bluuebunny/crossref_metadata_2025 huggingface dataset:
A Developmental Approach to Forebrain Organization in Elasmobranchs: New Perspectives on the Regionalization of the Telencephalon
Authors: Rodríguez-Moldes Isabel
Published: September 2009

It is essential to consider chondrichthyans (cartilaginous fishes) in analyzing ancestral brain organization because this radiation represents the out-group to all other living gnathostomes (jawed vertebrates). It is particularly crucial to understand the evolution of the telencephalon in chondrichthyans, as this structure develops by evagination (as in most other vertebrates), whereas in most osteichthyans (bony fishes), it develops by eversion, a markedly different process. Among chondrichthyans, the Lesser Spotted Dogfish Scyliorhinus canicula (Elasmobranchii) appears to offer the most potential as a model species for study. Developmental studies of Scyliorhinus have revealed a segmentary pattern in the developing forebrain, similar to that described in other vertebrates, as well as the occurrence of tangential cell migration within the telencephalon, especially in relation to the pallial-subpallial boundary. These observations indicate that major morphogenetic processes thought to be a hallmark of mammalian brains actually existed much earlier in vertebrate phylogeny. In addition, analysis of telencephalic development in Scyliorhinus indicates the existence of telencephalic structures that are probably related to the ganglionic eminences of mammals.
Topo IIIα and BLM Act within the Fanconi Anemia Pathway in Response to DNA-Crosslinking Agents
Authors: Hemphill A.W. , Akkari Y. , Newell A.H. , Schultz R.A. , Grompe M. , North P.S. , Hickson I.D. , Jakobs P.M. , Rennie S. , Pauw D. , Hejna J. , Olson S.B. , Moses R.E.
Published: September 2009

The Bloom protein (BLM) and Topoisomerase IIIα are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents. In order to determine if the association reflects a functional interaction for the maintenance of genome stability, we have analyzed the effects of siRNA-mediated depletion of the proteins in human cells. Depletion of Topoisomerase IIIα or BLM leads to increased radial formation, as is seen in FA. BLM and Topoisomerase IIIα are epistatic to the FA pathway for suppression of radial formation in response to DNA interstrand crosslinks since depletion of either of them in FA cells does not increase radial formation. Depletion of Topoisomerase IIIα or BLM also causes an increase in sister chromatid exchanges, as is seen in Bloom syndrome cells. Human Fanconi anemia cells, however, do not demonstrate increased sister chromatid exchanges, separating this response from radial formation. Primary cell lines from mice defective in both Blm and Fancd2 have the same interstrand crosslink-induced genome instability as cells from mice deficient in the Fancd2 protein alone. These observations demonstrate that the association of BLM and Topoisomerase IIIα with Fanconi proteins is a functional one, delineating a BLM-Topoisomerase IIIα-Fanconi pathway that is critical for suppression of chromosome radial formation.
Karyological Characterization of the Butterfly Lizard (Leiolepis reevesii rubritaeniata, Agamidae, Squamata) by Molecular Cytogenetic Approach
Authors: Srikulnath K. , Matsubara K. , Uno Y. , Thongpan A. , Suputtitada S. , Apisitwanich S. , Matsuda Y. , Nishida C.
Published: September 2009

