bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of anti‐immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection
Authors: Cruz A. A. , Lima F. , Sarinho E. , Ayre G. , Martin C. , Fox H. , Cooper P. J.
Published: January 2007

Background
Although the role of immunoglobulin E (IgE) in immunity against helminth parasites is unclear, there is concern that therapeutic antibodies that neutralize IgE (anti‐IgE) may be unsafe in subjects at risk of helminth infection.

Objective
We conducted an exploratory study to investigate the safety of omalizumab (anti‐IgE) in subjects with allergic asthma and/or perennial allergic rhinitis at high risk of intestinal helminth infection. The primary safety outcome was risk of infections with intestinal helminths during anti‐IgE therapy.

Methods
A randomized, double‐blind, placebo‐controlled trial was conducted in 137 subjects (12–30 years) at high risk of geohelminth infection. All subjects received pre‐study anthelmintic treatment, followed by 52 weeks' treatment with omalizumab or placebo.

Results
Of the omalizumab subjects 50% (34/68) experienced at least one intestinal geohelminth infection compared with 41% (28/69) of placebo subjects [odds ratio (OR) 1.47, 95% confidence interval (CI) 0.74–2.95, one‐sided P=0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94–5.15); one‐sided P=0.035], providing some evidence for a potential increased incidence of geohelminth infection in subjects receiving omalizumab. Omalizumab therapy was well tolerated, and did not appear to be associated with increased morbidity attributable to intestinal helminths as assessed by clinical and laboratory adverse events, maximal helminth infection intensities and additional anthelmintic requirements. Time to first infection (OR 1.30, 95% CI 0.79–2.15, one‐sided P=0.15) was similar between treatment groups. Infection severity and response to anthelmintics appeared to be unaffected by omalizumab therapy.

Conclusions
In this exploratory study of allergic subjects at high risk of helminth infections, omalizumab therapy appeared to be safe and well tolerated, but may be associated with a modest increase in the incidence of geohelminth infection.
Galectin‐3 and CD44v6 positivity by RT‐PCR method in fine needle aspirates of benign thyroid lesions
Authors: Mateša N. , Šamija I. , Kusić Z.
Published: January 2007

Objective:  To investigate whether the presence of macrophages and Hürthle cells (HC) in benign thyroid lesions could explain the false‐positive expression of galectin‐3 and CD44v6 detected by reverse transcriptase‐polymerase chain reaction (RT‐PCR).

Methods:  For galectin‐3 and CD44v6, RT‐PCR was performed on RNA isolated from aspirates obtained by ultrasound guided fine needle aspiration cytology (FNAC) from 123 patients with benign thyroid lesions. The results of RT‐PCR analysis were evaluated against the definitive FNAC diagnosis.

Results:  Galectin‐3 expression was found in 29% follicular adenoma (FA), 26% Hashimoto thyroiditis (HT), and in 24% nodular goitre (NG). We found a statistically significant relationship between the presence of macrophages and galectin‐3 positivity in NG and HT samples (P < 0.0001 and P = 0.0087 respectively). We found a statistically significant (P = 0.0219) relationship between the presence of HC and galectin‐3 positivity in HT and a tendency of such a relationship (P = 0.0838) in NG.

CD44v6 expression was found in 29% FA, 33% HT and in 18% NG. We found a statistically significant relationship between the presence of HC and positive expression of CD44v6 in NG (P = 0.0003) and a strong tendency of such a relationship in HT (P = 0.0571). We did not find a statistically significant relationship between the presence of macrophages and CD44v6 positivity.

In FA, we did not find a statistically significant relationship between the presence of macrophages or HC and galectin‐3 or CD44v6 positivity.

Conclusion:  Our results suggest that the presence of macrophages and/or HC may explain the positive expression of galectin‐3 and CD44v6 detected by RT‐PCR in HT and NG cytological samples.
Is primary postpartum haemorrhage a good predictor of inherited bleeding disorders?
Authors: KADIR R. A. , KINGMAN C. E. C. , CHI C. , LEE C. A. , ECONOMIDES D. L.
Published: January 2007

Summary.  A study was conducted to evaluate the value of screening for inherited bleeding disorders in women with primary postpartum haemorrhage (PPH). Over a 2‐year period, women identified to have PPH (defined as >500 mL blood loss for spontaneous vaginal delivery, >700 mL for instrumental deliveries and >1000 mL for caesarean sections within 24 h of delivery) were invited to participate in this study testing for a possible underlying bleeding disorder at 3–9 months postdelivery. Women known to have an inherited bleeding disorder were excluded. Of the 5744 deliveries in our unit during the study period, 152 (3%) fulfilled the criteria for primary PPH and 50 women agreed to participate in the study. Of these, 25 (50%) had a spontaneous vaginal delivery, 8 (16%) had an instrumental delivery and 17 (34%) had a caesarean section. Half of the women were multiparous and five (20%) had PPH in their previous pregnancy. Nineteen (38%) and 12 (24%) reported at least one significant personal and family bleeding history, respectively. One (2%) woman was identified to have von Willebrand disease. In conclusion, primary PPH does not appear to be a strong predictor of inherited bleeding disorders. Further studies are required to assess the prevalence of inherited bleeding disorders among these women.
The retrocyclin analogue RC‐101 prevents human immunodeficiency virus type 1 infection of a model human cervicovaginal tissue construct
Authors: Cole Amy L. , Herasimtschuk Anna , Gupta Phalguni , Waring Alan J. , Lehrer Robert I. , Cole Alexander M.
Published: January 2007

