter the most in explaining the variance in the value that is captured from these options. We contribute to real options research by highlighting the implications of understanding proprietary and shared options and by extending extant research beyond its current decisiontheoretic focus to begin to investigate the unique performance outcomes that real options theory ascribes to firms.
B‐Cell Chronic Lymphocytic Leukemia, a Clonal Disease of B Lymphocytes with Receptors that Vary in Specificity for (Auto)antigens
Authors: CHIORAZZI NICHOLAS , HATZI KATERINA , ALBESIANO EMILIA
Published: February 2006

Abstract: B‐Cell chronic lymphocytic leukemia (B‐CLL) is an incurable disease that is relatively common among aging Caucasians. Patients with this leukemia can be divided into prognostic categories using clinical staging parameters, as well as molecular features [presence or absence of IgVH mutations in rearranged VHDJH segments that code for the leukemic B cell's receptor for antigen (BCR)]. In addition, the deduced amino acid structure of the BCRs from patients that fall into different prognostic categories is shared, to varying degrees, within these groups. In this paper, the molecular features of the genes that code for the BCRs of B‐CLL patients are reviewed, and these are comapred to antibodies of known specificity. These comparisons suggest that the BCRs of many cases resemble autoantibodies, and in some cases, antibodies to microbial antigens. Antigen‐binding analyses confirm these impressions, and also indicate that polyreactivity appears to distinguish cases with worse clinical outcomes differ from those with better outcomes. The persistence of autoreactivity and polyreactivity is somewhat surprising, because IgV DNA sequence analyses suggest that many of the B cells that become leukemic have undergone one form or another of receptor editing. Thus, B‐CLL appears to be a disease of B‐cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen‐binding properties.
Immune Response to Premalignancy: Insights from Patients with Monoclonal Gammopathy
Authors: DHODAPKAR MADHAV V.
Published: February 2006

Abstract: Many patients with preneoplastic gammopathy remain clinically stable, in spite of the presence of multiple genomic abnormalities in tumor cells. Our hypothesis is that the development of clinical cancer depends not just on the genomic changes in tumor cells, but also their interactions with the host‐tumor microenvironment. Recent studies have shown that the host immune system is capable of responding to preneoplastic cells. Improved understanding of this response may provide novel opportunities for early detection and immune prevention of cancer.
CD154 Gene Therapy for Human B‐Cell Malignancies
Authors: MESSMER DAVORKA , KIPPS THOMAS J.
Published: February 2006

Abstract: Patients with chronic lymphocytic leukemia cells (CLL) who received a one‐time bolus infusion of autologous leukemia cells transduced with adenovirus encoding recombinant CD154 experienced acute and long‐term reductions in leukemia cell counts and lymph‐node size. This was associated with increases in the numbers of leukemia‐specific CD4+ T cells and high serum‐levels of IL‐12 and IFN‐γ. CD40‐ligation induces CLL cells to express the proapoptotic molecule Bid and death receptors CD95 (Fas) and DR5, rendering CLL B cells first resistant and then sensitive to Fas‐mediated apoptosis. Increasing sensitivity to Fas‐mediated apoptosis was also due to differential expression of pro‐ and antiapoptotic proteins at early versus late time points after activation. Additional treatment with inhibitors to the X‐linked inhibitor to apoptosis (XIAP) rendered the CD40‐activated cells sensitive to Fas‐mediated apoptosis even at early time points after CD40‐activation, suggesting that XIAP inhibitors might enhance the effectiveness of CD154‐based immune‐gene therapy strategies for patients of B‐cell malignancies.
The Immune Response to BCG Vaccination of Newborns
Authors: HANEKOM WILLEM A.
Published: February 2006

Abstract: The aim of this study is to identify immune correlates of protection against tuberculosis induced by the current vaccine, Bacille Calmette Guerin (BCG). This knowledge should be valuable for developing and testing novel tuberculosis vaccines. Blood from 5675 10‐week‐old South African infants, routinely vaccinated with BCG at birth, was collected, processed, and stored. Subsequently, infants who have developed tuberculosis disease—“not protected by the vaccine”—and infants who have remained healthy despite exposure to adults with tuberculosis—“protected by the vaccine”—have been identified. Recall immune responses to mycobacterial antigens in whole blood samples from the infants have been elicited; the next step will be to retrieve stored blood of “unprotected” and “protected” infants and compare immunity induced by BCG in the two groups. To guide the immune analysis, various pilot studies are being conducted to characterize the vaccination‐induced host response. Preliminary results indicate that BCG does indeed induce a potent CD8 T‐cell response, with cytokine‐producing or cytotoxic potential, in infants. An induction of FoxP3 mRNA expression in some mycobacteria‐stimulated whole‐blood samples is also being found, which suggests the presence of BCG‐induced regulatory CD4 T cells. Finally, stimulation of whole blood with mycobacterial antigens has resulted in a consistent pattern of cytokine release: significant numbers of infants make either large amounts of the effector cytokine interferon‐γ, or large amounts of the regulatory cytokine interleukin‐10, but not both. Tests will, therefore, be made to determine whether CD8 or regulatory CD4 T‐cell responses, as well as “outlier” cytokine responses, are associated with vaccination‐induced protection against tuberculosis.
Human B Cell Tolerance and Its Failure in Rheumatoid Arthritis
Authors: SAMUELS JONATHAN , NG YEN‐SHING , COUPILLAUD CLAIRE , PAGET DANIEL , MEFFRE ERIC
Published: February 2006

