bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine
Authors: Hou Ruihua H. , Scaife Jessica , Freeman Clare , Langley Rob W. , Szabadi Elemer , Bradshaw Chris M. 
Published: February 2006

AimsTo examine the relationship between sedation and pupillary function by comparing the effects of diazepam and diphenhydramine on arousal and pupillary activity.MethodsFifteen male volunteers participated in three weekly sessions in which they received (i) diazepam 10 mg, (ii) diphenhydramine 75 mg and (iii) placebo, according to a balanced, double‐blind protocol. Pupil diameter was measured with infrared pupillometry under four luminance levels. Alertness was assessed by visual analogue scales (VAS) and by critical flicker fusion frequency (CFFF). Blood pressure, heart rate and skin conductance were recorded by conventional methods. Data were analysed with analysis of variance (anova) with multiple comparisons.ResultsThere were significant effects of ambient luminance (F3,42 = 305.7, P < 0.001) and treatment condition (F2,28 = 9.0, P < 0.01) on pupil diameter; diphenhydramine caused miosis at all luminance levels (P < 0.05). The light reflex response was not affected. Both active drugs reduced the pre‐post treatment changes compared with placebo [mean difference from placebo (95% confidence interval)]: in CFFF (Hz), diazepam −0.73 (−1.63, 0.17), diphenhydramine −1.46 (−2.40, −0.52); and VAS alertness (mm), diazepam −11.49 (−19.19, −3.79), diphenhydramine −19.83 (−27.46, −12.20). There were significant effects of both session (F2,26 = 145.1, P < 0.001) and treatment (F2,26 = 5.5, P < 0.01) on skin conductance; skin conductance was reduced by both drugs (P < 0.05).ConclusionsThe miosis by diphenhydramine and the reduction in skin conductance by both drugs may indicate central sympatholytic effects. A lack of a sympatholytic effect of diazepam on the pupil may be due to the masking of the miosis by mydriasis resulting from the inhibition of the parasympathetic output to the iris.
Self-aggregated deglycosylated IgA1 with or without IgG were associated with the development of IgA nephropathy
Authors: Yan Y , Xu L-X , Zhang J-J , Zhang Y , Zhao M-H 
Published: February 2006

Summary
IgA nephropathy (IgAN) is the most common primary glomerulonephritis, with various pathological phenotypes. Our previous study suggested that aberrant glycosylation of serum IgA1 was associated with different pathological phenotypes of IgAN, and substantial evidence indicated that deglycosylated IgA1 had an increased tendency to form macromolecules. The aim of the current study was to investigate the composition of IgA1-containing macromolecules in different pathological phenotypes of IgAN. Sera from 10 patients with mild mesangial proliferative IgAN (mIgAN), 10 with focal proliferative sclerosing IgAN (psIgAN) and 10 healthy blood donors were collected. The sera were applied and IgA1 binding proteins (IgA1-BP) were eluted from the columns immobilized with desialylated IgA1 (DesIgA1/Sepharose) or desialylated/degalactosylated IgA1 (DesDeGalIgA1/Sepharose), respectively. The amounts of IgA1 and IgG and the glycoform of IgA1 in the IgA1-BP were detected by enzyme-linked immunosorbent assays (ELISAs) and were compared between patients with different pathological phenotypes and normal controls. The amount of IgA1 in IgA1-BP eluted from both columns was significantly higher in patients with both pathological phenotypes of IgAN than in normal controls. In IgA1-BP eluted from DesDeGalIgA1/Sepharose, the desialylation of IgA1 was much more pronounced in patients with both pathological phenotypes of IgAN than in normal controls, while the degalactosylation of IgA1 was much more pronounced only in patients with psIgAN than in normal controls. Furthermore, the amount of IgG in IgA1-BP eluted from DesDeGalIgA1/Sepharose was significantly higher in patients with psIgAN than in normal controls. In patients with psIgAN, the amount of IgG eluted from DesDeGalIgA1/Sepharose was much greater than from DesIgA1/Sepharose. In conclusion, self-aggregated deglycosylated IgA1 with or without IgG were associated with the development of IgAN.
Lipopolysaccharide hyporesponsiveness as a risk factor for intensive care unit hospitalization in infants with respiratory syncitial virus bronchiolitis
Authors: Mandelberg A , Tal G , Naugolny L , Cesar K , Oron A , Houri S , Gilad E , Somekh E 
Published: February 2006

