bluuebunny/crossref_metadata_2025 huggingface dataset:
Abl Silencing Inhibits CAS-Mediated Process and Constriction in Resistance Arteries
Authors: Anfinogenova Yana , Wang Ruping , Li Qing-fen , Spinelli Amy M. , Tang Dale D.
Published: July 2007

The tyrosine phosphorylated protein Crk-associated substrate (CAS) has previously been shown to participate in the cellular processes regulating dynamic changes in the actin architecture and arterial constriction. In the present study, treatment of rat mesenteric arteries with phenylephrine (PE) led to the increase in CAS tyrosine phosphorylation and the association of CAS with the adapter protein CrkII. CAS phosphorylation was catalyzed by Abl in an in vitro study. To determine the role of Abl tyrosine kinase in arterial vessels, plasmids encoding Abl short hairpin RNA (shRNA) were transduced into mesenteric arteries by chemical loading plus liposomes. Abl silencing diminished increases in CAS phosphorylation on PE stimulation. Previous studies have shown that assembly of the multiprotein compound containing CrkII, neuronal Wiskott–Aldrich Syndrome Protein (N-WASP) and the Arp2/3 (Actin Related Protein) complex triggers actin polymerization in smooth muscle as well as in nonmuscle cells. In this study, Abl silencing attenuated the assembly of the multiprotein compound in resistance arteries on contractile stimulation. Furthermore, the increase in F/G-actin ratios (an index of actin assembly) and constriction on contractile stimulation were reduced in Abl-deficient arterial segments compared with control arteries. However, myosin regulatory light chain phosphorylation (MRLCP) elicited by contractile activation was not inhibited in Abl-deficient arteries. These results suggest that Abl may play a pivotal role in mediating CAS phosphorylation, the assembly of the multiprotein complex, actin assembly, and constriction in resistance arteries. Abl does not participate in the regulation of myosin activation in arterial vessels during contractile stimulation.
Diffusion-Weighted Imaging-Negative Patients With Transient Ischemic Attack Are at Risk of Recurrent Transient Events
Authors: Boulanger Jean-Martin , Coutts Shelagh B. , Eliasziw Michael , Subramaniam Suresh , Scott James , Demchuk Andrew M.
Published: July 2007

Background and Purpose—

Among patients presenting with a transient ischemic attack (TIA), some clinical features predispose to recurrent TIA, whereas others predispose to subsequent strokes. We assessed the implication of negative diffusion-weighted imaging on a baseline MRI in predicting subsequent TIA.

Methods—

We prospectively studied patients presenting in the emergency department within 12 hours of a TIA (motor or speech). All patients had a MRI within 24 hours of the index event. The primary outcome was TIA within 1 year of study entry. The 1-year risk of stroke was also evaluated.

Results—

A total of 85 patients had a MRI, among which 35 patients (41.2%) had a diffusion-weighted imaging lesion. The mean time from symptom onset to MRI was 12.1 hours. Patients without a diffusion-weighted imaging lesion on baseline MRI were 4.6 times (27.4% versus 5.9%;
P
<0.05) more likely to have a subsequent TIA at 1 year than patients with a diffusion-weighted imaging lesion, but 4.3 times (2.1% versus 9.1%;
P
=0.19) less likely to have a subsequent stroke.

Conclusions—

The absence of a diffusion-weighted imaging lesion on the baseline scan predicts recurrent transient events rather than stroke.
National Healthline Responses to a Stroke Scenario
Authors: Jarrell Brett , Tadros Allison , Whiteman Charles , Crocco Todd , Davis Stephen M.
Published: July 2007

Background and Purpose—

Acute stroke is a time-dependent emergency in which patients often arrive outside of the therapeutic treatment windows. To determine the role that healthlines may have in promoting early presentation, this study evaluated patterns of healthline triage of potential stroke patients.

Methods—

Phone numbers of healthlines at 82 United States hospitals with neurology residencies were acquired. Each healthline was called and the operator was presented with a standardized scripted stroke patient scenario. The operator was asked to choose 1 of 4 responses that could be given to the patient (wait for symptom resolution, contact a primary care physician, drive to a local urgent care center, call 911 for ambulance transport). The operator was then asked to name common signs and symptoms of stroke. If the operator transferred the call, the process was repeated.

Results—

Forty-six healthlines participated, with 22% recommending that the patient contact a primary care physician. The remaining 78% recommended calling 911. Calls were transferred at least once in 18 cases, and 24% of the operators could not name 1 sign or symptom of stroke.

Conclusions—

Nearly one-quarter of potential stroke patients were routed away from emergent treatment for the described scenario. By diverting patients away from emergency therapy, patients are in jeopardy of “falling” out of the windows for therapy. Improved stroke education for healthline personnel may result in stroke patients arriving at an emergency department more urgently.
Changing Sex, Changing Self
Authors: Johnson Katherine
Published: July 2007

This article explores how transsexual men and women talk about shifts in self-perceptions and embodiment. Often there are remarkable changes in transsexual people's fleshy physicality that affect not only how their gendered bodies are perceived but also how they experience themselves as embodied subjects. Yet despite the advances of medical science and a growing investment in new bodily technologies, the author argues that the transsexual body cannot be seen as entirely malleable, because it is often marked by previous physical features and cultural bodily practices that are difficult to shake off. This is particularly the case for male-to-female transsexuals, because the markers of masculinity appear harder to escape. Thus, in a move toward a theory of embodied subjectivity, the author argues that transitions in a sense of gendered subjectivity are intrinsically tied to and inseparable from shifts in gendered embodiment.
Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer
Authors: Damaraju Vijaya L , Bouffard David Y , Wong Clarence KW , Clarke Marilyn L , Mackey John R , Leblond Lorraine , Cass Carol E , Grey Mike , Gourdeau Henriette
Published: July 2007

Background

Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials.