Abstract: Random V(D)J gene assembly generates many autoreactive B cell receptors (BCRs). In healthy donors, most autoreactive developing B cells are removed either in the bone marrow or in the periphery, revealing two B cell tolerance checkpoints. The regulation and the mechanisms that ensure this human B cell tolerance are poorly characterized, but they require proper BCR signaling. Indeed, patients with X‐linked agammaglobulinemia who carry mutations in the BTK gene, which encodes an essential BCR signaling component, fail to establish proper central B cell tolerance, as demonstrated by the release of self‐reactive B cells in the periphery. In autoimmune diseases such as rheumatoid arthritis (RA), B cell tolerance is broken and autoantibodies are secreted. Our recent results show that RA patients suffer from defective central and peripheral B cell tolerance checkpoints, which may favor the development of autoimmunity. Also, about half of our RA patients display unusual immunoglobulin light chain repertoires showing impaired secondary recombination regulation, which indicates that receptor editing, one of the mechanisms that normally ensures B cell tolerance, may often be defective in RA.
Analysis of Significance Patterns Identifies Ubiquitous and Disease‐Specific Gene‐Expression Signatures in Patient Peripheral Blood Leukocytes
Authors: CHAUSSABEL DAMIEN , ALLMAN WINDY , MEJIAS ASUNCION , CHUNG WENDY , BENNETT LYNDA , RAMILO OCTAVIO , PASCUAL VIRGINIA , PALUCKA A. KAROLINA , BANCHEREAU JACQUES
Published: February 2006

Abstract: The utilization of gene‐expression microarrays in patient‐based research creates new prospects for the discovery of diagnostic biomarkers and the identification of genes or pathways linked to pathogenesis. Gene‐expression signatures in peripheral blood mononuclear cells isolated from over one hundred patients with conditions presenting a strong immunological component (patient with autoimmune, graft versus host and infectious diseases, as well as immunosuppressed transplant recipients) were generated. This dataset provides the opportunity to carry out comparative analyses and define disease signatures in a broader context. Transcriptional changes of 22,283 probe sets were evaluated through statistical group comparison performed systematically for seven diseases versus their respective healthy control group. Patterns of significance were generated by hierarchical clustering of P‐values. This approach led to the identification of a SLE‐specific “diagnostic signature,” formed by genes that did not change compared to healthy subjects in the other six diseases. Conversely, a “sentinel signature” that was common to all seven diseases was characterized. These findings bring new perspectives for the application of blood leukocyte expression signatures for diagnosis and early disease detection.
Appreciating the Heterogeneity in Autoimmune Disease: Multiparameter Assessment of Intracellular Signaling Mechanisms
Authors: PEREZ OMAR D.
Published: February 2006

Abstract: Autoimmune disease pathologies are multifactorial with complex interactive networks of cells and chemical messengers that initiate cascades of aberrant cellular activity. Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by systemic inflammation, destruction of the joints, and production of autoantibodies recognizing dozens of putative autoantigens. The presence of autoreactive T cells in individuals leads to pathological autoimmunity by activating additional cellular constituents to mediate inflammation and joint destruction. The etiology of RA is unknown, and knowledge is lacking of the molecular mechanisms underlying the production and subsequent regulation of autoreactive T cells and predicting patient responses to treatments. Biochemical investigations into mechanisms of the disease have relied on animal models that are helpful in dissecting elements of the disease but that are not necessarily reflective of human RA development. The study of multiple activated signaling pathways in complex populations of cells, such as peripheral blood, at the single‐cell level has not previously been possible. This article describes how intracellular phosphoepitope staining methodology in conjunction with surface‐cell immunophenotyping can be used to deconvolute cellular subsets and allow functional characterization of patient‐derived material. Multiparameter flow cytometric analysis allows for small subpopulations—representing different cellular subsets and differentiation or activation states—to be discerned and simultaneously assessed for intracellular biochemical activities. This article also describes how single‐cell signal network analysis can be used to stratify patients and may be useful for understanding mechanisms of disease progression, treatment resistance, and development of diagnostic indicators.
Potential Contribution of VH Gene Replacement in Immunity and Disease
Authors: LIU YANWEN , FAN RUN , ZHOU SONG , YU ZHIHONG , ZHANG ZHIXIN
Published: February 2006

