bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically Modified Autoactivated Cells Expressing Intracellular Forms of GM‐CSF as a Model for Regulated Administration of Cytokines
Authors: Arteaga H. J. , Mohamed A. J. , Christensson B. , Mahdy E. , Gahrton G. , Smith C. I. E. , Dilber M. S. 
Published: November 2005

AbstractThe application of cytokines for immunotherapy is frequently hampered by undesirable side effects. To avoid systemic effects, cytokines can be directly expressed in the target cells by using gene transfer. However, the uncontrolled cellular secretion of cytokines could still exert some undesirable bystander effects. Therefore, it is important to develop additional methods for a more restricted administration of cytokines. Recently, using the murine granulocyte–macrophage colony‐stimulating factor (mGM‐CSF), we have demonstrated that cytokines can be targeted to different subcellular compartments as stable and biologically active proteins. This model could be used as a method of highly restricted administration of cytokines. Here, as model for the proof of principle, we have used a cell line (DA‐3) strictly dependent on mGM‐CSF for growth and demonstrated that these cells acquired autonomous growth after gene modification with plasmids encoding either extracellular or intracellular forms of mGM‐CSF. Cell lines expressing secreted forms of mGM‐CSF displayed the highest rates of autonomous growth and released substantial amounts of mGM‐CSF. However, cell lines expressing intracellular forms of mGM‐CSF also acquired autonomous growth induced by a mechanism of restricted autocrine stimulation and did not release detectable mGM‐CSF to the extracellular medium. Cocultivation experiments of DA‐3 cell lines expressing intracellular mGM‐CSF with unmodified cells showed that there was no activation of the bystander cells. Taken together, these results support the concept that genes encoding intracellular cytokines may be used to provide the desired effect of cytokines on the target cells while avoiding the side effects of their uncontrolled secretion.
The BAFF/APRIL System in Systemic Autoimmune Diseases with a Special Emphasis on Sjögren's Syndrome
Authors: Szodoray P. , Jonsson R. 
Published: November 2005

AbstractSystemic autoimmune diseases, such as Sjögren's syndrome (SS), are characterized by a complex aetiology with multiple pathogenic factors. In SS, disturbed B‐cell biology and humoral immunity including B‐cell‐activating factor (BAFF)‐mediated processes have been described. Dysregulated BAFF expression has been described to lead to disease progression and perpetuation of humoral autoimmunity. Moreover, BAFF has been proposed to contribute to the development of B‐cell malignancies. In this review, we summarize the current knowledge on BAFF with regard to SS pathology and discuss special features such as germinal centre (GC) formation and lymphomagenesis. Locally, in SS salivary glands, the reduced level of apoptosis among BAFF‐expressing cells might lead to longer‐existing BAFF expression and thereby maintain signalling for tissue‐infiltrating B cells to proliferate and supposedly to become autoantibody‐producing plasma cells. We assume that prolonged BAFF signalization may contribute to GC formation and/or lymphoma development in the disease. Finally, we discuss possibilities of novel treatments targeting the BAFF‐system in SS.
No Role of α‐Gal in Human Monocyte–Endothelial Cell Interactions in Vitro
Authors: Ehrnfelt C. , He Z. , Holgersson J. 
Published: November 2005