Methods

The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software.

Results

Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. In vivo testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine.

Conclusion

These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.
Impairment of alternative splice sites defining a novel gammaretroviral exon within gagmodifies the oncogenic properties of Akv murine leukemia virus
Authors: Sørensen Annette Balle , Lund Anders H , Kunder Sandra , Quintanilla-Martinez Leticia , Schmidt Jörg , Wang Bruce , Wabl Matthias , Pedersen Finn Skou
Published: July 2007

Background

Mutations of an alternative splice donor site located within the gag region has previously been shown to broaden the pathogenic potential of the T-lymphomagenic gammaretrovirus Moloney murine leukemia virus, while the equivalent mutations in the erythroleukemia inducing Friend murine leukemia virus seem to have no influence on the disease-inducing potential of this virus. In the present study we investigate the splice pattern as well as the possible effects of mutating the alternative splice sites on the oncogenic properties of the B-lymphomagenic Akv murine leukemia virus.

Results

By exon-trapping procedures we have identified a novel gammaretroviral exon, resulting from usage of alternative splice acceptor (SA') and splice donor (SD') sites located in the capsid region of gag of the B-cell lymphomagenic Akv murine leukemia virus. To analyze possible effects in vivo of this novel exon, three different alternative splice site mutant viruses, mutated in either the SA', in the SD', or in both sites, respectively, were constructed and injected into newborn inbred NMRI mice. Most of the infected mice (about 90%) developed hematopoietic neoplasms within 250 days, and histological examination of the tumors showed that the introduced synonymous gag mutations have a significant influence on the phenotype of the induced tumors, changing the distribution of the different types as well as generating tumors of additional specificities such as de novo diffuse large B cell lymphoma (DLBCL) and histiocytic sarcoma. Interestingly, a broader spectrum of diagnoses was made from the two single splice-site mutants than from as well the wild-type as the double splice-site mutant. Both single- and double-spliced transcripts are produced in vivo using the SA' and/or the SD' sites, but the mechanisms underlying the observed effects on oncogenesis remain to be clarified. Likewise, analyses of provirus integration sites in tumor tissues, which identified 111 novel RISs (retroviral integration sites) and 35 novel CISs (common integration sites), did not clearly point to specific target genes or pathways to be associated with specific tumor diagnoses or individual viral mutants.

Conclusion

We present here the first example of a doubly spliced transcript within the group of gammaretroviruses, and we show that mutation of the alternative splice sites that define this novel RNA product change the oncogenic potential of Akv murine leukemia virus.
Intraperitoneal Chemotherapy for Ovarian Cancer: Overview and Perspective
Authors: Rao Gautam , Crispens Marta , Rothenberg Mace L.
Published: July 2007

Intraperitoneal (IP) chemotherapy has theoretical, pharmacologic, and clinical advantages over intravenous (IV) chemotherapy in women with optimally debulked epithelial ovarian cancer confined to the abdominal cavity. Consistent, statistically significant improvements in both progression-free and overall survival have been demonstrated in three large phase III trials conducted in the United States during the past 10 years. Nevertheless, concerns over IP drug distribution and systemic absorption, technical challenges of IP catheter placement and the incidence of IP catheter-related complications, and the clinical relevance of these studies have limited the adoption of IP therapy in ovarian cancer. Current interest in the evaluation of molecularly targeted therapies should build on the progress that has been made through the use of IP chemotherapy in women with optimally debulked ovarian cancer.
A Functional Serine 118 Phosphorylation Site in Estrogen Receptor-α Is Required for Down-Regulation of Gene Expression by 17β-Estradiol and 4-Hydroxytamoxifen
Authors: Cheng Jingwei , Zhang Chen , Shapiro David J.
Published: July 2007

To evaluate the contribution of ERK1/2 phosphorylation of estrogen receptor (ER)-α to activation and repression of endogenous genes, we produced stably transfected lines of HeLa cells with functional ERK1/2 pathways that express similar levels of wild-type human ERα and ERα mutated to inactivate the well-known MAPK site at serine 118 (ERαS118A). We compared effects of the S118A mutation on 17β-estradiol (E2)-mediated transactivation, which is heavily dependent on activation function (AF) 2 of ERα and on 4-hydroxytamoxifen (OHT)-mediated transactivation, which is heavily dependent on AF1, which includes S118. To examine whether S118 was the key ERK/MAPK phosphorylation site in ERα action, we compared the effects of the S118A mutant and the ERK inhibitor U0126 on expression of endogenous genes. In several estrogen response element-containing genes, the S118A mutation strongly reduced induction by E2, and U0126 did not further reduce expression. Expression of another group of estrogen response element-containing genes was largely unaffected by the S118A mutation. The S118A mutation had variable effects on genes induced by ER tethering or binding near specificity protein-1 and activator protein-1 sites. For five mRNAs whose expression is strongly down-regulated by E2 and partially or completely down-regulated by OHT, the S118A mutation reduced or abolished down-regulation by E2 and nearly abolished down-regulation by OHT. In contrast, for Sma and mothers against decapentaplegic-3-related, which is down-regulated by E2 and not OHT, the S118A mutation had little effect. These data suggest that there may be distinct groups of genes down-regulated by ERα and suggest a novel role for ERK phosphorylation at serine 118 in AF1 in regulating expression of the set of genes down-regulated by OHT.
Erythropoietin Inhibits Basal and Stimulated Corticotropin-Releasing Hormone Release from the Rat Hypothalamus via a Nontranscriptional Mechanism
Authors: Tringali Giuseppe , Pozzoli Giacomo , Lisi Lucia , Navarra Pierluigi
Published: July 2007