SummaryFactors such as genetic heterogeneity in the immune response contribute to respiratory syncytial virus (RSV) bronchiolitis severity. Such heterogeneity may manifest by an aberrant proliferation of phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) in response to lipopolysaccharide (LPS). The proliferation of PBMC was analysed in 52 infants: 21 ambulatory infants with mild RSV bronchiolitis (group I), 26 hospitalized infants with RSV bronchiolitis on ward (group II) and five intensive care unit (ICU) hospitalized infants (group III). Proliferation was analysed in response to negative control, PHA (LPS) and LPS/PHA. The TLR4 mutations were genotyped using reverse-transcriptase–polymerase chain reaction. The optical density (OD) post-LPS/PHA of group II (1·27 ± 0·63) was significantly higher than group II (0·65 ± 0·38, P = 0·005) or group I (0·63 ± 0·33, P = 0·003), suggesting hyporesponsiveness to the LPS attenuation effect. None of the ICU hospitalized infants demonstrated OD readings post-LPS/PHA under the 0·75 threshold as opposed to group I (67% under 0·75) and group II (69%) (P &lt; 0·05). The responses to negative-control, LPS and PHA stimulation alone were similar across groups. The presence of TLR4 mutations (Asp299Gly and Thr399Ile) were associated with severe RSV bronchiolitis and were significantly over-represented in groups II and III. These findings suggest that impairments of PBMC function manifested by hyporesponsiveness to LPS as well as the presence of TLR4 mutations are associated with an increased risk for more severe RSV bronchiolitis in previously healthy infants. A certain threshold of LPS hyporesponsiveness may have a very high negative predictive value for ICU hospitalization, even better than the determination of known TLR4 mutations for this purpose.
Yo antibodies in ovarian and breast cancer patients detected by a sensitive immunoprecipitation technique
Authors: Monstad S E , Storstein A , Dørum A , Knudsen A , Lønning P E , Salvesen H B , Aarseth J H , Vedeler C A 
Published: February 2006

Summary
Onconeural antibodies are found in patients with cancer and are associated with paraneoplastic neurological syndromes (PNS). The objective of the present study was to assess the frequency of Yo antibodies in ovarian and breast cancer using a sensitive immunoprecipitation technique, and to look for any association of Yo antibodies with neurological symptoms and prognostic factors. A multiwell adapted fluid-phase immunoassay using radiolabelled recombinant cerebellar degeneration related protein (cdr2), produced by coupled in vitro transcription/translation was used for the detection of Yo antibodies. This technique combines high specificity and sensitivity with high sample analysing capacity for the antibody in question. Sera or EDTA-blood from 810 ovarian (n = 557) and breast cancer (n = 253) patients were analysed for Yo antibodies by immunoprecipitation, as well as immunofluorescence and immune blots. Two hundred healthy blood donors and sera from 17 patients with paraneoplastic cerebellar degeneration and Yo antibodies served as controls. Immunoprecipitation was more sensitive in detecting Yo antibodies than immunofluorescence and immune blots. The prevalence of Yo antibodies was 13/557 (2·3%) in ovarian cancer and 4/253 (1·6%) in breast cancer using immunoprecipitation. Yo antibodies were not correlated with specific histological subgroups. The Yo index of ovarian cancer patients in FIGO stage IV was higher compared to FIGO stage I-III. The prevalence of Yo antibodies was 3 times higher in patients with stage III breast cancer than in stage I and II. Only 2/17 (11·8%) patients with Yo antibodies detected during the screen of 810 cancer patients had PNS. The results show that the prevalence of Yo antibodies is low in ovarian and breast cancer. Yo antibodies may be associated with advanced cancer, but less often with PNS.
Inhibition of five lipoxygenase activating protein (FLAP) by MK‐886 decreases atherosclerosis in apoE/LDLR‐double knockout mice
Authors: Jawien J. , Gajda M. , Rudling M. , Mateuszuk L. , Olszanecki R. , Guzik T. J. , Cichocki T. , Chlopicki S. , Korbut R. 
Published: February 2006