Abstract: VH replacement occurs through RAG‐mediated recombination between a cryptic recombination signal sequence (cRSS) presented in a rearranged VH gene and a 23‐bp RSS from an upstream VH gene. VH replacement renews the entire VH coding region and extends the immunoglobulin heavy‐chain (IgH) CDR3 regions preferentially with charged amino acids. VH replacement occurs in bone marrow‐immature B cells and contributes significantly to the primary B‐cell repertoire in humans. However, the biological significance of VH replacement is not clear. Our recent studies revealed elevated frequencies of VH replacement products in different autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Moreover, elevated frequencies of VH replacement products were also found in patients with human immunodeficiency virus or hepatitis C virus infections. These results provide the first clue that VH replacement contributes to autoimmune disease and antiviral immunity, and they also suggest a potential link between viral infection and autoimmune disease.
Immunologic Role of the Cholinergic Anti‐Inflammatory Pathway and the Nicotinic Acetylcholine α7 Receptor
Authors: GALLOWITSCH‐PUERTA MARGOT , TRACEY KEVIN J.
Published: February 2006

Abstract: Cytokines are small protein molecules that facilitate communication between cells of the immune system and other tissues. Their messenger function elicits responses in other cells, ranging from DNA binding and tissue remodeling to coordinating the local cellular response to inflammation. The magnitude of the cytokine response is regulated closely, because an over‐ or underabundance of cytokine activity can impair organ function and cause shock and tissue injury. Counterregulatory molecular and humoral mechanisms protect the host from cytokine excess, including the pituitary‐adrenal‐glucocorticoid system, and the anti‐inflammatory cytokine system. These humoral systems are protective, but they are relatively slow‐acting, concentration‐gradient dependent, and not integrated. We recently discovered that the “cholinergic anti‐inflammatory pathway,” a nervous system‐based, rapid, and locally acting mechanism, can inhibit the cytokine response. Signals transmitted via the vagus nerve converge on cytokine‐producing cells that express the nicotinic acetylcholine receptor alpha 7 (nAChR α7). The α7 receptor is an essential component of the cholinergic anti‐inflammatory pathway, because activation of this receptor prevents cytokine release. Advances in understanding the molecular structure and function of α7 have begun to provide a better understanding of potential mechanisms regarding its assembly, expression, and cytokine‐inhibiting functions. It may be possible to exploit this pathway to therapeutic advantage for diseases caused by excessive cytokine activity.
Toll‐Like Receptor Activation in the Pathogenesis of Systemic Lupus Erythematosus
Authors: MEANS TERRY K. , LUSTER ANDREW D.
Published: February 2006

Abstract: Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies to nucleoproteins and DNA. The level of anti‐DNA antibodies correlates with disease severity, and the deposition of these immune complexes (ICs) in the kidneys is thought to contribute to disease pathogenesis. Recent evidence suggests that the DNA component of ICs purified from SLE patients (SLE DNA‐ICs) contributes to the development of SLE pathology. SLE DNA‐ICs induce proliferation of self‐reactive B cells and cytokine production by plasmacytoid dendritic cells (PDCs) in a TLR9‐dependent manner. One of the cytokines induced by DNA‐containing ICs is interferon α (IFN‐α). Elevated serum levels of IFN‐α and overexpression of interferon‐induced genes have been observed in SLE patient blood and shown to correlate with disease severity. We have recently found that the mechanism of IFN‐α production by PDCs depends on TLR9 and FcγRIIa (CD32), and CD32 delivers SLE DNA‐ICs to intracellular lysosomes containing TLR9. This CD32‐TLR9 pathway, which is operative in PDCs, is distinct from the BCR/TLR9 pathway in B cells and may prove to be a novel target for future SLE therapies. In this article, the role of toll‐like receptors, cytokines, and Fc receptors expressed by PDCs in the pathogenesis of SLE is summarized.
A Densitometric and Morphometric Analysis of the Skeleton in Adults with Varying Degrees of Growth Hormone Deficiency
Authors: Murray Robert D. , Adams Judith E. , Shalet Stephen M.
Published: February 2006

Context: Low bone mass is a characteristic feature of the adult GH deficiency (GHD) syndrome, but recent dual-energy x-ray absorptiometry (DXA) studies in patients with GH-receptor and GHRH-receptor gene mutations suggest that the situation is more complex.

Objective: The objective was to define bone areal and volumetric densities and morphometry in hypopituitary adults.

Design: The study was a cross-sectional case-controlled study performed between 1999 and 2001.

Setting: The study was undertaken at an endocrine tertiary referral center.

Patients: Thirty patients with GHD, 24 with GH insufficiency (GHI) [peak GH, 3–7 μg/liter (9–21 mU/liter)], and 30 age- and sex-matched controls were included for study.

Main Outcome Measures: DXA and peripheral quantitative computed tomography (pQCT) derived bone density and morphometry were measured.

Results: No densitometric or morphometric abnormalities were detected in GHD patients who acquired their deficiency during adult life. GHD adults of childhood-onset (CO-GHD) showed decreased bone mineral density at the lumbar spine and hip on DXA. pQCT of the radius showed that CO-GHD patients have normal trabecular bone mineral density and only a 2% decrease in cortical density. Radial bone area was reduced 14.5%, cortical thickness 20%, and cortical cross-sectional area 23%, culminating in a reduction in cortical bone of 25%. The “apparent” low DXA bone density in CO-GHD adults therefore relates primarily to reduced cortical thickness and smaller bone area. DXA and pQCT data derived from adults with GHI revealed no evidence of densitometric or morphometric abnormalities.

