bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of OV‐6 in primary colorectal cancer and rectal cancer with preoperative chemoradiotherapy: a clinicopathological study
Authors: Lin Chih‐Hung , Liu Chia‐Hsing , Tsai Hsiang‐Lin , Wang Jaw‐Yuan , Tsai Hung‐Pei , Chai Chee‐Yin 
Published: November 2012

AimsOV‐6 is among the best available markers of liver stem cells. The aim of this study was to investigate OV‐6 expression and its clinical implications in colorectal cancer.Methods and resultsExpression of OV‐6 and its clinical implications were investigated in 94 patients with American Joint Committee on Cancer (AJCC) stage I–III primary colorectal cancer and in 37 rectal cancer patients who had received preoperative chemoradiotherapy. The two main expression patterns of OV‐6 were cytoplasmic and membranous. Overexpression of OV‐6, which was identified on the basis of overall staining intensity, was associated with perineural invasion, lymphovascular invasion, and early relapses. Membranous OV‐6 overexpression was also significantly associated with depth of tumour invasion, AJCC stage, lymphovascular and perineural invasion, and postoperative early relapse. Disease‐free survival and overall survival were significantly poorer in patients with high overall OV‐6 expression than in those with low overall OV‐6 expression (P = 0.015 and P = 0.029, respectively), and significantly poorer in patients with high membranous OV‐6 expression than in those with low membranous OV‐6 expression (P < 0.001 and P < 0.001, respectively). Membranous OV‐6 expression was a more reliable prognostic marker than overall expression.ConclusionsOV‐6 is not unique to the hepatobiliary system, and may be a novel prognostic marker in colorectal cancer.
The infarct‐limiting effect of cerebral ischaemic postconditioning in rats depends on the middle cerebral artery branching pattern
Authors: Shcherbak Natalia , Popovetsky Maxim , Galagudza Michael , Barantsevitch Eugene , Shlyakhto Eugene 
Published: November 2012

SummaryCerebral ischaemic postconditioning (PostCon) is a recently discovered endogenous neuroprotective phenomenon that occurs after several brief bouts of reperfusion/ischaemia instituted immediately after prolonged cerebral ischaemia. Data on the extent of PostCon‐mediated infarct size limitation in models of focal cerebral ischaemia–reperfusion are controversial. In this study, we investigated the infarct‐limiting effect of PostCon in the rat model of focal cerebral ischaemia–reperfusion. The relationship between anatomic pattern of the middle cerebral artery (MCA) and infarct size was also studied. The protocol of PostCon consisting of five episodes each of 10‐s ischaemia and 10‐s reperfusion was protective in terms of infarct size limitation only in animals with the typical bifurcating MCA branching pattern. The anatomic pattern of the MCA should be considered as one of the important factors influencing the outcome of neuroprotection studies.
Evolution of the biochemistry of the photorespiratory C2 cycle
Authors: Hagemann M. , Fernie A. R. , Espie G. S. , Kern R. , Eisenhut M. , Reumann S. , Bauwe H. , Weber A. P. M. 
Published: November 2012

AbstractOxygenic photosynthesis would not be possible without photorespiration in the present day O2‐rich atmosphere. It is now generally accepted that cyanobacteria‐like prokaryotes first evolved oxygenic photosynthesis, which was later conveyed via endosymbiosis into a eukaryotic host, which then gave rise to the different groups of algae and streptophytes. For photosynthetic CO2 fixation, all these organisms use RubisCO, which catalyses both the carboxylation and the oxygenation of ribulose 1,5‐bisphosphate. One of the reaction products of the oxygenase reaction, 2‐phosphoglycolate (2PG), represents the starting point of the photorespiratory C2 cycle, which is considered largely responsible for recapturing organic carbon via conversion to the Calvin–Benson cycle (CBC) intermediate 3‐phosphoglycerate, thereby detoxifying critical intermediates. Here we discuss possible scenarios for the evolution of this process toward the well‐defined 2PG metabolism in extant plants. While the origin of the C2 cycle core enzymes can be clearly dated back towards the different endosymbiotic events, the evolutionary scenario that allowed the compartmentalised high flux photorespiratory cycle is uncertain, but probably occurred early during the algal radiation. The change in atmospheric CO2/O2 ratios promoting the acquisition of different modes for inorganic carbon concentration mechanisms, as well as the evolutionary specialisation of peroxisomes, clearly had a dramatic impact on further aspects of land plant photorespiration.
The ‘green whistle’: A novel method of analgesia for transrectal prostate biopsy
Authors: Grummet Jeremy , Huang Sean , Konstantatos Alex , Frydenberg Mark 
Published: November 2012