Brain hypoxia-ischemia induces a local increase in the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF); this condition is also associated with acute activation of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that increased levels of EPO and VEGF in the hypothalamus may play a role in the control of HPA function. Thus, in this study we used rat hypothalamic explants to investigate whether EPO and VEGF can directly modulate CRH release; the latter was assessed by RIA measurement of the peptide in the incubation medium and hypothalamic tissue. EPO and VEGF effects were studied in short-term (1–3 h) experiments under basal conditions or after stimulation with 56 mM KCl or 10 μM veratridine. We observed that EPO (1–10 nm) significantly reduced CRH release and, in parallel, increased intrahypothalamic CRH content. VEGF tended to reduce CRH release without reaching statistical significance. Moreover, EPO, but not VEGF, inhibited KCl- and veratridine-stimulated CRH release and counteracted the parallel decrease in intrahypothalamic CRH induced by the two secretagogues. EPO effects were not mediated by modification of CRH gene expression, either in the absence or the presence of KCl or veratridine; in this paradigm, KCl and veratridine per se did not modify CRH gene expression. Our findings suggest that EPO contributes to the regulation of the HPA axis activation; in pathological conditions such as brain ischemia, this growth factor may control the HPA axis function, preventing possible detrimental effects of HPA overactivation.
The Veiled Monologues
Authors: Roosen Adelheid
Published: July 2007

Translated by Discordia Translations
Who's Afraid of Rachel Corrie?
Authors: Carlson Marvin , Heilpern John , Shinn Christopher , Solomon Alisa , Stuart Kelly
Published: July 2007

Compiled, introduced, and moderated by Shawn-Marie Garrett
Activity patterns and use of resting sites by polecats in an endangered population
Authors: Baghli Adil , Verhagen Ron
Published: July 2007

We investigated the activity and the use of resting sites of polecats Mustela
putorius in the Gutland area of Luxembourg. Three years of radio-telemetry
on 10 animals provided 103 all-night tracking sessions and 262 locations of
diurnal resting sites. Polecats were active during 62% of the night. Males were
more active than females, and activity increased from winter to summer. During
daytime, polecats were located in 53 different resting sites. Above ground
shelters were used more often than underground shelters. Heaps of branches,
barns and stables, garden sheds and rat dens were the most used sites, without
specific preference for any one type of shelter. However, human settlements
seem to be of prime importance during severe weather conditions. The selection
of such resting sites appeared to be based on thermal characteristics. This
pattern of resting site use suggests that presence of suitable resting sites in
winter is important for the conservation of the endangered polecat population
in Luxembourg.
Taxonomic status ofMicronycteris homezi(Chiroptera, Phyllostomidae)
Authors: Ochoa José G. , Sánchez Javier H.
Published: July 2007

There are currently six species ofMicronycteris(sensu stricto) recognized in Venezuela, of which three have pale venters:M. homezi,M. minutaandM. schmidtorum. Since the original description ofM. homezias a subspecies ofM. megalotis(based on the presence of a cutaneous fossa in the interauricular region), this taxon has not appeared in checklists for Venezuelan mammal inventories due to confusion and uncertainty related to the original description. However, it was recently reconsidered as a valid taxon on the basis of an additional series of males collected in French Guiana, Guyana, and Brazil. The examination of a larger number of specimens ofMicronycteriscollected in Venezuela (73 of them within the pale venter group), allows us to reject the cutaneous fossa as a valid character to diagnoseM. homezi, suggesting that the namehomezirepresents a junior synonym ofM. minuta. Among the arguments supporting this statement are: 1) the discovery of a cutaneous fossa in two congeneric forms (M. megalotisandM. microtis); 2) the existence of histological evidence verifying the presence of this structure (incipiently developed) in specimens assignable toM. minuta; 3) the development of the fossa only in adult males (associated with a hypertrophy of the interauricular band); and 4) the similarity, in both chromatic and morphological features of Venezuelan specimens assignable to eitherM. minutaorM. homezi. The presence of a developed cutaneous fossa only in some adult males, as well as its correlation with the growth of the interauricular band and the modification of histological components could be the result of hormonal effects influenced by social rank or reproductive condition. Both structures are elements of a coordinated system, whereby the interauricular band is responsible for the production of sebaceous substances associated with the cutaneous fossa.
Localization of gonadotrophin-releasing hormone I, bradykinin and their receptors in the ovaries of non-mammalian vertebrates
Authors: Singh Padmasana , Krishna Amitabh , Sridaran Rajagopala
Published: July 2007

