bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression of Commensal
Lactobacillus johnsonii
Strain NCC533 during In Vitro Growth and in the Murine Gut
Authors: Denou Emmanuel , Berger Bernard , Barretto Caroline , Panoff Jean-Michel , Arigoni Fabrizio , Brüssow Harald
Published: September 2007

Work with pathogens like
Vibrio cholerae
has shown major differences between genes expressed in bacteria grown in vitro and in vivo. To explore this subject for commensals, we investigated the transcription of the
Lactobacillus johnsonii
NCC533 genome during in vitro and in vivo growth using the microarray technology. During broth growth, 537, 626, and 277 of the 1,756 tested genes were expressed during exponential phase, “adaptation” (early stationary phase), and stationary phase, respectively. One hundred one, 150, and 33 genes, respectively, were specifically transcribed in these three phases. To explore the in vivo transcription program, we fed
L. johnsonii
containing a resistance plasmid to antibiotic-treated mice. After a 2-day washout phase, we determined the viable-cell counts of lactobacilli that were in the lumina and associated with the mucosae of different gut segments. While the cell counts showed a rather uniform distribution along the gut, we observed marked differences with respect to the expression of the
Lactobacillus
genome. The largest number of transcribed genes was in the stomach (
n
= 786); the next-largest numbers occurred in the cecum (
n
= 391) and the jejunum (
n
= 296), while only 26
Lactobacillus
genes were transcribed in the colon. In vitro and in vivo transcription programs overlapped only partially. One hundred ninety-one of the transcripts from the lactobacilli in the stomach were not detected during in vitro growth; 202 and 213 genes, respectively, were transcribed under all in vitro and in vivo conditions; but the core transcriptome for all growth conditions comprised only 103 genes. Forty-four percent of the NCC533 genes were not detectably transcribed under any of the investigated conditions. Nontranscribed genes were clustered on the genome and enriched in the variable-genome part. Our data revealed not only major differences between in vitro- and in vivo-expressed genes in a
Lactobacillus
gut commensal organism but also marked changes in the expression of genes along the digestive tract.
Molecular alterations ofKITandPDGFRAin GISTs: evaluation of a Portuguese series
Authors: Gomes A L , Gouveia A , Capelinha A F , de la Cruz D , Silva P , Reis R M , Pimenta A , Lopes J M
Published: September 2007

Aim:

To assessKITandPDGFRAmutations frequencies in a Portuguese series of gastrointestinal stromal tumours (GISTs).

Methods:

78 GISTs were evaluated for CD117 expression and screened for mutations inKIT(exons 9, 11, 13, 14 and 17) andPDGFRA(exons 12, 14 and 18) genes.

Results:

KITactivating mutations were identified in 44 (56%) of the 78 GISTs. Forty cases (91%) presented a mutation inKITexon 11, and 4 (9%) in exon 9. One case showed a 4 bp deletion in intron 14.PDGFRAmutations were observed in 5 cases (6%): 2 (3%) in exon 12 and 3 (4%) in exon 18. Survival analysis was performed in 63 of the 78 GISTs. The presence of mutatedKITwas significantly correlated with shorter survival of patients (p = 0.0460), and inversely associated with epithelioid histological type of GISTs (p = 0.0064).

Conclusions:

Overall, the incidence of bothKITandPDGFRAmutations in these Portuguese series was 63%, being in agreement with other studies, mainly of Iberian populations. The great majority of mutations were located inKITexon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs.
Colorectal carcinoma with dome-like phenotype: an under-recognised subset of colorectal carcinoma?
Authors: Asmussen L , Pachler J , Holck S
Published: September 2007

Background:

The term dome carcinoma has been applied to a variant of colorectal carcinoma, thought to derive from M-cells of the gut-associated lymphoid tissue. Its distinguishing morphological features include a non-polypoid plaque-like lesion composed of closely apposed cystically dilated glands lined by a single layer of non-mucinous cells, intensely PAS-positive intraluminal material, and a close spatial relation to lymphoid stroma.

Aims and Methods:

A search in the literature for such cases and the authors’ experience with carcinomas sharing morphological details with dome carcinoma are presented to direct focus on this unique phenotype of colorectal carcinoma and to expand on its morphology.

Results:

Four such examples, all stage pT1, pN0 have been previously reported. Here two additional cases, with several features of dome carcinoma, stage pT1 and pT2, respectively, are added. An extensive intramucosal component, unassociated with adenomatous growth, a pink quality of the lesional cells, low grade budding, absence of cytoplasmic pseudofragments, and absence of necrosis characterised the present cases as well as intact MMR-proteins and loss of APC. As opposed to two of the previously reported cases, intraepithelial lymphocytes were unapparent in these cases and the lymphoid stroma was effaced along with tumour progression in one of the present cases. Hence, a range of appearances is encompassed by the dome carcinoma. The uncommon reporting of dome carcinoma may be due to lack of awareness of this particular subset of colorectal carcinoma. Indeed, one of the current cases was signed out as a conventional carcinoma, despite the comment in the pathology report of an unusual morphology.

