bluuebunny/crossref_metadata_2025 huggingface dataset:
Restructuring Life
Authors: Silva-Smith Amy L.
Published: January 2007

Family caregivers of stroke survivors who are just beginning their role must learn new skills and incorporate new knowledge into their daily activities. This can be a time of increased anxiety and stress for them. Nurses and other health professionals need more knowledge about this transition from the perspective of the caregivers. The purpose of this grounded theory study was to describe the process associated with preparing for and beginning a new caregiving role following a family member's stroke. Caregivers who were new to the role were interviewed prior to the stroke survivor's discharge and 4 weeks after discharge. The grounded theory, Restructuring Life for Caregiving, was associated with five dimensions of participants' lives: daily life, managing multiple roles, relationship with the stroke survivor, future hopes and plans, and time for self. The process of waiting, rearranging, and stabilizing further explained the timing and elements of restructuring activities.
Parent as Proxy Reporting
Authors: Sherifali Diana , Pinelli Janet
Published: January 2007

Improved disease management in children has resulted in an increased interest in the quality of life in children. Quality of life research in children may enlist either the substitute or complementary perspective. Much of the quality of life literature has been guided by the substitute perspective, which infers that parents may best report their child's quality of life. However, the complementary perspective values both parent and child perspectives equally. The purpose of this article was to critically review the quality of life literature with respect to children with diabetes. Limitations in the literature were addressed as conceptual and methodological, demographic, and underlying proxy perspectives. Benefits and limitations of quality of life measurements and perspectives were also discussed. Recommendations and future implications for quality of life research in children extend current understanding from both substitute and complementary perspectives.
Meaning and Action in Employed Mothers' Health Work
Authors: Kushner Kaysi Eastlick
Published: January 2007

The purpose of this critical feminist study was to examine employed mothers' meanings of family and personal health as they frame the context of daily experience in caring for their families' and their own health. Twenty mothers employed in support staff positions with a large institution in Western Canada participated in repeat interviews over 2 years. Women considered individual family members and the family group as they emphasized everyday function and satisfaction, and the presence or absence of various attributes of health as a multifaceted and dynamic experience. Women's health work included keeping track, constructing routines, facing challenges, setting priorities, being there for each other, finding joy and fulfillment, and fostering personal development. A preliminary typology of four orientations to family health work is suggested. Common themes between women's and family health and congruence between women's health meanings and actions provide guidance to nurses in family health promotion practice.
A Content Analysis of the Content Analysis Literature in Organization Studies: Research Themes, Data Sources, and Methodological Refinements
Authors: Duriau Vincent J. , Reger Rhonda K. , Pfarrer Michael D.
Published: January 2007

We use content analysis to examine the content analysis literature in organization studies. Given the benefits of content analysis, it is no surprise that its use in organization studies has been growing in the course of the past 25 years (Erdener & Dunn, 1990; Jauch, Osborn, & Martin 1980). First, we review the principles and the advantages associated with the method. Then, we assess how the methodology has been applied in the literature in terms of research themes, data sources, and methodological refinements. Although content analysis has been applied to research topics across the subdomains of management research, research in strategy and managerial cognition have yielded particularly interesting results. We conclude with suggestions for enhancing the utility of content analytic methods in organization studies.
An Evidence-Based Perspective on HRD
Authors: Hamlin Robert G.
Published: January 2007

The problem and the solution. Historically, human resource development (HRD) has been a “fourth-order” consideration in strategic discussion within most organizations and is likely to continue to be so unless HRD professionals adopt new approaches to practice that have first-or second-order impact in helping to create high-performance organizations and sustainable success.The purpose of this article is to provoke thought and reflection on the recent emergence of “evidencebased” approaches to HRD practice by discussing their relevance to organizational leaders, managers, HRD practitioners, and other HR professionals concerned with bringing about effective and beneficial organizational change and development. How such approaches might become commonplace throughout the HRD business is also discussed and illustrated.
A Media Perspective on HRD
Authors: McGuire David , Cross Christine , Murphy Claire
Published: January 2007

The problem and the solution. Media perceptions of human resource development (HRD) matter. Corporate identity works in the context of corporate mission, corporate visual image, and corporate reputation.These are applied to the HRD field here and illustrated with a content analysis of instances of HRD in six major newspapers in the United Kingdom and the United States.The article concludes that branding and cultivating the right media perception of HRD is essential to attracting the right personnel, enhancing the field's reputation, maintaining relevance, and cultivating growth.
Ectopic expression of PAX5 promotes maintenance of biphenotypic myeloid progenitors coexpressing myeloid and B-cell lineage-associated genes
Authors: Anderson Kristina , Rusterholz Corinne , Månsson Robert , Jensen Christina T. , Bacos Karl , Zandi Sasan , Sasaki Yutaka , Nerlov Claus , Sigvardsson Mikael , Jacobsen Sten Eirik W.
Published: January 2007