GnRH I and its receptors have been demonstrated in the ovaries of various vertebrates, but their physiological significance in reproductive cascade is fragmentary. Bradykinin is a potent GnRH stimulator in the hypothalamus. In the present study, the presence of GnRH I and its receptor, and bradykinin and its receptor in the ovaries of non-mammalian vertebrates were investigated to understand their physiological significance. GnRH I immunoreactivity in the ovaries of fish, frog, reptile and bird were mainly found in the oocyte of early growing follicles and granulosa cells and theca cells of previtellogenic follicles. Vitellogenic follicles showed mild GnRH immunoreactivity. GnRH I-receptor and bradykinin were localized in the same cell types of the ovaries of these vertebrates. The presence of GnRH I, GnRH I-receptor and bradykinin in the ovaries of these vertebrates was confirmed by immunoblotting. The presence of GnRH I mRNA was demonstrated in the ovary of vertebrates using RT-PCR. The ovaries of reptiles and birds showed significantly higher intensity of immunoreactivity for GnRH I-receptor as compared with the fish and amphibian. This may have a correlation with the higher yolk content in the ovary of reptile and bird. These results suggest the possibility of GnRH I and bradykinin as important regulators of follicular development and vitellogenesis in the vertebrate ovary.
Mast cell degranulation in rat uterine cervix during pregnancy correlates with expression of vascular endothelial growth factor mRNA and angiogenesis
Authors: Bosquiazzo V L , Ramos J G , Varayoud J , Muñoz-de-Toro M , Luque E H
Published: July 2007

Vascular growth of the uterine cervix during pregnancy is associated with mast cell (MC) degranulation. To better understand the mechanism underlying this process, uterine cervices of intact pregnant rats were dissected and endothelial cell proliferation was measured by a bromodeoxyuridine incorporation technique. Total vascular endothelial growth factor (VEGF) mRNA expression and the relative abundance of VEGF splice variants (120, 164, and 188) were determined by RT-PCR. VEGF protein expression was evaluated by immunohistochemistry. To investigate the role of MCs on cervical angiogenesis, a second set of pregnant animals were treated with an MC stabilizer (disodium cromoglycate) to inhibit MC degranulation. Furthermore, 17β-estradiol (E2) serum levels were established by RIA. In intact pregnant rats, VEGF mRNA expression was positively correlated with endothelial cell proliferation and circulating E2 levels. All selected splice variants of VEGF gene were detected and their relative abundance did not show any change throughout pregnancy. Animals treated with disodium cromoglycate showed a decrease in endothelial cell proliferation and in VEGF mRNA expression compared with controls. Relative abundance of VEGF mRNA splice variants and E2 serum levels showed no differences between these experimental groups. These results show a time-dependent correlation between VEGF mRNA expression and E2 serum levels in the uterine cervix of intact pregnant rats, while MC stabilizer-treated animals reduced the VEGF expression without modifying E2 serum levels. We suggest that cervical angiogenesis during pregnancy could be regulated by a mechanism which involves endogenous E2 and chemical mediators stored in MC granules via a VEGF-dependent pathway.
Detection of osteopontin on Holstein bull spermatozoa, in cauda epididymal fluid and testis homogenates, and its potential role in bovine fertilization
Authors: Erikson David W , Way Amy L , Chapman David A , Killian Gary J
Published: July 2007

Osteopontin (OPN) is a secreted extracellular matrix phosphoprotein identified in various tissues and fluids including those of the male and female reproductive tracts. OPN was previously identified as a 55 kDa high fertility marker in Holstein bull seminal plasma, produced by the ampulla and the vesicular gland. The objectives of this study were to characterize OPN on ejaculated and cauda epididymal sperm using immunofluorescence and western blot analysis, and to assess the role of sperm OPN in fertilization. Solubilized sperm membrane proteins from ejaculated and cauda epididymal sperm were separated by 1D SDS-PAGE, transferred to nitrocellulose, and probed with an antibody to bovine milk OPN. A 35 kDa protein was detected by this antibody in both ejaculated and cauda epididymal sperm membranes. Analyses also recognized OPN at 55 and 25 kDa in cauda epididymal fluid and testicular parenchyma homogenates respectively. Immunofluorescent analysis of ejaculated and cauda epididymal sperm showed OPN localization in a well-defined band in the postacrosomal region of the sperm head and also on the midpiece. Results of in vitro fertilization experiments showed that sperm treated with an antibody to OPN fertilized fewer oocytes than sperm treated with control medium while increasing incidence of polyspermy, suggesting a role of sperm-associated OPN in fertilization and a block to polyspermy. These studies demonstrate that OPN exists at multiple molecular weight forms in the bull reproductive tract and its presence on ejaculated sperm may signal its importance in fertilization by interacting with integrins or other proteins on the oocyte plasma membrane.
Regulation of the prostaglandin enzymatic system by estradiol and progesterone in nonpregnant sheep cervix
Authors: Zhang Qi , Collins Valta , Chakrabarty Kaushik , Rose James C , Wu Wen Xuan
Published: July 2007