Conclusion:

Dome carcinoma may be more under-recognised than rare. The reporting of variants of colorectal carcinoma, displaying histological features suggestive of dome carcinoma, is encouraged in order to obtain more exact knowledge on its putative clinical significance.
Intersexual social behavior of urban white-tailed deer and its evolutionary implications
Authors: Richardson Katherine E. , Weckerly Floyd W.
Published: September 2007

White-tailed deer ( Odocoileus virginianus (Zimmermann, 1780)) are now common in many urban environments throughout their geographic range. Yet, how male and female deer in the urban environment associate, behave socially, and the evolutionary implications of that behavior remains unstudied. We examined predictions of the predation risk and the social factor hypotheses to explain intersexual grouping patterns and social behavior observed in white-tailed deer inhabiting the small city of San Marcos (population size ~45 000) in central Texas. Two routes were surveyed weekly from a vehicle at dawn and dusk for 1 year. Group size, composition, distance to vehicle, and alarm state of deer to the vehicle were recorded. Focal animal sampling was used to measure the time males and females spent and number of aggressions within one body length of each other when in groups. Female-only groups were most prevalent year round followed by mixed-sex groups, which increased in prevalence in summer and during the mating season. Alarm state was weakly related to group size but not to group composition. Males were farther apart and more aggressive than females in groups. Proportion of males in mixed-sex groups declined with increased group size. Intersexual patterns of grouping and social behavior of urban deer supported the social factor hypothesis but not the predation risk hypothesis.
Electrophysiology and pacemaker function of the developing sinoatrial node
Authors: Baruscotti Mirko , Robinson Richard B.
Published: September 2007

The sinoatrial node performs its task as a cardiac impulse generator throughout the life of the organism, but this important function is not a constant. Rather, there are significant developmental changes in the expression and function of ion channels and other cellular elements, which lead to a postnatal slowing of heart rate and may be crucial to the reliable functioning of the node during maturation. In this review, we provide an overview of current knowledge regarding these changes, with the main focus placed on maturation of the ion channel expression profile. Studies on Na+ and pacemaker currents have shown that their contribution to automaticity is greater in the newborn than in the adult, but this age-dependent decrease is at least partially opposed by an increased contribution of L-type Ca2+ current. Whereas information regarding age-dependent changes in other transmembrane currents within the sinoatrial node are lacking, there are data on other relevant parameters. These include an increase in the nodal content of fibroblasts and in the area of nonexpression of connexin43, considered a molecular marker of nodal tissue. Although much remains to be done before a comprehensive view of the developmental biology of the node is available, important evidence in support of a molecular interpretation of developmental slowing of the intrinsic sinoatrial rate is beginning to emerge.
Effects of cystic fibrosis transmembrane conductance regulator and ΔF508CFTR on inflammatory response, ER stress, and Ca2+of airway epithelia
Authors: Hybiske Kevin , Fu Zhu , Schwarzer Christian , Tseng Jill , Do Jiun , Huang Natalie , Machen Terry E.
Published: September 2007

We tested whether cystic fibrosis (CF) airway epithelia have larger innate immune responses than non-CF or cystic fibrosis transmembrane conductance regulator (CFTR)-corrected cells, perhaps resulting from ER stress due to retention of ΔF508CFTR in the endoplasmic reticulum (ER) and activation of cytosolic Ca2+(Cai) and nuclear factor (NF)-κB signaling. Adenovirus infections of a human CF (ΔF508/ΔF508) nasal cell line (CF15) provided isogenic comparisons of wild-type (wt) CFTR and ΔF508CFTR. In the absence of bacteria, there were no or only small differences among CF15, CF15-lacZ (β-galactosidase-expressing), CF15-wtCFTR (wtCFTR-corrected), and CF15-ΔF508CFTR (to test ER retention of ΔF508CFTR) cells in NF-κB activity, interleukin (IL)-8 secretion, Cairesponses, and ER stress. Non-CF and CF primary cultures of human bronchial epithelial cells (HBE) secreted IL-8 equivalently. Upon infection with Pseudomonas aeruginosa (PA) or flagellin (key activator for airway epithelia), CF15, CF15-lacZ, CF15-wtCFTR, and CF15ΔF508CFTR cells exhibited equal PA binding, NF-κB activity, and IL-8 secretion; cells also responded similarly to flagellin when both CFTR (forskolin) and Caisignaling (ATP) were activated. CF and non-CF HBE responded similarly to flagellin + ATP. Thapsigargin (Tg, releases ER Ca2+) increased flagellin-stimulated NF-κB and ER stress similarly in all cells. We conclude that ER stress, Cai, and NF-κB signaling and IL-8 secretion were unaffected by wt- or ΔF508CFTR in control and during exposure to PA, flagellin, flagellin + ATP, or flagellin + ATP + forskolin. Tg, but not wt- or ΔF508CFTR, triggered ER stress. Previous measurements showing hyperinflammatory responses in CF airway epithelia may have resulted from cell-specific, rather than CFTR- or ΔF508CFTR-specific effects.
Microtubule dynamics and Rac-1 signaling independently regulate barrier function in lung epithelial cells
Authors: Lorenowicz Magdalena J. , Fernandez-Borja Mar , van Stalborch Anne-Marieke D. , van Sterkenburg Marian A. J. A. , Hiemstra Pieter S. , Hordijk Peter L.
Published: September 2007