Conclusions: 1) Adult-onset GHD patients have normal bone density and size. 2) CO-GHD adults have marginally reduced cortical density but significantly reduced cortical bone as a result of reduced cortical thickness and bone size. 3) GHI has no measurable impact on the skeleton.
Overweight Humans Are Resistant to the Weight-Reducing Effects of Melanocortin4–10
Authors: Hallschmid Manfred , Smolnik Rüdiger , McGregor Gerard , Born Jan , Fehm Horst L.
Published: February 2006

Context: By enhancing energy expenditure and suppressing appetite, melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. In a recent study in normal-weight adults, the 6-wk intranasal administration of the MSH/ACTH4–10 core fragment of proopiomelanocortin resulted in a distinct reduction of body weight and body fat, accompanied by significant decreases in leptin and insulin plasma concentrations.

Objective: The present study aimed to generalize this finding to overweight patients.

Design, Subjects, and Intervention: MSH/ACTH4–10 (0.5 mg) and placebo were intranasally administered once in the morning and once in the evening over a period of 12 wk in 23 overweight men (body mass index, mean ± sem: 29.72 ± 0.43 kg/m2).

Results: MSH/ACTH4–10 did not induce any significant reduction in body weight, body fat, and plasma levels of insulin and leptin as compared with the effects of placebo. Melanocortin treatment was accompanied by reduced cortisol concentrations.

Conclusions: We conclude that contrasting with normal-weight humans, overweight subjects are not susceptible to the effects of melanocortin administration on hypothalamic weight regulatory systems. In overweight subjects, a decreased sensitivity to ACTH/MSH peptides may derive from alterations at the level of the melanocortin receptor or at subsequent steps in the processing of the body fat signal.
The Effects of Growth Hormone and/or Testosterone in Healthy Elderly Men: A Randomized Controlled Trial
Authors: Giannoulis Manthos G. , Sonksen Peter H. , Umpleby Margot , Breen Louise , Pentecost Claire , Whyte Martin , McMillan Carolyn V. , Bradley Clare , Martin Finbarr C.
Published: February 2006

Context: Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men.

Objective: To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men.

Design, Settings, and Participants: A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65–80 yr).

Interventions: Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches.

Results: Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects.

Conclusion: Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.
Real-Time Prognosis for Metastatic Thyroid Carcinoma Based on 2-[18F]Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography Scanning
Authors: Robbins Richard J. , Wan Qiang , Grewal Ravinder K. , Reibke Roland , Gonen Mithat , Strauss H. William , Tuttle R. Michael , Drucker William , Larson Steven M.
Published: February 2006

Context/Objective: Approximately 15% of thyroid cancer patients develop subsequent metastases. The clinical course of patients with metastatic thyroid carcinoma is highly variable. We hypothesized that the metabolic activity of metastatic lesions, as defined by retention of 2-[18F]fluoro-2-deoxyglucose (FDG), would correlate with prognosis.

Design/Patients: The initial FDG-positron emission tomography (PET) scans from 400 thyroid cancer patients were retrospectively reviewed and compared with overall survival (median follow-up, 7.9 yr). We examined the prognostic value of clinical information such as gender, age, serum thyroglobulin, American Joint Committee on Cancer (AJCC) stage, histology, radioiodine avidity, FDG-PET positivity, number of FDG-avid lesions, and the glycolytic rate of the most active lesion.

Results: Age, initial stage, histology, thyroglobulin, radioiodine uptake, and PET outcomes all correlated with survival by univariate analysis. However, only age and PET results continued to be strong predictors of survival under multivariate analysis. The initial American Joint Committee on Cancer stage was not a significant predictor of survival by multivariate analysis. There were significant inverse relationships between survival and both the glycolytic rate of the most active lesion and the number of FDG-avid lesions.

Conclusions: FDG-PET scanning is a simple, expensive, but powerful means to restage thyroid cancer patients who develop subsequent metastases, assigning them to groups that are either at low (FDG negative) or high (FDG positive) risk of cancer-associated mortality. We propose that the aggressiveness of therapy for metastases should match the FDG-PET status.
Dihydrotestosterone Decreases Tumor Necrosis Factor-α and Lipopolysaccharide-Induced Inflammatory Response in Human Endothelial Cells
Authors: Norata Giuseppe Danilo , Tibolla Gianpaolo , Seccomandi Paul Maria , Poletti Angelo , Catapano Alberico Luigi
Published: February 2006

Context: An increasing body of evidence suggests that testosterone may exert beneficial effects on the development of atherosclerosis. It was suggested that testosterone may act after conversion into estradiol and activation of the estrogen receptors; however, a direct role of androgens on the vascular wall has been proposed.

Objective: We investigated the effects of dihydrotestosterone on the proinflammatory response observed in human endothelial cells.

