bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of hydatidiform mole and persistent trophoblastic disease: diagnostic accuracy of total human chorionic gonadotropin (hCG), free hCG α- and β-subunits, and their ratios
Authors: van Trommel Nienke E , Sweep Fred C G J , Schijf Charles P T , Massuger Leon F A G , Thomas Chris M G
Published: September 2005

Objective: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Predicting PTD after molar pregnancy might be beneficial since prophylactic chemotherapy reduces the incidence of PTD.

Design: A retrospective study based on blood specimens collected in the Dutch Registry for Hydatidiform Moles. A group of 165 patients with complete moles (of which 43 had PTD) and 39 patients with partial moles (of which 7 had PTD) were compared with 27 pregnant women with uneventful pregnancy.

Methods: Serum samples from patients with hydatidiform mole with or without PTD were assayed using specific (radio) immunoassays for free α-subunit (hCGα), free β-subunit (hCGβ) and ‘total’ hCG (hCG + hCGβ). In addition, we calculated the ratios hCGα/hCG + hCGβ, hCGβ/hCG + hCGβ, and hCGα/hCGβ. Specificity and sensitivity were calculated and paired in receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curves (AUCs).

Results: hCGβ, hCGβ/hCG + hCGβ and hCGα/hCGβ show AUCs ranging between 0.922 and 0.999 and, therefore, are excellent diagnostic tests to distinguish complete and partial moles from normal pregnancy. To distinguish partial from complete moles the analytes hCGβ, hCG + hCGβ and the ratio hCGα/hCGβ have AUCs between 0.7 and 0.8. Although hCGα, hCGβ and hCG + hCGβ concentrations are significantly elevated in patients who will develop PTD compared with patients with spontaneous regression after evacuation of their moles, in predicting PTD, these analytes and parameters have AUCs <0.7.

Conclusions: Distinction between hydatidiform mole and normal pregnancy is best shown by a single blood specimen with hCGβ, but hCGβ/hCG + hCGβ and hCGα/hCGβ are also excellent diagnostic parameters. To predict PTD, hCGα, hCGβ, hCG + hCGβ and hCGα/hCGβ are moderately accurate tests, although they are not accurate enough to justify prophylactic chemotherapy treatment for prevention of PTD.
Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy
Authors: Veldhuis Johannes D , Keenan Daniel M , Mielke Kristi , Miles John M , Bowers Cyril Y
Published: September 2005

Objective: Testosterone supplementation increases GH and IGF-I concentrations in healthy older men via unknown mechanisms. We examine the hypotheses that (i) testosterone amplifies stimulation of GH secretion by GH-releasing peptide (GHRP)-2 or GH-releasing hormone (GHRH) infused with l-arginine to limit somatostatin outflow (i.e. upregulates each agonistic pathway), (ii) testosterone augments the effect of both peptidyl secretagogues infused together (i.e. reduces opposition by hypothalamic somatostatin) and (iii) abdominal visceral fat (AVF) mass is a negative determinant of specific secretagogue-stimulated GH secretion.

Design: Randomized double-blind crossover design of placebo versus testosterone administration in healthy older men.

Methods: Deconvolution analysis was used to estimate basal GH secretion and the mass (integral) and waveform (time-shape) of GH secretory bursts.

Results: Statistical contrasts revealed that administration of testosterone compared with placebo in seven men aged 60–77 years increased fasting concentrations of GH (P < 0.01) and IGF-I (P = 0.003), and basal (P < 0.005) and pulsatile (P < 0.01) GH secretion. Testosterone did not alter the absolute value or rank order of secretagogue efficacy: l-arginine/GHRP-2 (23-fold effect over saline) = GHRH/GHRP-2 (20-fold) > l-arginine/GHRH (7.5-fold). Waveform reconstruction indicated that each stimulus pair accelerated initial GH secretion within a burst (P < 0.01). Regression analysis disclosed a significant inverse association between GH secretory-burst mass and computer tomography-estimated AVF following stimulation with l-arginine/GHRH after testosterone supplementation (R2 = 0.54, P = 0.015).