Karyological characterization of the butterfly lizard (Leiolepis reevesii rubritaeniata) was performed by conventional Giemsa staining, Ag-NOR banding, FISH with the 18S-28S and 5S rRNA genes and telomeric (TTAGGG)n sequences, and CGH. The karyotype was composed of 2 distinct components, macrochromosomes and microchromosomes, and the chromosomal constitution was 2n = 2x = 36 (L4m + L2sm + M2m + S4m + 24 microchromosomes). NORs and the 18S-28S rRNA genes were located at the secondary constriction of the long arm of chromosome 1, and the 5S rRNA genes were localized to the pericentromeric region of chromosome 6. Hybridization signals of (TTAGGG)n sequences were observed at the telomeric ends of all chromosomes and interstitially at the same position as the 18S-28S rRNA genes, suggesting that in the Leiolepinae tandem fusion probably occurred between chromosome 1 and a microchromosome where the 18S-28S rRNA genes were located. CGH analysis, however, failed to identify sex chromosomes, suggesting that this species may have a TSD system or exhibit GSD with morphologically undetectable cryptic sex chromosomes. Homologues of 6 chicken Z-linked genes (ACO1/IREBP, ATP5A1, CHD1, DMRT1, GHR, RPS6) were all mapped to chromosome 2p in the same order as on the snake chromosome 2p.
Distribution of Eu- and Heterochromatin in Plantagoovata
Authors: Dhar M.K. , Fuchs J. , Houben A.
Published: September 2009

Plantago ovata (2n = 8) is the only cultivated species in the monotypic genus Plantago. The seed husk of the plant constitutes the psyllium (Isabgol) which has many medicinal properties. The 1C DNA content was determined to be 0.635 pg (621 Mb) with an AT content of 59.7%. Applying Giemsa C-banding and fluorescence in situ hybridization (FISH) using the Cot-1 fraction of DNA on prometaphase and metaphase chromosomes we investigated the chromosomal distribution of eu- and heterochromatin. All applied techniques revealed that the euchromatin is located at the distal ends of all chromosome arms, besides the NOR-bearing ones. Interestingly, in addition one arm of chromosome 1 seems to be entirely euchromatic. Furthermore, we have analysed the correlation between the global distribution of histone H3 mono-, di- or trimethylated at either lysine 4, 9 or 27 and the microscopically detectable eu- and heterochromatin. Methylated H3K4 was found to be enriched exclusively within euchromatin. From the other tested methylation marks only H3K9me1, H3K9me2 and H3K27me1 showed, in addition to a more or less disperse labelling, an enrichment within the heterochromatic chromocentres. The cell cycle dependent phosphorylation of histone H3 at serine 10 and threonine 11 was enriched in all pericentromeric regions.
Primary Ovarian Dysfunction Contributes to the Hypogonadism in Women with Prader-Willi Syndrome
Authors: Eldar-Geva Talia , Hirsch Harry J. , Rabinowitz Ron , Benarroch Fortu , Rubinstein Orit , Gross-Tsur Varda
Published: September 2009

Background/Aims: To investigate the etiology of hypogonadism in women with Prader-Willi Syndrome (PWS). Methods: Ten women aged 23 ± 5.5 years with PWS and 10 age- and BMI-matched controls were included. Blood samples were drawn and abdominal ultrasounds were performed on days 2–4 of spontaneous cycles or at random from amenorrheic women. Anti-Müllerian hormone (AMH), inhibin B (INB), gonadotropins, sex steroids, TSH, prolactin, ovarian volume and antral follicle count (AFC) in PWS women were compared with results from controls and the reference ranges. Results: Compared to controls, PWS women had lower INB (mean ± SD = 17.6 ± 12.8 pg/ml vs. 110.6 ± 54.5; p = 0.0002) and AMH levels (1.18 ± 0.86 ng/ml vs. 3.53 ± 2.42; p = 0.01). INB levels were exceptionally low in all PWS women, but individual AMH levels overlapped with the levels in the controls. Ovarian volume (mean ± SD = 3.7 ± 2.3 ml vs. 30.5 ± 28.8; p = 0.03) and AFC (6.4 ± 6.9 vs. 14.0 ± 8.2; p = 0.01) were lower in the PWS group compared to the controls. Three PWS patients had abnormally high follicle-stimulating hormone levels, while only 1 had hypogonadotropic hypogonadism. Conclusions: Our results suggest a unique follicular stage-specific insult in women with PWS. Thus, primary ovarian dysfunction is a major component of hypogonadism in PWS.
Forearm Length – A New Tool to Standardize Bone Parameters of the Forearm Measured with Peripheral Quantitative Computed Tomography in Individuals with Disproportional Growth of Forearm Length and Body Height
Authors: Fricke Oliver , Semler Oliver , Beccard Ralf , Land Christof , Ehrlich Roland , Remer Thomas , Schoenau Eckhard
Published: September 2009