The transcription factor PAX5 is a critical regulator of B-cell commitment and development. Although normally not expressed in myeloid progenitors, PAX5 has recently been shown to be frequently expressed in myeloid malignancies and to suppress expression of myeloid differentiation genes, compatible with an effect on the differentiation or maintenance of myeloid progenitors. However, previous studies in which PAX5 was ectopically expressed in normal myeloid progenitors in vivo and in vitro provided conflicting results as to the effect of PAX5 on myeloid development. Herein, we demonstrate that on ectopic expression of PAX5 in bone marrow multipotent stem/progenitor cells, cells with a biphenotypic B220+GR-1/MAC-1+ phenotype are produced. These remain cytokine-dependent, but unlike control-transduced cells they sustain long-term generation of myeloid progenitors in vitro and remain capable of myeloid differentiation. Notably, PAX5+B220+GR-1/MAC-1+ myeloid progenitors coexpress, at the single-cell level, myeloid genes and otherwise B-cell–specific PAX5 target genes. These findings establish that ectopic expression of PAX5 introduces extensive self-renewal properties in otherwise short-lived myeloid progenitors. Along with the established ectopic expression of PAX5 in acute myeloid leukemia, this motivates a careful investigation of the potential involvement of ectopic PAX5 expression in myeloid and biphenotypic leukemias.
Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage
Authors: Cain Jennifer A. , Xiang Zhifu , O'Neal Julie , Kreisel Friederike , Colson AnnaLynn , Luo Hui , Hennighausen Lothar , Tomasson Michael H.
Published: January 2007

Expression of the constitutively activated TEL/PDGFβR fusion protein is associated with the t(5;12)(q33;p13) chromosomal translocation found in a subset of patients with chronic myelomonocytic leukemia. TEL/PDGFβR activates multiple signal transduction pathways in cell-culture systems, and expression of the TEL-PDGFRB fusion gene induces myeloproliferative disease (MPD) in mice. We used gene-targeted mice to characterize the contribution of signal transducer and activator of transcription (Stat) and Src family genes to TEL-PDGFRB–mediated transformation in methylcellulose colony and murine bone marrow transduction/transplantation assays. Fetal liver hematopoietic stem and progenitor cells harboring targeted deletion of both Stat5a and Stat5b (Stat5abnull/null) genes were refractory to transformation by TEL-PDGFRB in methylcellulose colony assays. Notably, these cell populations were maintained in Stat5abnull/null fetal livers and succumbed to transformation by c-Myc. Surprisingly, targeted disruption of either Stat5a or Stat5b alone also impaired TEL-PDGFRB–mediated transformation. Survival of TPiGFP→Stat5a−/− and TPiGFP→Stat5a+/− mice was significantly prolonged, demonstrating significant sensitivity of TEL-PDGFRB–induced MPD to the dosage of Stat5a. TEL-PDGFRB–mediated MPD was incompletely penetrant in TPiGFP→Stat5b−/− mice. In contrast, Src family kinases Lyn, Hck, and Fgr and the Stat family member Stat1 were dispensable for TEL-PDGFRB disease. Together, these data demonstrate that Stat5a and Stat5b are dose-limiting mediators of TEL-PDGFRB–induced myeloproliferation.
Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity
Authors: Quere Ronan , Baudet Aurelie , Cassinat Bruno , Bertrand Gerald , Marti Jacques , Manchon Laurent , Piquemal David , Chomienne Christine , Commes Therese
Published: January 2007

Disease relapse sometimes occurs after acute promyelocytic leukemia (APL) therapy with all-trans retinoic acid (ATRA). Among the diagnostic parameters predicting relapse, heterogeneity in the in vitro differentiation rate of blasts is an independent factor. To identify biologic networks involved in resistance, we conducted pharmacogenomic studies in APL blasts displaying distinct ATRA sensitivities. Although the expression profiles of genes invested in differentiation were similarly modulated in low- and high-sensitive blasts, low-sensitive cells showed higher levels of transcription of ATRA-target genes, transcriptional regulators, chromatin remodelers, and transcription factors. In opposition, only high-sensitive blasts expressed the CYP26A1 gene, encoding the p450 cytochrome which is known to be involved in retinoic acid catabolism. In NB4 cells, ATRA treatment activates a novel signaling pathway, whereby interleukin-8 stimulates the expression of the homeobox transcription factor HOXA10v2, an effective enhancer of CYP26A1 transcription. These data were corroborated in primary APL cells, as maturation levels correlated with CYP26A1 expression. Treatment with a retinoic acid metabolism blocking agent (RAMBA) results in high-nucleoplasmic concentrations of retinoid and growth of NB4-resistant subclones. Hence, for APL blasts associated with poor prognosis, the low CYP26A1 expression may explain high risk of resistance installation, by increased retinoid pressure. Pharmacogenomic profiles of genes involved in retinoid acid metabolism may help to optimize anticancer therapies, including retinoids.
Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study
Authors: Gouw Samantha C. , van der Bom Johanna G. , Auerswald Günter , Ettinghausen Carmen Escuriola , Tedgård Ulf , van den Berg H. Marijke
Published: January 2007