Conclusion: Supraphysiological testosterone concentrations augment GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone upregulation.
Molecular genetics of adrenocortical tumours, from familial to sporadic diseases
Authors: Libé Rossella , Bertherat Jérôme
Published: September 2005

Adrenal masses can be detected in up to 4% of the population, and are mostly of adrenocortical origin. Adrenocortical tumours (ACTs) may be responsible for excess steroid production and, in the case of adrenocortical cancers, for morbidity or mortality due to tumour growth. Our understanding of the pathogenesis of ACTs is more limited than that for other tumours. However, studies of the genetics of ACTs have led to major advances in this field in the last decade. The identification of germline molecular defects in the hereditary syndrome responsible for ACTs has facilitated progress. Indeed, similar molecular defects have since been identified as somatic alterations in sporadic tumours. The familial diseases concerned are Li–Fraumeni syndrome, which may be due to germline mutation of the tumour-suppressor geneTP53and Beckwith–Wiedemann syndrome, which is caused by dys-regulation of the imprintedIGF-IIlocus at 11p15. ACTs also occur in type 1 multiple endocrine neoplasia (MEN 1), which is characterized by a germline mutation of themeningene. Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) has been observed in Carney complex patients presenting inactivating germlinePRKAR1Amutations. Interestingly, allelic losses at 17p13 and 11p15 have been demonstrated in sporadic adrenocortical cancer and somaticPRKAR1Amutations have been found in secreting adrenocortical adenomas. More rarely, mutations in Gs protein (gsp) and the gene for ACTH receptor have been observed in ACTs. The genetics of another group of adrenal diseases that can lead to adrenal nodular hyperplasia – congenital adrenal hyperplasia (CAH) and glucocorticoid-remediable aldosteronism (GRA) – have also been studied extensively. This review summarizes recent advances in the genetics of ACTs, highlighting both improvements in our understanding of the pathophysiology and the diagnosis of these tumours.
GnRH-II receptor-like antigenicity in human placenta and in cancers of the human reproductive organs
Authors: Eicke Nicola , Günthert Andreas R , Viereck Volker , Siebold Doreen , Béhé Martin , Becker Tamara , Emons Günter , Gründker Carsten
Published: September 2005

We have recently demonstrated that the antiproliferative activity of GnRH-II on human endometrial and ovarian cancer cell lines is not mediated through the GnRH-I receptor. A functional receptor for human GnRH-II has not yet been identified. In this study, we have generated a polyclonal antiserum to the putative human GnRH-II receptor using a peptide (YSPTMLTEVPPC) corresponding to the third extracellular domain coupled to keyhole limpet haemocyanin via the Cys residue. A database search showed no identical peptide sequences in any other human gene. To avoid cross-reactions against two similar amino acid sequences the antiserum was pre-absorbed using these peptides. Immune histological sections of human placenta and human endometrial, ovarian and prostate cancers using rabbit anti-human GnRH-II receptor antiserum showed GnRH-II receptor-like staining. Western blot analysis of cell membrane preparations of human endometrial and ovarian cancer cell lines yielded a band at approximately 43 kDa whereas Western blot analysis of cell membrane preparations of ovaries obtained from the marmoset monkey (Callithrix jacchus) yielded a band at approximately 54 kDa. To identify the GnRH-II receptor-like antigen we used the photo-affinity labelling technique. Photochemical reaction of 125I-labelled (4-azidobenzoyl)-N-hydroxysuccinimide-[d-Lys6]-GnRH-II (10−9 M) with cell membrane preparations of human endometrial and ovarian cancer cells yielded a band at approximately 43 kDa. In competition experiments, the GnRH-I agonist Triptorelin (10−7 M) showed a weak decrease of 125I-labelled (4-azidobenzoyl)-N-hydroxysuccinimide-[d-Lys6]-GnRH-II binding to its binding site. The GnRH-I antagonist Cetrorelix (10−7 M) showed a clearly stronger decrease, whereas GnRH-II agonist [d-Lys6]-GnRH-II (10−7 M) was the most potent competitor. Western blot analysis of the same gel using rabbit anti-human GnRH-II receptor antiserum identified this band as GnRH-II receptor-like antigen.
Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women
Authors: Kanaley J A , Giannopoulou I , Collier S , Ploutz-Snyder R , Carhart R
Published: September 2005

Objective: This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise.

Methods: 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO2max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay.

Results: The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 ± 53 min μg l−1; exercise, 711 ± 57 min μg l−1; P < 0.01) than in the non-HRT women (rest, 157 ± 87 min μg l−1; exercise, 248 ± 94 min μg l−1). The incremental GH response was greater in the HRT users than in the non-HRT women (358 ± 130 versus 90.8 ± 94 min μg l−1, respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise.