AbstractVascularized organ xenografts undergoing acute vascular rejection (AVR) are infiltrated by innate immune cells such as monocytes/macrophages. Herein, human monocyte static and dynamic adhesion to, and migration across, human and porcine aortic endothelial cells (HAEC and PAEC) were investigated. To elucidate the role of Galα1,3Gal (α‐Gal) epitopes in these processes in the absence of anti‐Gal antibodies (Ab), this determinant was aberrantly expressed in HAEC. HAEC were transduced with a lentiviral vector encoding the porcine α1,3 galactosyltransferase to express α‐Gal at high frequencies (75–95%). α‐Gal expression on HAEC did not increase their ability to support monocyte transendothelial migration or adhesion under either static or flow conditions. Porcine and human endothelium supported static adhesion and migration of monocytes equally well. However, human monocytes adhered less to PAEC than to HAEC (P = 0.03) under flow following human, but not porcine, tumour necrosis factor‐α stimulation. In the absence of anti‐Gal Ab, the α‐Gal epitope does not contribute to increased monocyte adhesion to, or migration across, endothelium. Thus, inhibiting adhesion receptor–ligand interactions essential for the adhesion of human monocytes to porcine endothelium may be more important than carbohydrate remodelling of donor pigs to prevent adhesion/infiltration of monocytes into organ xenografts during AVR.
The prognostic value of p53, Ki‐67 and matrix metalloproteinases MMP‐2 and MMP‐9 in transitional cell carcinoma of the renal pelvis and ureter
Authors: KAMIJIMA SHUICHI , TOBE TOYOFUSA , SUYAMA TAKAHITO , UEDA TAKESHI , IGARASHI TATSUO , ICHIKAWA TOMOHIKO , ITO HARUO 
Published: November 2005

Aim: To investigate the prognostic and predictive relevance of p53 protein, Ki‐67 antigen, MMP‐2 and MMP‐9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract.Methods: The expression of p53 protein, Ki‐67 antigen, MMP‐2 and MMP‐9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki‐67, MMP‐2 and MMP‐9 over‐expression with conventional pathological parameters and patient survival was examined.Results: p53 over‐expression was signiﬁcantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki‐67 over‐expression was signiﬁcantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki‐67 over‐expression was a signiﬁcant prognostic factor in the univariate analysis (P < 0.05), but it did not have a signiﬁcant impact on survival in the multivariate analysis. Ki‐67 labeling index was a signiﬁcant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index.Conclusion: Ki‐67 over‐expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP‐2 and MMP‐9 are of limited value.
Factors inﬂuencing practices for chronic prostatitis: A nationwide survey of urologists in South Korea
Authors: KU JA HYEON , PAICK JAE‐SEUNG , KIM SOO WOONG 
Published: November 2005

Background: We investigated the inﬂuence of physicians’ attitudes on the treatment of chronic prostatitis, and attempted to correlate demographic and professional characteristics with patterns of therapy regarding chronic prostatitis.Methods: Probability samples were drawn from the Korean Urological Association Registry of Physicians, and a random sample of 850 Korean urologists were asked to complete a questionnaire which explored practice characteristics, attitudes, and diagnostic and treatment strategies for the management of chronic prostatitis. The returned questionnaires were statistically analysed.Results: Of the 850 questionnaires sent, 302 were returned, and 275 of those were included in the ﬁnal analysis (response rate 32.4%). Multivariate logistic regression analysis indicated that the type of hospital (P < 0.001) and belief that culture tests helped diagnose chronic prostatitis (P = 0.001) were the most determinant factors with respect to the routine performance or non‐performance of culture tests. Most Korean urologists (96.4%) prescribed antibiotics for the primary treatment of chronic prostatitis. Even when primary antibiotic treatment was unsuccessful, urologists frequently prescribed a second course of antibiotics (57.8%). In the multivariate model used, the likelihood of prescribing antibiotics as a secondary treatment varied by the type of hospital, with 0.4‐fold odds (odds ratio [OR], 0.43; 95% conﬁdence interval [CI], 0.21–0.87; P = 0.019) of the practice occurring in university hospitals, as opposed to primary clinics. According to the same model, the belief that culture tests help to diagnose chronic prostatitis was also an independent inﬂuencing factor (OR, 2.29; 95% CI, 1.39–3.77; P = 0.001), whereas the actual performance of culture tests had no statistical signiﬁcance.Conclusion: Our ﬁndings suggest that the personal beliefs and professional characteristics of physicians may inﬂuence the diagnosis and treatment of chronic prostatitis in Korea.
Identification and validation of risk factors for vesicourethral leaks following radical retropubic prostatectomy
Authors: GNANAPRAGASAM VINCENT J , BAKER PAUL , NAISBY GEOFFREY P , CHADWICK DAVID 
Published: November 2005