In the present study, we examined the in vivo effects of estradiol (E2) and progesterone on cyclooxygenase (COX) 2, prostaglandin F synthase (PTGFS, also known as PGFS), and membrane-associated prostaglandin E synthase 1 (mPTGES1) expression at both mRNA and protein levels using a nonpregnant ovariectomized (OVX) sheep model. Sixteen ewes were OVX shortly after ovulation. After 40 days, ewes were treated with saline (Cont, n=5), or E2 infused intravenously for 2 days (50 μg/day, n=5) or intravaginal progesterone (P) sponges for 10 days (0.3 g P, n=6). Cervical COX2, PTGFS, and mPTGES1 mRNA and protein were quantified by northern and western blot analyses respectively. In situ hybridization and/or immunocytochemistry were used to localize the cellular distribution of COX2, PTGFS, and mPTGES1 mRNAs and proteins. COX2 mRNA abundance increased significantly in the cervix after E2 treatment (P<0.05). However, progesterone was a more potent stimulator than E2 of COX2 mRNA and protein abundance in the cervix (P<0.01). In contrast, PTGFS and mPTGES1 mRNA and protein concentrations did not change after E2 or progesterone treatment (P>0.05). COX2, PTGFS, and mPTGES1 mRNA and protein were only localized in cervical glandular epithelial cells. This study shows that increased cervical COX2 mRNA and protein, but not PTGFS and mPTGES1 mRNA and protein, were associated with E2 and progesterone treatment in nonpregnant sheep. More strikingly, progesterone was a more potent stimulator of cervical COX2 expression than E2. The expression of COX2, PTGFS, and mPTGES1 mRNA and/or protein was confined in the cervical glandular epithelial cells of nonpregnant sheep.
Sex-specific expression of a novel gene Tmem184a during mouse testis differentiation
Authors: Svingen Terje , Beverdam Annemiek , Bernard Pascal , McClive Peter , Harley Vincent R , Sinclair Andrew H , Koopman Peter
Published: July 2007

During mouse embryogenesis, the fate of the bipotential gonads is sealed around 10.5 days post coitum (dpc) when the Y-linked gene Sry specifies the differentiation of testes in males, whereas in females, absence of Sry results in ovary formation. Apart from the pivotal action of Sry, many other genes are known to be involved in sex determination and subsequent differentiation. Much is still unknown regarding the regulatory hierarchy governing these events and many more sex differentiation genes are yet to be discovered. In this study, we investigated the expression of Tmem184a, a novel gene encoding a protein of unknown function, but with predicted kinase activity, during mouse embryogenesis. We show that Tmem184a is expressed at high levels in the developing testis from 11.5 dpc, a time of active proliferation and differentiation. Tmem184a expression is further shown to be expressed exclusively within the Sertoli cells of the developing testis cords, suggesting that it may mediate sex-specific signaling events during Sertoli cell differentiation.
“Turnaround time”: a new parameter for the characterization of the overall efficacy of laboratory diagnostic processes
Authors: Antal-Szalmás Péter , Ivády Gergely , Molnár Attila , Hevessy Zsuzsa , Kissné Sziráki Valéria , V. Oláh Anna , Lenkey Ágota , Kappelmayer János
Published: July 2007

Bevezetés:A szerzők a laboratóriumi diagnosztikai tevékenység hatékonyságát jellemző paraméter, az ún. „turnaround time” meghatározására alkalmas számítógépes programot dolgoztak ki laboratóriumukban. A turnaround time a minta laboratóriumba való beérkezése és az orvosi validálást követő eredménykiadás között eltelt idő, mely jól jellemzi az eredménykiadás hatékonyságát, és ezért a laboratóriumok működésének fontos minőségügyi paramétere.Módszer:Analízisük során a sürgős, rutin- és speciális vizsgálatokat külön kezelve 6 hónap adatait dolgozták fel, és a turnaround time medián, 5- és 95-percentil értékeit adták meg. Meghatározták emellett a maximálisnak definiált turnaround time értéket (sürgős 1 óra, rutin 4 óra, speciális 2–14 nap) meghaladó turnaround time értékű vizsgálatok („kiesők”) arányát is az összes vizsgálati számra vonatkoztatva.Eredmények:A sürgős vizsgálatok esetében a medián turnaround time 9–70 perc, a rutinvizsgálatoknál pedig 33–190 perc között volt. A speciális vizsgálatok jóval heterogénebb képet mutattak, és általában megállapítható volt, hogy a kis mintaszámú, nem automatizált, immunkémiai és hemosztázis-tesztek esetében magas a turnaround time értéke és a kiesők aránya. A rutinvizsgálatok longitudinális analízise egyértelműen mutatta, hogy 2006 első félévében javultak a vizsgálatok turnaround time értékei a laboratórium valamennyi részlegén. A turnaround time hosszát befolyásoló egyik lényeges paraméter az orvosi validálás ideje, ami jelentősen csökkenthető egy autovalidáló program segítségével. A szerzők adatai alapján az autovalidálás bevezetése akár 1–2 órával is csökkentette a rutinvizsgálatok medián turnaround time értékeit. Az alkalmazott számítógépes program alkalmas akár a mintaszállítás effektivitásának jellemzésére is, amit a szerzők két különböző mintaszállítási infrastruktúrával rendelkező sürgősségi részlegük összevetésével mutattak be.Következtetések:Az itt ismertetett turnaround time analízis az általános rutin része a világ fejlettebb országaiban tevékenykedő diagnosztikai laboratóriumokban, ugyanakkor az első ilyen próbálkozást jelenti Magyarországon.
Hepatitis B and liver transplantation
Authors: Fehérvári Imre , Görög Dénes , Kóbori László , Varga Marina , Sárvári Enikő , Gerlei Zsuzsa , Nemes Balázs
Published: July 2007