Conclusion: HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.
Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism
Authors: Kawata Takehisa , Imanishi Yasuo , Kobayashi Keisuke , Kenko Takao , Wada Michihito , Ishimura Eiji , Miki Takami , Nagano Nobuo , Inaba Masaaki , Arnold Andrew , Nishizawa Yoshiki
Published: September 2005

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.
Assessment of gas‐fluidized beds mixing and hydrodynamics by zirconia sensors
Authors: Solimene Roberto , Marzocchella Antonio , Passarelli Gabriella , Salatino Piero
Published: September 2005

Gas‐mixing and bed hydrodynamics associated with the rise of isolated bubbles in gas‐fluidized beds of two granular solids are investigated by means of a novel technique. These diagnostics consist of an array of miniaturized zirconia‐based oxygen sensors located along the axis of a hot (1123 K) incipiently fluidized bed, in which isolated bubbles of a tracer gas (nitrogen) are injected. Time‐resolved oxygen concentrations and relative pressures are recorded at several levels along the bed. It is shown how the response of the sensors array can be related to the concurrent effects of bubble motion, bubble‐emulsion phase, mass transfer and interstitial gas flow in the emulsion phase, combined with each other to give rise to the propagation of two perturbations to the basal value of oxygen concentration. Analysis of time‐resolved oxygen concentration profiles enables the assessment of: (a) the bubble rise velocity; (b) the gas velocity associated with the interstitial flow; and (c) the interphase bubble‐emulsion phase, mass‐transfer rate and coefficient. Analysis of the response of sensors located in the splash zone of the fluidization column provides indirect inference of the hydrodynamic patterns associated with bubble bursting at the surface of the bed. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Long‐term remission of blastic natural killer‐cell lymphoma after autologous peripheral blood stem‐cell transplantation
Authors: Yamaguchi Masaki , Maekawa Mio , Nakamura Yoshihisa , Ueda Mikio
Published: September 2005

We report here a case of blastic natural killer (NK)‐cell lymphoma treated successfully with autologous peripheral blood stem‐cell transplantation (APBSCT). A 57‐year‐old man had skin tumors and was diagnosed as having blastic NK‐cell lymphoma by tumor biopsy. Skin, lymph nodes, left tonsil, and bone marrow were involved at presentation. Chemotherapy led to complete remission (CR). To sustain CR, the patient underwent high‐dose chemotherapy in combination with 12 Gy of total‐body irradiation (TBI) followed by autologous peripheral blood stem‐cell rescue. He showed rapid recovery of hematopoiesis and could tolerate regimen‐related toxicity after APBSCT. He has maintained long‐term remission for 20 months after APBSCT. From this case, we concluded that APBSCT with preconditioning by TBI‐containing regimens might be a cure‐attaining treatment for disseminated blastic NK‐cell lymphoma and should be considered as a choice of treatment in cases where no suitable donors for allogeneic transplantation are available. Am. J. Hematol. 80:124–127, 2005. © 2005 Wiley‐Liss, Inc.
Hypereosinophilic syndrome: An update
Authors: Wilkins H. Jeffrey , Crane Martin M. , Copeland Kelly , Williams William V.
Published: September 2005

Hypereosinophilic syndrome (HES) is a rare disorder that is characterized by persistent and marked eosinophilia combined with organ system dysfunction. HES has substantial clinical heterogeneity but can be fatal without treatment, especially in patients who present with a myelodysplastic variant of the disorder. Although the pathophysiology of HES is poorly defined, dysregulation of cytokines (interleukin 5 [IL‐5], IL‐3, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF]) responsible for the maturation of eosinophils is a primary feature. Of these cytokines, IL‐5 appears to have the greatest role in the regulation of eosinophil maturation. There is no Food and Drug Administration‐approved treatment for HES as yet; current strategies are designed to lower blood eosinophils and attempt to limit end‐organ damage. Historically, corticosteroids and cytotoxic agents have been the mainstays of therapy, with biological response modifiers such as interferon‐alpha also effective in some patients. However, despite improvements in survival, available agents have significant limitations in terms of efficacy, tolerability, and long‐term toxicity. More recently, new agents directed at specific targets in the pathogenesis of HES have been developed. These include imatinib mesylate, a tyrosine kinase inhibitor, and more recently, mepolizumab, an anti‐IL‐5 monoclonal antibody. In a small case series of patients, these agents have been shown to produce hematological and clinical responses in patients with HES, although they may be effective in different subsets of patients. These targeted therapies have the potential to improve clinical outcomes and to further the understanding the pathophysiology of this difficult‐to‐treat condition. Am. J. Hematol. 80:148–157, 2005. © 2005 Wiley‐Liss, Inc.
Compound heterozygote state for GγAγ(δβ)°‐thalassemia and hereditary persistence of fetal hemoglobin
Authors: Fucharoen Supan , Panyasai Sitthichai , Surapot Satja , Fucharoen Goonnapa , Sanchaisuriya Kanokwan
Published: September 2005