It has been suggested that plasma-derived factor VIII products induce fewer inhibitors than recombinant factor VIII products. We investigated the relationship of factor VIII product type and switching between factor VIII products with the risk to develop inhibitors. This multicenter retrospective cohort study included 316 patients with severe hemophilia A born between 1990 and 2000. The outcome was clinically relevant inhibitor development, defined as the occurrence of at least 2 positive inhibitor titers with decreased recovery. The risk of inhibitor development was not clearly lower in plasma-derived compared with recombinant factor VIII products (relative risk [RR], 0.8; 95% confidence interval [CI], 0.5-1.3). Among high-titer inhibitors, the possible reduction in risk was even less pronounced (RR, 0.9; CI, 0.5-1.5). Plasma-derived products with considerable quantities of von Willebrand factor (VWF) carried the same risk for inhibitor development as recombinant factor VIII products (RR, 1.0; CI, 0.6-1.6). Switching between factor VIII products did not increase the risk for inhibitors (RR, 1.1; CI, 0.6-1.8). In conclusion, our findings support neither the notion that plasma-derived factor VIII products with considerable concentrations of VWF confer a lower risk to develop inhibitory antibodies than recombinant factor VIII products, nor that switching between factor VIII product brands increases inhibitor risks in previously untreated patients with severe hemophilia A.
Autoantibodies against the chromosomal passenger protein INCENP found in a patient with Graham Little-Piccardi-Lassueur syndrome
Authors: Rodríguez-Bayona Beatriz , Ruchaud Sandrine , Rodríguez Carmen , Linares Mario , Astola Antonio , Ortiz Manuela , Earnshaw William C , Valdivia Manuel M
Published: January 2007

Background

Graham Little – Piccardi – Lassueur (GLPL) syndrome is a rare dermatosis characterized by scarring alopecia, loss of pubic and axillary hair, and progressive development of variously located follicular papules. We report a first case ever of an autoimmune response in a patient suffering from GLPL syndrome.

Methods

Immunofluorescence and immunoblot analysis were used in a variety of cell cultures including human, monkey, hamster, mouse and bovine cells to analyze the presence of autoantibodies in a GLPL patient.

Results

The autoimmune serum showed a pattern of centromere and spindle microtubule staining resembling that of the chromosomal passenger protein complex. By using a complex of proteins expressed in baculovirus, immunoblot analysis demonstrated that the INCENP protein is a major autoantigen in this patient with GLPL syndrome.

Conclusion

An autoimmune response in GLPL syndrome is reported against the INCENP centromere protein. The occasional development of autoimmunity in GLPL patients could serve as a test in continuing efforts to detect this disease and for a more directed therapy based on the autoantigen response.
pkaPS: prediction of protein kinase A phosphorylation sites with the simplified kinase-substrate binding model
Authors: Neuberger Georg , Schneider Georg , Eisenhaber Frank
Published: January 2007

Background

Protein kinase A (cAMP-dependent kinase, PKA) is a serine/threonine kinase, for which ca. 150 substrate proteins are known. Based on a refinement of the recognition motif using the available experimental data, we wished to apply the simplified substrate protein binding model for accurate prediction of PKA phosphorylation sites, an approach that was previously successful for the prediction of lipid posttranslational modifications and of the PTS1 peroxisomal translocation signal.

Results

Approximately 20 sequence positions flanking the phosphorylated residue on both sides have been found to be restricted in their sequence variability (region -18...+23 with the site at position 0). The conserved physical pattern can be rationalized in terms of a qualitative binding model with the catalytic cleft of the protein kinase A. Positions -6...+4 surrounding the phosphorylation site are influenced by direct interaction with the kinase in a varying degree. This sequence stretch is embedded in an intrinsically disordered region composed preferentially of hydrophilic residues with flexible backbone and small side chain. This knowledge has been incorporated into a simplified analytical model of productive binding of substrate proteins with PKA.

Conclusion

The scoring function of the pkaPS predictor can confidently discriminate PKA phosphorylation sites from serines/threonines with non-permissive sequence environments (sensitivity of ~96% at a specificity of ~94%). The tool "pkaPS" has been applied on the whole human proteome. Among new predicted PKA targets, there are entirely uncharacterized protein groups as well as apparently well-known families such as those of the ribosomal proteins L21e, L22 and L6.

Availability

The supplementary data as well as the prediction tool as WWW server are available at http://mendel.imp.univie.ac.at/sat/pkaPS.

Reviewers

Erik van Nimwegen (Biozentrum, University of Basel, Switzerland), Sandor Pongor (International Centre for Genetic Engineering and Biotechnology, Trieste, Italy), Igor Zhulin (University of Tennessee, Oak Ridge National Laboratory, USA).
The Rat Thyroid Hormone Receptor (TR) Δβ3 Displays Cell-, TR Isoform-, and Thyroid Hormone Response Element-Specific Actions
Authors: Harvey Clare B. , Bassett J. H. Duncan , Maruvada Padma , Yen Paul M. , Williams Graham R.
Published: January 2007

The THRB gene encodes the well-described thyroid hormone (T3) receptor (TR) isoforms TRβ1 and TRβ2 and two additional variants, TRβ3 and TRΔβ3, of unknown physiological significance. TRβ1, TRβ2, and TRβ3 are bona fide T3 receptors that bind DNA and T3 and regulate expression of T3-responsive target genes. TRΔβ3 retains T3 binding activity but lacks a DNA binding domain and does not activate target gene transcription. TRΔβ3 can be translated from a specific TRΔβ3 mRNA or is coexpressed with TRβ3 from a single transcript that contains an internal TRΔβ3 translation start site. In these studies, we provide evidence that the TRβ3/Δβ3 locus is present in rat but not in other vertebrates, including humans. We compared the activity of TRβ3 with other TR isoforms and investigated mechanisms of action of TRΔβ3 at specific thyroid hormone response elements (TREs) in two cell types. TRβ3 was the most potent isoform, but TR potency was TRE dependent. TRΔβ3 acted as a cell-specific and TRE-dependent modulator of TRβ3 when coexpressed at low concentrations. At higher concentrations, TRΔβ3 was a TRE-selective and cell-specific antagonist of TRα1, -β1, and -β3. Both TRβ3 and TRΔβ3 were expressed in the nucleus in the absence and presence of hormone, and their actions were determined by cell type and TRE structure, whereas TRΔβ3 actions were also dependent on the TR isoform with which it interacted. Analysis of these complex responses implicates a range of nuclear corepressors and coactivators as cell-, TR isoform-, and TRE-specific modulators of T3 action.
Development of Conductive Organic Molecular Assemblies: Organic Metals, Superconductors, and Exotic Functional Materials
Authors: Saito Gunzi , Yoshida Yukihiro
Published: January 2007