AbstractWhat's known on the subject? and What does the study add?Periprostatic infiltration of local anaesthetic (PILA) is accepted as the current ‘gold standard’ of analgesia for TRUS‐guided biopsy. However, it does not account for discomfort of anal probe insertion and has not received wide uptake amongst clinicians. A better method is therefore sought. PenthroxTM (methoxyflurane) is an effective systemic analgesic that is self‐administered via a hand‐held inhaler. Its use in TRUS‐guided biopsy has not been previously reported.An initial experience with a novel analgesic for TRUS‐guided biopsy, which appears to be safe and effective. It has led to the planning of a randomised control trial, which will compare Penthrox with PILA for TRUS‐guided biopsy.Objectives
To determine the feasibility of using a novel inhaled analgesic agent (PenthroxTM, methoxyflurane)) for transrectal ultrasonography (TRUS)‐guided biopsies of the prostate.
Patients and methods
Patients undergoing TRUS‐guided biopsies were each given a Penthrox inhaler to self‐administer during the procedure and instructed in its use.
Immediately after the procedure, patients were asked to rate their pain using a verbal rating scale from 0 to 10.
Results
In all, 42 consecutive men underwent a TRUS‐guided biopsy.
The median pain score was 3.
All 42 patients stated they would be happy to undergo the same procedure again. The only adverse effects reported by patients were brief light‐headedness and a sickly sweet taste.
Conclusion
This study of our initial experience using Penthrox suggests that it may have a role in analgesia for TRUS‐guided biopsy.
It may provide safe, adequate analgesia that is easy for urologists to use and avoids excessive use of resources.
Planning for a randomised control trial comparing Penthrox to the current ‘gold standard’ of prostatic infiltration of local anaesthetic is presently underway.
Renal angiomyolipoma
Authors: Lienert Andrew R. , Nicol David 
Published: November 2012

AbstractWhat's known on the subject? and What does the study add?Renal angiomyolipomas (AMLs) were first described in 1900 by Grawitz when he published a description of a large renal tumour composed of fat, muscle and blood vessels. Over the subsequent 100 years a lot has been discovered about the AML of the kidney. Initially, it was thought to be a hamartoma, an abnormal proliferation of tissues that are normally present in the kidney. More recent studies and observations have led to these lesions being classed a form of neoplasm of the renal parenchyma.The present paper is a review of the presenting features of renal AMLs, as well as an overview of how they are diagnosed and some of the difficulties in diagnosis. It is aimed as a brief overview of the presenting features and diagnostics of renal AMLs. We hope it will be useful to refresh the knowledge of practicing urologists and as a study aid for training urologists.
Renal angiomyolipomas (AMLs) are usually easy to diagnose with imaging alone. They have unique characteristics on ultrasonography, computerised tomography and magnetic resonance imaging that usually allow AMLs to be differentiated from other renal masses.
If this is not possible on imaging criteria then biopsy can be performed and AMLs have unique immunohistochemical staining that allows them to be accurately differentiated from other renal tumours.
Pelvic Limb Kinetic and Kinematic Analysis inLabradorRetrievers Predisposed or at a Low Risk for Cranial Cruciate Ligament Disease
Authors: Ragetly Chantal A. , Griffon Dominique J. , Klump L. Michaela , Hsiao‐Wecksler Elizabeth T. 
Published: November 2012