We report a hitherto undescribed interaction of a deletional (δβ)°‐thalassemia and a deletional hereditary persistence of fetal hemoglobin (HPFH) in an adult Thai individual. He was a 40‐year‐old Thai male who had the following hematologic data: Hb 13.9 g/dL, Hct 43.8%, MCV 78.0 fL, MCH 24.7 pg, MCHC 31.6 g/dL, and RDW 17.1%. Hemoglobin analysis revealed 97% Hb F with Gγ‐globin chain predominant. Globin gene analyses demonstrated that he carried the GγAγ(δβ)°‐thalassemia deletion in trans to the HPFH‐6. Hematologic data of the patient were compared to those of the heterozygotes for these high‐Hb F determinants found in his parents and an unrelated Thai patient with a compound HPFH‐6/deletion–inversion Gγ(Aγδβ)°‐thalassemia previously described. Am. J. Hematol. 80:119–123, 2005. © 2005 Wiley‐Liss, Inc.
Differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin‐activated umbilical cord blood T cells
Authors: Lin Syh‐Jae , Cheng Po‐Jen , Hsiao Shiu‐Shan , Lin Hui‐Hao , Hung Pei‐Fen , Kuo Ming‐Ling
Published: September 2005

Cytokine immunotherapy using interleukin (IL)‐2 and IL‐15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post‐transplant T‐cell apoptosis. The present study compares the differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin (PHA)‐activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL‐2, IL‐15 preferentially enhanced the survival of CB PHA‐activated T cells by decreasing the caspase‐3+ population and by increasing the Bcl‐2+ population. Activated CB T cells were more susceptible to TNF‐α‐induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL‐15 but not by IL‐2. IL‐15 but not IL‐2 down‐regulated CD28 expression on both activated CB and APB CD8+ T cells, with a much greater effect seen with CB. Western‐blot analysis shows that IL‐15 Rα is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL‐15 significantly enhanced CB IL‐15 Rα expression to levels comparable to that of adults. Thus, IL‐15 may provide a better therapeutic choice for immune reconstitution than IL‐2 post‐CB transplantation due to its preferential survival enhancing effect on CB T cells. Am. J. Hematol. 80:106–112, 2005. © 2005 Wiley‐Liss, Inc.
Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count
Authors: Keidar A. , Feldman M. , Szold A.
Published: September 2005

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university‐affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: ≤20 × 109/L (n = 12), (20–50) × 109/L (n = 18), and >50 × 109/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of ≤20 × 109/L had a much longer hospital stay, received more blood transfusions, and suffered more complications than patients with platelet counts of (20–50) × 109/L or higher (P < 0.05). Transfused patients had a longer hospital stay than non‐transfused patients (2.08 vs. 6.4 days, P = 0.029). The strongest predictor for transfusion was the platelet count (odds ratio = 23, P = 0.008). LS in patients with very low platelet counts is feasible and reasonably safe, but the platelet count is a major determinant of morbidity. Every effort should be made to elevate platelet levels to >20 × 109/L before surgery. Patients with counts >20 × 109/L can safely undergo LS. Am. J. Hematol. 80:95–100, 2005. © 2005 Wiley‐Liss, Inc.
Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: Comparison of megadose methylprednisolone and conventional‐dose prednisolone treatments
Authors: Alikasifoglu Ayfer , Yetgin Sevgi , Cetin Mualla , Tuncer Murat , Gumruk Fatma , Gurgey Aytemiz , Yordam Nursen
Published: September 2005

During recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long‐term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high‐dose methylprednisolone (HDMP) versus conventional‐dose prednisolone (CDP) for remission‐induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty‐six boy and 23 girl survivors, treated for ALL, were cross‐sectionally studied, at a mean age of 11.7 years (range 6–19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol‐L, 900–600 mg/m2, orally). All other therapies were similar in both groups. Cranial irradiation was added for high‐risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was −1.75 (0.83) SDS in group 1 and −1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high‐dose steroid therapy over a short period of time in remission‐induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy. Am. J. Hematol. 80:113–118, 2005. © 2005 Wiley‐Liss, Inc.
Adenosine A2A receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington's disease
Authors: Maglione V. , Giallonardo P. , Cannella M. , Martino T. , Frati L. , Squitieri F.
Published: September 2005

Huntington's disease (HD) may manifest at an earlier age in affected offspring than in transmitting parents. Earlier onset in successive generations (anticipation) only partially depends on intergenerational parent–child elongation of the CAG expanded mutation. An aberrant amplification of adenosine A2A receptor signaling documented in peripheral blood cells of subjects with HD implies that this cellular dysfunction may be related to clinical and genetic features. Prompted by evidence of higher receptor densities in siblings of HD subjects with stronger onset anticipation, in this study we investigated a possible relationship between A2A receptor densities and age at onset. We measured adenosine A2A receptor densities in blood cell platelets from 32 patients with HD and healthy control siblings, and sought a possible linear correlation between maximum platelet A2A receptor binding (Bmax) values for the whole cohort of HD subjects and anticipation in years. The increased Bmax values for the 32 subjects with HD (220 in patients vs. 137 in healthy control subjects, P = 0.0001) correlated significantly with anticipation in years (r2, 0.48, P = 0.0001 by linear correlation analysis). An increased platelet A2A receptor Bmax may belong in a cascade of toxic events leading to earlier onset of HD: as such it could be a useful marker of onset anticipation. © 2005 Wiley‐Liss, Inc.
Haplotype diversity and somatic instability in normal and expanded SCA8 alleles
Authors: Martins Sandra , Seixas Ana I. , Magalhães Paula , Coutinho Paula , Sequeiros Jorge , Silveira Isabel
Published: September 2005