Design: Human endothelial cells isolated from umbilical cords were incubated with lipopolysaccharide or TNFα in the presence or absence of dihydrotestosterone (DHT). mRNA and cellular proteins were processed for gene expression studies, and transient transfection experiments were performed to investigate molecular mechanisms involved in the effects observed.

Setting: These studies took place at the Department of Pharmacological Sciences, University of Milan, Milan, Italy.

Results: Lipopolysaccharide and TNFα induced VCAM-1 and ICAM-1 mRNA and protein expression, as detected by real-time quantitative PCR, fluorescence-activated cell sorting, and confocal microscopy, but this effect was inhibited when cells were incubated with DHT. In addition, DHT inhibited mRNA expression of IL-6, MCP-1, CD40, TLR4, PAI-1, and Cox-2 and the release of cytokines and chemokines such as GRO, granulocyte-macrophage colony-stimulating factor, and TNF. The DHT effect was counteracted by bicalutamide, an antagonist of the androgen receptor. Furthermore, when cells were cotransfected with a Cox-2 promoter or a 3X-NF-κB luciferase reporter vector and a plasmid expressing the human androgen receptor, DHT treatment inhibited the increase of the luciferase activity observed with TNFα.

Conclusion: DHT could positively regulate endothelial function through the control of the inflammatory response mediated by nuclear factor-κB in endothelial cells.
Adolescent Girls with Polycystic Ovary Syndrome Have an Increased Risk of the Metabolic Syndrome Associated with Increasing Androgen Levels Independent of Obesity and Insulin Resistance
Authors: Coviello Andrea D. , Legro Richard S. , Dunaif Andrea
Published: February 2006

Context: Adult women with polycystic ovary syndrome (PCOS) have an increased prevalence of the metabolic syndrome (MBS). The prevalence of MBS is also increasing in adolescents.

Objective: Our objective was to test the hypothesis that the prevalence of MBS is increased in adolescent girls with PCOS compared with the general population and to determine the factors associated with an increased risk of the MBS in PCOS.

Design and Setting: We conducted a cross-sectional case-control study at academic medical centers with general clinical research centers.

Participants: Participants included 49 adolescent girls with PCOS and 165 girls from the Third National Health and Nutrition Examination Survey (NHANES III) adolescent population of similar age and ethnic background.

Main Outcome Measure: We assessed the prevalence of MBS according to currently proposed adolescent MBS criteria.

Results: Thirty-seven percent of adolescent girls with PCOS had MBS compared with 5% of NHANES III girls (P < 0.0001). None of the girls of normal body mass index (BMI) had MBS, whereas 11% of overweight and 63% of obese girls with PCOS had MBS compared with 0 and 32% of NHANES III girls, respectively. Girls with PCOS were 4.5 times more likely to have MBS than age-matched NHANES III girls after adjusting for BMI (odds ratio, 4.5; 95% confidence interval, 1.1–17.7; P = 0.03). The odds of having the MBS were 3.8 times higher for every quartile increase in bioavailable testosterone in girls with PCOS after adjusting for BMI and insulin resistance (odds ratio, 3.8; 95% confidence interval, 1.4–10.2; P = 0.008).

Conclusions: Adolescent girls with PCOS have a higher prevalence of MBS than the general adolescent population. Hyperandrogenemia is a risk factor for MBS independent of obesity and insulin resistance.
Somatic and Germline Mosaicism for a Mutation of the PHEX Gene Can Lead to Genetic Transmission of X-Linked Hypophosphatemic Rickets That Mimics an Autosomal Dominant Trait
Authors: Goji Katsumi , Ozaki Kayo , Sadewa Ahmad H. , Nishio Hisahide , Matsuo Masafumi
Published: February 2006

Context: Familial hypophosphatemic rickets is usually transmitted as an X-linked dominant disorder (XLH), although autosomal dominant forms have also been observed. Genetic studies of these disorders have identified mutations in PHEX and FGF23 as the causes of X-linked dominant disorder and autosomal dominant forms, respectively.

Objective: The objective of the study was to describe the molecular genetic findings in a family affected by hypophosphatemic rickets with presumed autosomal dominant inheritance.

Patients: We studied a family in which the father and the elder of his two daughters, but not the second daughter, were affected by hypophosphatemic rickets. The pedigree interpretation of the family suggested that genetic transmission of the disorder occurred as an autosomal dominant trait.

Methods and Results: Direct nucleotide sequencing of FGF23 and PHEX revealed that the elder daughter was heterozygous for an R567X mutation in PHEX, rather than FGF23, suggesting that the genetic transmission occurred as an X-linked dominant trait. Unexpectedly, the father was heterozygous for this mutation. Single-nucleotide primer extension and denaturing HPLC analysis of the father using DNA from single hair roots revealed that he was a somatic mosaic for the mutation. Haplotype analysis confirmed that the father transmitted the genotypes for 18 markers on the X chromosome equally to his two daughters. The fact that the father transmitted the mutation to only one of his two daughters indicated that he was a germline mosaic for the mutation.