Retrocyclins are cyclic antimicrobial peptides that exhibit potent activity towards a broad range of primary and laboratory‐adapted strains of human immunodeficiency virus type 1 (HIV‐1) in vitro. The current study shows that RC‐101, an analogue of retrocyclin, prevented HIV‐1 infection in an organ‐like construct of human cervicovaginal tissue and retained full activity in the presence of vaginal fluid. The peptide remained within the cervicovaginal tissues throughout the 9‐day incubation period without altering tissue viability, inducing damage or inducing the release of inflammatory cytokines. Collectively, these data support the potential development of RC‐101 as a topical microbicide to prevent HIV‐1 infection and transmission.
Minimizing errors in identifying Lévy flight behaviour of organisms
Authors: SIMS DAVID W. , RIGHTON DAVID , PITCHFORD JONATHAN W.
Published: January 2007

Lévy flights are specialized random walks with fundamental properties such as superdiffusivity and scale invariance that have recently been applied in optimal foraging theory. Lévy flights have movement lengths chosen from a probability distribution with a power‐law tail, which theoretically increases the chances of a forager encountering new prey patches and may represent an optimal solution for foraging across complex, natural habitats.

An increasing number of studies are detecting Lévy behaviour in diverse organisms such as microbes, insects, birds, and mammals including humans. A principal method for detecting Lévy flight is whether the exponent (µ) of the power‐law distribution of movement lengths falls within the range 1 < µ ≤ 3. The exponent can be determined from the histogram of frequency vs. movement (step) lengths, but different plotting methods have been used to derive the Lévy exponent across different studies.

Here we investigate using simulations how different plotting methods influence the µ‐value and show that the power‐law plotting method based on 2k (logarithmic) binning with normalization prior to log transformation of both axes yields low error (1·4%) in identifying Lévy flights. Furthermore, increasing sample size reduced variation about the recovered values of µ, for example by 83% as sample number increased from n = 50 up to 5000.

Simple log transformation of the axes of the histogram of frequency vs. step length underestimated µ by c.40%, whereas two other methods, 2k (logarithmic) binning without normalization and calculation of a cumulative distribution function for the data, both estimate the regression slope as 1 − µ. Correction of the slope therefore yields an accurate Lévy exponent with estimation errors of 1·4 and 4·5%, respectively.

Empirical reanalysis of data in published studies indicates that simple log transformation results in significant errors in estimating µ, which in turn affects reliability of the biological interpretation. The potential for detecting Lévy flight motion when it is not present is minimized by the approach described. We also show that using a large number of steps in movement analysis such as this will also increase the accuracy with which optimal Lévy flight behaviour can be detected.
The Role of the Vagus Nerve in Mediating the Long‐Term Anorectic Effects of Leptin
Authors: Sachot C. , Rummel C. , Bristow A. F. , Luheshi G. N.
Published: January 2007

Leptin, the product of the obese (ob) gene, is mainly known for its regulatory role of energy balance by direct activation of hypothalamic receptors. Recently, its function in the acute control of food intake was additionally attributed to activation of the vagus nerve to regulate meal termination. Whether vagal afferent neurones are involved in longer term effects of leptin on food intake, however, remains undetermined. Using vagotomised (VGX) rats, we sought to clarify the contributions of vagal afferents in mediating the long‐lasting effect of leptin on appetite suppression. Intraperitoneal (i.p.) injection of leptin (3.5 mg/kg) attenuated food intake at 4, 6, 8 and 24 h and body weight at 24 h postinjection in SHAM‐operated rats; however, this response was not abrogated by vagotomy. In a separate study using immunohistochemistry, we observed leptin‐induced Fos expression in the nucleus tractus solitarii, a brain structure where vagal afferent fibres terminate. This signal was not attenuated in VGX animals compared to the SHAM group. Moreover, leptin treatment led to a similar level of nuclear STAT3 translocation, a marker of leptin signalling, in the hypothalami of SHAM and VGX animals. In addition to the effects of leptin, vagotomy surgery itself resulted in a decrease of 24 h food intake. Analyses of brains from saline‐treated VGX animals revealed a significant induction of Fos in the nucleus tractus solitarii and changes in agouti‐related peptide and pro‐opiomelanocortin mRNA expression in the hypothalamus compared to their SHAM counterparts, indicating that the vagotomy surgery itself induced a modification of brain activity in areas involved in regulating appetite. Collectively, our data suggest that vagal afferents do not constitute a major route of mediating the regulatory effect of leptin on food intake over a period of several hours.
A disparity in the association of asthma, rhinitis, and eczema with allergen‐specific IgE between Finnish and Russian Karelia
Authors: Pekkarinen P. T. , Von Hertzen L. , Laatikainen T. , Mäkelä M. J. , Jousilahti P. , Kosunen T. U. , Pantelejev V. , Vartiainen E. , Haahtela T.
Published: January 2007

Background:  A substantial variation in the association of asthma, rhinitis and eczema with elevated serum allergen‐specific immunoglobulin E (sIgE) levels between different populations has been reported. Here, we wanted to clarify whether these proportions are different in Finnish and Russian Karelia, and compared the ability of questionnaires, skin prick tests (SPT) and sIgE measurements to detect atopic conditions in these adjacent areas with different living conditions.