Spinocerebellar ataxia type 8 (SCA8) is an autosomal dominant late‐onset neurodegenerative disorder, belonging to the group of diseases caused by trinucleotide repeat expansions. SCA8 remains one of the most intriguing SCAs, regarding the reduced disease penetrance, and the high instability and poorly understood functional meaning of the (CTA)n(CTG)n expansion. We performed haplotype and sequencing analysis in a large region, encompassing the repeat, in four SCA8 and 20 control Portuguese families. The results from the haplotype study including the combined repeat and six SNP markers showed two different haplotypes, AG‐Exp‐GTTG and AG‐Exp‐CTTG, in the SCA8 families. Among the control population, these were also the most frequent, in a total of five haplotypes found unequally distributed throughout repeat sizes. From cloning fragments of control, unstable normal and expanded chromosomes, eleven different base substitutions were identified in exon A of the SCA8 gene. In some instances, somatic variability in repeat size or base composition was found for a same chromosome, regardless of its normal or expanded nature. In conclusion, our results in Portuguese families with ataxia show that SCA8 expansions arose in common backgrounds; in addition, this region seems to be unstable beyond the repeat. © 2005 Wiley‐Liss, Inc.
Radiation curing of collagen/divinyl ether enhanced by pyridinium salts
Authors: Jiang Bo , Zhou Yong , Yang Zheng , Wu Zhihong , Huang Guanglin , Lin Libin , Zhang Xingdong
Published: September 2005

The radiation curings of collagen/divinyl ether enhanced by several nitrogenous onium salts having relatively stable nonnucleophilic anion (PF6−) have been investigated. Results of glass transformation temperature (Tg) measurements and IR spectroscopy analysis and solvent extractions to the crosslinked polymer networks demonstrate that the curing reactions have been initiated by electron beam irradiation in the mixture system of collagen/divinyl ether and onium salts under different atmosphere conditions. The experimental data show the presence of an approximating linear relationship between double bond conversion and gel fraction after the calculation of conversion from IR spectra in oligomer and the measure of gel content at different total radiation doses. Practical values approximate theoretical values in applying gelation theory of the relationship of gel fraction and double bond conversion. In comparison with the influence of different inhibitors, the curing reaction with pyridinium salts is a polymerization and crosslinking of cationic mechanism, but radicals play an important role in initiation. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2094–2100, 2005
Influence of bound polymer on cure characteristics of natural rubber compounds reinforced with different types of carbon blacks
Authors: Choi Sung‐Seen , Hwang Ki‐Jun , Kim Beom‐Tae
Published: September 2005

Rubber compounds are reinforced with fillers such as carbon black and silica. The cure characteristics of a filled rubber compound vary with the filler type and content. The influence of the type of carbon black on the cure characteristics of carbon black filled natural rubber compounds is investigated using two types of carbon black (N220 and N550), which are different in primary size and structure. The cure time and cure rate become faster as the carbon black content increases. The crosslink density also increases and reversion resistance is improved with the increase of carbon black content. The cure time and cure rate of the compound filled with N550 are faster than those of the compound filled with N220 at the same level of bound rubber content. In addition, higher crosslink density is also observed in the compound filled with N550 compared to that of the compound filled with N220 at the same level of bound rubber content. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2282–2289, 2005
Synthesis and characterization of poly(n‐butyl methacrylate)‐b‐polystyrene diblock copolymers by atom transfer radical emulsion polymerization
Authors: Peng Hui , Cheng Shiyuan , Fan Zhiqiang
Published: September 2005

Poly(n‐butyl methacrylate) (PBMA)‐b‐polystyrene (PSt) diblock copolymers were synthesized by emulsion atom transfer radical polymerization (ATRP). PBMA macroinitiators that contained alkyl bromide end groups were obtained by the emulsion ATRP of n‐butyl methacrylate with BrCH3CHCOOC2H5 as the initiator; these were used to initiate the ATRP of styrene (St). The latter procedure was carried out at 85°C with CuCl/4,4′‐di(5‐nonyl)‐2,2′‐bipyridine as the catalyst and polyoxyethylene(23) lauryl ether as the surfactant. With this technique, PBMA‐b‐PSt diblock copolymers were synthesized. The polymerization was nearly controlled; the ATRP of St from the macroinitiators showed linear increases in number‐average molecular weight with conversion. The block copolymers were characterized with IR spectroscopy, 1H‐NMR, and differential scanning calorimetry. The effects of the molecular weight of the macroinitiators, macroinitiator concentration, catalyst concentration, surfactant concentration, and temperature on the polymerization were also investigated. Thermodynamic data and activation parameters for the ATRP are also reported. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2123–2129, 2005
Electrical conductivity and electromagnetic interference shielding of polyaniline/polyacrylate composite coatings
Authors: Jing Xinli , Wang Yangyong , Zhang Baiyu
Published: September 2005

