bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of Developmental Toxicity and Teratogenicity of Macrolide Antibiotics in Cultured Rat Embryos
Authors: Karabulut A. K. , Uysal I. I. , Acar H. , Fazliogullari Z. 
Published: June 2008

SummaryMacrolides are considered to be one of the safest anti‐infective groups in clinical use, with severe adverse reactions being rare. However, there are limited data about their embryotoxicity and teratogenicity. We aimed to investigate and compare the effects of these agents on embryonic growth and development. Rat embryos were cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of spiramycin and azithromycin (1.25–6.25 μg/ml), and clarithromycin (2.5–30 μg/ml) were added to rat serum for the experimental groups. Dose‐dependent effects of macrolides on embryonic developmental parameters were compared using morphological methods. Embryos were evaluated for the presence of any malformations. After morphological examination of the embryos, total DNA was extracted from the cells using standard procedures to determine fragmentation of nuclear DNA of embryonic cells. When compared with the control embryos, the macrolides significantly decreased all growth and developmental parameters dose dependently. While clarithromycin was found to cause more developmental toxicity than spiramycin and azithromycin, azitromycin was determined to have more teratogenicity potential. Compared with controls, there was no difference regarding the fragmentation of nuclear DNA of all the agents used. According to these results, when the toxic and teratogenic potential of the used agents compared, because of the lower toxic and teratogenic effects observed with spiramycin, this agent may be preferred for parturients.
Isolation of a Novel Tomato Caffeoyl CoA 3‐O‐methyltransferase Gene Following Infection with the Bacterium Ralstonia solanacearum
Authors: Miao L. , Shou S. , Zhu Z. , Jiang F. , Zai W. , Yang Y. 
Published: June 2008

AbstractWe combined cDNA amplified fragment length polymorphism (cDNA‐AFLP) with bulked segregant analysis (BSA) to detect genes that control tomato (Lycopersicon esculentum) bacterial wilt infected with Ralstonia solanacearum, resistance in F2 population derived from a cross between a bacterial wilt‐resistant variety, T51A, and a bacterial wilt‐susceptible variety, T9230. In cDNA‐AFLP analysis among bulked‐resistant F2 (BR) pool, bulked‐susceptible F2 (BS) pool, bulked‐resistant T51A (BA) pool and bulked‐susceptible T9230 (BB) pool, 34 differentially expressed transcript‐derived fragments (DE‐TDFs) that were present in only BR and BA pools were detected. Analysis of differential DE‐TDF expression in individual resistant F2 resulted in the isolation of a caffeoyl CoA 3‐O‐methyltransferase (CCoAOMT) gene not previously described from tomato and which showed similarity to an CCoAOMT gene from tobacco and potato plants. This CCoAOMT gene may play a role in innate generalized response to pathogen infection as it was downregulated in susceptible tomato following infection with the bacterium. CCoAOMT gene plays an essential role in the synthesis of guaiacyl lignin units and supply substrates for the synthesis of syringyl lignin units.
Partial Uprooting and Pulling to Induce Recovery in Bois noir‐Infected Grapevines
Authors: Romanazzi Gianfranco , Murolo Sergio 
Published: June 2008

AbstractGrapevine yellows (GY) are diseases caused by phytoplasmas, which are able to induce severe loss of production and death of plants. Bois noir (BN) and Flavescence dorée are the most important GY diseases prevalent in several European countries. As of now, there are no known effective disease‐control methods for application in grapevines infected by these phytoplasmas. In these plants, it is possible to have, remission of these symptoms, better known as ‘recovery’. In April 2006 in the Marche region, central‐eastern Italy, grapevines cv. Chardonnay, Verdicchio and Sangiovese grafted onto Kober 5BB; rootstock symptomatically infected by VK type II BN were subjected to partial uprooting, which was effected by breaking most of their roots using a small excavator. Almost all of these plants failed to show disease symptoms in the autumn of 2006 and 2007. Similar trials were carried out on BN‐infected plants cv. Chardonnay grafted onto 420A rootstock in 2006 and 2007; in this case, the treatment was only partially successful in both these years. In another trial in April 2007, BN‐infected plants cv. Chardonnay grafted onto 420A rootstock and cv. Primitivo grafted onto Kober 5BB, rootstock were ‘pulled’ and some of these showed no disease symptoms in the following autumn, whereas others had only mild infections. Partial uprooting and pulling are agronomical practices that induce stress in the plants. In the case of grapevines affected by GY, such stress can result in the recovery of the vines. However, the effectiveness in the induction of recovery in these treatments can depend on the rootstock.
Seasonal Variation of Reproductive Performance, Foetal Development and Progesterone Concentrations of Sheep in the Subtropics
Authors: Ali A , Hayder M 
Published: June 2008