We introduce the development of conductive organic molecular assemblies including organic metals, superconductors, single component conductors, conductive films, and conductive liquids, particularly focusing on our own research achievements of molecular design within the framework of both real and energy spaces.
A New Europium(III) PVC Membrane Potentiometric Sensor Based on 4-(2-Hydroxybenzylideneamino)-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one
Authors: Zamani Hassan Ali , Rajabzadeh Ghadier , Ganjali Mohammad Reza
Published: January 2007

A new europium ion-selective electrode based on 4-(2-hydroxybenzylideneamino)-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one (HMTDT) as membrane carrier was prepared. The electrode has a wide concentration range between 1.0 × 10−1 and 1.0 × 10−6 mol dm−3 with a near-Nernstian slope of 19.7 ± 0.4 mV per decade and a detection limit of 7.8 × 10−7 mol dm−3. The potentiometric response is independent of the pH of the solution in the pH range 3.5–7.8. It has a relatively fast response time and can be used for at least 2 months without any considerable divergence in potentials. The proposed sensor had very good selectivities for a wide variety of metal ions. The practical utility of the electrodes has been demonstrated by their use as indicator electrodes in the potentiometric titration of Eu3+ ions with EDTA and for the determination of Eu3+ in different solutions.
Remarkable Stabilization of a Ligand-Based Mixed-Valence State in the Metal-Based Mixed Valent Ru2II,IIIMII(μ3-O) (M = Co, Ni) Trinuclear Cluster Complexes
Authors: Tanaka Maiko , Kariya Nobuko , Abe Masaaki , Sasaki Yoichi
Published: January 2007

Two consecutive one-electron reductions of the mixed-metal trinuclear complexes [RuIII2MII(μ3-O)(μ-CH3COO)6(S)(bzpy)2] {(M = Co, S = H2O) and (M = Ni, S = N,N′-dimethylformamide); bzpy = 4-benzoylpyridine} in acetonitrile give stable “double” mixed-valence states where both Ru2II,III and (bzpy−)(bzpy) states coexist. Splitting of the ligand-based redox waves, (bzpy)2/(bzpy−)(bzpy)/(bzpy−)2, is 0.35 and 0.34 V for the Co and Ni complexes, respectively.
Short-term hypothyroidism after Levothyroxine-withdrawal in patients with differentiated thyroid cancer: clinical and quality of life consequences
Authors: Duntas Leonidas H , Biondi Bernadette
Published: January 2007

Acute hypothyroidism induced by thyroid hormone withdrawal in patients with differentiated thyroid cancer during monitoring for remnant or metastatic disease, seriously affects multiple organs and systems, and especially in severe cases can impair quality of life. Indeed, it may induce untoward cardiovascular effects and can be hazardous in patients with underlying cardiovascular disease, particularly in the elderly. Moreover, acute hypothyroidism deranges the lipid profile and exacerbates neuropsychiatric illness. The introduction of recombinant human TSH (rhTSH) as a diagnostic and therapeutic tool in the care of patients with thyroid cancer has widened the scope of disease management. The use of rhTSH prevents derangement of various systems at approximately equivalent societal costs to that of withdrawal and promotes compliance while preserving the patient’s normal daily functioning and productivity. Its reliability allied with its safety render this compound a valid alternative in the monitoring of patients with differentiated thyroid carcinoma as well as providing an alternative therapeutic procedure whenever LT4-withdrawal may be hazardous or in cases of patient non-compliance.
Genetic and environmental determinants of circulating resistin level in a community-based sample
Authors: Pantsulaia I , Livshits G , Trofimov S , Kobyliansky E
Published: January 2007

Objective: Resistin is a hormone secreted by adipose tissue, monocytes, bone marrow, and other tissues. It was also proclaimed as an important link between obesity and diabetes. The main objective of this study was to elucidate the contribution of a number of endogenous factors, such as sex, age, obesity characteristics, and genetic effects to the production of resistin in apparently healthy individuals. We also tested the possible relationships between circulating levels of resistin and other adipokines (leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)).

Measurements: The plasma levels of studied adipokines were determined by enzyme-linked immunoassay in pedigree-based sample (n = 616), and subjected to model-based quantitative genetic analysis.

Results: Resistin levels were significantly higher in women than in men (3.60 ± 2.53 vs 3.15 ± 2.48 ng/ml, P < 0.001), and varied independently of age in either sex. Statistical-genetic analysis revealed significant familial correlations (P < 0.01) for resistin. Adjusted for covariates, 66.38 ± 10.28% of the resistin variation was attributable to putative genetic factors. A relatively small portion of the resistin variation (11.54 ± 5.77%) was attributable to sharing a common household environment. The remaining variation, 22.12 ± 17.69% was due to random environmental (i.e., unmeasured non-additive genetic) effects. The results of our analysis showed modest significant correlation of resistin with TNF-α and IL-6, and only in some groups; thus, while resistin was correlated with TNF-α in men, the correlation with IL-6 was significant only in the post-menopausal women group.