Aim: To investigate the relationship of forearm length (FL) or height to bone parameters of the forearm of a normal pediatric population in comparison to individuals with osteogenesis imperfecta (OI). Methods: Data on FL, height and peripheral quantitative computed tomography measurements of the forearm were collected from participants of the DONALD study (140 males and 156 females; age 5–19 years) and from 73 patients with OI (53 males; mean age ± SD: 11.7 ± 3.3 years). Bone mineral content (BMC) was transformed into standard deviation score (SDS) according to height or FL. Results: Height and Tanner stages significantly predicted FL in males (R2adjusted = 0.960) and females (R2adjusted = 0.934). Height was a stronger predictor of FL than Tanner stages. Compared to controls, patients with OI were characterized by lower BMC-SDSFL and lower BMC-SDSheight (–0.37 ± 1.77 vs. 0.00 ± 0.97, p = 0.002, and –0.15 ± 5.0 vs. –0.02 ± 1.01, p = 0.011, respectively). BMC-SDSFL was not significantly lower than BMC-SDSheight in controls, and also not lower in patients with OI (p = 0.865 and p = 0.809). The height/FL ratio was significantly decreased in patients with OI (mean ± SD: 6.34 ± 0.38 vs. 6.45 ± 0.21, p = 0.001) compared with controls. Conclusion: Because of disproportional growth, BMC may be overestimated in OI patients.
Target Height Estimation in Children with Idiopathic Short Stature Who Are Referred to the Growth Clinic
Authors: Poyrazoglu Sukran , Darendeliler Feyza , Bas Firdevs , Bundak Ruveyde , Saka Nurcin , Darcan Sukran , Wit Jan M. , Gunoz Hulya
Published: September 2009

Aim: It was the aim of this study to evaluate adult height (AH) and different methods used for estimation of target height (TH) in children with idiopathic short stature (ISS). Methods: Eighty-five ISS children (36 female, 49 male) were followed until AH was evaluated retrospectively. TH was calculated according to the following 4 methods: (1) as ±6.5 cm to the mean parental heights for boys or girls, respectively, (2) as the mean standard deviation score (SDS) of the parents’ heights, (3) as the sum of the SDS of the parents’ heights divided by 1.61, and (4) as the mean SDS of the parents’ heights multiplied by 0.72. ISS was classified as familial short stature (FSS) if the height was within the TH range and as nonfamilial short stature (NFSS) if it was below the TH range. Results: The number of FSS and NFSS children differed by the method chosen. The mean AH SDS was lower than the TH SDS in FSS in all methods, except in method 3. NFSS children did not attain their TH in either of the methods. Conclusions: Classification of ISS depends on the method of the TH range chosen. ISS children reach a mean AH SDS lower than the mean TH SDS. Only FSS children classified by method 3 reached a mean AH SDS close to the mean TH SDS.
Association between Markers of Inflammation, Fibrosis and Hypervolemia in Peritoneal Dialysis Patients
Authors: Gangji Azim S. , Brimble K. Scott , Margetts Peter J.
Published: August 2009