ObjectiveTo compare kinematics, net moments, powers, ground and joint reaction forces (GRF,JRF) across the hock, stifle and hip joints inLabradorRetrievers at low risk or predisposed to cranial cruciate ligament disease (CCLD).Study DesignCross‐sectional clinical study.AnimalsClinically normalLabradors predisposed (n = 11) or at low risk forCCLD(n = 9).MethodsRight pelvic limbs were classified as predisposed or not toCCLDusing a predictive score equation based on combining tibial plateau angle (TPA) and femoral anteversion angle (FAA) measured on radiographs. Kinematic,GRF, and morphometric data were combined in an inverse dynamics approach to compute hock, stifle and hip kinematics, net moments, powers, and JRF while trotting.ResultsThe extensor moment of the hock joint was greater in predisposed limbs compared with nonpredisposed limbs (0.37 versus 0.28 Nm/kg). The power generated around the hock and stifle joints in predisposed limbs was increased (0.69 versus 0.44 W/kg for the hock, 1.59 versus 1.05 W/kg for the stifle). Trotting velocity, stance time, vertical and craniocaudalGRFandJRFdid not differ between groups.ConclusionsExtensor moment at the hock was increased in predisposed limbs compared with nonpredisposed limbs. Predisposed limbs generated more energy than nonpredisposed limbs around the hock and stifle joints.
Minimally Invasive Transxiphoid Approach to the Cardiac Apex and Caudoventral Intrathoracic Space
Authors: Nelson David A. , Miller Matthew W. , Gordon Sonya G. , Saunders Ashley , Fossum Theresa W. 
Published: November 2012

ObjectiveTo describe a minimally invasive surgical technique for procedures involving the caudoventral compartment of the thoracic cavity.Study DesignCase series.AnimalsDogs (n = 13).MethodsThirteen dogs; undergoing epicardial pacemaker implantation (9), palliative pericardial window (2), perforated right ventricle repair with epicardial pacemaker implantation (1), and peritoneopericardial diaphragmatic hernia (1) were operated by a transxiphoid approach. Dogs were positioned in dorsal recumbency and the bony xiphoid process was dissected free of adjoining tissue and transected proximally and distally. The distal transection was proximal to the cartilaginous junction of the process and the diaphragm. Entry to the thoracic cavity without penetration of the abdomen provided access for surgical treatment.ResultsAll dogs recovered without complication. No dogs required thoracostomy tube placement.ConclusionsTransxiphoid approach is minimally invasive and provides adequate exposure for disorders of the caudoventral thoracic cavity.
Study in 1790 Baltic men:FSHRAsn680Ser polymorphism affects total testes volume
Authors: Grigorova M. , Punab M. , Poolamets O. , Sõber S. , Vihljajev V. , Žilaitienė B. , Erenpreiss J. , Matulevičius V. , Tsarev I. , Laan M. 
Published: November 2012

SummaryFollicle‐stimulating hormone receptor (FSHR) contains two common linked polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), shown to modulate ovarian function in women. The effect on male fertility and reproductive parameters has been inconclusive. We studiedFSHRAsn680Ser polymorphism in a large study group (n = 1790) from the Baltic countries. The population‐based Baltic male cohort (Estonians, Latvians, Lithuanians;n = 1052) and Estonian oligo‐/azoospermic (sperm concentration <20 × 106/mL) idiopathic infertile patients (n = 738) were genotyped for the FSHR Asn680Ser using PCR‐RFLP. Genetic associations were tested using linear regression under additive model and results were combined in meta‐analysis. No statistical difference was detected in allelic distribution of the FSHR Asn680Ser between the Baltic cohort and Estonian male infertility group. A consistent significant association was detected between the FSHR Ser680 allele and lower total testes volume in both, the Baltic cohort (p = 0.010, effect = −1.16 mL) and Estonian idiopathic infertility group (p = 0.007, effect = −1.77 mL). In meta‐analysis, the statistical significance was enhanced (p = 0.000066, effect = −1.40 mL). Meta‐analysis supported further associations with moderate effect between the FSHR Ser680 variant and higher serum FSH (p = 0.072), lower Inhibin B (p = 0.037) and total testosterone (p = 0.034). No statistically significant associations were identified with serum LH and estradiol, and sperm parameters. In conclusion, the study in 1790 Baltic men shows statistically highly significant association of theFSHRAsn680Ser with total testes volume and supportive association with serum reproductive hormone levels indicative to the functional effect of the alternativeFSHRvariants on male reproductive physiology.
Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients
Authors: Welter H. , Kampfer C. , Lauf S. , Feil R. , Schwarzer J. U. , Köhn F.‐M. , Mayerhofer A. 
Published: November 2012