Methods:  Randomly selected schoolchildren, aged 6–16 years, and their mothers from Finland (n = 344 children, 344 mothers) and Russia (427 and 284 respectively) participated. SPTs and sIgE measurements to common inhalant and food allergens were performed. The occurrence of asthma, rhinitis, eczema and related symptoms was assessed with an International Study of Asthma and Allergies in Childhood‐based questionnaire. Correlation between SPT and sIgE was estimated using the Spearman correlation coefficient.

Results:  The rate of positive sIgE results was significantly higher in Finland among both mothers and children. Seventy‐seven per cent of Finnish children and 43% of Russian children with asthma were sIgE positive. The respective figures for hay fever were 94% and 67%, and for eczema 68% and 41%. This discrepancy was similar but of lower magnitude among mothers. The overall occurrence of asthma, rhinitis and eczema was very low in Russian Karelia. The correlation between SPT and sIgE results was generally good.

Conclusion:  Asthma, rhinitis and eczema in Russian Karelia are not only rare but also, to a large extent, have no sIgE component. Therefore, the ability of questionnaires to detect sIgE‐mediated atopic conditions in this area of Russia is poor.
Evolution of viviparity in warm‐climate lizards: an experimental test of the maternal manipulation hypothesis
Authors: JI X. , LIN C.‐X. , LIN L.‐H. , QIU Q.‐B. , DU Y.
Published: January 2007

The maternal manipulation hypothesis for the evolution of reptilian viviparity has been claimed to apply to any situation where gravid females are able to maintain body temperatures different from those available in external nests, but empirical data that support this hypothesis are very limited. Here, we tested this hypothesis using gravid females of a warm‐climate lizard, Mabuya multifasciata, by subjecting them to five thermal regimes for the whole gestation period. We found gravid females selected lower body temperatures and thermoregulated more precisely than did nongravid females. Offspring produced in different treatments differed in head size, limb length and sprint speed, but not in overall body size or mass. Variation in morphological traits of offspring was induced primarily by extreme temperatures. Sprint speed of offspring was more likely affected by the mean but not by the variance of gestation temperatures. Gravid females maintained more stable body temperatures than did nongravid females not because these temperatures resulted in the optimization of offspring phenotypes but because the range of temperatures optimal for embryonic development was relatively narrow. Our data conform to the main predictions from the maternal manipulation hypothesis that females should adjust thermoregulation during pregnancy to provide optimal thermal conditions for developing embryos and that phenotypic traits forged by maternal thermoregulation should enhance offspring fitness.
IgE‐bearing Cells in Bronchoalveolar Lavage Fluid and Allergen‐specific IgE Levels in Sera from RAO‐affected Horses
Authors: Künzle F. , Gerber V. , Van Der Haegen A. , Wampfler B. , Straub R. , Marti E.
Published: January 2007

Recurrent airway obstruction (RAO) is a common condition in stabled horses characterized by small airway inflammation, airway neutrophilia and obstruction following exposure of susceptible horses to mouldy hay and straw and is thus regarded as a hypersensitivity reaction to mould spores. However, the role of immunoglobulin E antibodies (IgE) in the pathogenesis of RAO is unclear. We hypothesized that the number of cells with receptor‐bound IgE in bronchoalveolar lavage fluid (BALF) and IgE levels in serum would be higher in RAO‐affected than in healthy horses living in the same environment. Therefore, IgE‐positive (+) cells were identified by immunocytochemistry on cytospins from BALF and counted. IgE levels against the mould extractsAspergillus fumigatus(Asp. f.) andAlternaria alternata(Alt. a.) and the recombinant mould allergenAspergillus fumigatus8 (rAsp f 8) were measured by enzyme‐linked immunosorbent assay (ELISA) in the sera of seven RAO‐affected and 22 clinically healthy mature horses housed in the same conventional stable environment. After correcting for the number of neutrophils, there were no significant differences in IgE+ cells on cytospins from BALF between both groups of horses (5% versus 7%,P > 0.1). Serum IgE levels against the mould extracts were significantly higher in RAO‐affected than in clinically healthy horses [median = 119 versus 66 relative ELISA units (REU),P < 0.05]. Furthermore, significantly more RAO‐affected than healthy horses had detectable serum IgE against the recombinant allergen rAsp f 8 (4/7 and 3/22, respectively,P < 0.05). Age had no significant effect on BALF cell ratios or on specific serum IgE levels. These results show that high IgE levels against mould antigens are associated with RAO under controlled environmental conditions but ranges of mould‐specific serum IgE levels overlapped too much between diseased and clinically healthy animals to be of any diagnostic value. Further studies are needed to assess whether IgE‐mediated reactions contribute to the pathogenesis of RAO.
Microbiological Screening Test Validation for Detection of Tylosin Excretion in Milk of Cows with Low and High Somatic Cell Counts
Authors: Litterio N. J. , Calvinho L. F. , Flores M. M. , Tarabla H. D. , Boggio J. C.
Published: January 2007