Conclusions: Our observations indicate that resistin is strongly influenced by genetic factors. The high heritability estimates for resistin concentrations clearly suggest the continuing need for further molecular genetic investigations.
Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome
Authors: Raivio Taneli , Wikström Anne M , Dunkel Leo
Published: January 2007

Background: Boys with prepubertal onset of hypogonadotropic hypogonadism (HH) are at a risk of poor testis growth and impaired spermatogenesis. One potential cause for this is deficient proliferation of immature Sertoli cells before and during puberty due to the absence of FSH.

Objective: To evaluate the effects of recombinant human FSH (r-hFSH) and human chorionicgonadotropin (hCG) on testicular function and pubertal development in boys with prepubertal onset of HH.

Design: Retrospective clinical study.

Setting: Two university central hospitals, pediatric referral endocrinology outpatient clinics.

Patients: Fourteen boys (aged, 9.9–17.7 years) with prepubertal (testicular volume (TV) <3 ml) onset of HH (idiopathic HH, n=2; Kallman syndrome, n=2; idiopathic panhypopituitarism, n=4; organic panhypopituitarism, n=6).

Intervention: Treatment with r-hFSH alone (2 mo–2.8 years) prior to induction of puberty with the combination of FSH and hCG.

Main outcome measures: Progression of puberty, change in serum inhibin B, spermatogenesis.

Results: r-hFSH alone increased testicular volume twofold, from 0.9±0.6 ml (mean±s.d.) to 1.8 ± 1.1 ml (P<0.005), and serum inhibin B threefold, from 27±14 to 80±57 pg/ml (P<0.01). Three boys with an apparent absence of postnatal hypothalamic–pituitary–testicular axis activation displayed attenuated inhibin B responses to long-term (≥1 year) r-hFSH (P<0.01). Further significant increase in both TVand inhibin B occurred with induction of puberty with FSH and hCG (P<0.001). Seven boys provided semen samples: one had azoospermia, and others displayed a maximal sperm count range from 2.9 to 92 million/ml (median 8.5 million/ml).

Conclusions: (i) r-hFSH induces prepubertal testis growth and increases circulating inhibin B levels, findings suggesting proliferation of immature Sertoli cells. (ii) Puberty was successfully induced with hCG and r-hFSH following r-hFSH priming. (iii) Inhibin B appears useful for monitoring spermatogenetic activity in boys treated with hCG. (iv) Despite the extremely small initial testis volume, six out of seven patients (86%) primed with r-hFSH displayed sperm in the ejaculate suggesting beneficial effect of r-hFSH priming on testicular function later in life.
Nocturnal calcium, phosphorus and parathyroid hormone in the diagnosis of concealed and subclinical hypoparathyroidism
Authors: Even Leah , Bader Tarif , Hochberg Ze’ev
Published: January 2007

Context: Circadian rhythms of plasma parathyroid hormone (PTH) show peak values at night, whereas serum calcium levels peak in the evening and display a nadir at night.

Hypotheses: Subclinical hypoparathyroidism (HPT) can be detected by utilizing the knowledge of diurnal variations. Thalassemia major (TM) may provide a model system of subclinical HPT.

Design: Nocturnal plasma PTH and serum calcium values were determined in 13 TM patients with normal morning serum calcium levels as compared with the corresponding values in eight healthy control subjects.

Results: Six patients with TM presented a nadir serum calcium level of 8.3 mg/dl or lower (hypoCa TM) at 0200 h, whereas the remaining seven showed nadir levels of 8.4 mg/dl or higher (normoCa TM). Patients with hypoCa TM displayed a drop between peak and nadir of 1.2 ± 0.5 mg/dl as compared with a considerably smaller fall of 0.3 ± 0.7 mg/dl in control subjects (P < 0.05). NormoCa TM patients experienced comparable nocturnal variation to that of control subjects. Patients from both the hypoCa and normoCa TM groups presented significantly lower nocturnal PTH levels than those of control subjects and lost the nocturnal PTH variation characteristic of healthy subjects. A plot of all serum calcium against plasma PTH levels provides a clear distinction of the three groups.

Conclusions: All 13 daytime normocalcemic TM patients presented a certain degree of HPT. The hypoCa TM group displayed a concealed HPT detected in all, except the morning sampling, whereas normoCa TM patients experienced sub clinical HPT observed in the absence of nocturnal HPT variation. Nocturnal measurements of serum minerals thus enhance the sensitivity of HPT diagnosis.
Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as determinants of bone mineral density
Authors: Zarrabeitia Maria T , Hernandez Jose L , Valero Carmen , Zarrabeitia Ana , Amado Jose A , Gonzalez-Macias Jesus , Riancho Jose A
Published: January 2007

Objectives: Bone mineral density (BMD) is a complex trait resulting from the interplay of genetic and acquired factors. The objective of this study was to explore the influence of several anthropometric, lifestyle, genetic, and hormonal factors on BMD and analyze the possible differences in men and women.

Methods: We studied 572 individuals over 50 years of age (381 postmenopausal women and 191 men). Lumbar spine and femoral neck BMD were measured by dual energy x-ray absorptiometry. The free estrogen index (FEI) was calculated as the ratio of serum estradiol to sex hormone binding globulin in 241 individuals. Three polymorphisms in the genes coding for 17-hydroxylase/liase, sulfotransferase, and 5α-reductase were studied in DNA isolated from blood cells.