Conclusions: Somatic and germline mosaicism for an X-linked dominant mutation in PHEX may mimic autosomal dominant inheritance.
Limitation of the Homeostasis Model Assessment to Predict Insulin Resistance and β-Cell Dysfunction in Older People
Authors: Chang Annette M. , Smith Marla J. , Bloem Cathie J. , Galecki Andrzej T. , Halter Jeffrey B. , Supiano Mark A.
Published: February 2006

Context: Studies in older people have shown inconsistent agreement between homeostasis model assessment of insulin resistance (HOMA-IR) and dynamic measures of insulin action and have not evaluated HOMA β-cell.

Objective: We compared measures of insulin sensitivity and β-cell function from the frequently sampled iv glucose tolerance test (FSIGT) to HOMA models.

Design/Patients/Setting/Intervention: Two hundred fourteen young and old with normal glucose tolerance (NGT) and old with impaired glucose tolerance (IGT) participated in a retrospective analysis of FSIGT data in a university medical setting.

Main Outcome Measure: Sensitivity to insulin (SI) and acute insulin response to glucose (AIRg) from FSIGT were compared with HOMA models.

Results: SI and HOMA-IR measures identified similar patterns of increasing insulin resistance in the two older groups, compared with younger people with NGT, with the greatest degree of insulin resistance in older people with IGT (P < 0.05 vs. young and old NGT for both SI and HOMA-IR). Agreement between HOMA-IR and SI was moderate (weighted kappa = 0.51). AIRg was similar in young and old NGT but was markedly decreased in old IGT (P < 0.05 vs. young and old NGT). HOMA-β-cell was similar in the three groups. Agreement between HOMA β-cell and AIRg was weak (weighted kappa = 0.35).

Conclusions: HOMA-IR may detect age-related insulin resistance when comparing large populations of older people. However, dynamic testing appears to be necessary to quantitate diminished insulin secretion in older people.
Transient Testicular Warming Enhances the Suppressive Effect of Testosterone on Spermatogenesis in Adult Cynomolgus Monkeys (Macaca fascicularis)
Authors: Lue Yanhe , Wang Christina , Liu Yi-Xun , Hikim Amiya P. Sinha , Zhang Xue-Sen , Ng Chiu-Ming , Hu Zhao-Yuan , Li Yin-Chuan , Leung Andrew , Swerdloff Ronald S.
Published: February 2006

Context: The context of the study was to examine whether combined testosterone (T) and heat (H) treatment have additive or synergistic effects on suppression of spermatogenesis.

Objective: The objective of the study was to determine whether T+H induces a greater suppression of spermatogenesis than either treatment alone in monkeys.

Design: The study was a randomized, placebo-controlled study.

Setting: The study was conducted at a primate center in China.

Participants: The study population was comprised of 32 adult cynomolgus monkeys.

Interventions: Groups of eight adult monkeys were treated for 12 wk with: 1) two empty implants (C); 2) two T implants (T); 3) daily testicular heat exposure (43 C for 30 min) for 2 consecutive days (H); or 4) two T implants plus testicular heat exposure (T+H). Treatment was followed by an 8-wk recovery period.

Main Outcome Measures: Measures included sperm counts and germ cell apoptosis.

Results: Serum T levels were elevated in both the T and T+H groups during treatment but not in the C or H group. Sperm counts were transiently suppressed after heat to 16.4% of baseline at 4 wk and then returned to pretreatment levels. Sperm counts were suppressed slowly after T treatment to nadir of 6.4% of pretreatment levels at 12 wk. T+H rapidly suppressed sperm output as early as 4 wk to 3.9% of pretreatment levels that was maintained throughout treatment. The decreased sperm counts were due to increased germ cell apoptosis in all treatment groups. Sperm counts recovered to the pretreatment levels in all groups by 8 wk after treatment.

Conclusion: This proof-of-concept study demonstrates that transient testicular warming enhances and hastens the effect of T implant on the suppression of spermatogenesis in monkeys.
Linear Relationship between Activity of a New Ru-catalyst and Acidity of Substituted Benzoic Acids in the Dimerization of Acrylonitrile
Authors: Kashiwagi Kohichi , Sugise Ryoji , Shimakawa Toshihiro , Matuura Tunao , Shirai Masashi
Published: February 2006

A new type of catalyst system using ruthenium and carboxylic acid is useful for the tail-to-tail dimerization of acrylonitrile, proceeding without the formation of undesired by-product propionitrile. Carboxylic acids having pKa 3.5–5 are suitable as co-catalysts for the dimerization of acrylonitrile. The relationship between the logarithm of the relative rate in the dimer formation and the pKa of m- and p-substituted benzoic acids (Brønsted plot) was linear (R2 = 0.946) with a slope of −0.199. The role of the carboxylic acids can be considered to be effective protonation in the protonolysis of the carbon–ruthenium bond of an intermediate Ru complex.
Fabrication of Ordered Nanostructures in Ta Films Using 2D Array of Ferritin Molecules as Template
Authors: Masuda Hideki , Matsui Yoshitaka , Miwa Tetsuya , Nagae Mitsutaka , Tanji Miyuki , Nishio Kazuyuki
Published: February 2006