Antibiotic residues in milk above tolerance levels interfere with dairy product processing and pose potential health risks to consumers. Residue avoidance programmes include, among other components, the observance of withdrawal times indicated in label instructions. Persistence of antibiotics in milk following treatment is influenced by drug, dosage, route of administration, body weight and mammary gland health status. Compositional changes that take place during intramammary infection (IMI) can affect antibiotic excretion in milk, thus modifying milk withdrawal time. The objectives of this study were to validate sensitivity and specificity of a qualitative microbiological method (Charm®AIM‐96) to detect tylosin in bovine composite milk and to determine the influence of subclinical IMI in tylosin excretion following intramuscular administration. For test validation, two groups of approximately 120 cows were used; one received a single intramuscular injection of tylosin tartrate at a dose of 20 mg/kg, while the other group remained as untreated control. Test sensitivity and specificity were 100% and 94.1% respectively. To determine the influence of subclinical IMI in tylosin excretion, two groups of seven cows, one with somatic cell counts (SCC) ≤250 000 cells/ml and the other with SCC ≥900 000, were administered a single intramuscular injection of tylosin tartrate at a dose of 20 mg/kg. Milk samples were obtained every 12 h for 10 days following treatment. Milk tylosin excretion averaged between 5 and 9 days for cows with low and high SCC respectively (P < 0.0001). Compositional changes in cows with high SCC most likely affect the pharmacokinetic characteristics of tylosin, extending the presence of the antibiotic in milk, thus influencing milk withdrawal times.
Atoxoplasma spp. Infection in Captive Canaries (Serinus canaria)
Authors: Sánchez‐Cordón P. J. , Gómez‐Villamandos J. C. , Gutiérrez J. , Sierra M. A. , Pedrera M. , Bautista M. J.
Published: January 2007

Clinical signs, histopathological and ultrastructural findings associated with Atoxoplasma spp. natural infection in captive canaries (Serinus canaria) are described. Intracytoplasmic Atoxoplasma‐like protozoa were found in the liver and lung. In the liver, protozoa were found in hepatocytes and Kupffer's cells and were associated with granulomatous hepatitis and a marked bile duct hyperplasia. An usual finding was the presence of infected mononuclear cells adhered to the endothelium of the blood vessels in lung. The diagnosis was confirmed by ultrastructural examination of reprocessed paraffin‐embedded tissues.
Effect of Repeated Stress Treatments During the Follicular Phase and Early Pregnancy on Reproductive Performance of Gilts
Authors: Soede NM , Roelofs JB , Verheijen RJE , Schouten WPG , Hazeleger W , Kemp B
Published: January 2007

Contents

In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty‐one cyclic gilts were assigned to one of four treatments, namely, stress treatment during the follicular phase (n = 20), stress treatment during early pregnancy (n = 20), stress treatment during both phases (n = 21) and no stress treatment (n = 20). All gilts were housed individually, but gilts in the stress treatments had no opportunity for visual or physical contact with other gilts. Further, animals in a stress‐treatment were grouped for half an hour at the start of the treatment and during the treatment period nose‐sling and an unpredictable feeding scheme were applied regularly. The extent of stress was monitored using heart rate measurements, behavioural observations and saliva cortisol levels during nose‐sling fixation. Of the 81 gilts, 93% showed oestrus and were inseminated. Of these, 93% were pregnant at day 35, having 17.9 ± 0.3 ovulations and 15.6 ± 0.3 foetuses. These parameters were not affected by treatment. The stress treatment during the follicular phase tended to shorten cycle length (stress: 20.8 ± 0.20; control: 21.2 ± 0.17 days, p = 0.07) and weight of foetuses at day 35 (stress: 4.47 ± 0.08 g; no stress: 4.69 ± 0.08 g, p = 0.06); stress during early pregnancy did not affect any of the reproduction parameters. Percentage stereotypic behaviour, heart rate and saliva cortisol levels varied greatly between animals and between days, but did not differ between the treatments. No relationships were found between any of the reproductive parameters and any of the stress parameters (heart rate, cortisol, stereotypic behaviour). These results indicate that the repeatedly applied acute stressors did not generate a chronic stress‐response and that these stressors during the follicular phase and/or during early pregnancy did not affect reproductive processes. It is not clear how these findings relate to suggested effects of stress(ors) on reproductive performance in pig husbandry.
Barth's ‘Other’ Doctrine of Election in the Church Dogmatics
Authors: McDONALD SUZANNE
Published: January 2007

Abstract:  In the Göttingen Dogmatics Barth gives an account of the doctrine of election which differs radically from that which he will go on to develop after 1936. This article contends that more consideration needs to be given to the presence of this earlier understanding of election in CD I/1 and 2, both with regard to its influence on the presentation of key loci within these volumes and to the tensions created in the unfolding of major themes before and after his christological reorientation of the doctrine.
Development of microsatellite markers for Dryobalanops aromatica (Dipterocarpaceae), a tropical emergent tree in Southeast Asia
Authors: NANAMI S. , IKEDA S. , TANI N. , TAN S. , DIWAY B. , HARADA K. , TSUMURA Y. , ITOH A. , YAMAKURA T.
Published: January 2007

Eight polymorphic microsatellite markers were developed in Dryobalanops aromatica, an emergent tree in tropical rain forests in Southeast Asia, using an enriched library method. For the assessment of microsatellite variation, 36 individuals from a natural population were analysed. The number of alleles per locus ranged from three to 16, with observed heterozygosity of 0.056–0.833 and expected heterozygosity of 0.054–0.882. These microsatellite markers will be useful for studies of population genetics, reproductive ecology and regeneration dynamics of D. aromatica.
Human hepatic progenitor cells express vasoactive intestinal peptide receptor type 2 and receive nerve endings
Authors: Cassiman David , Sinelli Nicoletta , Bockx Ilse , Vander Borght Sara , Petersen Bryon , De Vos Rita , Van Pelt Jos , Nevens Frederik , Libbrecht Louis , Roskams Tania
Published: January 2007

Background: We recently showed that human hepatic progenitor cells (HPCs) express muscarinic acetylcholine (Ach) receptor subtype 3 and that – following liver transplantation – HPC numbers are significantly reduced. To further elaborate on this, we examined whether HPC also express receptors for vasoactive intestinal peptide (VIP), which, besides Ach, also is an important parasympathetic neurotransmitter. VIP expressing nerves are known to be present in the liver.