Background/Aim: Volume expansion in peritoneal dialysis (PD) patients is associated with left ventricular hypertrophy. The link between inflammation and hypervolemia has not been extensively studied. The aim of this study was to determine if an association exists between hypervolemia and markers of inflammation in PD patients. Methods: In this cross-sectional study of 22 prevalent PD patients, volume was determined by bioelectrical impedance analysis. Serum and peritoneal effluent interleukin-6 (IL-6) and peritoneal transforming growth factor (TGF)-β1 were measured. A fast peritoneal equilibration test determined peritoneal transport status. Results: Bioimpedance-derived measures of hypervolemia correlated with peritoneal effluent IL-6 and TGF-β1. Peritoneal IL-6 was also associated with high peritoneal transport status. Conclusions: Markers of inflammation and fibrosis (peritoneal IL-6 and TGF-β1) are associated with markers of hypervolemia.
ELISA to Determine Immunoreactive Pseudomonasaeruginosa Elastase in Chronic Suppurative Otitis Media
Authors: Jin Chun Shun , Hamaguchi Yukiyoshi , Sakakura Yasuo
Published: September 2009

A sensitive sandwich ELISA has been developed to measure the levels of Pseudomonas aeruginosa elastase (PE) in ear discharges from chronic suppurative otitis media (CSOM) patients. Preincubation of the sample with EDTA-2Na before ELISA was employed to inhibit PE activity which hydrolyzes the anti-PE IgG antibody into a smaller molecular form. The PE levels of 10 middle ear effusions (MEE) from chronic otitis media with effusion were also measured. In CSOM, 9 of 10 samples had significant PE levels, ranging from 6.8 to 62.1 μg/ml, which were significantly higher than those in MEE (p < 0.01), the majority of which was below the detection limit. Two samples of CSOM with the P. aeruginosa infection showed high PE levels. This sandwich ELISA for the measurement of PE is a very sensitive method requiring only a small sample amount.
Dynamics of 125I-Labelled Horse Serum Albumin Presentation in vivo in Guinea Pigs
Authors: Pongracz Judit , Csaba B.
Published: September 2009

Low antibody production in guinea-pig sera was determined by passive hemagglutination after 125I-labelled horse serum albumin (HoSA) injection. The appearance of radiolabelled HoSA on T cells, B cells and monocytes/macrophages (Mo) of guinea pigs was detected and followed as a function of time. The radioactivity peaks appeared first on B cells and Mo, later on the T cells. The circulating T lymphocytes contained labelled antigen 7 days after the injection while T and B lymphocytes in the spleen preserved their radioactivity 15 and 20 days later. Helper, suppressor and effector T cells were able to fix 125I-HoSA, this was shown by autoradiography using monoclonal antibodies 4 days following the antigen injection.
Complement Activation by House Dust: Reduced Reactivity of Serum Complement in Patients with Bronchial Asthma
Authors: Castro F.F.M. , Schmitz-Schumann M. , Rother U. , Kirschfink M.
Published: September 2009

Among ten different allergens, house-dust extract proved to be the most potent complement activator. It was therefore chosen to investigate the susceptibility of complement in the serum and bronchoalveolar lavage fluid of patients with extrinsic asthma and control persons. Complement activation in serum was assessed by the appearance of C3d as well as the activation-specific protein-protein complexes C1rs-C1inhibitor (classical pathway) and C3b(Bb)P (alternative pathway). Complement was activated via both the classical and the alternative pathway in a dose- and time-dependent manner. In contrast to earlier observations, however, complement was less affected in the serum of asthmatics than in the serum of normal individuals. Differences were restricted to alternative-pathway activation, probably due to preactivation and/or a significantly higher serum concentration of the regulatory protein factor H in asthmatic patients. In vitro generation of C3a in bronchoalveolar lavage fluid could not be achieved, although the presence of alternative pathway proteins C3, B and D was demonstrated.
Cytoarchitecture of a Cichlid Fish Telencephalon
Authors: Burmeister Sabrina S. , Munshi Rashmi G. , Fernald Russell D.
Published: August 2009