Metal (Ta) films with ordered structures of nanometer-scale dimensions were fabricated by replicating the structure of a 2D array of ferritin molecules as a template. The deposition of a Ta layer onto a 2D array of ferritin molecules using ion-beam sputtering and subsequent removal of the ferritin molecules generated Ta films with an ordered array of concave with a 13 nm interval. The uniformity and chemical stability of Ta formed by ion-beam sputtering contributed to the precise replication of the fine structures of the 2D array of ferritin molecules.
Large-scale Synthesis of SrCrO4 Nanowires and PbCrO4 Nanorods by a Solution-phase Method at Room Temperature
Authors: Wang Wen-Shou , Xu Cheng-Yan , Zhen Liang , Yang Li , Shao Wen-Zhu
Published: February 2006

A facile, large-scale, solution-phase method has been developed to the synthesis of ABO4-type chromate nanowires/rods at room temperature. Single-crystalline strontium chromate nanowires and lead chromate nanorods were fabricated by this method without heating or adding any surfactants or polymers. The structure and morphology of the nanowires/rods were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and selected-area electron diffraction (SAED). This simple method may also be extended to the synthesis of other ABO4-type chromate one-dimensional nanostructures with a large-scale and low-cost production.
Ink-jet Microchip Interface between Liquid Flow and Flame-ionization Detector
Authors: Nishiyama Takahide , Endo Fumihiro , Eguchi Hiroko , Tsunokawa Jun , Nakagama Tatsuro , Seino Nobuko , Shinoda Masaki , Shimosaka Takuya , Hobo Toshiyuki , Uchiyama Katsumi
Published: February 2006

An ink-jet microchip interface between the continuous liquid flow and flame-ionization detector (FID) for gas chromatography (GC) has been developed. An ink-jet microchip for a conventional recorder was modified for the interface. When the interface was used for a flow-injection analysis (FIA) system with FID, 3.3 ng of the detection limit (S/N = 3) of ethanol in water was performed.
Highly Efficient Water Splitting over K3Ta3B2O12 Photocatalyst without Loading Cocatalyst
Authors: Kurihara Toshiyasu , Okutomi Hiroaki , Miseki Yugo , Kato Hideki , Kudo Akihiko
Published: February 2006

K3Ta3B2O12 with pillared structure showed a high photocatalytic activity for water splitting into H2 and O2 without assistance of cocatalysts. The bandgap of K3Ta3B2O12 was 4.2 eV. K3Ta3B2O12 showed blue photoluminescence at 77 K by the bandgap excitation as well as other tantalate photocatalysts for water splitting.
Shape- and Size-controlled Synthesis of Tetrahedral Pd Nanoparticles Using Tetranuclear Pd Cluster as Precursor
Authors: Norimatsu Fujie Y , Mizokoshi Yugo , Mori Kohsuke , Mizugaki Tomoo , Ebitani Kohki , Kaneda Kiyotomi
Published: February 2006

Structurally well-defined tetrahedral Pd nanocrystals were obtained by a simple stabilizer- and reductant-free synthesis method using a tetranuclear Pd cluster as a precursor. The Pd tetrahedral nanoparticles were successfully immobilized on the surface of a solid support maintaining not only their size but also their shape.
Cognitive executive function in Down's syndrome
Authors: Rowe John , Lavender Anthony , Turk Vicky
Published: February 2006

Objectives. The study investigated executive function in adults with Down's syndrome.

Design. Participants with Down's syndrome (N=26) were compared with non‐Down syndrome learning disabled participants (N=26).

Method. The two group's performance on a range of tests of executive function were compared. Groups were matched on age and a measure of vocabulary.

Results. The Down's syndrome group performed at a significantly lower level on a number of tests of executive function.

Conclusion. It is suggested that impaired executive function in Down's syndrome is due to abnormal development of the prefrontal cortex in Down's syndrome. Tests of executive function may be sensitive to cognitive changes with the onset of dementia in people with Down's syndrome. Longitudinal studies examining changes in executive function in people with Down's syndrome are recommended.
There's nothing more practical than a good theory: Integrating motivational interviewing and self‐determination theory
Authors: Vansteenkiste Maarten , Sheldon Kennon M.
Published: February 2006

In this article we compare and integrate two well‐established approaches to motivating therapeutic change, namely self‐determination theory (SDT; Deci & Ryan, 1985, 2000) and motivational interviewing (MI; Miller & Rollnick, 1991, 2002). We show that SDT's theoretical focus on the internalization of therapeutic change and on the issue of need‐satisfaction is fully compatible with key principles and clinical strategies within MI. We further suggest that basic need‐satisfaction might be an important mechanism accounting for the positive effects of MI. Conversely, MI principles may provide SDT researchers with new insight into the application of SDT's theoretical concept of autonomy‐support, and suggest new ways of testing and developing SDT. In short, the applied approach of MI and the theoretical approach of SDT might be fruitfully married, to the benefit of both.
Do empirically supported treatments generalize to private practice? A benchmark study of a cognitive‐behavioural group treatment programme for social phobia
Authors: Gaston Jonathan E. , Abbott Maree J. , Rapee Ronald M. , Neary Sally A.
Published: February 2006

Objectives. There is much debate as to whether the treatment effects achieved in well‐controlled studies such as randomized controlled trials (RCTs) are generalizable to more ‘naturalistic’ clinical populations, such as that seen in private practice. The current study sought to examine this issue in relation to social phobia.