AbstractBackground  Recent reports point to an important role of leukotrienes in atherogenesis. Leukotrienes are produced by 5‐lipoxygenase co‐operating with five lipoxygenase activating protein (FLAP). We hypothesized that MK‐886, an inhibitor of FLAP, could attenuate the development of atherosclerosis in the atherogenic apolipoprotein E/low density lipoprotein receptor (apoE/LDLR) double knockout (DKO) mouse model.Materials and methods  Female apoE/LDLR‐DKO mice at the age of 8 weeks were put on Western diet. The experimental group (n = 10) received the same diet as the control group (n = 10), but mixed with MK‐886 (Merck, Rahway, NJ) at a dose of 4 µg per 100 mg of body‐weight per day. At age 6 months the mice were sacrificed under anaesthesia.Results  Measured by the en face method, the percentage of area occupied by lesions in aortas in the control group was 25·15 ± 2·9%, whereas in the MK‐886‐treated group it was 11·16 ± 0·7% (P < 0·05). Lesion area measured by cross‐section of aortic roots was 455 494 ± 29 564 µm2 in the control group versus 263 042 ± 20 736 µm2 in the MK‐886‐treated group (P < 0·05). The MK‐886 did not change the plasma cholesterol lipoprotein profile as compared with the control mice. Finally, we show that MK‐886 may increase plaque stability by decreasing the macrophage content as well as increasing the collagen and smooth‐muscle cell content.Conclusions  Our results show for the first time that inhibition of FLAP by MK‐886 reduces development of atherosclerosis in gene‐targeted apoE/LDLR‐DKO mice.
Increased inflammatory markers in children with familial hypercholesterolaemia
Authors: Ueland T. , Vissers M. N. , Wiegman A. , Rodenburg J. , Hutten B. , Gullestad L. , Ose L. , Rifai N. , Ridker P. M. , Kastelein J. J. P. , Aukrust P. , Semb A. G. 
Published: February 2006

AbstractBackground  While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high‐sensitivity C‐reactive protein (hsCRP), and soluble CD40 ligand (sCD40L).Materials and methods  In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2‐year treatment with pravastatin (20–40 mg qd) or placebo on plasma levels of those markers.Results  Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high‐density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group.Conclusion  These findings indicate low‐grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti‐inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.
Microarray profiling of human white adipose tissue after exogenous leptin injection
Authors: Taleb S. , Van Haaften R. , Henegar C. , Hukshorn C. , Cancello R. , Pelloux V. , Hanczar B. , Viguerie N. , Langin D. , Evelo C. , Zucker J. , Clément K. , Saris W. H. M. 
Published: February 2006

AbstractBackground  Leptin is a secreted adipocyte hormone that plays a key role in the regulation of body weight homeostasis. The leptin effect on human white adipose tissue (WAT) is still debated.Objective  The aim of this study was to assess whether the administration of polyethylene glycol‐leptin (PEG‐OB) in a single supraphysiological dose has transcriptional effects on genes of WAT and to identify its target genes and functional pathways in WAT.Materials and methods  Blood samples and WAT biopsies were obtained from 10 healthy nonobese men before treatment and 72 h after the PEG‐OB injection, leading to an approximate 809‐fold increase in circulating leptin. The WAT gene expression profile before and after the PEG‐OB injection was compared using pangenomic microarrays. Functional gene annotations based on the gene ontology of the PEG‐OB regulated genes were performed using both an ‘in house’ automated procedure and GenMAPP (Gene Microarray Pathway Profiler), designed for viewing and analyzing gene expression data in the context of biological pathways.Results  Statistical analysis of microarray data revealed that PEG‐OB had a major down‐regulated effect on WAT gene expression, as we obtained 1822 and 100 down‐ and up‐regulated genes, respectively. Microarray data were validated using reverse transcription quantitative PCR. Functional gene annotations of PEG‐OB regulated genes revealed that the functional class related to immunity and inflammation was among the most mobilized PEG‐OB pathway in WAT. These genes are mainly expressed in the cell of the stroma vascular fraction in comparison with adipocytes.Conclusion  Our observations support the hypothesis that leptin could act on WAT, particularly on genes related to inflammation and immunity, which may suggest a novel leptin target pathway in human WAT.
Influence of clinical factors on the haemolysis marker haptoglobin
Authors: Körmöczi G. F. , Säemann M. D. , Buchta C. , Peck‐Radosavljevic M. , Mayr W. R. , Schwartz D. W. M. , Dunkler D. , Spitzauer S. , Panzer S. 
Published: February 2006