Results: Body mass index was strongly correlated to spine and femoral BMD both in women and in men (r= 0.32–0.49;P< 0.001). FEI was also independently correlated with spine BMD in both sexes (r= 0.23 and 0.34,P< 0.01), and with femoral neck in women (r= 0.30). Women with G alleles of the sulfotransferase gene tended to have higher spine BMD than those with C alleles (P= 0.025). No other genotype-related differences in BMD were found.

Conclusions: In conclusion, the results of this study point toward body weight and estradiol levels as major factors determining BMD both in women and in men. A common polymorphism of the sulfotransferase gene also appears to be associated to spine BMD in women.
Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors
Authors: Vezzosi D , Cartier D , Régnier C , Otal P , Bennet A , Parmentier F , Plantavid M , Lacroix A , Lefebvre H , Caron P
Published: January 2007

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is rare and generally presents as a sporadic disease. We describe a familial case of AIMAH with in vivo and in vitro demonstration of aberrant 5-HT4 and vasopressin adrenal receptors. Two sisters presented with clinical and biological features of mild Cushing’s syndrome with bilateral macronodular adrenal enlargement on computerized tomography (CT)-scan evaluation. In vivo pharmacological tests showed a significant increase in plasma cortisol after terlipressin and metoclopramide administration. Unilateral adrenalectomy was performed in one of these patients. Reverse transcriptase-PCR analysis of the hyperplastic tissue revealed expression of 5-HT4 receptor isoforms (a), (b), (c), (i), and (n), and of vasopressin receptors, V1 and V2. Their father and brother were overweight, had easy bruisability and presented with biological features of subclinical Cushing’s syndrome. CT scan showed moderate adrenal enlargement. In vivo pharmacological screening tests for the detection of adrenal aberrant receptors in the brother were negative. Finally, three out of the two sisters’ children were evaluated. They had neither clinical nor biological features of Cushing’s syndrome. Their adrenal glands were normal on CT-scan evaluation. In vivo evaluation for the detection of aberrant adrenocortical receptors performed in one of these subjects was negative. In conclusion, this study shows that (i) familial AIMAH could be an autosomal dominantly inherited disorder; (ii) aberrant 5-HT4 serotonin and vasopressin receptors can be expressed in familial AIMAH; and (iii) phenotypic expression of familial AIMAH could be varied in a same family and more pronounced in female than in male patients.
Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Esters with Chiral Yttrium–Biaryldiol Complexes
Authors: Kakei Hiroyuki , Tsuji Riichiro , Ohshima Takashi , Morimoto Hiroyuki , Matsunaga Shigeki , Shibasaki Masakatsu
Published: January 2007

The full details of the asymmetric epoxidation of α,β‐unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium–biphenyldiol catalyst, generated from Y(OiPr)3–biphenyldiol ligand–triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various α,β‐unsaturated esters. With this catalyst, β‐aryl α,β‐unsaturated esters gave high enantioselectivities and good yields (≤99 % ee). The reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5–2 mol % (the turnover number was up to 116), while high enantiomeric excesses were maintained. For β‐alkyl α,β‐unsaturated esters, an yttrium–binol catalyst, generated from Y(OiPr)3–binol ligand–triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (≤97 % ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (−)‐ragaglitazar, a potential antidiabetes agent.
Supramolecular Tilt Chirality Derived from Symmetrical Benzene Molecules: Handedness of the 21 Helical Assembly
Authors: Tanaka Akira , Hisaki Ichiro , Tohnai Norimitsu , Miyata Mikiji
Published: January 2007

Achiral molecules can form aggregates with chirality. This depends on the relative position of the molecules, in other words, the tilt of the molecules (so‐called supramolecular tilt chirality). In this paper, we describe supramolecular chirality appearing in a 21 column composed of symmetrical benzene molecules, which is formed in the host cavity of inclusion crystals of cholic acid. Moreover, we determined the handedness, that is, right or left, of the 21 helical column of benzene on the basis of the molecular tilt. Determination of the 21 helical handedness was performed on assemblies of other benzene derivatives in cholic acid crystals and benzene assemblies in other host frameworks selected from the Cambridge Structural Database. Finally, we demonstrated complementarity of the handedness between the 21 symmetrical host framework of cholic acid and the benzene column.
Ruthenium‐Catalyzed Sequential Reactions: Deracemization of Secondary Benzylic Alcohols
Authors: Shimada Yusuke , Miyake Yoshihiro , Matsuzawa Hiroshi , Nishibayashi Yoshiaki
Published: January 2007

The deracemization of secondary benzylic alcohols proceeds successfully by a two‐step process with the appropriate combination of two different ruthenium complexes for catalysis in the first oxidation and second reduction steps. The sequential catalytic system provides a novel approach to obtaining optically active alcohols, including diols, in high yields with excellent enantioselectivity (up to 95 % ee), in contrast to the conventional kinetic resolution of racemic alcohols.
Construction of Robust Ruthenium(salen)(CO) Complexes and Asymmetric Aziridination with Nitrene Precursors in the Form of Azide Compounds That Bear Easily Removable N‐Sulfonyl Groups
Authors: Kawabata Hirotoshi , Omura Kazufumi , Uchida Tatsuya , Katsuki Tsutomu
Published: January 2007