Aims: To identify risk factors for anastomotic leaks at cystography following radical retropubic prostatectomy (RRP).Methods: In phase 1 the records of a 107 RRP patients were reviewed. Data collected included comorbidity, pathological factors and intra‐ and postoperative complications. From these, risk factors were identified that were associated with a leak at cystography. In phase 2 (n = 46) we prospectively tested if the risk factors identified could predict an anastomotic leak.Results: In phase 1 the only identifiable risk factors were that of a difficult anastamosis, an unsatisfactory intraoperative test flush and the presence of a urinary tract infection. One or more of these events were found in 17/25 (68%) of the patients who leaked (P < 0.0001). Of the eight leaks missed, five were classed as minimal and did not require repeat cystography. Within the prospective phase 2 cohort one or more risk factors were present in 7/10 (70%) of the patients who leaked. In contrast, the identified risk factors were present in only 5/36 (13.8%) of the patients who did not leak (P < 0.001). The specificity of the test was 86.1% with a sensitivity of 70%. This gave a positive predictive value of 58.3% and a negative predictive value of 91.1%. Three leaks (two minimal and one moderate) would have been missed but 31 (67.3%) patients would have avoided an unnecessary radiological study.Conclusion: Using a retrospective and prospective cohort of patients we have shown that a cystogram following RRP can be safely avoided in the absence of the identified risk factors.
Is there a possible correlation between chromosomal variants and spermatogenesis?
Authors: YAKIN KAYHAN , BALABAN BASAK , URMAN BULENT 
Published: November 2005

Aim: Heterochromatin polymorphism is considered a variant of a normal karyotype but is more frequent in infertile men. The aim of this study was to evaluate the correlation between heterochromatic variants and male infertility and to discuss the possible mechanisms of how heterochromatic polymorphism might affect spermatogenesis.Methods: Cytogenetic analysis was undertaken in 210 infertile males who had been taken into assisted reproductive techniques and in 183 men with proven fertility. Additionally, C‐banding was performed in men with heterochromatin polymorphism. Sperm ﬂuorescence in situ hybridization (FISH) was applied in 54 men with normal karyotype presenting either normal or abnormal sperm parameters as well as in 8 men with heterochromatin polymorphism. The outcomes of assisted reproductive techniques were compared between infertile men with normal karyotype and men with heterochromatin polymorphism.Results: The incidence of heterochromatin polymorphism was higher in infertile men. The most frequent chromosome involved in heterochromatin polymorphism was chromosome 9. Sperm FISH analysis revealed an increased rate of aneuploidy in men with heterochromatin polymorphism. Laboratory and clinical outcomes in assisted reproductive techniques were compromised in men with heterochromatin polymorphism.Conclusions: An increased rate of heterochromatin polymorphism in infertile males seems to be more than an incidental ﬁnding, and must not be considered as a normal variant. Polymorphic heterochromatin may have deleterious effects on the genetic constitution of spermatozoa. More attention must be directed to infertile men with heterochromatin polymorphism.
Signiﬁcance of routine transition zone biopsies in Japanese men undergoing transrectal ultrasound‐guided prostate biopsies
Authors: MIYAKE HIDEAKI , KURAHASHI TOSHIFUMI , MURAMAKI MOTOTSUGU , YAMANAK KAZUKI , HARA ISAO 
Published: November 2005

Background: The objective of this study was to evaluate the clinical signiﬁcance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)‐guided systematic 8‐core peripheral zone (PZ) biopsies.Methods: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS‐guided systematic biopsy of the prostate for the ﬁrst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens.Results: Prostate cancer was detected by 10‐core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed signiﬁcantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone.Conclusions: Routine TZ biopsy did not signiﬁcantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.
Synchronized network activity in developing rat hippocampus involves regional hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channel function
Authors: Bender Roland A. , Galindo Rafael , Mameli Manuel , Gonzalez‐Vega Rebeca , Valenzuela C. Fernando , Baram Tallie Z. 
Published: November 2005