ContentsThe aim of the present study was to investigate the effect of breeding season [late spring (LSP) vs winter (WIN)] on reproductive performances, foetal development and progesterone (P4) concentrations of sheep in the subtropics. Ewes of Farafra breed were exposed for mating in LSP (n = 79) and WIN (n = 45). Ultrasonographic examinations were performed at days 25, 45 and 75 of mating to estimate the pregnancy rate, incidence of twinning and percentage of foetal losses. Foetal growth rate was determined at 10‐day interval, and blood samples were taken on days 0 (oestrus), 8, 18 of oestrous cycle and on days 30, 45, 60 and 90 of pregnancy for P4 analysis. The results showed that pregnancy and lambing rates were greater (p < 0.01) for ewes mated in LSP (93.7% and 92.4%) than for those mated in WIN (75.6% and 71.1%), respectively. There was no effect of season on the incidence of twinning (overall 19.1%) or the frequency of foetal losses (overall 7.3%). Transient reduction of placental size, foetal growth and P4 concentration was observed following LSP matings. In conclusion, pregnancy and lambing rates were higher following LSP matings. Summer heat stress of the late spring mated ewes transiently interferes with foetal growth and P4 concentrations.
Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins
Authors: Barr Alasdair M. , Fish Kenneth N. , Markou Athina , Honer William G. 
Published: June 2008

AbstractPost mortem, reduced brain reelin is noted in schizophrenia. Accordingly, the reelin‐haploinsufficient heterozygous reeler mouse (HRM) has been posited as a murine model of the illness. One study reported that HRM exhibit deficits in prepulse inhibition (PPI) of the acoustic startle reflex, a sensorimotor‐gating behavior that is disrupted in schizophrenia, although this finding has not been reproduced. To extend the characterization of putative sensorimotor‐gating deficits in HRM, these mice were subjected to a sophisticated series of PPI tests. Mice were tested in a cross‐modal PPI protocol that combined an acoustic prepulse with a tactile startle stimulus and also in a protocol that included varying prepulse–pulse intervals and varying acoustic startle pulse intensities. Levels of acoustic startle habituation and cross‐modal PPI were significantly lower in HRM, although unimodal PPI did not differ. The HRM also exhibited increased PPI compared to wildtypes at short interstimulus intervals between prepulse and pulse stimuli when the interval between the acoustic prepulse and pulse were varied, and were more reactive to higher intensity startle stimuli. Some of these deficits in sensorimotor gating parallel those of schizophrenia, a disease characterized by alterations in synaptic protein expression. Therefore, levels of presynaptic proteins were measured in multiple brain regions using ELISA in HRM. No significant alterations in presynaptic protein expression were found. Thus, HRM exhibit a complex pattern of changes in startle reactivity and sensorimotor gating, with both similarities to and differences from schizophrenia. However, it is unlikely that these behavioral differences may be accounted for by altered regional levels of presynaptic proteins.
Vascular changes in the cerebellum of Norrin /Ndph knockout mice correlate with high expression of Norrin and Frizzled‐4
Authors: Luhmann Ulrich F. O. , Neidhardt John , Kloeckener‐Gruissem Barbara , Schäfer Nikolaus F. , Glaus Esther , Feil Silke , Berger Wolfgang 
Published: June 2008