Lightweight and flexible composite coatings of p‐toluene sulfonic acid doped polyaniline (PANI–TSA) with various mass fractions and polyacrylate were prepared for electromagnetic interference (EMI) shielding. Both the volume and surface conductivities of the composite coatings increased with increasing PANI–TSA; furthermore, the volume conductivity showed a typical percolation behavior with a percolation threshold at about 0.21. The EMI shielding effectiveness (SE) of the PANI–TSA/polyacrylate coatings over the range of 14 kHz to 15 GHz increased with increasing PANI–TSA as the direct‐current conductivity did. EMI SE of the coatings at the low frequencies (14 kHz to 1 GHz) was around 30–80 dB, higher than that at the high frequencies (1–15 GHz); this indicated possible commercial application of the coatings for far‐field EMI shielding. The highest EMI SE value was 79 dB at 200 MHz with a coating thickness of 70 ± 5 μm. The moderate SE, light weight, and easy preparation of the coating are advantages for future applications for EMI shielding. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2149–2156, 2005
Study of the morphology and kinetics of novel Ziegler–Natta catalysts for propylene polymerization
Authors: Abboud Mohammed , Denifl Peter , Reichert Karl‐Heinz
Published: September 2005

The morphological and kinetic characteristics of novel Ziegler–Natta catalysts were studied. Catalysts were prepared by Borealis Polymers Oy using a new synthesis technique (emulsion technology). Video microscopy was used to study the growth of single catalyst particles during polymerization in the gas and liquid phases. The distribution of single particle activity was very narrow in the catalyst without external support and was rather broad in the the silica‐supported catalyst. Video microscopy of molten polymer particles allowed observation of the process and degree of fragmentation of the catalyst particles. A correlation between the activation period during the initial stage of polymerization and catalyst fragmentation was found. Fragmentation was faster and more uniform with the catalyst without external support than with the silica‐supported catalyst. Scanning electron microscopy provided information on morphology evolution and shape replication of the catalyst particles. With the catalyst without external support, good shape replication was observed, and compact and spherical particles were formed. With the silica‐supported catalyst, shape replication was poor, and nonspherical porous polymer particle were formed. Modeling of the kinetics of propylene polymerization was done using a simple three‐step reaction scheme neglecting mass and heat transport effects. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2191–2200, 2005
Effect of some water‐soluble melamine formaldehyde‐free polycondensates on the rheological properties of cement pastes
Authors: Aiad Ismail
Published: September 2005

Water‐soluble melamine formaldehyde‐free polycondensate products were prepared. The chemical structure of these polymers was confirmed with different spectroscopic techniques. The effects of these polymers on the rheological properties of the cement pastes were investigated. The rheological parameters (shear stress, yield stress, and plastic viscosity) were calculated with the Bingham model. The minislump of superplasticized cement pastes at different interval times (5, 30, 60, 90, and 120 min) was determined. The results showed that the new superplasticizers increased the fluidity and minislump of the cement pastes and reduced the minislump loss of the cement pastes not only at early ages (30 min) but also at later early ages (120 min). © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2212–2218, 2005
Mechanism of dielectric‐barrier discharge initiated wet‐strength development
Authors: Vander Wielen L. C. , Östenson M. , Gatenholm P. , Ragauskas A. J.
Published: September 2005

The fundamental mechanism of wet‐strength development for dielectric‐barrier discharge treated thermomechanical pulp fibers was explored. Electron spectroscopy for chemical analysis (ESCA), vapor phase fluorine surface derivatization followed by ESCA, and dynamic contact angle analysis were performed to assess the surface chemistry in terms of both chemical functionality and wettability. Effects of the intensity of dielectric‐barrier discharge treatment on the surface chemistry of lignocellulosic fibers and the corresponding impacts to fiber wet‐tensile properties are described. This study indicates that low treatment intensities result in increased wettability due to surface oxidation, which leads to a small reduction in wet‐tensile index. However, increased treatment intensity brings about diminished wettability due to covalent crosslinking, which leads to increases in wet‐tensile index. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 2219–2225, 2005
Comparison of four non‐hydrostatic models for flow over the Isle of Arran
Authors: Al‐Maskari Juma , Gadian Alan M.
Published: September 2005