AbstractThe principal form of synchronized network activity in neonatal hippocampus consists of low frequency ‘giant depolarizing potentials’ (GDPs). Whereas contribution of both GABA and glutamate to their generation has been demonstrated, full understanding of the mechanisms underlying these synchronized activity bursts remains incomplete. A contribution of the h‐current, conducted by HCN channels, to GDPs has been a topic of substantial interest. Here we focus on HCN1, the prevalent HCN channel isoform in neonatal hippocampus, and demonstrate an HCN1 spatiotemporal expression pattern in both CA3 principal cells and interneurons that correlates with the developmental profile of GDPs. Abrogation of HCN physiological function in CA3, via the selective Ih‐blocker ZD7288, disrupts GDP generation. Furthermore, ZD7288 specifically abolishes spontaneous bursting of the CA3 pyramidal cells at frequencies typical of GDPs without major influence on interneuronal firing. These findings support a pivotal role for HCN channels expressed by CA3 neurons, and particularly CA3 pyramidal cells, in GDP‐related network synchronization.
Basolateral amygdala glutamatergic activation enhances taste aversion through NMDA receptor activation in the insular cortex
Authors: Ferreira G. , Miranda M.I. , De la Cruz V. , Rodríguez‐Ortiz C.J. , Bermúdez‐Rattoni F. 
Published: November 2005

AbstractIn conditioned taste aversion (CTA), a subject learns to associate a novel taste with visceral malaise. Brainstem, limbic and neocortical structures have been implicated in CTA memory formation. Nevertheless, the role of interactions between forebrain structures during these processes is still unknown. The present experiment was aimed at investigating the possible interaction between the basolateral nucleus of the amygdala (BLA) and the insular cortex (IC) during CTA memory formation. Injection of a low dose of lithium chloride (30 mg/kg, i.p.) 30 min after novel taste consumption (saccharin 0.1%) induces a weak CTA. Unilateral BLA injection of glutamate (2 µg in 0.5 µL) just before low lithium induces a stronger CTA. Unilateral injection of an N‐methyl‐d‐aspartate (NMDA) receptor antagonist (AP5, 5 µg in 0.5 µL) in IC has no effect. However, AP5 treatment in IC at the same time or 1 h after the ipsilateral BLA injection reverses the glutamate‐induced CTA enhancement. Injection of AP5 in IC 3 h after BLA injection does not interfere with the glutamate effect. Moreover, the CTA‐enhancing effect of glutamate was also blocked by contralateral IC injection of AP5 at the same time. These results provide strong evidence that NMDA receptor activation in the IC is essential to enable CTA enhancement induced by glutamate infusion in the BLA during a limited time period that extends to 1 but not to 3 hours. These findings indicate that BLA–IC interactions regulate the strength of CTA. The bilateral nature of these amygdalo–cortical interactions is discussed.
A lateralized avian hippocampus: preferential role of the left hippocampal formation in homing pigeon sun compass‐based spatial learning
Authors: Gagliardo Anna , Vallortigara Giorgio , Nardi Daniele , Bingman Verner P. 
Published: November 2005

AbstractThe hippocampal formation (HF) plays a crucial role in amniote spatial cognition. There are also indications of functional lateralization in the contribution of the left and right HF in processes that enable birds to navigate space. The experiments described in this study were designed to examine left and right HF differences in a task of sun compass‐based spatial learning in homing pigeons (Columba livia). Control, left (HFL) and right (HFR) HF lesioned pigeons were trained in an outdoor arena to locate a food reward using their sun compass in the presence or absence of alternative feature cues. Subsequent to training, the pigeons were subjected to test sessions to determine if they learned to represent the goal location with their sun compass and the relative importance of the sun compass vs. feature cues. Under all test conditions, the control pigeons demonstrated preferential use of the sun compass in locating the goal. By contrast, the HFL pigeons demonstrated no ability to locate the goal by the sun compass but an ability to use the feature cues. The behaviour of the HFR pigeons demonstrated that an intact left HF is sufficient to support sun compass‐based learning, but in conflict situations and in contrast to controls, they often relied on feature cues. In conclusion, only the left HF is capable of supporting sun compass‐based learning. However, preferential use of the sun compass for learning requires an intact right HF. The data support the hypothesis that the left and right HF make different but complementary contributions toward avian spatial cognition.
Delaying visually guided saccades by microstimulation of macaque V1: spatial properties of delay fields
Authors: Tehovnik Edward J. , Slocum Warren M. , Schiller Peter H. 
Published: November 2005