AbstractX‐linked Norrie disease, familial exudative vitreoretinopathy (FEVR), Coat’s disease and retinopathy of prematurity are severe human eye diseases and can all be caused by mutations in the Norrie disease pseudoglioma gene. They all show vascular defects and characteristic features of retinal hypoxia. Only Norrie disease displays additional neurological symptoms, which are sensorineural hearing loss and mental retardation. In the present study, we analysed transcript levels of the ligand Norrin (Ndph) and its two receptors Frizzled‐4 (Fzd4) and LDL‐related protein receptor 5 (Lrp5) in six different brain regions (cerebellum, cortex, hippocampus, olfactory bulb, pituitary and brain stem) of 6‐ to 8‐month‐old wild‐type and Ndph knockout mice by quantitative real‐time PCR. No effect of the Ndph knockout allele on Fzd4 or Lrp5 receptor expression was found. Furthermore, no alterations of the transcript levels of three hypoxia‐regulated angiogenic factors (Vegfa, Itgrb3 and Tie1) were observed in the absence of Norrin. Interestingly, we identified significant differences in Ndph, Fzd4 and Lrp5 transcript levels in brain regions of wild‐type mice and observed highest expression of Norrin and frizzled‐4 in cerebellum. Transcript analyses were correlated with morphological data obtained from cerebellum and immunohistochemical studies of blood vessels in different brain regions. Vessel density was reduced in the cerebellum of Ndph knockout mice but the number of Purkinje and granular cells was not altered. This provides the first description of a brain phenotype in Ndph knockout mice, which will help to elucidate the role of Norrin in the brain.
Decreased olfactory mucus secretion and nasal abnormality in mice lacking type 2 and type 3 IP3 receptors
Authors: Fukuda Nanaho , Shirasu Mika , Sato Koji , Ebisui Etsuko , Touhara Kazushige , Mikoshiba Katsuhiko 
Published: June 2008

AbstractAlthough nasal mucus is thought to play important roles in the mammalian olfactory system, the mechanisms of secretion of it and its physiological roles are poorly understood. Here we show that type 2 and type 3 IP3 receptors (IP3R2 and IP3R3) play critical roles in olfactory mucus secretion. Histological studies showed that IP3R2 and IP3R3 are predominantly expressed in two types of nasal glands, the anterior glands of the nasal septum and the lateral nasal glands (LNG), which contain mucosal proteins secreted to the main olfactory epithelium. We therefore examined LNG acinar cells, and found that acetylcholine‐mediated calcium responses and fluid‐ and protein‐ secretion in the acinar cells were markedly decreased in IP3R2–R3 double‐knockout (KO) mice. We also found nasal inflammation and a decrease in olfactory capacity in IP3R2–R3 KO mice. Despite intact signal transduction in the olfactory epithelium, IP3R2–R3 KO mice exhibited elevated threshold sensitivity to odorants on in vivo imaging of olfactory glomerular responses and behavioral tests. Our findings suggest that IP3R2 and IP3R3 mediate nasal mucus secretion, which is important for the maintenance of nasal tissue as well as the perception of odors.
Selective visual responses to expansion and rotation in the human MT complex revealed by functional magnetic resonance imaging adaptation
Authors: Wall Matthew B. , Lingnau Angelika , Ashida Hiroshi , Smith Andrew T. 
Published: June 2008

AbstractMany neurons in the macaque visual area MSTd are sensitive to the global structure of a pattern of moving dots, responding to optic flow components such as expansion and rotation. Direct evidence for neurons with similar properties in humans has been lacking. We have explored sensitivity to optic flow in the human occipital cortex using an event‐related functional magnetic resonance imaging adaptation paradigm. On each trial, two brief random‐dot kinematograms were presented sequentially. Attention was controlled with a demanding task at fixation. In human MST, the compound response was smaller (indicating adaptation) when the two had the same flow structure than when they were different, suggesting the presence of separate neural populations sensitive to rotation and expansion. Surprisingly, the middle‐temporal (MT) gyrus visual area also showed signs of flow specificity, and even V3A showed weak specificity. In V1, which is expected to respond only to local dot motions, no evidence of flow‐specific neurons was found. The same was true in V2, V3, V3B and V4. Control experiments showed that the results cannot be attributed to adaptation to local translation within the flow pattern, or to attentional effects. Our results clearly demonstrate selective responses to specific optic flow structures in MST, and we tentatively suggest that the human MT and even V3A may show similar properties.
Leptin—a predictor of abnormal glucose tolerance and prognosis in patients with myocardial infarction and without previously known Type 2 diabetes
Authors: Wallander M. , Söderberg S. , Norhammar A. 
Published: June 2008