Methods: We performed immunohistochemistry for VIP receptor subtypes 1 and 2 (VIPR1 and 2), on sections of normal and diseased human liver (n=17), and double staining for VIPR2 and known HPC markers. We performed RT‐PCR for VIPR1 and 2 on total RNA from purified rat HPC. To document the probability of direct interaction, we also performed double immunostaining for nerve markers and HPC markers on human liver sections.

Results: VIPR2 immunostaining was clearly positive in HPC and reactive bile ductules on paraffin‐embedded and frozen tissue sections. We could not demonstrate VIPR1 protein expression in the liver, with either of two VIPR1 antibodies tested. The presence of VIPR2 mRNA in HPC was confirmed by RT‐PCR. Nerve endings were shown to abut on reactive bile ductules.

Conclusion: We show here for the first time that HPC express VIPR2 and receive nerve endings. These features, and the fact that HPC numbers are influenced by the presence or absence of the autonomic innervation of the liver, suggest a direct interaction.
Pseudoepitheliomatous hyperplasia formation after skin injury
Authors: Fu Xiaobing , Jiang Duying , Chen Wei , Sun, BS Tongzhou , Sheng Zhiyong
Published: January 2007

Pseudoepitheliomatous hyperplasia (PEH) is characteristic of reactive epithelial downward proliferation into the dermis. To explore the mechanism of PEH formation, we investigated the cause, clinical characteristics, histopathologic change, and clinical treatment of PEH, the expression characteristics of stem cell factor (SCF), and its receptor c‐Kit in PEH and normal skin of PEH edge (PEH‐N). The clinical data of 11 patients with PEH were reviewed, and biopsy examination and bacterial cultures were performed. The histological features of PEH and expression levels of SCF, c‐Kit were examined with the pathological method and immunohistochemical methods. The results showed that in each case, histological examination revealed epidermal hyperplasia with irregular cords of epithelial cells extending into the dermis. The bacteria could be cultured and isolated from all PEH biopsies. These bacteria were resistant to several antibiotics, except vancomycin. Radical excision and daily dressing with vancomycin could cure PEH. SCF protein was expressed at stronger levels in sweat gland epithelial cells and interstitial cells of the PEH group vs. the PEH‐N group. c‐Kit was more strongly expressed by interstitial cells in PEH than in PEH‐N. It was concluded that the improper management of cutaneous wounds might cause PEH formation, which can be cured by surgical excision and administration of effective antibiotics. SCF and c‐Kit might be involved in the epidermal hyperplasia observed in PEH.
Responses of reactive astrocytes containing S100β protein and fibroblast growth factor‐2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: implications for wound repair and neuroregeneration
Authors: Do Carmo Cunha Jinger , De Freitas Azevedo Levy Beatriz , De Luca Bianca Aparecida , De Andrade Michele Schultz Ramos , Gomide Vânia Canterucci , Chadi Gerson
Published: January 2007

This paper demonstrates glial reaction and changes in the S100β protein and basic fibroblast growth factor (bFGF, FGF‐2) in the border and in the adjacent preserved tissue of the rat spinal cord after a contusion. In view of the expression of FGF‐2 and S100β in reactive glial cells and their ability to promote gliogenesis and neuronal trophism, the molecules have been considered to participate in the wound repair and regenerative events after nervous tissue injury. Adult rats were submitted to a moderate spinal cord (10th thoracic level) contusion induced by a New York University Impactor by dropping a 10 g rod from a distance of 25 mm onto the dorsal surface of the exposed dura spinal cord. Impactor curves and parameters were used to monitor the severity of the trauma. Control rats were submitted to sham operation. The motor behavioral spontaneous recovery was demonstrated by means of a BBB test and the combining behavior score up to 3 weeks after injury. Animals were killed 72 hours, 2, and 3 weeks after surgery and spinal cords were processed for immunohistochemistry to show glial fibrillary acidic protein positive astrocytes and OX‐42‐positive microglia/macrophages as well as changes in the S100β and FGF‐2 in the border and in the adjacent preserved tissue of the lesioned cords. The changes in the immunoreaction products were quantified by means of morphometric/microdensitometric image analysis, and the cell type expressing S100β and FGF‐2 was analyzed by means of two‐color immunofluorescence procedures. Massive increases of S100β and FGF‐2 were found in reactive astrocytes, not in reactive microglia, in the border and in the white and gray matters of adjacent preserved tissue of the contused spinal cord in the periods studied. The results are discussed in view of possible paracrine trophic actions of the reactive astrocytes, mediated by S100β and FGF‐2, triggering wound repair events in the border of the trauma, and also leading to neurotrophism and neuronal plasticity in the adjacent regions. These cellular and molecular responses may interfere with the pattern of behavioral recovery after a contusion injury of the spinal cord.
Impaired Emotional Facial Expression Recognition in Alcohol Dependence: Do These Deficits Persist With Midterm Abstinence?
Authors: Foisy Marie‐Line , Kornreich Charles , Fobe Anaïs , D'Hondt Laetitia , Pelc Isidore , Hanak Catherine , Verbanck Paul , Philippot Pierre
Published: January 2007

Background: Emotional facial expression (EFE) decoding has been repetitively shown to be impaired in alcoholic inpatients. The present study aimed to replicate and extend previous findings on EFE recognition deficits in alcoholism.