Four non‐hydrostatic atmospheric models were compared for a case study of southerly airflow over the Isle of Arran in Scotland. The model results are contrasted with each other and aircraft wind observations. All resolve qualitatively similar the background gravity wave flow, despite different formulations. Copyright © 2005 Royal Meteorological Society
Application of an electric DNA‐chip for the expression analysis of bioprocess‐relevant marker genes of Bacillus subtilis
Authors: Jürgen Britta , Barken Kim Bundvig , Tobisch Steffen , Pioch Daniel , Wümpelmann Mogens , Hecker Michael , Schweder Thomas
Published: September 2005

The knowledge of critical process‐relevant genes can be used for an improved control of bioprocesses. So far bioprocess‐relevant marker genes can be analyzed by established expression analysis methods only off‐line. In this study, an alternative approach for a potential at‐line monitoring of gene expression during bioprocesses is suggested. This approach is based on the measurement of specific mRNAs on an electric DNA‐chip in connection with a magnetic bead‐based sandwich hybridization. In order to allow an at‐line measurement of specific mRNAs an improved method for a fast and partially automated isolation of high quality‐RNA samples was developed. The expression analysis of the electric DNA‐chip was compared with optical DNA micro arrays and the real time RT‐PCR for three selected process‐relevant genes of Bacillus subtilis. We demonstrate that the mRNA analysis by means of the electric DNA‐chip gives similar results compared to the micro array analysis and the real time RT‐PCR technique. © 2005 Wiley Periodicals, Inc.
Differentiation and lineage selection of mouse embryonic stem cells in a stirred bench scale bioreactor with automated process control
Authors: Schroeder Magnus , Niebruegge Sylvia , Werner Andreas , Willbold Elmar , Burg Monika , Ruediger Manfred , Field Loren J. , Lehmann Juergen , Zweigerdt Robert
Published: September 2005

It is well established that embryonic stem (ES) cells can differentiate into functional cardiomyocytes in vitro. ES‐derived cardiomyocytes could be used for pharmaceutical and therapeutic applications, provided that they can be generated in sufficient quantity and with sufficient purity. To enable large‐scale culture of ES‐derived cells, we have developed a robust and scalable bioprocess that allows direct embryoid body (EB) formation in a fully controlled, stirred 2 L bioreactor following inoculation with a single cell suspension of mouse ES cells. Utilizing a pitched‐blade‐turbine, parameters for optimal cell expansion as well as efficient ES cell differentiation were established. Optimization of stirring conditions resulted in the generation of high‐density suspension cultures containing 12.5 × 106 cells/mL after 9 days of differentiation. Approximately 30%–40% of the EBs formed in this process vigorously contracted, indicating robust cardiomyogenic induction. An ES cell clone carrying a recombinant DNA molecule comprised of the cardiomyocyte‐restricted alpha myosin heavy chain (αMHC) promoter and a neomycin resistance gene was used to establish the utility of this bioprocess to efficiently generate ES‐derived cardiomyocytes. The genetically engineered ES cells were cultured directly in the stirred bioreactor for 9 days, followed by antibiotic treatment for another 9 days. The protocol resulted in the generation of essentially pure cardiomyocyte cultures, with a total yield of 1.28 × 109 cells in a single 2 L bioreactor run. This study thus provides an important step towards the large‐scale generation of ES‐derived cells for therapeutic and industrial applications. © 2005 Wiley Periodicals, Inc.
Determination of the endocannabinoid anandamide in human plasma by high‐performance liquid chromatography
Authors: Schmidt Andreas , Brune Kay , Hinz Burkhard
Published: September 2005

Anandamide (N‐arachidonylethanolamine) is an endogenous cannabinoid receptor ligand that has been implicated in various physiological and pathophysiological functions. In the present study, a liquid–liquid extraction‐based reversed‐phase HPLC method with fluorometric detection was validated and applied for the analysis of anandamide in human plasma. Following derivatization with the fluorogenic reagent 4‐(N,N‐dimethylaminosulfonyl)‐7‐(N‐chloroformylmethyl‐N‐methyl‐amino)‐2,1,3‐benzoxadiazole (DBD‐COCl), the analyte was separated using an acetonitrile–water gradient at a flow rate of 0.8 mL/min, and spectrophotometric detection at 560 nm with an excitation wavelength of 450 nm. The retention times for anandamide and R(+)‐methanandamide (internal standard) were 27.1 and 30.7 min, respectively. The validated quantification range was 1–15 ng/mL. The developed procedure was applied to determine anandamide levels in human plasma following a 24 h incubation of human whole blood at 37°C in the presence or absence of phenylmethylsulfonyl fluoride, an inhibitor of the anandamide‐degrading enzyme fatty acid amide hydrolase. Anandamide levels determined under both conditions were within the validated concentration range with anandamide levels being 2.3‐fold higher in plasma from PMSF‐treated blood. Copyright © 2005 John Wiley & Sons, Ltd.
Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats
Authors: Kutlu Selim , Colakoglu Neriman , Halifeoglu Ihsan , Sandal Suleyman , Seyran Ayse D. , Aydin Mehmet , Yılmaz Bayram
Published: September 2005