AbstractAims  High levels of leptin and low adiponectin are associated with Type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease. We studied the prognostic implications of leptin and adiponectin in patients with acute myocardial infarction (AMI) without previously known Type 2 DM.Methods  One hundred and eighty‐one patients were included. Based on an oral glucose tolerance test at hospital discharge (day 4–5), 168 (67% men) had normal or abnormal glucose tolerance (AGT), defined as impaired glucose tolerance or T2DM. Sex‐ and age‐matched healthy persons served as control subjects (n = 185). The associations between fasting serum leptin and adiponectin (day 2) and newly discovered AGT and CV events (CV mortality, non‐fatal stroke, reinfarction or severe heart failure) during a median follow‐up of 34 months were investigated.Results  Compared with control subjects, patients of both genders had significantly higher levels of leptin 2 days after an AMI. These levels were higher than those obtained at hospital discharge and 3 months later. Circulating levels of (ln) leptin 2 days after the AMI predicted AGT at discharge (odds ratio 2.03, P = 0.042). Ln leptin at day 2 was the only biochemical variable that significantly predicted CV events both on univariate [hazard ratio (HR) 1.60, P = 0.018] and on multivariate analysis (HR 1.75, P = 0.045). Adiponectin levels did not differ between patients and control subjects and did not relate to AGT or CV events.Conclusions  Elevated circulating levels of leptin on the first morning after an AMI are associated with the presence of AGT at discharge and with a poorer long‐term prognosis.
Alterations in renal cilium length during transient complete ureteral obstruction in the mouse
Authors: Wang Leanne , Weidenfeld Raphael , Verghese Elizabeth , Ricardo Sharon D. , Deane James A. 
Published: June 2008

AbstractThe renal cilium is a non‐motile sensory organelle that has been implicated in the control of epithelial phenotype in the kidney. The contribution of renal cilium defects to cystic kidney disease has been the subject of intense study. However, very little is known of the behaviour of this organelle during renal injury and repair. Here we investigate the distribution and dimensions of renal cilia in a mouse model of unilateral ureteral obstruction and reversal of ureteral obstruction. An approximate doubling in the length of renal cilia was observed throughout the nephron and collecting duct of the kidney after 10 days of unilateral ureteral obstruction. A normalization of cilium length was observed during the resolution of renal injury that occurs following the release of ureteral obstruction. Thus variations in the length of the renal cilium appear to be a previously unappreciated indicator of the status of renal injury and repair. Furthermore, increased cilium length following renal injury has implications for the specification of epithelial phenotype during repair of the renal tubule and duct.
Effects of Opioid Receptor Gene Variation on Targeted Nalmefene Treatment in Heavy Drinkers
Authors: Arias Albert J. , Armeli Stephen , Gelernter Joel , Covault Jonathan , Kallio Antero , Karhuvaara Sakari , Koivisto Tiina , Mäkelä Rauno , Kranzler Henry R. 
Published: June 2008

Background:  Recent studies examining the moderating effects of polymorphic variation in opioid receptor genes have yielded conflicting results. We examined opioid receptor gene polymorphisms as moderators of the therapeutic effects of the opioid antagonist nalmefene.Methods:  Participants (n = 272) were subjects who consented to the pharmacogenetic analysis of a multi‐site, randomized, placebo‐controlled trial of targeted nalmefene for the reduction of heavy drinking. We genotyped two single nucleotide polymorphisms (SNPs) in OPRM1 (including A118G, a commonly studied SNP that encodes an Asn40Asp amino acid substitution), two SNPs in OPRD1, and one SNP in OPRK1, which encode the μ‐, δ‐, and κ‐opioid receptors, respectively. Regression analysis served to examine the moderating effects of these SNPs on medication response.Results:  As previously described by Karhuvaara et al. (2007), nalmefene significantly reduced the number of heavy drinking and very heavy drinking days per week, compared with placebo. There were no main or moderating effects of the genotypes examined on these outcomes.Conclusions:  Our finding that the therapeutic effects of targeted nalmefene were not moderated by polymorphic variation in opioid receptor genes is consistent with two recent reports showing that variation in opioid receptor genes does not moderate the response to naltrexone. However, these findings contrast with those from two other studies, in which the Asn40Asp polymorphism in OPRM1 moderated the naltrexone treatment response. Additional research is needed to clarify the role of variation in opioid receptor genes on the response to opioid antagonist treatment of alcoholism.
Aneuploidy, but not Ki‐67 or EGFR expression, is associated with recurrences in basal cell carcinoma
Authors: Janisson‐Dargaud Delphine , Durlach Anne , Lorenzato Marianne , Grange Florent , Bernard Philippe , Birembaut Philippe 
Published: June 2008