Methods: Alcoholic and control participants' performances were compared on an EFE decoding task with a transversal and a longitudinal design. More specifically, 49 alcoholic individuals were recruited at a long‐stay postdetoxification treatment center at the third or fourth week of their detoxification process. Twenty‐two of them [abstinent alcoholic participants (AA)] were met at the end of their hospitalization process, 2 months later. The 27 remaining patients [dropping alcoholic participants(AD)] dropped out from treatment before the second meeting. A control group (C) of 22 participants was constituted, and assessed twice with the same average time as AA between the 2 assessments. The 3 groups were similar regarding age, sex, and education level. Participants were presented at both times with an EFE decoding test consisting of 16 photographs depicting EFE of happiness, anger, disgust, and sadness.

Results: The results corroborated previous findings highlighting more EFE decoding deficits in alcoholic participants compared with control participants, with no improvement after 3 months of abstinence. Transversal analyses further evidenced more EFE decoding difficulties in AD than in AA compared with controls.

Conclusions: EFE decoding deficits in alcoholism persist with midterm abstinence. Alcoholic patients who dropped from treatment had the worst EFE decoding performance at baseline. Emotional facial expression decoding deficit could have a prognostic value in alcohol dependence.
Bayesian Modeling of Multiple Episode Occurrence and Severity with a Terminating Event
Authors: Herring Amy H. , Yang Juan
Published: January 2007

SummaryAn individual's health condition can affect the frequency and intensity of episodes that can occur repeatedly and that may be related to an event time of interest. For example, bleeding episodes during pregnancy may indicate problems predictive of preterm delivery. Motivated by this application, we propose a joint model for a multiple episode process and an event time. The frequency of occurrence and severity of the episodes are characterized by a latent variable model, which allows an individual's episode intensity to change dynamically over time. This latent episode intensity is then incorporated as a predictor in a discrete time model for the terminating event. Time‐varying coefficients are used to distinguish among effects earlier versus later in gestation. Formulating the model within a Bayesian framework, prior distributions are chosen so that conditional posterior distributions are conjugate after data augmentation. Posterior computation proceeds via an efficient Gibbs sampling algorithm. The methods are illustrated using bleeding episode and gestational length data from a pregnancy study.
Prospective Accuracy for Longitudinal Markers
Authors: Zheng Yingye , Heagerty Patrick J.
Published: January 2007

Summary In this article we focus on appropriate statistical methods for characterizing the prognostic value of a longitudinal clinical marker. Frequently it is possible to obtain repeated measurements. If the measurement has the ability to signify a pending change in the clinical status of a patient then the marker has the potential to guide key medical decisions. Heagerty, Lumley, and Pepe (2000, Biometrics56, 337–344) proposed characterizing the diagnostic accuracy of a marker measured at baseline by calculating receiver operating characteristic curves for cumulative disease or death incidence by time t. They considered disease status as a function of time, D(t) = 1(T≤t), for a clinical event time T. In this article we aim to address the question of how well Y(s), a diagnostic marker measured at time s(s≥ 0, after the baseline time) can discriminate between people who become diseased and those who do not in a subsequent time interval [s, t]. We assume the disease status is derived from an observed event time T and thus interest is in individuals who transition from disease free to diseased. We seek methods that also allow the inclusion of prognostic covariates that permit patient‐specific decision guidelines when forecasting a future change in health status. Our proposal is to use flexible semiparametric models to characterize the bivariate distribution of the event time and marker values at an arbitrary time s. We illustrate the new methods by analyzing a well‐known data set from HIV research, the Multicenter AIDS Cohort Study data.
Cognitive alterations in groups at risk for psychosis: neutral markers of genetic risk or indicators of social disability?
Authors: Jabben N. , Van Os J. , Janssen I. , Versmissen D. , Krabbendam L.
Published: January 2007

Objective:  To investigate whether cognitive alterations associated with vulnerability to psychosis, are associated with expression of psychopathology and functional outcome in groups at different levels of risk for psychotic illness.

Method:  Neurocognition, psychopathology and functional outcome were measured in subjects with variable risk for psychosis: i) 29 patients with psychotic disorder, ii) 46 subjects at familial risk, iii) 41 subjects at psychometric risk and iv) 54 control subjects.

Results:  Dose‐response relationships between cognitive dysfunction and increasing risk for psychosis were found. Cognitive alterations were predicted by negative symptoms in patients and by positive psychotic experiences in the familial risk group. In both at risk groups, cognitive speed was associated with functional outcome.