Although the telencephalon of ray-finned fishes has garnered considerable attention from comparative neuroanatomists, detailed descriptions of telencephalic organization are available for only a few species. This necessarily limits our understanding of telencephalic evolution, particularly in light of the extraordinary diversity of ray-finned fishes. Thus, we have charted the cyctoarchitecture of the telencephalon of the African cichlid fish, Astatotilapia (Haplochromis) burtoni. We examined tissue sectioned in the transverse plane, and categorized cell groups based on size, shape, and staining intensity of cells, the density and distribution of cells, cell-poor zones, and relationship of cell groups to the anterior commissure and external sulci. In addition, to facilitate visualization of the transitions among cell groups, we aligned and animated a series of 100 sequential brain sections. We found that the A. burtoni telencephalon was similar to other percomorphs in being highly elaborated with many distinct cell groups. In the pallium, Dm, Dl, and Dc had a large number of cell groups, whereas Dd and Dp were more uniform. Although we recognized many similarities between the pallium of A. burtoni and other teleosts, we also recognized two cell groups (Dl-g and Dm-2) that might represent specializations of cichlids. We found that the subpallium had a similar organization to that of other ray-finned fishes.
Dysbindin and D-Amino-Acid-Oxidase Gene Polymorphisms Associated with Positive and Negative Symptoms in Schizophrenia
Authors: Wirgenes Katrine V. , Djurovic Srdjan , Agartz Ingrid , Jönsson Erik G. , Werge Thomas , Melle Ingrid , Andreassen Ole A.
Published: August 2009

Background: Schizophrenia is a genetically complex disorder with an unknown pathophysiology. Several genes implicated in glutamate metabolism have been associated with the disorder. Recent studies of polymorphisms in the dystrobrevin-binding protein 1 gene (DTNBP1; dysbindin) and D-amino-acid-oxidase (DAO) gene, both involved in glutamate receptor function, reported associations with negative symptoms and with anxiety and depression, respectively, when measured with the Positive and Negative Syndrome Scale (PANSS). Methods: In the present study, the suggested association between dysbindin and DAO single nucleotide polymorphisms (SNPs) and PANSS scores was analyzed in 155 Norwegian schizophrenia patients. Results: There was a significant association between the dysbindin SNP rs3213207 and severity of both negative symptoms and total symptom load, as well as between the DAO SNP rs2070587 and total symptom score and severity of anxiety and depression. Conclusion: The present association of dysbindin SNPs with negative symptoms and DAO SNPs with anxiety and depression is a replication of earlier findings and strengthens the hypothesis of a genetic association. It further indicates involvement of glutamate abnormalities in schizophrenia pathophysiology, as suggested by previous studies, and suggests that polymorphisms may be associated with subgroups of clinical characteristics in schizophrenia.
Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part I: Young Subjects
Authors: Spivak Baruch , Schechtman Mila , Blumensohn Rachel , Schönherz-Pine Yael , Yoran-Hegesh Roni , Deckmann Michael , Mayer Rina , Weizman Abraham , Shinitzky Meir
Published: August 2009

Background: It has been hypothesized that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous open screenings have recorded significantly higher blood titers of platelet-associated autoantibodies (PAA) in schizophrenic patients as compared to normal healthy subjects. In addition, young schizophrenic patients at the early stages of their disorder displayed higher PAA titers than older patients with a longer duration of the disorder. A blood test based on these observations was proposed. Aim: To verify by a blind test a significant difference in PAA between young schizophrenic patients and matched healthy control subjects, for the validation of a blood test for schizophrenia. Methods: A total of 36 young schizophrenic patients in an active psychotic state, aged 13–20 years (mean ± SD: 16.2 ± 2.1 years) with an average PANSS score of 115.6 ± 14.5 and illness duration of 9.5 ± 9.4 months, were examined. The control group consisted of 49 healthy young subjects between the ages of 13 and 21 years (16.2 ± 2.2 years). The blood titers of PAA were evaluated blindly using an optimized ELISA test, expressed by a linear optical density (OD) scale. The blood samples of all participants were tested anonymously, and were scored under a code number. A test recording above 1.3 OD units was defined as positive. Results: The PAA titers of schizophrenia patients (1.6 ± 0.4 OD units, range: 0.7–2.3 OD units) were significantly higher than those of the control group (1.0 ± 0.4 OD units, range: 0.4–1.8 OD units; p < 0.0001). In 61% of the young schizophrenic patients (22 out of the 36 patients), a positive result (OD >1.3 units) was recorded. In the control group, only 12.2% (6 of the 49 subjects) displayed a positive result (p < 0.0001). Conclusions: These findings support further assessment of PAA titers as a potential biomarker for patients with clinical signs and symptoms of schizophrenia.
Mortality Trends Associated with Acute Renal Failure Requiring Dialysis after CABG Surgery in the United States
Authors: Nicoara Alina , Patel Uptal D. , Phillips-Bute Barbara G. , Shaw Andrew D. , Stafford-Smith Mark , Milano Carmelo A. , Swaminathan Madhav
Published: August 2009