SummaryFibrotic remodelling of the testicular tubular wall is common in human male infertility caused by impaired spermatogenesis. We hypothesized that this morphological change bears witness of an underlying fundamentally altered state of the cells building this wall, that is, peritubular smooth muscle‐like cells. This could include a loss of the contractile abilities of these cells and thus be a factor in male infertility. Immune cells are increased in the tubular wall in these cases, hence local immune cell‐related factors, including a prostaglandin (PG) metabolite may be involved. To explore these points in the human, we used testicular biopsies, in which tubules with normal spermatogenesis and impaired spermatogenesis are next to each other [mixed atrophy (MA)], normal biopsies and cultured human testicular peritubular cells. Proteins essential for contraction, myosin heavy chain (MYH11), calponin (Cal) and relaxation, cGMP‐dependent protein kinase 1 (cGKI), were readily detected by immunohistochemistry and were equally distributed in all peritubular cells of biopsies with normal spermatogenesis. In all biopsies, vascular smooth muscle cells also stained and served as important intrinsic controls, which showed that in MA samples when spermatogenesis was impaired, staining was restricted to only few peritubular cells or was absent. When spermatogenesis was normal, regular peritubular staining became obvious. This pattern suggests complex regulatory influences, which in face of the identical systemic hormonal situation in MA patients, are likely caused by the local testicular micromilieu. The PG metabolite 15dPGJ2 may represent such a factor and it reduced Cal protein levels in peritubular cells from patients with/without impaired spermatogenesis. The documented phenotypic switch of peritubular, smooth muscle‐like cells in MA patients may impair the abilities of the afflicted seminiferous tubules to contract and relax and must now be considered as a part of the complex events in male infertility.
Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats
Authors: Stojkov N. J. , Janjic M. M. , Kostic T. S. , Andric S. A. 
Published: November 2012

SummaryDoxazosin (Doxa) is an α1‐selective adrenergic receptor (ADR) antagonist widely used, alone or in combination, to treat high blood pressure, benign prostatic hyperplasia symptoms, and recently has been suggested as a potential drug for prostate cancer prevention/treatment. This study was designed to evaluate the effect of in vivo Doxa po‐application, in clinically relevant dose, on: (i) steroidogenic machinery homeostasis; (ii) cAMP/cGMP signalling; (iii) transcription profile of ADR in Leydig cells of adult rats. The results showed that po‐application of Doxa for once (1×Doxa), or for two (2×Doxa) or 10 (10×Doxa) consecutive days significantly disturbed steroidogenic machinery homeostasis in Leydig cells. Doxa po‐application significantly decreased circulating luteinizing hormone and androgens levels. The level of androgens in testicular interstitial fluid and that extracted from testes obtained from 1×Doxa/2×Doxa rats decreased, although it remained unchanged in 10×Doxa rats. Similarly, the ex vivo basal androgen production followed in testes isolated from 1×Doxa/2×Doxa rats decreased, while remained unchanged in 10×Doxa rats. Differently, ex vivo testosterone production and steroidogenic capacity of Leydig cells isolated from 1×Doxa/2×Doxa rats was stimulated, while 10×Doxa had opposite effect. In the same cells, cAMP content/release showed similar stimulatory effect, but back to control level in Leydig cells of 10×Doxa. 1×Doxa/2×Doxa decreased transcripts for cAMP specific phosphodiesterases Pde7b/Pde8b, whereas 10×Doxa increased Pde4d. All types of treatment reduced the expression of genes encoding protein kinase A (PRKA) regulatory subunit (Prkar2b), whereas only 10×Doxa stimulated catalytic subunit (Prkaca). Doxa application more affected cGMP signalling: stimulated transcription of constitutive nitric oxide synthases (Nos1, Nos3) in time‐dependent manner, whereas reduced inducible Nos2. 10×Doxa increased guanylyl cyclase 1 transcript and PRKG1 protein in Leydig cells. Orally applied Doxa significantly disturbed the transcriptional ‘signature’ of steroidogenic machinery, cAMP/cGMP signalling and ADRs and β‐ADRs kinases in Leydig cells, thus giving new molecular insights into the role of cAMP/cGMP/adrenalin signalling in Leydig cells homeostasis.
Parallel and nonparallel ecological, morphological and genetic divergence in lake–stream stickleback from a single catchment
Authors: Ravinet M. , Prodöhl P. A. , Harrod C. 
Published: November 2012