A szerzők elemzik a HBV-fertőzés miatt végzett májátültetés hazai tapasztalatait, áttekintik a HBV okozta májbetegség transzplantáció szempontjából sajátos pre- és posztoperatív kezelési igényeit. A transzplantációs program során 2006. december 31-ig 4 betegnél történt HBV-fertőzés talaján kialakult végstádiumú májbetegség miatt májátültetés. Közülük 1 beteget veszítettek el a korai posztoperatív időszakban, 3 beteg él, aktív. Elemzik a transzplantációt követően 6 esetben észlelt de novo HBV-fertőzést és annak hatását a betegek túlélésére.
Cardiovascular prevention with peripherial artery disease
Authors: Vértes András
Published: July 2007

A perifériás érbetegség globális megbetegedés. Jelenléte esetén emelkedik a cardiovascularis események és halálozás előfordulása. A perifériás érbetegségben szenvedő betegek a nagy CV-rizikójú kategóriába tartoznak. A prevenciós ajánlás alapján PAD jelenléte esetén gyógyszeres és nem gyógyszeres kezelés szükséges. Az életmód-változtatás, vérnyomáscsökkentés, diabetes mellitus kezelése, koleszterin-célértékek elérése, az ACE-gátló, a statin és a thrombocyta-gátló kezelés csökkenti a CV-események előfordulását. A Doppler-index korai meghatározása segíthet az atherothrombosis korai felismerésében.
Exotic Plant Species in Old-Growth Forest in Indiana
Authors: Weber J. S. , Gibson K. D.
Published: July 2007

Old-growth forest in Indiana consists of a few remnant stands in a fragmented agricultural landscape. Old-growth stands can differ substantially from more recently disturbed stands in species composition and may be less susceptible to invasion by exotic plant species. Herbaceous species were sampled in quadrats placed in a repeating pattern along two perpendicular transects in six Old-growth stands in Indiana in spring and summer of 2005. Transects extended from forest edges to the center of each stand. Woody exotic species were sampled in 10-m-wide belts centered on each transect during the summer sampling run. Herbaceous exotic species were a minor component of the understory community in all stands and accounted for less than 1% of total herbaceous cover in all six stands. Exotic woody species generally followed a similar pattern. Four sites contained no more than two woody exotic species, and these were encountered at relatively low frequencies and densities. However, European privet and multiflora rose were present in 27 and 48% of quadrats in one stand, respectively. Thus, although both herbaceous and woody exotic species were relatively rare, heavy infestations of woody exotic species are possible. This suggests that, for some Old-growth sites, exotic species can overcome both local and landscape factors that limit their abundance.
Restoring Species Richness and Diversity in a Russian Knapweed (Acroptilon repens)–infested Riparian Plant Community Using Herbicides
Authors: Sheley Roger L. , Laufenberg Stephen M. , Jacobs James S. , Borkowski John
Published: July 2007

Species richness and diversity are important indicators of ecosystem function and may be related to plant community resistance to invasion by nonindigenous species. Our specific objective was to determine the influence of clopyralid plus 2,4-D, glyphosate, and fosamine, at different application rates and timings, on richness and diversity of total species, total native species, and total nonnative species within a Russian knapweed–infested plant community. Twenty-eight treatments (3 herbicides by 3 rates by 3 application timings, and an untreated control) were applied to two sites located along the Missouri River riparian corridor in Montana. Clopyralid plus 2,4-D, glyphosate, and fosamine were applied in June (spring rosette stage of Russian knapweed), July (bud to bloom stage of Russian knapweed), and August (flowering stage of Russian knapweed). Herbicide rates were clopyralid plus 2,4-D at 0.08 (clopyralid) + 0.42 (2,4-D), 0.13 + 0.67, and 0.18 + 0.92 kg ai ha−1; glyphosate at 0.6, 1.2, and 1.8 kg ai ha−1; fosamine at 3.6, 7.2, and 10.8 kg ai ha−1. Density of each species was recorded during June and August of 2001 and 2002. Species richness and Simpson's Reciprocal Index (1/D) were calculated. By August 2002, only the glyphosate treatment (4.6 species m−2) yielded greater total richness over that of the control (3.5 species m−2). At that time, diversity after applying clopyralid plus 2,4-D remained similar to that of the control (1.4), but glyphosate (2.3) and fosamine (2.0) increased total species diversity. Nonnative grasses and forbs accounted for the increases in richness and diversity. Glyphosate may be appropriate for enhancing ecosystem function and possibly niche occupation to preempt reinvasion by Russian knapweed, but restoring native species seems unlikely using any of these herbicides alone.
Ex Vivo Gene Therapy for Hemophilia A That Enhances Safe Delivery and Sustained In Vivo Factor VIII Expression from Lentivirally Engineered Endothelial Progenitors
Authors: Matsui Hideto , Shibata Masaru , Brown Brian , Labelle Andrea , Hegadorn Carol , Andrews Chandler , Hebbel Robert P. , Galipeau Jacques , Hough Christine , Lillicrap David
Published: July 2007