Cadherin-mediated cell-cell adhesion controls the morphology and function of epithelial cells and is a critical component of the pathology of chronic inflammatory disorders. Dynamic interactions between cadherins and the actin cytoskeleton are required for stable cell-cell contact. Besides actin, microtubules also target intercellular, cadherin-based junctions and contribute to their formation and stability. Here, we studied the role of microtubules in conjunction with Rho-like GTPases in the regulation of lung epithelial barrier function using real-time monitoring of transepithelial electrical resistance. Unexpectedly, we found that disruption of microtubules promotes epithelial cell-cell adhesion. This increase in epithelial barrier function is accompanied by the accumulation of β-catenin at cell-cell junctions, as detected by immunofluorescence. Moreover, we found that the increase in cell-cell contact, induced by microtubule depolymerization, requires signaling through a RhoA/Rho kinase pathway. The Rac-1 GTPase counteracts this pathway, because inhibition of Rac-1 signaling rapidly promotes epithelial barrier function, in a microtubule- and RhoA-independent fashion. Together, our data suggest that microtubule-RhoA-mediated signaling and Rac-1 control lung epithelial integrity through counteracting independent pathways.
Mechanisms of breathing instability in patients with obstructive sleep apnea
Authors: Younes Magdy , Ostrowski Michele , Atkar Raj , Laprairie John , Siemens AnDrea , Hanly Patrick
Published: September 2007

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 ± 24 h−1) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following ≈30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5th breath following administration of 6% CO2 combined with ≈4% desaturation, was large (187 ± 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.
Atherosclerosis Is Attenuated by Limiting Superoxide Generation in Both Macrophages and Vessel Wall Cells
Authors: Vendrov Aleksandr E. , Hakim Zeenat S. , Madamanchi Nageswara R. , Rojas Mauricio , Madamanchi Chaitanya , Runge Marschall S.
Published: September 2007

Objective—

We previously showed that NAD(P)H oxidase deficiency significantly reduces atherosclerosis in apoE
−/−
mice. The present study was designed to determine the relative contribution of monocyte/macrophage versus vascular wall cell NAD(P)H oxidase to atherogenesis in this model.

Methods and Results—

Cell-specific NAD(P)H oxidase inhibition was achieved via allogenic, sex-mismatched bone marrow transplantation. Aortic atherosclerosis and superoxide production in apoE
−/−
mice (Control) with functional NAD(P)H oxidase in both monocytes/macrophages and vascular wall cells was compared with that in apoE
−/−
mice with nonfunctional monocyte/macrophage NAD(P)H oxidase (BMO) or nonfunctional vessel wall NAD(P)H oxidase (VWO). A significant decrease in superoxide production and atherosclerotic lesions was observed in BMO and VWO mice compared with control mice. Interestingly, BMO mice had significantly lower plasma oxidized LDL levels compared with control and VWO mice, whereas aortic sections of VWO mice showed decreased expression of cellular adhesion molecules compared with control and BMO mice. NAD(P)H oxidase deficiency also attenuated neointimal hyperplasia and mitogenic protein activation in apoE
−/−
mice after arterial injury.

Conclusions—

We conclude that (1) both monocyte/macrophages and vessel wall cells play critical roles in atherogenesis; (2) decrease in atherosclerosis results from attenuated superoxide generation in monocyte/macrophages or vessel wall cells; and (3) superoxide generation may impact atherosclerosis, in part, by activating smooth muscle cell mitogenic signaling pathways.
Cardiac Myosin-Binding Protein C Is Required for Complete Relaxation in Intact Myocytes
Authors: Pohlmann Lutz , Kröger Irena , Vignier Nicolas , Schlossarek Saskia , Krämer Elisabeth , Coirault Catherine , Sultan Karim R. , El-Armouche Ali , Winegrad Saul , Eschenhagen Thomas , Carrier Lucie
Published: September 2007

The role of cardiac myosin-binding protein C (cMyBP-C) in cardiac contraction is still not fully resolved. Experimental ablation of cMyBP-C by various means resulted in inconsistent changes in Ca
2+
sensitivity and increased velocity of force of skinned preparations. To evaluate how these effects are integrated in an intact, living myocyte context, we investigated consequences of cMyBP-C ablation in ventricular myocytes and left atria from cMyBP-C knock-out (KO) mice compared with wild-type (WT). At 6 weeks, KO myocytes exhibited mild hypertrophy that became more pronounced by 30 weeks. Isolated cells from KO exhibited markedly lower diastolic sarcomere length (SL) without change in diastolic Ca
2+
. The lower SL in KO was partly abolished by the actin-myosin ATPase inhibitors 2,3-butanedione monoxime or blebbistatin, indicating residual actin-myosin interaction in diastole. The relationship between cytosolic Ca
2+
and SL showed that KO cells started to contract at lower Ca
2+
without reaching a higher maximum, yielding a smaller area of the phase-plane diagram. Both sarcomere shortening and Ca
2+
transient were prolonged in KO. Isolated KO left atria exhibited a marked increase in sensitivity to external Ca
2+
and, in contrast to WT, continued to develop twitch force at low micromolar Ca
2+
. Taken together, the main consequence of cMyBP-C ablation was a defect in diastolic relaxation and a smaller dynamic range of cell shortening, both of which likely result from the increased myofilament Ca
2+
sensitivity. Our findings indicate that cMyBP-C functions as a restraint on myosin-actin interaction at low Ca
2+
and short SL to allow complete relaxation during diastole.
Exploring Stratification and Entrepreneurship: African American Women Entrepreneurs Redefine Success in Growth Ventures
Authors: Robinson Jeffrey , Blockson Laquita , Robinson Sammie
Published: September 2007