We synthesized new Ru(salen)(CO) complexes of high durability and achieved aziridination with good to excellent enantioselectivity by using azide compounds that contain an easily removable N‐sulfonyl group, such as the 2‐(trimethylsilyl)ethanesulfonyl group, as a nitrene precursor. Aziridination of less‐reactive α,β‐unsaturated esters (and amides) proceeded with excellent enantioselectivities, from which it is inferred that an electrophilic species is the active species of this reaction. The present asymmetric aziridination provides a useful tool for introducing optically active nonprotected amine groups.
A Novel Environmentally Benign Method for the Selective Oxidation of Alcohols to Aldehydes and Ketones
Authors: Shi Feng , Tse Man Kin , Beller Matthias
Published: January 2007

In the presence of [Ru(terpyridine)(2,6‐pyridinedicarboxylate)], aliphatic and benzylic alcohols are oxidized to the corresponding aldehydes or ketones with high selectivity by using hydrogen peroxide as the oxidant. There is no need for the addition of co‐catalysts or organic solvents. By applying an optimized reaction protocol, high catalyst productivity (turnover number>10 000) and activity (turnover frequency up to 14 800 h−1) has been achieved.
Analysis of the products from enzymatic scouring of cotton
Authors: Sae‐be Porntip , Sangwatanaroj Usa , Punnapayak Hunsa
Published: January 2007

This article discusses the analysis of the hydrolysis products from one‐step scouring of cotton using pectinase and two‐step scouring of cotton using lipase then cellulase, protease then cellulase, or lipase/protease then cellulase, to improve water absorbency of cotton. UV spectrophotometric analysis indicated that the pectinase scouring process produced approximately 18‐fold higher amounts of reducing sugars and galacturonic acid than any of the two‐step scouring processes. The production rate of reducing sugars and galacturonic acid from most of the scouring processes showed a decrease with an increase in time. HPLC analysis revealed that the lipase/protease/cellulase scouring processes produced approximately 5‐fold higher amounts of 17 amino acids than the pectinase scouring process. GC analysis for 18 fatty acids (C8‐C24) revealed that three major fatty acids, palmitic acid, stearic acid, and behenic acid, were found on both the scoured and the unscoured fabrics. Scoured fabrics were tested for content of proteins, extractable components, waxes, and anionic components including pectins, and some differences among the fabric scoured with different enzyme combinations were found.
The Complete Structure and Pro‐inflammatory Activity of the Lipooligosaccharide of the Highly Epidemic and Virulent Gram‐Negative Bacterium Burkholderia cenocepacia ET‐12 (Strain J2315)
Authors: Silipo Alba , Molinaro Antonio , Ieranò Teresa , De Soyza Anthony , Sturiale Luisa , Garozzo Domenico , Aldridge Christine , Corris Paul A. , Khan C. M. Anjam , Lanzetta Rosa , Parrilli Michelangelo
Published: January 2007

Members of genus Burkholderia include opportunistic Gram‐negative bacteria that are responsible for serious infections in immunocompromised and cystic fibrosis (CF) patients. The Burkholderia cepacia complex is a group of microorganisms composed of at least nine closely related genomovars. Among these, B. cenocepacia is widely recognized to cause epidemics associated with excessive mortality. Species that belong to this strain are problematic CF pathogens because of their high resistance to antibiotics, which makes respiratory infections difficult to treat and impossible to eradicate. Infection by these bacteria is associated with higher mortality in CF and poor outcomes following lung transplantation. One virulence factor contributing to this is the pro‐inflammatory lipopolysaccharide (LPS) molecules. Thus, the knowledge of the lipopolysaccharide structure is an essential prerequisite to the understanding of the molecular mechanisms involved in the inflammatory process. Such data are instrumental in aiding the design of antimicrobial compounds and for developing therapeutic strategies against the inflammatory cascade. In particular, defining the structure of the LPS from B. cenocepacia ET‐12 clone LMG 16656 (also known as J2315) is extremely important given the recent completion of the sequencing project at the Sanger Centre using this specific strain. In this paper we address this issue by defining the pro‐inflammatory activity of the pure lipopolysaccharide, and by describing its full primary structure. The activity of the lipopolysaccharide was tested as a stimulant in human myelomonocytic U937 cells. The structural analysis was carried out by compositional analysis, mass spectrometry and 2D NMR spectroscopy on the intact lipooligosacchride (LOS) and its fragments, which were obtained by selective chemical degradations.
Expression of Concern: Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck squamous cell carcinoma tumors and leukoplakia samples by promoter hypermethylation and its relation with microsatellite instability phenotype
Authors: Sengupta Shiladitya , Chakrabarti Susmita , Roy Anup , Panda Chinmay K. , Roychoudhury Susanta
Published: January 2007

BACKGROUND.

A subset of head and neck squamous cell carcinoma (HNSCC) exhibits a microsatellite instability (MIN) phenotype. The authors correlated alterations in the mismatch‐repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in primary head and neck squamous cell carcinoma (HNSCC) tumors and in samples of leukoplakia with the MIN phenotype.

METHODS.

One hundred twenty‐three paired HNSCC normal and tumor tissues and 27 leukoplakia samples were examined for hypermethylation of hMLH1 and hMSH2 promoters. The hypermethylation status of the tissues was confirmed by expression studies. Sixty‐three of 123 randomly selected tumors and all 27 leukplakia samples were genotyped with 8 microsatellite markers to determine MIN.

RESULTS.