Novel therapeutic strategies for hemophilia must be at least as effective as current treatments and demonstrate long-term safety. To date, several small clinical trials of hemophilia gene transfer have failed to show the promise of preclinical evaluations. Therefore, we wanted to develop and evaluate the feasibility of a novel ex vivo gene transfer strategy whereby cells derived from progenitor cells are engineered to express factor VIII (FVIII) and then implanted subcutaneously to act as a depot for FVIII expression. Circulating blood outgrowth endothelial cells (BOECs) were isolated from canine and murine blood and transduced with a lentiviral vector encoding the canine FVIII transgene. To enhance safety, these cells were implanted subcutaneously in a Matrigel scaffold, and the efficacy of this strategy was compared with i.v. delivery of engineered BOECs in nonhemophilic nonobese diabetic/severe combined immunodeficiency mice. Therapeutic levels of FVIII persisted for 15 weeks, and these levels of stable expression were extended to 20 weeks when the cytomegalovirus promoter was replaced with the thrombomodulin regulatory element. Subsequent studies in immunocompetent hemophilic mice, pretreated with tolerizing doses of FVIII or with transient immunosuppression, showed therapeutic FVIII expression for 27 weeks before the eventual return to baseline levels. This loss of transgene expression appears to be due to the disappearance of the implanted cells. The animals treated with either of the two tolerizing regimens did not develop anti-FVIII antibodies. Biodistribution analysis demonstrated that BOECs were retained inside the subcutaneous implants. These results indicate, for the first time, that genetically modified endothelial progenitor cells implanted in a subcutaneous scaffold can provide sustained therapeutic levels of FVIII and are a promising and safe treatment modality for hemophilia A.

Disclosure of potential conflicts of interest is found at the end of this article.
Molecular and Secretory Profiles of Human Mesenchymal Stromal Cells and Their Abilities to Maintain Primitive Hematopoietic Progenitors
Authors: Wagner Wolfgang , Roderburg Christoph , Wein Frederik , Diehlmann Anke , Frankhauser Maria , Schubert Ralf , Eckstein Volker , Ho Anthony D.
Published: July 2007

Mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment and are able to maintain the self-renewal capacity of hematopoietic progenitor cells (HPC). Isolation procedures for MSC vary extensively, and this may influence their biologic properties. In this study, we have compared human MSC isolated from bone marrow (BM) using two culture conditions, from cord blood (CB), and from adipose tissue (AT). The ability to maintain long-term culture-initiating cell frequency and a primitive CD34+CD38− immunophenotype was significantly higher for MSC derived from BM and CB compared with those from AT. These results were in line with a significantly higher adhesion of HPC to MSC from BM and CB versus MSC from AT. We have compared the cytokine production of MSC by cytokine antibody arrays, enzyme-linked immunosorbent assay, and a cytometric bead array. There were reproducible differences in the chemokine secretion profiles of various MSC preparations, but there was no clear concordance with differences in their potential to maintain primitive function of HPC. Global gene expression profiles of MSC preparations were analyzed and showed that adhesion proteins including cadherin-11, N-cadherin, vascular cell adhesion molecule 1, neural cell adhesion molecule 1, and integrins were highly expressed in MSC preparations derived from BM and CB. Thus, MSC from BM and CB are superior to MSC from AT for maintenance of primitive HPC. The latter property is associated with specific molecular profiles indicating the significance of cell-cell junctions but not with secretory profiles.

Disclosure of potential conflicts of interest is found at the end of this article.
Diffuse pollution in Japan: issues and perspectives
Authors: Yamada K.
Published: July 2007

Many parts of Japan have experienced rapid urbanization and industrialization over the past 50 years. This trend resulted in severe water pollution in many urban areas. To address the pollution problems, several measures such as construction of sewerage systems and enactment of laws and regulations have been undertaken. Because of these measures, the water quality has been improved to some extent. However, many water quality concerns still remain and are attributed in part to diffuse pollution. In this paper, historical progress, present situation and future aspects of diffuse pollution problems in Japan are reviewed. It is noted that solving diffuse pollution problems will require a combination of several measures including application of conventional treatment technologies and natural purification systems, implementation of appropriate policy measures, and promotion of citizen participation.
Emission reduction by multipurpose buffer strips on arable fields
Authors: Sloots K. , van der Vlies A.W.
Published: July 2007

In the area managed by Hollandse Delta, agriculture is under great pressure and the social awareness of the agricultural sector is increasing steadily. In recent years, a stand-still has been observed in water quality, in terms of agrochemicals, and concentrations even exceed the standard. To improve the waterquality a multi-purpose Field Margin Regulation was drafted for the Hoeksche Waard island in 2005. The regulation prescribes a crop-free strip, 3.5 m wide, alongside wet drainage ditches. The strip must be sown with mixtures of grasses, flowers or herbs. No crop protection chemicals or fertilizer may be used on the strips. A total length of approximately 200 km of buffer strip has now been laid. Besides reducing emissions, the buffer strips also stimulate natural pest control methods and encourage local tourism. Finally, the strips should lead to an improvement in the farmers' image. The regulation has proved to be successful. The buffer strips boosted both local tourism and the image of the agricultural sector. Above all, the strips provided a natural shield for emission to surface water, which will lead to an improvement of the water quality and raise the farmers' awareness of water quality and the environment.
HSPF-Paddy simulation of water flow and quality for the Saemangeum watershed in Korea
Authors: Jeon J.-H. , Yoon C.G. , Jung K.-W. , Jang J.-H.
Published: July 2007