The relationship between social stratification and entrepreneurship is one that is underexplored in the literature of management and organizations. In the authors' view, social stratification (social structure, institutions, and culture) influences the context, process, experience, and outcomes of entrepreneurship. In this article, the authors discuss these relationships in the context of African American women engaged in high-growth entrepreneurship. The authors support their premise by presenting the limitations of prevailing approaches that exist within the current minority and women entrepreneurship literatures. Using the concept of entrepreneurial success as an example, the authors demonstrate how a social stratification and entrepreneurship framework may be useful for scholars who seek to understand the process of entrepreneurship.
Tax Refunds and Microbusinesses: Expanding Family and Community Wealth Building in the Borderlands
Authors: Robles Bárbara J.
Published: September 2007

The Earned Income Tax Credit (EITC) is the largest antipoverty fiscal policy program for working families administered by the Internal Revenue Service (EITCs totaled $42 billion in 2003). For the 2004 tax season, U.S.-Mexico border county EITC refunds reached $1.9 billion while total tax refund amounts for low-income borderlands families topped $2.6 billion. Questionnaires administered during the tax-filing season to working families in Texas, New Mexico, Arizona, and California border counties collected more than forty-five hundred surveys that canvassed respondents on a variety of financial behaviors and tax refund expenditures. Additionally, researchers recorded data on tax filers using their tax refunds to capitalize microbusinesses and respondents' desires to know more about operating a microbusiness. Empirical analysis employing logistic regression produces results that parallel previous findings in the literature and suggests actionable policy prescriptions that may support family and community entrepreneurial activities in the borderlands.
A Reliability Generalization Study of Scores on Rotter's and Nowicki-Strickland's Locus of Control Scales
Authors: Beretvas S. Natasha , Suizzo Marie-Anne , Durham Jennifer A. , Yarnell Lisa M.
Published: September 2007

The most commonly used measures of locus of control are Rotter's Internality-Externality Scale (I-E) and Nowicki and Strickland's Internality-Externality Scale (NSIE). A reliability generalization study is conducted to explore variability in I-E and NSIE score reliability. Studies are coded for aspects of the scales used (number of response points, number of items) and for sample demographic descriptors (percentage female, average age). Results indicate no statistically significant difference in the predicted internal consistency estimate for I-E Scale versus NSIE Scale scores. Only the percentage female variable is found to predict variation in internal consistency estimates. Testing interval length explains variability in test-retest coefficient estimates. Results and directions for future research are discussed.
Religiosity and Coping in Mothers of Children Diagnosed With Cancer: An Exploratory Analysis
Authors: Elkin T. David , Jensen Scott A. , McNeil Lacy , Gilbert Mary Elizabeth , Pullen Jeanette , McComb Linda
Published: September 2007

Although several factors related to coping in parents of children diagnosed with cancer have been explored, little is known about their religious beliefs and behavior and its relationship to coping. The purpose of this study was to provide preliminary data on the religious beliefs and behaviors of mothers of children with cancer and the relation to their psychological adjustment. Twenty-seven mothers of children diagnosed with cancer completed several measures of religious beliefs and behaviors as well as the Beck Depression Inventory—II. The sample was highly religious and specifically Christian. Thirty percent of the mothers reported elevated levels of depressive symptoms, and these mothers reported lower levels of religious belief and behavior than the mothers who denied depressive symptoms. These data suggest a relationship between religiosity and positive coping behavior that should continue to be explored.
Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura
Authors: Breunis Willemijn B. , van Mirre Edwin , Bruin Marrie , Geissler Judy , de Boer Martin , Peters Marjolein , Roos Dirk , de Haas Masja , Koene Harry R. , Kuijpers Taco W.
Published: September 2007

Gene copy number variation (CNV) and single nucleotide polymorphisms (SNPs) count as important sources for interindividual differences, including differential responsiveness to infection or predisposition to autoimmune disease as a result of unbalanced immunity. By developing an FCGR-specific multiplex ligation-dependent probe amplification assay, we were able to study a notoriously complex and highly homologous region in the human genome and demonstrate extensive variation in the FCGR2 and FCGR3 gene clusters, including previously unrecognized CNV. As indicated by the prevalence of an open reading frame of FCGR2C, Fcγ receptor (FcγR) type IIc is expressed in 18% of healthy individuals and is strongly associated with the hematological autoimmune disease idiopathic thrombocytopenic purpura (ITP) (present in 34.4% of ITP patients; OR 2.4 (1.3-4.5), P < .009). FcγRIIc acts as an activating IgG receptor that exerts antibody-mediated cellular cytotoxicity by immune cells. Therefore, we propose that the activating FCGR2C-ORF genotype predisposes to ITP by altering the balance of activating and inhibitory FcγR on immune cells.
Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer
Authors: Nottingham Wade T. , Jarratt Andrew , Burgess Matthew , Speck Caroline L. , Cheng Jan-Fang , Prabhakar Shyam , Rubin Eddy M. , Li Pik-Shan , Sloane-Stanley Jackie , Kong-a-San John , de Bruijn Marella F. T. R.
Published: September 2007