AbstractElectrical microstimulation of macaque primary visual cortex (area V1) is known to delay the execution of saccadic eye movements made to a punctate visual target placed into the receptive field of the stimulated neurons. We examined the spatial extent of this delay effect, which we call a delay field, by placing a 0.2° visual target at various locations relative to the receptive field of the stimulated neurons and by stimulating different sites within the operculum of V1. A 100‐ms train of stimulation consisting of current pulses at or less than 100 µA was delivered immediately before monkeys generated a saccadic eye movement to the visual target. The region of tissue activated was within 0.5 mm from the electrode tip. The depth of stimulation for a given site ranged from 0.9 to 2.0 mm below the cortical surface. The location of the receptive fields of the stimulated neurons ranged from 1.8 to 4.4° of eccentricity from the center of gaze. Within this range, the size of the delay field increased from 0.1 to 0.55° of visual angle. The shape of the field was roughly circular. The size of the delay field increased as the stimulation site was located further from the foveal representation of V1. These results are consistent with the finding that phosphenes evoked by electrical stimulation of human V1 are circular and increase in size as the stimulating electrode is placed more distant from the foveal representation of V1.
Regional enrichment of local assemblages is robust to variation in local productivity, abiotic gradients, and heterogeneity
Authors: Freestone Amy L. , Harrison Susan 
Published: November 2005

AbstractTheory predicts that the effects of regional richness on the richness of local communities may depend on the productivity, resource availability, and/or heterogeneity of local sites. Using the wetland plant communities of 50 independent streams as ‘regions’, we tested whether: (1) local richness in 1‐m2 quadrats and 50‐m stream segments was positively related to regional richness, even after environmental influences were considered; and (2) the effect of regional richness would interact with the effects of biomass, soil moisture, and/or heterogeneity on local richness. In models that explained up to 88% of variation in local richness, we found that richness at both local scales was positively related to regional richness, and that regional richness did not interact with any of the environmental gradients that also shaped local richness. We conclude that species availability from the regional pool may consistently enrich local communities, even while other constraints on local richness operate.
Interactions between arbuscular mycorrhizal fungi and bacteria and their potential for stimulating plant growth
Authors: Artursson Veronica , Finlay Roger D. , Jansson Janet K. 
Published: November 2005

SummaryArbuscular mycorrhizal (AM) fungi and bacteria can interact synergistically to stimulate plant growth through a range of mechanisms that include improved nutrient acquisition and inhibition of fungal plant pathogens. These interactions may be of crucial importance within sustainable, low‐input agricultural cropping systems that rely on biological processes rather than agrochemicals to maintain soil fertility and plant health. Although there are many studies concerning interactions between AM fungi and bacteria, the underlying mechanisms behind these associations are in general not very well understood, and their functional properties still require further experimental confirmation. Future mycorrhizal research should therefore strive towards an improved understanding of the functional mechanisms behind such microbial interactions, so that optimized combinations of microorganisms can be applied as effective inoculants within sustainable crop production systems. In this context, the present article seeks to review and discuss the current knowledge concerning interactions between AM fungi and plant growth‐promoting rhizobacteria, the physical interactions between AM fungi and bacteria, enhancement of phosphorus and nitrogen bioavailability through such interactions, and finally the associations between AM fungi and their bacterial endosymbionts. Overall, this review summarizes what is known to date within the present field, and attempts to identify promising lines of future research.