Background/Aims: Acute renal failure is associated with a high risk of mortality when it complicates coronary artery bypass graft (CABG) surgery. We examined a large nationwide database from 1988 to 2003 and hypothesized that mortality in CABG-associated acute renal failure needing dialysis (ARF-D) had declined during this period. Methods: The Nationwide Inpatient Sample containing data on inpatient stays across 20% of US hospitals was used for our study. Multivariate logistic regression was used to determine an association between year and ARF-D mortality with standardized risk adjustment. Results: Incidence of ARF-D increased from 0.2 to 0.6% while mortality simultaneously decreased from 47.4% in 1988 to 29.7% in 2003. In the multivariable model, year was significantly associated with declining ARF-D mortality. Conclusions: The incidence of post-CABG ARF-D more than doubled from 1988 to 2003, while mortality simultaneously decreased by over one-third. Improved survival after ARF-D following CABG may be counterbalanced by increased morbidity and resource utilization.
Apoptosis in Endometriosis
Authors: Agic Admir , Djalali Schima , Diedrich Klaus , Hornung Daniela
Published: September 2009

Apoptosis is a physiologic process that eradicates undesired cells without inducing an inflammatory reaction. It is an important regulator of eutopic endometrial function and evidence suggests that apoptosis aids in maintaining cellular homeostasis during the menstrual cycle by eliminating aging cells from the functional layer of the uterine endometrium. Endometriosis, which is characterized by the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. Eutopic endometrium from women with endometriosis has several differences compared with normal endometrium of women without endometriosis. These differences may contribute to the survival of regurgitated endometrial cells into the peritoneal cavity and thus to the development of endometriosis. In this article, we will summarize recent literature concerning apoptosis-related genes such as Bcl-2 and Fas, outline the molecular basis of apoptosis and review the literature focused on the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis.
Reduction Clitoro-Labioplasty versus Clitoro-Labiectomy in Managing Adult Onset Clitoro-Labiomegaly
Authors: Ali Athmar Hussein , Thabet Saeed Mohamad Ahmad
Published: September 2009