AbstractBackground  Plasma haptoglobin determination is clinically used as parameter for haemolysis. To date, however, the influence of the mode of haemolysis (extravascular vs. intravascular) and of nonhaemolytic conditions on haptoglobin concentration and its reliability as a haemolysis marker remain poorly defined.Materials and methods  In a total of 479 individuals, the influence of haemolytic and nonhaemolytic conditions on plasma haptoglobin levels was investigated.Results  All studied types of haemolytic disease (n = 16) were associated with markedly decreased plasma haptoglobin levels, without significant differences between intravascular vs. predominantly extravascular haemolysis. Diminished haptoglobin values were also observed in patients with liver cirrhosis, which normalized after liver transplantation. In contrast, markedly increased haptoglobin levels were found in patients with inflammation. In patients with haemolysis and a concomitant acute‐phase response, however, haemolysis‐dependent haptoglobin depletion was not attenuated. Interestingly, patients with a strongly positive direct antiglobulin test or high cold agglutinin titre but no further evidence for haemolysis had normal haptoglobin values. Likewise, anaemia owing to bone marrow failure, acute gastrointestinal or chronic diffuse blood loss, and end‐stage kidney disease were associated with normal haptoglobin levels.Conclusions  Plasma haptoglobin depletion is a reliable marker for the instant diagnosis of accelerated red cell destruction irrespective of the site of haemolysis or the presence of inflammation. The capacity of this parameter to predict haemolysis appears to be limited in patients with liver cirrhosis and decreased haptoglobin production only.
Defining the limits to local density: alternative views of abundance–environment relationships
Authors: LANCASTER JILL , BELYEA LISA R. 
Published: February 2006

Summary1. In many ecosystems, the local abundance of organisms is spatially heterogeneous. Ecologists often seek to explain this variation by modelling the central tendency of abundance as a function of a single dominant factor (central response, CR). An alternative approach is to model maximum and minimum abundance in relation to the dominant factor (limiting response, LR), thereby acknowledging that multiple factors may constrain abundance and create scatter in the relationship. In many ecosystems, including streams, abundance–environment relationships are traditionally expected to be CR models with a single dominant factor determining local abundance, but this hypothesis lacks rigorous test. This omission is of concern because CR modelled relationships form the foundations of many ecological tests, predictive and management tools that, consequently, may provide erroneous interpretations.2. In a survey designed to minimise variance in the data, we related densities of three taxa of stream invertebrates to near‐bed flow. Data were analysed using both ordinary least squares (OLS) regression and quantile regression, which have different characteristic results depending on whether the relationship is better described as a CR or LR model. For all three taxa, invertebrate responses to flow conformed most closely to LR models and were best described by quantile regression, although OLS regression revealed broadly similar general trends in this case.3. Based on the statistically modelled relationships, we were able to hypothesise which ecological mechanisms limited maximum abundance at this site, including dislodgement with high flow (Heptageniidae, Leuctridae), reduced oxygen uptake at low flow (Baetidae) and reduced provision of interstitial spaces at high flow (Leuctridae). Scatter in the relationships was attributable to multiple factors that may operate at different scales, including inter‐individual variation, alternative environmental gradients and biotic processes at the patch scale, and potential constraints of dispersal and settlement operating outside the patch.4. We illustrate how the choice of CR or LR model to describe abundance–environment relationships may affect tests of ecological theory and applied ecology. If our results are typical of other streams and other types of systems, greater use of LR models may transform the way many ecologists view ecosystems, thus having positive consequences for survey and experimental designs and highlighting weaknesses in existing management tools that are underpinned by CR models.
Releases of ingested phytoplankton carbon by Daphnia magna
Authors: HE XUEJIA , WANG WEN‐XIONG 
Published: February 2006