Design. A benchmarking strategy was used to compare the effectiveness of a cognitive‐behaviour therapy group programme for social phobia that was developed and evaluated in a research unit, to that of a private practice population.

Methods. Fifty‐eight participants from a university research unit and 54 participants from an independent private practice who met the principal diagnostic criteria for social phobia completed the 10‐session group programme. Symptom severity was measured at pre‐treatment, post‐treatment, and 3 months after treatment.

Results. No significant treatment differences were found between the research unit and private practice groups. Both groups showed significant treatment effects that were maintained at 3‐month follow‐up.

Conclusion. These findings suggest that treatments developed for RCTs are potentially transportable to private practice settings.
Mood fluctuations in people putatively at risk for bipolar disorders
Authors: Hofmann Beate U. , Meyer Thomas D.
Published: February 2006

Objectives. The dysregulation of the Behavioural Activation System (BAS) is discussed as a vulnerability marker for bipolar disorders, resulting in fluctuations of activity and mood. People putatively at risk for bipolar disorders (BD) should therefore show mood fluctuations.

Method. Using the ‘Hypomanic Personality Scale’ (HPS) three groups of young adults with high (N=17), medium (N=19), and low scores (N=18) were selected and completed a 28‐day diary including CES‐D and PANAS.

Results. People at risk for bipolar disorders exhibited high levels of manic symptoms, positive and negative affect. They also generally reported more mood instability.

Conclusions. The results support the hypothesis that fluctuations of mood and symptoms might be a core characteristic of the hypothesized vulnerability for BD. These fluctuations of mood were, however, not restricted to positive affect as a dysregulation of the BAS would suggest.
I see what you see: The lack of a self‐serving body‐image bias in eating disorders
Authors: Jansen Anita , Smeets Tom , Martijn Carolien , Nederkoorn Chantal
Published: February 2006

Objectives. Eating‐disordered subjects feel unattractive, and the current idea is that this feeling reflects a distorted body image. A distorted body image requires a mismatch between the negative self‐judgments and more objective judgments of the body.

Design and methods. To examine whether eating‐disordered subjects have valid reasons for their feelings of unattractiveness, the body images of eating‐symptomatic subjects and control models were compared with inter‐subjective evaluations of these bodies given by two community samples (panels; N=72, N=88).

Results. Although the objective body sizes of the eating‐symptomatic subjects were in the normal range and not different from control bodies, the first panel rated the (headless) bodies of the eating‐symptomatic subjects as less attractive. This finding was replicated with the second panel. There was also large agreement between the eating‐symptomatic subjects and the second panel on the specific body parts that were indicated as unattractive. Contrary to the eating‐symptomatic subjects, the control models showed a strong positively biased perception of their own attractiveness: they rated their own bodies more positively than others rated them.

Conclusion. Consensual validation of the harsh body appraisals of eating‐symptomatic subjects was found. Interestingly, the normal controls were the ones that showed a biased body image; they rated themselves far more attractive than other people rated them. These data suggest that the real problem in eating disorders is not a distorted body image but a lack of a distorted body image, that is, the lack of a self‐serving body‐image bias.
The Nature of Fit and the Origins of “Feeling Right”: A Goal-Systemic Perspective
Authors: Kruglanski Arie W.
Published: February 2006

This article considers the notion of regulatory fit from a goal-systemic perspective. It is suggested that regulatory fit, as Avnet and Higgins (2006) define it, corresponds to a match between a person's activity and his or her (background) process goal of pursuing an (focal) attainment goal in a desired manner. The author considers prior regulatory fit data from this perspective and raises additional issues for further research and theoretical elucidation.
Household Life Cycles and Lifestyles in the United States
Authors: Du Rex Y. , Kamakura Wagner A.
Published: February 2006

Household life cycle has been widely used as a determinant of consumer behavior and a basis for market segmentation. However, there is considerable disagreement about how life stages should be defined and how households progress through these stages. Existing studies use a priori definitions, which are tested on a cross-sectional survey of households collected at a single point in time and thus cannot reveal the real dynamics of the household life cycle. The Panel Study of Income Dynamics provides longitudinal data on household composition in the United States for a period of 34 years; the authors use this to identify empirically the most typical stages and paths that U.S. households have followed since 1968. They develop a hidden Markov model in which the stages of the household life cycle are taken as latent, unobservable states that are uncovered from the manifest household demographic profiles over the 34 years, assuming that households evolve through these latent stages following a first-order Markov process. The authors apply their results to classify members of another panel (Consumer Expenditure Survey) into life stages, which enables them to study the impact of the household life cycle on households' budgetary allocations, providing a comprehensive analysis of lifestyles (through expenditure patterns) over the household life cycle.