The transcription factor Runx1/AML1 is an important regulator of hematopoiesis and is critically required for the generation of the first definitive hematopoietic stem cells (HSCs) in the major vasculature of the mouse embryo. As a pivotal factor in HSC ontogeny, its transcriptional regulation is of high interest but is largely undefined. In this study, we used a combination of comparative genomics and chromatin analysis to identify a highly conserved 531-bp enhancer located at position + 23.5 in the first intron of the 224-kb mouse Runx1 gene. We show that this enhancer contributes to the early hematopoietic expression of Runx1. Transcription factor binding in vivo and analysis of the mutated enhancer in transient transgenic mouse embryos implicate Gata2 and Ets proteins as critical factors for its function. We also show that the SCL/Lmo2/Ldb-1 complex is recruited to the enhancer in vivo. Importantly, transplantation experiments demonstrate that the intronic Runx1 enhancer targets all definitive HSCs in the mouse embryo, suggesting that it functions as a crucial cis-regulatory element that integrates the Gata, Ets, and SCL transcriptional networks to initiate HSC generation.
Consent for long-term storage of blood samples by Indigenous Australian research participants: the DRUID Study experience
Authors: Cunningham Joan , Dunbar Terry
Published: September 2007

Background

Little is known about the characteristics of people who do and do not agree to the long-term storage and use of their biological materials, or about potential biases that may be introduced as a result of differential consent. More specifically, concerns about tissue storage and use are especially relevant among population groups for whom blood and other biological materials are culturally significant, such as Indigenous Australians. Using data from a 2003–2005 study of 1,004 Indigenous Australians, we examined participants' choices regarding long-term storage of excess blood for possible use in future studies.

Results

Overall, 55% of participants agreed to long-term storage. Among 854 participants with a fasting blood sample and completed questionnaire, consent for storage was more likely among those aged 45+ years than those 15–44 (odds ratio (OR) = 1.55, 95% confidence interval (CI): 1.14, 2.11), and was similar for males and females. After adjustment for age and other covariates using logistic regression, consent was more likely for never smokers than current smokers (OR = 1.48, 95% CI: 1.04, 2.10), those reporting any non-Indigenous grandparent(s) (OR = 2.07, 95% CI: 1.50, 2.85), and those whose consent form was administered/witnessed by an Indigenous staff member (OR 1.43, 95% CI: 1.05, 1.94). Consent for long-term storage was associated with only small differences (generally less than ± 5%) in the results of assays performed on all participants' blood samples as part of the baseline health examination.

Conclusion

These data show that consent for blood storage among these research participants was neither rare nor universal. It was associated with some socio-demographic/cultural factors but not with blood biochemistry. Decisions about requesting or giving consent for storage and later use of tissue samples must recognize a number of important, and potentially competing, ethical and logistical considerations.
Hypoxic Radiosensitization: Adored and Ignored
Authors: Overgaard Jens
Published: September 2007

Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new imaging and physiologic techniques, and a substantial amount of data indicates the presence of hypoxia in many types of human tumors, although with a considerable heterogeneity among individual tumors. Controlled clinical trials during the last 40 years have indicated that this source of radiation resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated systematic review identified 10,108 patients in 86 randomized trials designed to modify tumor hypoxia in patients treated with curative attempted primary radiation therapy alone. Overall modification of tumor hypoxia significantly improved the effect of radiotherapy, with an odds ratio of 0.77 (95% CI, 0.71 to 0.86) for the outcome of locoregional control and with an associated significant overall survival benefit (odds ratio = 0.87; 95% CI, 0.80 to 0.95). No significant influence was found on the incidence of distant metastases or on the risk of radiation-related complications. Ample data exist to support a high level of evidence for the benefit of hypoxic modification. However, hypoxic modification still has no impact on general clinical practice.
Estrogen Enhances Gonadotropin-Releasing Hormone-Stimulated Transcription of the Luteinizing Hormone Subunit Promoters via Altered Expression of Stimulatory and Suppressive Transcription Factors
Authors: Kowase Takanori , Walsh Heidi E. , Darling Douglas S. , Shupnik Margaret A.
Published: September 2007