Conclusion:  Some cognitive impairments serve as neutral endophenotypic marker across the psychosis continuum. However, other cognitive alterations associated with transmission of psychosis may have a direct impact on the pathway from risk to psychopathology and alterations in functioning.
Predominant immature CD8α+ dendritic cells prevent graft‐vs.‐host disease but do not increase the risk of leukemia recurrence
Authors: Xu Lin , Duan Lianning , Cao Kaiyuan , Yuan Guangqing , Peng Yanwen , Huang Xiaorong , Xiang Peng , Li Shunong
Published: January 2007

Graft‐vs.‐host disease (GVHD) remains the major limitation of allogeneic bone marrow transplantation (BMT) and stem cell transplantation, and leukemia recurrence is another important complication in leukemia treatment. Immature CD8α+ dendritic cells (DC) have good potential in GVHD treatment and immunological tolerance studies. To find a new way to prevent GVHD, not increasing the risk of leukemia recurrence, in this study, predominant CD8α+ immature DC were induced from murine bone marrow (BM) cells by 5 ng/mL granulocyte‐macrophage colony stimulating factor (GM‐CSF) plus 20‐ng/mL interleukin (IL)‐4, 100‐ng/mL stem cell factor (SCF) and 25‐ng/mL Flt3L, and 97.09 of prepared DC were CD8α+ on day 3. These DC were identified as morphologically and phenotypically immature CD8α+ DC. The suppressive function was observed in vitro, and then in vivo on allo‐BMT leukemia model. The prepared predominant immature CD8α+ DC were weak syngeneic lymphocyte stimulators and could suppress mixed leukocyte reaction in vitro. In vivo, they prevented the pathological changes of GVHD and prolonged the surviving time of allo‐BMT leukemia mice. The effect showed a dose–effect relationship. 86.7% of allo‐BMT plus 1 million predominant CD8α+ DC leukemia mice reached long‐term survival. Although predominant immature CD8α+ DC had the function of GVHD suppression, they did not increase leukemia recurrence. The method and findings may have important potency for GVHD treatment in clinical application.
Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations
Authors: Kunishima Shinji , Yoshinari Miyako , Nishio Hisanori , Ida Komei , Miura Takuma , Matsushita Tadashi , Hamaguchi Motohiro , Saito Hidehiko
Published: January 2007

Objective: MYH9 disorders are characterised by giant platelets, thrombocytopenia, and Döhle body‐like cytoplasmic granulocyte inclusion bodies that result from mutations in MYH9, the gene for non‐muscle myosin heavy chain‐IIA (NMMHC‐IIA). MYH9 R702 mutations are highly associated with Alport manifestations and result in Epstein syndrome. The aim of our study was to determine the haematological characteristics of MYH9 disorders as a result of R702 mutations to aid in making a proper diagnosis. Patients and methods: Platelet size of patients with MYH9 disorders was determined as platelet diameter by microscopic observation of 200 platelets on stained peripheral blood smears. Double in situ hybridisation using a biotinylated oligo(dT) probe and immunofluorescence analysis of neutrophil NMMHC‐IIA was performed on peripheral blood smears. Results: Patients carrying R702 mutations had significantly larger platelets than those with other MYH9 mutations. Although granulocyte inclusion bodies were mostly invisible on stained blood smears, immunofluorescence analysis for NMMHC‐IIA showed an abnormal type II localisation in all neutrophils. We first showed that poly(A)+ RNA coincided with accumulated NMMHC‐IIA at inclusion bodies in patients with MYH9 disorders. However, no condensation of poly(A)+ RNA at inclusion bodies was observed in patients with R702 mutations. Conclusion: Our study shows that R702 mutations result in especially large platelets and inclusion bodies being faint and mostly invisible on conventionally stained blood smears. We further demonstrated that poly(A)+ RNA content but not NMMHC‐IIA accumulation is responsible for the morphological appearance/stainability of inclusion bodies on stained blood smears and the amount of poly(A)+ RNA is decreased in those with R702 mutations.
Diffuse large B‐cell lymphoma arising independently to lymphoplasmacytic lymphoma: a case of two lymphomas
Authors: Sekikawa Tetsuaki , Takahara Shinobu , Suzuki Hideaki , Takeda Nobuakira , Yamada Hisashi , Horiguchi‐Yamada Junko
Published: January 2007

Richter's syndrome occurs in 5–10% of patients with chronic lymphocytic leukemia, either by transformation of the primary neoplastic lymphocyte, or as a distinct B‐cell neoplasm. We report a Japanese patient with lymphoplasmacytic lymphoma in whom a diffuse large B‐cell lymphoma developed after treatment with rituximab. Molecular examination on immunoglobulin VH genes revealed that the lymphomas had arisen in two separate clones. We reviewed clinical case reports in literature, and found 30–40% of cases with Richter's syndrome and composite lymphoma had a second B‐cell lymphoma of a different origin.
An acridone‐producing novel multifunctional type III polyketide synthase from Huperzia serrata
Authors: Wanibuchi Kiyofumi , Zhang Ping , Abe Tsuyoshi , Morita Hiroyuki , Kohno Toshiyuki , Chen Guoshen , Noguchi Hiroshi , Abe Ikuro
Published: January 2007