Fifty percent of HNSCC tumors and 63% of leukoplakia samples harbored hypermethylation at either or both hMLH1 and hMSH2 promoters. Normal tissues adjacent to methylation‐positive tumors also demonstrated hypermethylation of both promoters at a high frequency (25%). A positive correlation between tobacco habit and promoter hypermethylation was observed (P = .001). A correlation was observed between MIN and the frequency of promoter hypermethylation in the leukoplakia samples, but no such trend was observed in the HNSCC tumors. It is noteworthy that patients who had a high frequency of MIN‐positive tumors exhibited hypermethylation in both the affected tissues and the adjacent normal tissues (P = .007). Patients with a tobacco habit who had promoter hypermethylation at both the affected tissues and the adjacent normal tissues had tumors that mostly were MIN positive (P = .047).

CONCLUSIONS.

The current results suggested that tobacco‐addicted individuals are more susceptible to promoter hypermethylation of hMLH1 and hMSH2 and that, if such hypermethylation occurs in the normal squamous epithelium of the head and neck region, then those tissues are likely to develop into tumors that involve the MIN pathway. Cancer 2007;109:703–12. © 2007 American Cancer Society.
Adjuvant and neoadjuvant chemotherapy for Ewing sarcoma family tumors in patients aged between 40 and 60
Authors: Bacci Gaetano , Balladelli Alba , Forni Cristiana , Ferrari Stefano , Longhi Alessandra , Bacchini Patrizia , Alberghini Marco , Fabbri Nicola , Benassi MariaSerena , Briccoli Antonio , Picci Piero
Published: January 2007

BACKGROUND.

The clinical and pathologic features of 46 patients 40 to 60 years old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute between 1972 and 2000 were reviewed.

METHODS.

Ten patients with metastatic tumors at presentation went elsewhere for treatment; 35 of 36 remaining cases with localized disease were treated at the authors' institution according to different chemotherapy protocols activated in successive years. In patients with nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in 16, and surgery followed by radiotherapy in 10.

RESULTS.

At follow‐up times ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained continuously disease‐free, 19 experienced recurrence, and 1 died of chemotherapy‐related toxicity. The 5‐ and 10‐year event‐free survivals were 42.9% and 35.2%, respectively, and the 5‐ and 10‐year overall survivals were 46.1% and 42.8%, respectively. Comparing this group of patients with 586 cases of younger patients seen in the same period at Rizzoli, the only difference between the 2 groups was a significantly higher rate of tumors located in the soft tissues with a larger volume in the older group. The results achieved were comparable in the 2 groups, although the older group had a lower chemotherapy dose‐intensity and a higher rate of WHO grade 4 hematologic toxicity.

CONCLUSIONS.

For patients with localized disease treated with adjuvant and neoadjuvant chemotherapy the results were essentially comparable in the 2 groups. It is concluded that patients 40 years or older with ESFT should be treated in the same way as younger patients and included in treatment trials for these tumors. Cancer 2007. © 2007 American Cancer Society.
Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic leukemia
Authors: Aribi Ahmed , Borthakur Gautam , Ravandi Farhad , Shan Jianqin , Davisson Jan , Cortes Jorge , Kantarjian Hagop
Published: January 2007

BACKGROUND.

Hypomethylating agents have activity in myelodysplastic syndrome (MDS) and have received approval for the treatment of both MDS and chronic myelomonocytic leukemia (CMML). The specific efficacy in CMML has not been detailed in a large number of patients. The aim of the study was to evaluate the activity and safety of decitabine in CMML.

METHODS.

Nineteen adults with a diagnosis of CMML treated on decitabine studies were analyzed. Decitabine was given at 100 mg/m2 per course every 4 weeks. The median number of courses given was 9 (range, 1–18).

RESULTS.

Overall, 11 patients (58%) achieved complete response (CR) and 2 (11%) had hematologic improvement (HI), for an overall response rate of 69% according to the modified International Working Group (IWG) criteria. Median survival was 19 months. Severe (grade 3–4) extramedullary side effects were rare.

CONCLUSIONS.

Decitabine is active in CMML. Studies of combinations of decitabine with topoisomerase I inhibitors or other active anti‐CMML agents are indicated. Cancer 2007. © 2007 American Cancer Society.
Studies on the Growth Rates of Crystals
Authors: Dhanasekaran R. , Ramasamy P.
Published: January 2007

The crystal growth rates are calculated from the nucleation rate of two‐dimensional square shaped nucleus in four different models. In all these models, the growth is initiated by the birth of the critical nuclei. Two limiting values of the lateral spreading velocities perpendicular to the side of the growing island are considered in first two models and finite spreading velocities are treated in other two models.
Analysis of GaAs Growth Rate Anisotropy in Some CVD Systems
Authors: Lavrentieva L. G.
Published: January 2007

Growth rate anisotropy in the vicinity of singular faces is being analized for GaAs layers deposited in some chemical deposition systems. Classical crystal growth theory conceptions was being used. In accordance with them a linear connection between growth rate component in the direction of the normal to the singular face and the growth step density is shown to accur in the range of angle deviation 20, 10 and 6° from the faces (111)B, (001) and (111)A correspondingly. Step motion velocity has been calculated on the assumption that the atoms reaching the surface may be crystallized either by joining the step in echelon or by joining the interstep surface due to nucleation or normal growth mechanism. The discussion shows the model which takes into consideration the growth owing to nucleation and step echelon motion gives more selfconsistent results.