Background:  Basal cell carcinoma (BCC), the most common skin cancer, has an overall excellent prognosis, but recurrences are frequent. The value of classical clinical and histological prognostic factors to predict recurrences remain limited.Methods:  In order to evaluate the prognostic value of Epidermal Growth Factor Receptor (EGFR) expression, Ki‐67 antigen expression and DNA ploidy, we compared primary tumors in 20 patients who had subsequent local recurrences and 20 matched controls without recurrences. DNA ploidy was determined by image cytometry, and EGFR and Ki‐67 expression were studied by immunohistochemistry.Results:  Statistical analysis of the intensity and the percentage of EGFR expression and Ki‐67 antigen expression did not show any significant difference between the two groups. In contrast, we found that 78% of primary BCC in patients who experienced recurrences vs. 32% in the control group were aneuploid (p = 0.005).Conclusions:  Aneuploidy is a risk factor for recurrences. This factor should be useful in clinical practice and require evaluation in further studies.
The effect of FloSeal on post‐tonsillectomy pain: a randomised controlled pilot study
Authors: Blackmore K.J. , O’Hara J. , Flood L.M. , Martin F.W. 
Published: June 2008

Objectives:  To determine whether FloSeal as a haemostatic agent in tonsillectomy is associated with less postoperative pain than conventional haemostasis with ligatures.Design:  Randomised, controlled, single‐blinded pilot study.Setting:  James Cook University Hospital, Middlesbrough, Cleveland, UK.Participants:  Thirty patients over 16 years of age undergoing tonsillectomy for recurrent tonsillitis were recruited for the study. At surgery both tonsils were removed by cold steel dissection. Following randomisation one tonsil fossa had FloSeal applied and the other ligatures for haemostasis.Main outcome measures:  The primary outcome measure was postoperative pain following tonsillectomy measured on a visual analogue scale. Pain was recorded three times a day for the first 10 days following surgery. Haemorrhage rates were also recorded as a secondary outcome.Results:  Complete data was analysed for 26 patients (87%). The data was grouped into distinct time periods: 0–2, 3–6 and 7–10 days. The sum of the visual linear analogue scale over the time periods for each patient was calculated. Using Wilcoxon Signed Ranks Test, the data was analysed and it was found that there was no statistically significant difference in postoperative pain scores between the control and treatment side at any time. There was a postoperative reactionary haemorrhage rate of 6.7% on the FloSeal side.Conclusion:  In our pilot study there was no reduction in pain on the FloSeal side in the first 10 days following tonsillectomy which contrasts with previous findings in the literature.
Pre‐treatment haemoglobin level predicts response and survival after TPF induction polychemotherapy in advanced head and neck cancer patients
Authors: Baghi M. , Wagenblast J. , Hambek M. , Moertel S. , Gstoettner W. , Strebhardt K. , Knecht R. 
Published: June 2008

Objective:  To investigate the prognostic value of the pre‐treatment haemoglobin level in patients with advanced squamous cell head and neck cancer treated with induction polychemotherapy.Design:  Seventy‐two patients with advanced squamous cell head and neck cancer received primary combination chemotherapy consisting of docetaxel 75 mg/m² on day 1, cisplatin 100 mg/m² on day 1, and 5‐fluorouracil (5‐FU) 1000 mg/m²/day on days 1–4 (total dose 4000 mg/m²), repeated on days 1, 22 and 43 followed by chemoradiation. The data collected included pre‐treatment haemoglobin, response to treatment, disease‐free and overall survival.Results:  The pre‐treatment haemoglobin level was found to be a significant predictor of response to induction chemotherapy (P = 0.01) and an independent predictor of overall survival [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.58–1.03, P = 0.0001] and disease free survival (HR 2.09, 95% CI 1.41–3.09, P = 0.0001). Furthermore N‐stage was found to be a significant prognostic factor of overall survival (HR 9.24, 95% CI 6.90–21.34, P = 0.005). The Eastern Cooperative Oncology Group performance status scale was also found to be significant for disease free survival (HR 7.66, 95% CI 2.61–22.46, P = 0.003).Conclusion:  In patients with advanced squamous cell head and neck cancer, the haemoglobin level prior to induction chemotherapy is significantly related to outcome including response and survival.