AbstractParallel phenotypic evolution in similar environments has been well studied in evolutionary biology; however, comparatively little is known about the influence of determinism and historical contingency on the nature, extent and generality of this divergence. Taking advantage of a novel system containing multiple lake–stream stickleback populations, we examined the extent of ecological, morphological and genetic divergence between three‐spined stickleback present in parapatric environments. Consistent with other lake–stream studies, we found a shift towards a deeper body and shorter gill rakers in stream fish. Morphological shifts were concurrent with changes in diet, indicated by both stable isotope and stomach contents analysis. Performing a multivariate test for shared and unique components of evolutionary response to the distance gradient from the lake, we found a strong signature of parallel adaptation. Nonparallel divergence was also present, attributable mainly to differences between river locations. We additionally found evidence of genetic substructuring across five lake–stream transitions, indicating that some level of reproductive isolation occurs between populations in these habitats. Strong correlations between pairwise measures of morphological, ecological and genetic distance between lake and stream populations supports the hypothesis that divergent natural selection between habitats drives adaptive divergence and reproductive isolation. Lake–stream stickleback divergence inLoughNeagh provides evidence for the deterministic role of selection and supports the hypothesis that parallel selection in similar environments may initiate parallel speciation.
Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons
Authors: Kim Han‐Gyu , Lee Choong‐Ku , Cho Sung‐Min , Whang Kum , Cha Byong‐Ho , Shin Ju‐Hyun , Song Ki‐Hak , Jeong Seong‐Woo 
Published: November 2012

AbstractWe investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1β significantly increased the transcript and protein level of the nAChR α3 and β4 subunits. Consistent with these molecular data, nicotinic currents (IACh) were significantly up‐regulated in NRG1β‐treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the IACh. Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1β on the IACh. Stimulation of the ErbB receptors by NRG1β activated the phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K‐mediated activation of Akt preceded Erk1/2 activation in NRG1β‐treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up‐regulates nAChR expression via the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade and may be involved in maintaining the ACh‐mediated synaptic transmission in adult autonomic ganglia.
Enhanced expression of the Flt‐1 and Flk‐1 receptor tyrosine kinases in a newborn piglet model of ischemic tolerance
Authors: Ara Jahan , Shukla Panchanan , Frank Melissa 
Published: November 2012

AbstractVascular endothelial growth factor (VEGF), an angiogenic factor induced by hypoxia, also exerts direct effects on neural tissues. VEGF up‐regulation after hypoxia coincides with expression of its two tyrosine kinase receptors Flt‐1(VEGFR‐1) and Flk‐1 (KDR/VEGFR‐2), which are the key mediators of physiological angiogenesis. We have recently shown that hypoxic‐preconditioning (PC) leading to tolerance to hypoxia–ischemia in neonatal piglet brain resulted in increased expression of VEGF. In this study, we used a hypoxic‐preconditioning model of ischemic tolerance to analyze the expression and cellular distribution of VEGF receptors and phosphorylation of cAMP‐response element‐binding protein (CREB) in newborn piglet brain. The response of Flt‐1 and Flk‐1 mRNA to PC alone was biphasic with peaks early (6 h) and late (1 week) after PC. The mRNA expression of Flt‐1 and Flk‐1 in piglets preconditioned 24 h prior to hypoxia–ischemia was significantly higher than non‐preconditioned piglets and remained up‐regulated up to 7 days. Furthermore, PC prior to hypoxia–ischemia significantly increased the protein levels of Flt‐1 and Flk‐1 compared with hypoxia–ischemia in a time‐dependent manner. Double‐immunolabeling indicated that both Flt‐1 and Flk‐1 are expressed in neurons and endothelial cells with a similar time course of expression following PC and that PC leads to the growth of new vessels. Finally, our data demonstrate that PC significantly phosphorylated and activated cAMP‐response element‐binding protein in nucleus. These results suggest that mechanism(s) initiated by PC can induce VEGF receptor up‐regulation in newborn brain and that VEGF–VEGF receptor‐coupled signal transduction pathways could contribute to the establishment of tolerance following hypoxia–ischemia.