Transcription of the LH subunit genes is stimulated by GnRH and may be modulated physiologically by steroids such as 17β-estradiol (E). We found that E treatment amplified GnRH stimulation of the rat LHβ and α-subunit promoters, and expression of the endogenous mRNA, in LβT2 gonadotrope cells 2- to 5-fold above GnRH alone. We examined gene expression in LβT2 cells after E and/or GnRH treatment, and found that E suppressed expression of transcription factor Zfhx1a, and enhanced GnRH stimulation of Egr-1 mRNA and protein. E effects were abolished in the presence of antiestrogen. Egr-1 is critical for LHβ expression; however, the role of Zfhx1a, which binds to E-box sequences, was untested. We found E-box motifs in both the rat LHβ (−381, −182, and −15 bp) and α-subunit (−292, −64, −58 bp) promoters. Zfhx1a overexpression suppressed basal and GnRH-stimulated activity of both promoters. Mutation of the α-subunit promoter E boxes at either −64 or −58 bp eliminated Zfhx1a suppression, whereas mutation of the −292 bp E box had no effect. Gel shift assays demonstrated that Zfhx1a bound to the −64 and −58, but not −292, bp E-box DNA. Similarly, mutation of LHβ promoter E boxes at either −381 or −182, but not −15, bp reduced Zfhx1a suppression, correlating with binding of Zfhx1a. The −381 bp LHβ E box overlaps with an Sp1 binding site in the distal GnRH-stimulatory region, and increased Sp1 expression overcame Zfhx1a suppression. Thus, one mechanism by which E may enhance GnRH-stimulated LH subunit promoter activity is through regulation of both activators and suppressors of transcription.
Regulation of Serine (Ser)-31 and Ser40 Tyrosine Hydroxylase Phosphorylation during Morphine Withdrawal in the Hypothalamic Paraventricular Nucleus and Nucleus Tractus Solitarius-A2 Cell Group: Role of ERK1/2
Authors: Núñez Cristina , Laorden M. Luisa , Milanés M. Victoria
Published: September 2007

Our previous studies have shown that naloxone-induced morphine withdrawal increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity, which is dependent on a hyperactivity of noradrenergic pathways [nucleus tractus solitarius (NTS) A2] innervating the hypothalamic paraventricular nucleus (PVN). Short-term regulation of catecholamine biosynthesis occurs through phosphorylation of tyrosine hydroxylase (TH), which enhances enzymatic activity. In the present study, the effect of morphine withdrawal on site-specific TH phosphorylation in the PVN and NTS-A2 was determined by quantitative blot immunolabeling and immunohistochemistry using phosphorylation state-specific antibodies. We show that naloxone-induced morphine withdrawal phosphorylates TH at Serine (Ser)-31 but not Ser40 in PVN and NTS-A2, which is associated with both an increase in total TH immunoreactivity in NTS-A2 and an enhanced TH activity in the PVN. In addition, we demonstrated that TH neurons phosphorylated at Ser31 coexpress c-Fos in NTS-A2. We then tested whether pharmacological inhibition of ERK activation by ERK kinase contributes to morphine withdrawal-induced phosphorylation of TH at Ser31. We show that the ability of morphine withdrawal to stimulate phosphorylation at this seryl residue is reduced by SL327, an inhibitor of ERK1/2 activation. These results suggest that morphine withdrawal increases noradrenaline turnover in the PVN, at least in part, via ERK1/2-dependent phosphorylation of TH at Ser31.
Type 3 Deiodinase Deficiency Results in Functional Abnormalities at Multiple Levels of the Thyroid Axis
Authors: Hernandez Arturo , Martinez M. Elena , Liao Xiao-Hui , Van Sande Jacqueline , Refetoff Samuel , Galton Valerie Anne , St. Germain Donald L.
Published: September 2007

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T3 results in a serum T3 level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T3 and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.
Rapid Neuroendocrine Responses to Auditory Courtship Signals
Authors: Maney Donna L. , Goode Christopher T. , Lake Jessica I. , Lange Henry S. , O’Brien Sara
Published: September 2007

In many species, courtship signals enhance reproductive function in the receiver. How these social signals are processed by the brain, particularly how they induce an endocrine response, is not well understood. Songbirds provide an ideal model in which to study this phenomenon because of the large existing literature on both their auditory neurobiology and the control of their reproductive physiology by environmental cues. To date, all of the relevant studies on songbirds have involved measuring the effects of male vocalizations on ovarian function over a period of weeks, a time course that precludes detailed analysis of the neuroendocrine mechanisms operating during song perception. We played recordings of conspecific male song to laboratory-housed female white-throated sparrows and quantified the resulting rapid changes in LH as well as the induction of the immediate early gene Egr-1in the GnRH system and mediobasal hypothalamus (MBH). Hearing song for 42 min induced LH release and Egr-1 expression in the MBH, but did not alter Egr-1 expression in GnRH neurons. The time course of LH release and the pattern of Egr-1 expression together suggest that song acts as a trigger to induce GnRH release in a manner resembling photostimulation. The Egr-1 response in the MBH was qualitatively distinguishable from the responses to either photostimulation or pharmacologically induced LH release but seemed to involve overlapping neuronal populations. Song-induced Egr-1 expression in the MBH was correlated with the expression in midbrain and forebrain auditory centers, further supporting a role for the MBH in processing social information.
Kisspeptin Neurons in the Arcuate Nucleus of the Ewe Express Both Dynorphin A and Neurokinin B
Authors: Goodman Robert L. , Lehman Michael N. , Smith Jeremy T. , Coolen Lique M. , de Oliveira Cleusa V. R. , Jafarzadehshirazi Mohammad R. , Pereira Alda , Iqbal Javed , Caraty Alain , Ciofi Philippe , Clarke Iain J.
Published: September 2007