Summary1. The carbon budgets and assimilation efficiencies (AEs) of adults and juveniles of Daphnia magna were quantified using 14C as a tracer. Animals were fed pure Chlamydomonas reinhardtii or Scenedesmus obliquus at different food concentrations. Carbon AEs (46–70%) were comparable at food concentrations of 0.03–0.30 mg C L−1 for both algal species, but decreased to 34–49% when the food concentration further increased by 10‐fold. The carbon AEs were significantly and negatively correlated with the food level.2. During the postdigestive period, partitioning of ingested carbon into different compartments including excretion, respiration and egestion was not influenced by the food species and life stage. There was a negative correlation between respiration (as % of total loss) and food concentration and a positive correlation between egestion (as % of total loss) and food concentration. Dissolved organic carbon (DOC) and CO2 accounted for 55–72% and 9–37%, respectively, of the total carbon loss from juveniles fed both algal diets. For adults, DOC and CO2 contributed to 44–64% and 20–47% of the total carbon loss, respectively. Particulate organic carbon (POC) was a minor pathway for the overall carbon loss.3. The turnover and release budget of structural carbon (as moults and neonate reproduction) were further evaluated in long‐term experiments at different algal concentrations. Food concentration did not affect the carbon efflux or the carbon allocation into different physiological compartments except for respiration. Juveniles had twofold lower carbon turnover rate (0.12–0.16 day−1) than those of the adults (0.32–0.35 day−1). In adults, comparable carbon was allocated into DOC (35–42%) and reproduction (27–35%), which were the dominant routes for carbon loss. For the juveniles, DOC accounted for 42–64% of the total carbon loss.4. About 21–38% of the total DOC released by adults and juveniles was associated with the high molecular weight organic carbon fraction (>5 kDa). Our results show that carbon was mainly lost by D. magna in the form of DOC during assimilation process as well as from the structural materials. Reproduction or maternal transfer was another major drain of body carbon for adult D. magna.
The cognitive and behavioural phenotype of Roifman syndrome
Authors: De Vries P. J. , McCartney D. L. , McCartney E. , Woolf D. , Wozencroft D. 
Published: February 2006

AbstractBackground  Roifman syndrome (OMIM 300258) is a multi‐system disorder with a physical phenotype that includes Β‐cell immunodeficiency, intra‐uterine and postnatal growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy and characteristic facial dysmorphism. So far, six cases, all boys, have been reported in the literature. Roifman postulated that the syndrome may be due to a mutation in an X‐linked gene or an autosomal gene giving rise to a sex‐limited trait, but the definitive pathogenetic mechanism has still not been elucidated. Very little is known about the cognitive and behavioural phenotype of Roifman syndrome and no standardized measures of cognitive abilities have been reported.Methods  We report the seventh case of a boy with Roifman syndrome and present the first systematic documentation of the cognitive and behavioural phenotype of an individual with the syndrome.Results  In spite of having been reported as appearing intellectually ‘able’, formal evaluation showed very significant intellectual disability and neuropsychological impairment across cognitive domains.Conclusions  The findings suggest that Roifman syndrome may be an example of an X‐linked mental retardation syndrome (XLMRS).
Thymic carcinoid in multiple endocrine neoplasia 1: genotype–phenotype correlation and prevention
Authors: LIM L. C. , TAN M. H. , ENG C. , TEH B. T. , RAJASOORYA R. C. 
Published: February 2006

Abstract.Thymic carcinoid is a rare multiple endocrine neoplasia type 1 (MEN1)‐associated tumour that is a major cause of death in MEN1 patients. Here, we describe a previously unreported MEN1 family in which two siblings presented with malignant thymic carcinoids. All six siblings share a novel nonsense mutation Q395X on exon 8 of the MEN1 gene. The index patient developed a thymic carcinoid despite an earlier prophylactic transcervical thymectomy, and one other sibling had an incidental malignant thymic carcinoid discovered following prophylactic thymectomy, both cases demonstrating the weakness and strength of this surgical approach. We then review the spectrum of germline MEN1 mutations associated with thymic carcinoids to evaluate the possibility of a genotype–phenotype correlation. In the 22 separate MEN1 families with thymic carcinoids, all but two (91%) have mutations coding for a truncated protein. There is clearly a high prevalence of truncating mutations in MEN1‐related thymic carcinoids although when compared with the prevalence of truncating mutations in all reported MEN1 mutations, it is not statistically significant (P = 0.39). Further studies are warranted to evaluate pathways of tumorigenesis of thymic carcinoids with regard to loss of function of menin.