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats. Copyright © 2005 John Wiley & Sons, Ltd.
Synthesis and Structural Characterization of Neutral Higher‐Coordinate Silicon(iv) Complexes with Tridentate Dianionic Chelate Ligands
Authors: Seiler Oliver , Burschka Christian , Metz Stefan , Penka Martin , Tacke Reinhold
Published: September 2005

The neutral pentacoordinate silicon(iv) complexes 8 and 9 with an SiO2N3 skeleton and the neutral hexacoordinate silicon(iv) complex 10⋅ 1/2 CH3CN with an SiO4N2 skeleton were synthesized, starting from tetra(cyanato‐N)silane or tetra(thiocyanato‐N)silane. Compounds 8 and 9 contain one tridentate dianionic ligand derived from 4‐[(2‐hydroxyphenyl)amino]pent‐3‐en‐2‐one and two monodentate singly charged cyanato‐N or thiocyanato‐N ligands bound to the silicon(iv) coordination center, whereas the silicon(iv) center of 10 is coordinated by two of these tridentate dianionic ligands. All compounds were characterized by single‐crystal X‐ray diffraction and solid‐state and solution NMR spectroscopy. To get more information about the stereochemistry of the compounds studied, the experimental investigations were complemented by computational studies.
A New Tool in Peptide Engineering: A Photoswitchable Stilbene‐type β‐Hairpin Mimetic
Authors: Erdélyi Máté , Karlén Anders , Gogoll Adolf
Published: September 2005

Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogenous peptides with new physicochemical and pharmacological properties. The development, synthesis, photochemical investigation, and conformational analysis of a stilbene‐type β‐hairpin mimetic capable of light‐triggered conformational changes have been achieved. In addition to standard spectroscopic techniques (nuclear Overhauser effects, amide temperature coefficients, circular dichroism spectroscopy), the applicability of self‐diffusion measurements (longitudinal eddy current delay pulsed‐field gradient spin echo (LED‐PGSE) NMR technique) in conformational studies of oligopeptides is demonstrated. The title compound shows photoisomerization of the stilbene chromophore, resulting in a change in solution conformation between an unfolded structure and a folded β‐hairpin.
Probing the “additive effect” in the proline and proline hydroxamic acid catalyzed asymmetric addition of nitroalkanes to cyclic enones
Authors: Hanessian Stephen , Govindan Subramaniyan , Warrier Jayakumar S.
Published: September 2005

The effect of chirality and steric bulk of 2,5‐disubstituted piperazines as additives in the conjugate addition of 2‐nitropropane to cyclohexenone, catalyzed by l‐proline, was investigated. Neither chirality nor steric bulk affects the enantioselectivity of addition, which gives 86–93% ee in the presence of achiral and chiral nonracemic 2,5‐disubstituted piperazines. Proline hydroxamic acid is shown for the first time to be an effective organocatalyst in the same Michael reaction. © 2005 Wiley‐Liss, Inc. Chirality 17:540–543, 2005.
Calculated absorption and vibrational circular dichroism spectra of fundamental and overtone transitions for a chiral HCCH molecular fragment in the hypothesis of coupled dipoles
Authors: Gangemi Roberto , Longhi Giovanna , Abbate Sergio
Published: September 2005

We establish the general behavior of absorption and vibrational circular dichroism spectra (VCD) of a chiral HCCH fragment lacking all symmetry elements; the study is limited to CH‐stretching modes, and the Hamiltonian employed is written in terms of normal‐mode coordinates and momenta and approximates two different Morse oscillators interacting through a harmonic coupling term; rotational strengths are evaluated within a hypothesis of coupled electric dipoles. Van Vleck contact transformations written in terms of raising and lowering operators are used to calculate spectra up to the manifold Δv = 4. Three transformations are necessary to obtain fourth‐order terms in the relevant operators, namely, the electric and magnetic dipole moments. The dynamics of the system exhibits 1:1 resonance terms in addition to the Darling–Dennison coupling term. We discuss the importance of coupling between CH stretches with respect to differences in their local mechanical characteristics in determining the aspect of the absorption and VCD fundamental and overtone spectra of increasing quantum number. © 2005 Wiley‐Liss, Inc. Chirality 17:530–539, 2005.