Kisspeptin is a potent stimulator of GnRH secretion that has been implicated in the feedback actions of ovarian steroids. In ewes, the majority of hypothalamic kisspeptin neurons are found in the arcuate nucleus (ARC), with a smaller population located in the preoptic area. Most arcuate kisspeptin neurons express estrogen receptor-α, as do a set of arcuate neurons that contain both dynorphin and neurokinin B (NKB), suggesting that all three neuropeptides are colocalized in the same cells. In this study we tested this hypothesis using dual immunocytochemistry and also determined if kisspeptin neurons contain MSH or agouti-related peptide. To assess colocalization of kisspeptin and dynorphin, we used paraformaldehyde-fixed tissue from estrogen-treated ovariectomized ewes in the breeding season (n = 5). Almost all ARC, but no preoptic area, kisspeptin neurons contained dynorphin. Similarly, almost all ARC dynorphin neurons contained kisspeptin. In experiment 2 we examined colocalization of kisspeptin and NKB in picric-acid fixed tissue collected from ovary intact ewes (n = 9). Over three quarters of ARC kisspeptin neurons also expressed NKB, and a similar percentage of NKB neurons contained kisspeptin. In contrast, no kisspeptin neurons stained for MSH or agouti-related peptide. These data demonstrate that, in the ewe, a high percentage of ARC kisspeptin neurons also produce dynorphin and NKB, and we propose that a single subpopulation of ARC neurons contains all three neuropeptides. Because virtually all of these neurons express estrogen and progesterone re-ceptors, they are likely to relay the feedback effects of these steroids to GnRH neurons to regulate reproductive function.
Rab6 and the secretory pathway affect oocyte polarity inDrosophila
Authors: Januschke Jens , Nicolas Emmanuelle , Compagnon Julien , Formstecher Etienne , Goud Bruno , Guichet Antoine
Published: September 2007

The Drosophila oocyte is a highly polarized cell. Secretion occurs towards restricted neighboring cells and asymmetric transport controls the localization of several mRNAs to distinct cortical compartments. Here, we describe a role for the Drosophila ortholog of the Rab6 GTPase,Drab6, in establishing cell polarity during oogenesis. We found that Drab6 localizes to Golgi and Golgi-derived membranes and interacts with BicD. We also provide evidence that Drab6 and BicD function together to ensure the correct delivery of secretory pathway components, such as the TGFαhomolog Gurken, to the plasma membrane. Moreover, in the absence of Drab6, osk mRNA localization and the organization of microtubule plus-ends at the posterior of the oocyte were both severely affected. Our results point to a possible connection between Rab protein-mediated secretion, organization of the cytoskeleton and mRNA transport.
What’s Love Got to Do with It? Sexual Behaviors of Opposite‐Sex Couples Through Emerging Adulthood
Authors: Kaestle Christine Elizabeth , Halpern Carolyn Tucker
Published: September 2007

CONTEXT:  Sexual relationships in young adulthood may have important ramifications for individuals’ physical and emotional well‐being. Nonetheless, representative information about young adults’ sexual activities in long‐term relationships and the emotional context of such relationships is rare.

METHODS:  A subsample of 6,421 participants in Wave 3 of the National Longitudinal Study of Adolescent Health (18–26‐year‐olds) who were in a sexual relationship of at least three months’ duration were selected for analysis. Multiple logistic regression models were used to explore the relationship between love and various sexual activities.

RESULTS:  Eighty percent of respondents had engaged in cunnilingus and fellatio as well as vaginal intercourse in their current relationship; this group included 22% who also had engaged in anal sex. Compared with their peers who reported that they and their partner did not love each other a lot, both males and females who reported mutually loving relationships had significantly higher odds of having given oral sex (odds ratios, 3.9 and 2.6, respectively) and having received oral sex (1.8 and 3.3); males in mutually loving relationships also had elevated odds of having had anal sex (3.1).

CONCLUSIONS:  Most young adult couples in long‐term relationships engage in a variety of sexual practices with loving partners; the direction of causality in this association and its implications for relationship building require exploration. Furthermore, programs and interventions that address health and well‐being during emerging adulthood should cover issues relevant to a broad range of sexual activities, including oral and anal sex.
Towards a Whole School Approach to Pastoral Care: A Proposed Framework of Principles and Practices
Authors: de Jong Terry , Kerr-Roubicek Helen
Published: September 2007

Pastoral care in schools has traditionally been associated with notions of help, advice, values development, and children's moral welfare. In the past it has been viewed predominantly as a separate set of extra-curricula activities offered to students by school staff with particular support roles, or ‘pastors’ from affiliated church or religious communities. In some Australian schools and education sectors pastoral care continues to be conceptualised in this way. However, over the past two decades interest has intensified in a ‘whole school approach’ to pastoral care that supports the holistic development of students as they learn. What has influenced this change of direction? What are some of the key challenges encountered when implementing this approach? How might we define ‘a whole school approach’ to pastoral care? What are the core principles and associated school practices of this approach to pastoral care? We attempt to address these questions in this paper. In doing so, we have drawn on the MindMatters Plus Demonstration Project and constructed a ‘whole school’ framework for pastoral care. We emphasise the importance of distributed leadership in our framework, where all staff and students alike are responsible for developing an ethos of care. This is a ‘work-in-progress’. We invite feedback on our proposal.
Adolescent Peer Counselling: Enhancing the Natural Conversational Helping Skills of Young People
Authors: Geldard Kathryn , Patton Wendy
Published: September 2007