A cDNA encoding a novel plant type III polyketide synthase was cloned and sequenced from the Chinese club moss Huperzia serrata (Huperziaceae). The deduced amino acid sequence of Hu. serrata polyketide synthase 1 showed 44–66% identity to those of other chalcone synthase superfamily enzymes of plant origin. Further, phylogenetic tree analysis revealed that Hu. serrata polyketide synthase 1 groups with other nonchalcone‐producing type III polyketide synthases. Indeed, a recombinant enzyme expressed in Escherichia coli showed unusually versatile catalytic potential to produce various aromatic tetraketides, including chalcones, benzophenones, phloroglucinols, and acridones. In particular, it is remarkable that the enzyme accepted bulky starter substrates such as 4‐methoxycinnamoyl‐CoA and N‐methylanthraniloyl‐CoA, and carried out three condensations with malonyl‐CoA to produce 4‐methoxy‐2′,4′,6′‐trihydroxychalcone and 1,3‐dihydroxy‐N‐methylacridone, respectively. In contrast, regular chalcone synthase does not accept these bulky substrates, suggesting that the enzyme has a larger starter substrate‐binding pocket at the active site. Although acridone alkaloids have not been isolated from Hu. serrata, this is the first demonstration of the enzymatic production of acridone by a type III polyketide synthase from a non‐Rutaceae plant. Interestingly, Hu. serrata polyketide synthase 1 lacks most of the consensus active site sequences with acridone synthase from Ruta graveolens (Rutaceae).
Nitric oxide in blood
Authors: Elahi Maqsood M. , Naseem Khalid M. , Matata Bashir M.
Published: January 2007

There is growing evidence that altered production and/or spatio‐temporal distribution of reactive oxidant species and reactive nitrosative species in blood creates oxidative and/or nitrosative stresses in the failing myocardium and endothelium. This contributes to the abnormal cardiac and vascular phenotypes that characterize cardiovascular disease. These derangements at the system level can now be interpreted at the integrated cellular and molecular levels in terms of effects on signaling elements in the heart and vasculature. The end results of nitric oxide/redox disequilibrium have implications for cardiac and vascular homeostasis and may result in the development of atherosclerosis, myocardial tissue remodelling and hypertrophy. Reactive oxygen species/reactive nitrogen species generation is also attributed to the transit from hypertrophic to apoptotic phenotypes, a possible mechanism of myocardial failure. In this review, we highlight the possible roles of altered production and/or spatio‐temporal distribution of reactive oxidant species and reactive nitrosative species in blood on the pathogenesis of the failing cardiovascular system.
Nineteenth-Century Schools between Community and State: The Cases of Prussia and the United States
Authors: Herbst Jurgen
Published: January 2007

Forty years ago Bernard Bailyn remarked that American historians of education had carried out their work “in a special atmosphere of professional purpose” and had made the history of the public school the focus of their investigations. Lawrence Cremin seconded that observation and added that, for all intents and purposes, the history of American education had been “the history of the public school realizing itself over time.” In the tradition of Ellwood Patterson Cubberley that self-realization of the American public school was portrayed as a progression from local roots to state-wide systems. It became synonymous with the evolution of school government from local control on the district and ward levels to direction and oversight by state administrators. For many school professionals and historians that progression meant progress. They saw it as overcoming local control which they regarded as a relic of the past denoting an endorsement of inequality, discrimination, and special privilege. It persuaded them to see the solution to the schools' problems in strengthened state and, eventually, federal control.
Rhode Island's Last Holdout: Tenure and Married Women Teachers at the Brink of the Women's Movement
Authors: Donahue David M.
Published: January 2007

On 24 April 1946, Rhode Island Governor John O. Pastore signed “An Act to Guarantee and to Improve the Education of Children and Youth in This State by Providing Continuing Teaching Service.” The law stated that “three successive annual contracts shall be considered evidence of satisfactory teaching and shall constitute a probationary period” after which teachers would be granted tenure. Teachers could be dismissed only “for good and just cause” after they received tenure. However, the law contained one big loophole: it did not “prevent the retirement of any teacher under a rule of the school committee affecting marriage,” in effect leaving local school committees with the authority to fire women teachers as soon as they got married.
Education and the Emancipation of Jewish Girls in the Nineteenth Century: The Case of the Netherlands
Authors: Rietveld-van Wingerden Marjoke , Bakker Nelleke
Published: January 2007

In the Netherlands the first girl admitted to a qualifying secondary education and the first female university student were sisters, Frederika and Aletta Jacobs. These girls, twelve- and seventeen-years old, entered the respective institutions in 1871 after the father and Aletta had made successful requests. In each case the admission brought an end to a long-standing male privilege. And in each case contemporaries conceived of these ambitious girls as exceptional and therefore raised hardly any objections. In reality however, the arrival of the Jacobs sisters initiated what amounted to a revolution in girls' education, as Dutch girls and women began to follow their examples in unexpected numbers.
Applications of Sound Spectrum Analysis
Authors: Moran Timothy
Published: January 2007

The physics of sound is often studied in introductory physics class experiments involving a tube of resonating air. In typical setups, pistons control the length of a cylindrical space or a microphone is moved within a tube.1 While these activities are useful and can be made very quantitative, they don't directly demonstrate the sounds that are most familiar to students, such as human voices and musical instruments. Fortunately, several sound spectrum analysis programs are available that can bridge this gap.2
Using Gravitational Analogies to Introduce Elementary Electrical Field Theory Concepts
Authors: Saeli Susan , MacIsaac Dan
Published: January 2007

Since electrical field concepts are usually unfamiliar, abstract, and difficult to visualize, conceptual analogies from familiar gravitational phenomena are valuable for teaching. Such analogies emphasize the underlying continuity of field concepts in physics and support the spiral development of student understanding. We find the following four tables to be helpful in reviewing gravitational and electrical comparisons after students have worked through hands-on activities analyzed via extended student discourse.1