The Hydrological Simulation Program–FORTRAN (HSPF) is a comprehensive model that was developed to simulate many processes related to water flow and quality in watersheds of almost any size and complexity. Paddy rice fields often dominate extensive portions of the landscape in the Asian monsoon region. The hydrological and environmental conditions of paddy fields differ somewhat from those of other land uses, and HSPF may not adequately simulate watersheds in paddy farming regions. HSPF was previously modified to HSPF-Paddy; here, we examined the applicability of the modified model. The model was applied to simulate the water flow and quality of the Saemangeum watershed (2523 km2) in Korea, where paddy rice fields comprise about one-third of the total watershed area. Long-term monitoring data (5 years for water flow, 10 years for water quality) were used in the calibration and verification processes. Model performance was in the range of “very good” and “good” based on model efficiency (R2) and percent difference. The accuracy of the daily simulation was lower than that of monthly simulation for water flow. The water-quality simulation results were encouraging for this sizable watershed with mixed land uses; HSPF-Paddy proved adequate, and its application is recommended to simulate watershed processes in paddy farming regions.
Biosorption of lead(II) and copper(II) from stormwater by brown seaweed Sargassum sp.: Batch and column studies
Authors: Perumal S.V. , Joshi U.M. , Karthikeyan S. , Balasubramanian R.
Published: July 2007

This study evaluated the potential use of brown seaweed Sargassum sp to sequester lead and copper (Pb(II) and Cu(II)) from urban runoff based on batch as well as column experiments. The equilibrium data exhibited Langmuir isotherms. The adsorption capacity of this seaweed was found to be 196.1 mg g−1 and 84.0 mg g−1 for Pb(II) and Cu(II), respectively, which are in good agreement with those values obtained for the aqueous solution (188.6 mg g−1 for Pb(II) and 86.9 mg g−1 for Cu(II)). The functional group analysis of the seaweed using FTIR demonstrated that the carboxyl functional groups are mainly responsible for biosorption. The cation exchange capacity of the biosorbent was 2.25 meq/g. This observation suggested that ion exchange mechanism is predominantly responsible for the metal ion uptake. The column study showed that the highest bed height and the lowest flow rate result in a substantial enhancement of the metals uptake with the biosorption uptake capacities being 264.3 mg Pb(II) g−1 and 86.0 mg Cu(II) g−1. In the binary system, the biosorption capacity was observed to be 208.7 mg Pb(II) g−1 and 61.0 mg Cu(II) g−1. The predicted breakthrough curves by the Thomas adsorption model gave a good fit of the experimental data with r2 ranging from 0.92 to 0.99.
Treatment of winery wastewater in a conventional municipal activated sludge process: five years of experience
Authors: Bolzonella D. , Zanette M. , Battistoni P. , Cecchi F.
Published: July 2007

A full-scale wastewater treatment plant where municipal and winery wastewaters were co-treated was studied for five years. The experimental results showed that suspended solids, COD, nitrogen and phosphorous were effectively removed both during the treatment of municipal wastewater and the co-treatment of municipal and winery wastewater. The sludge production increase from 4 tons to 5.5 tons per day during the harvesting and wine making period. In any case the specific sludge production was 0.2 kgMLVSS per kgCODremoved despite the organic loading increasing. About 70% of the COD was removed through respiration. Also the energy demand increased from 6,000 to 7,000 kWh per day. The estimated costs for the treatment of the winery wastewater was 0.2–0.3 Euros per m3 of treated wastewater. With reference to the process efficiency, the nitrogen removal was just 20%. The co-treatment of municipal and winery wastewater in conventional activated sludge processes can be a feasible solution for the treatment of these streams at relatively low costs.
Winery wastewater treatment by constructed wetlands and the use of treated wastewater for cash crop production
Authors: Mulidzi A.R.
Published: July 2007

A 45 m long, 4 m wide and 1 m deep wetland was constructed at Goudini in 2002 to treat distillery and winery effluent. After the plants were fully established, the wastewater with an average chemical oxygen demand (COD) of 14,000 mg/l was introduced to the wetland system at a rate of 4,050 litres per day. After treatment, wastewater at the outlet had an average COD of 500 mg/ l, indicating more than 90% COD removal. After treatment, the wastewater was used to irrigate cash crops as part of poverty alleviation for farm workers. The experiment consisted of four treatment: clean irrigation water with fertilizer applied (B1); clean irrigation water without fertilizer applied (B2); wastewater irrigation with fertilizer applied (B3); and wastewater irrigation without fertilizer applied (B4). These were replicated seven times. Cabbage was cultivated as a cash crop. The results indicated that cabbage could be irrigated with winery wastewater treated by wetlands. The study found that there was significant difference between treatments that were fertilized compared with those that were not fertilized. The results indicated that wastewater irrigation improved the nutritional status of the soil.