During the developmental stage of adolescence young people face many stressful challenges (Dacey & Kenny, 1997). Some adolescents manage these challenges adaptively but others do not and are therefore at the risk of adopting maladaptive responses to stress (Frydenberg & Lewis, 2002; Patton & Noller, 1990). Because adolescents are generally reluctant to talk in the first instance to parents, or other adults including adult counsellors, programs have been established to train adolescents in peer counselling. The present study examined the conversational skills that young people prefer to use when helping their peers and investigated their response to the use of traditional counselling skills with regard to ease of use and helpfulness. The results suggest that adolescents find some commonly used counselling skills difficult to use and unhelpful. Additionally the study suggests that young people found that some normal adolescent conversational behaviours which have been discouraged in adolescent peer counsellor training programs were helpful. The findings of this study have important implications with regard to training adolescents.
Myotubular myopathy. Case report and review of the literature
Authors: Kovács S. Krisztián , Korcsik József , Szabó Hajnalka , Bódi István , Katona Márta , Bereg Edit , Endreffy Emőke , Túri Sándor , Hortobágyi Tibor , Sztriha László
Published: September 2007

X-kromoszómához kötötten, recesszíven öröklődő myotubularis myopathia első magyar nyelven ismertetett esetét írják le a szerzők. Már megszületéskor súlyos izomhypotoniát, szegényes spontán mozgásokat, arthrogryposist és légzési elégtelenséget észleltek a betegben. Az izombiopszia a congenitalis myopathiák csoportjába tartozó myotubularis myopathia képét mutatta. A diagnózist megerősítette a molekuláris genetikai vizsgálat, amely egy – eddig nem ismert – frameshiftet eredményező mutációt (1314-1315insT) talált a myotubularint kódoló
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Experiences in treatment and follow up of 50 patients with penile cancer
Authors: Riesz Péter , Nyirády Péter , Szűcs Miklós , Szendrői Attila , Majoros Attila , Bánfi Gergely , Kiss András , Lotz Gábor , Törzsök Péter , Kelemen Zsolt , Romics Imre
Published: September 2007

A hímvessző rosszindulatú daganata ritka kórelváltozás. Szövettanilag az esetek túlnyomó része elszarusodó laphámrák, de az elhelyezkedésük miatt a műtéti kezelést az urológus végzi. A daganatok szinte kizárólag a fitymabőr distalis részéből vagy a glansból indulnak ki.Célkitűzés és módszer:A szerzők bemutatják a hímvesszőrák kezelésével, gondozásával szerzett tapasztalataikat. Az eredmények feldolgozását részben retrospektív, részben prospektív módszerrel végezték.Eredmények:1996. június és 2006. június között 50 betegnél végeztek műtétet péniszkarcinóma miatt. A betegek átlagos életkora 63,1 (31–83) év volt. A daganatok 94%-a laphámrák volt, 2 (4%) esetben verrucosus carcinoma, egy esetben melanoma malignum. A patológiai T-stádium 23 (46%) esetben T1 volt, 19 (38%) betegen 2, 6 (12%) esetben T3 és 1 (2%) alkalommal T4. A differenciáltság, grade-1 volt 12 (24%), grade-2 volt 27 (54%) és grade-3 volt 10 (20%) esetben. A betegek közül 11-nek (22%) volt egyoldali, és 8-nak (16%) kétoldali inguinalis nyirokcsomóáttéte. Az előzményekben 4 (8%) betegen történt circumcisio fitymaszűkület miatt, míg 25 (50%) betegnek a rák felismerésekor volt phimosisa. A műtéti kezelés után 17 (34%) beteg részesült kemoterápiában. A betegek átlagos túlélési ideje 31,4 (2–114) hónap volt.Következtetések:A hímvesszőrák kialakulásában fontos szerepe van a fitymaszűkületnek, mely megbetegedésének kockázata a műtéti megoldás után is magasabb. A betegség lefolyása agresszív viselkedésű, a nyirokutakon terjedő, ahol az előrehaladt stádiumokban vagy alacsony differenciáltság esetén már felismeréskor kimutatható. A terápia meghatározásában a stádiumorientáltság kezelési elvének kell érvényesülnie. A korai műtéti kezeléssel hosszú távú túlélés érhető el.
The first Hungarian radiotherapy department was founded in the Uzsoki Hospital 75 years ago
Authors: Mayer Árpád , Zaránd Pál
Published: September 2007

A szerzők rövid ismertetést adnak fennállásának 75. évfordulója alkalmából Magyarország első önálló sugárterápiás intézményéről, mely kezdetben
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Ra brachyterápiát végzett. Vázolják az intézmény meghatározó vezetőinek legfontosabb tevékenységét, és röviden bemutatják a technikai lehetőségek fokozatos bővülését is. Ez létesítéskor megfelelt a kor európai színvonalának, de a II. világháború a fejlődést megszakította, és a lehetőségeinket jelentősen szűkítette. A megemlékezés bemutatja az intézmény mai felszereltségét és a fontosabb kutatási témákat.