Objectives: To compare a new procedure of reduction clitoro-labioplasty to clitoro-labiectomy in the management of adult onset clitoro-labiomegaly, and to show the disadvantages of the latter procedure that produces female genital mutilation and sexual dysfunction. Methods: This controlled, descriptive, comparative and prospective cohort study was performed at Kasr El-Aini School of Medicine, Cairo University, Egypt. 47 cases of clitoro-labiomegaly, 12 with known causes of intersex, were diagnosed and treated by reduction clitoro-labioplasty. In addition, a control group of 53 more cases, 6 with known causes of intersex, were followed after treatment by clitoro-labiectomy. Clitoro-labioplasty was performed by excision of the anterior part of the fused corpora after separation at the glans-corporal junction and a reduction in the size of the remaining part of the corpora to reform a normal clitoral size. The neurovascular bundles were essentially preserved during this procedure. The protruded parts of the labia minora are then excised to preserve their normal dimensions. The main outcome measures were the postoperative anatomical result, patient’s satisfaction, the pre- and postoperative sex scoring, and sexuality. Results: Restoration of normal anatomy was successfully obtained after clitoro-labioplasty compared to partial or complete loss of these sensitive parts after clitoro-labiectomy. In addition, significant operative and postoperative complications were recorded in 27 cases with clitoro-labiectomy compared to none of the clitoro-labioplasty cases. The sex scores and sexuality improved significantly after the clitoro-labioplasty operation compared to clitoro-labiectomy (p < 0.005). Normalization of the sex scores and sexuality was found to be significantly related to preservation of critical clitoral length necessary for producing clitoral orientation and interest in sexuality. Conclusion: The new clitoro-labioplasty technique is able to preserve proper clitoral and labial anatomy and restore normal sexuality. Therefore it must be considered an essential line of treatment for clitoro-labiomegaly.
The Effect of Lubricating Eye Drop Containing Hydroxypropyl Guar on Perimetry Results of Patients with Glaucoma and Trachomatous Dry Eye
Authors: Guzey Mustafa , Satici Ahmet , Karaman Suleyman Korhan , Sezer Sezgin , Bozkurt Omer
Published: September 2009

Purpose: To evaluate the effects of a mid-viscosity mucomimetic lubricant eye drop containing hydroxypropyl guar (HPG) as a gelling agent on computerized perimetry FASTPAC test results of primary open-angle glaucoma (POAG) patients with trachomatous dry eye. Methods: Both eyes of 33 patients with bilateral POAG and trachomatous dry eye were included in the study. They were treated with the same antiglaucomatous eye drop and underwent computerized perimetry. Before and after the treatment with lubricant eye drop (Systane™) for 8 weeks, tear function tests (Schirmer test with topical anesthesia, fluorescein staining and tear film break-up time) and FASTPAC test with computerized perimetry were performed. Pre- and posttreatment tear functions, visual field test global indices, reliability indices, test duration and numbers of depressed points in pattern deviation plots were compared. Results: We found significant improvements in tear function tests results, in computerized perimetry FASTPAC test indices, test duration and the number of depressed points in pattern deviation plots in the posttreatment evaluations. Conclusion: This study indicates that there was a benefit of mid-viscosity lubricant eye drop containing HPG treatment on computerized perimetry FASTPAC test performance in POAG subjects with trachomatous dry eye. We assume that the positive effect of this therapy is probably due to a better tear film stability, resulting in a higher optical quality of the repaired anterior corneal surface.
Validation of Endogenous Internal Real-Time PCR Controls in Renal Tissues
Authors: Cui Xiangqin , Zhou Juling , Qiu Jing , Johnson Martin R. , Mrug Michal
Published: August 2009

Background: Endogenous internal controls (‘reference’ or ‘housekeeping’ genes) are widely used in real-time PCR (RT-PCR) analyses. Their use relies on the premise of consistently stable expression across studied experimental conditions. Unfortunately, none of these controls fulfills this premise across a wide range of experimental conditions; consequently, none of them can be recommended for universal use. Methods: To determine which endogenous RT-PCR controls are suitable for analyses of renal tissues altered by kidney disease, we studied the expression of 16 commonly used ‘reference genes’ in 7 mildly and 7 severely affected whole kidney tissues from a well-characterized cystic kidney disease model. Expression levels of these 16 genes, determined by TaqMan® RT-PCR analyses and Affymetrix GeneChip® arrays, were normalized and tested for overall variance and equivalence of the means. Results: Both statistical approaches and both TaqMan- and GeneChip-based methods converged on 3 out of the 4 top-ranked genes (Ppia, Gapdh and Pgk1) that had the most constant expression levels across the studied phenotypes. Conclusion: A combination of the top-ranked genes will provide a suitable endogenous internal control for similar studies of kidney tissues across a wide range of disease severity.
Phase II Study of S-1 Combined with Irinotecan (CPT-11) in Patients with Advanced Colorectal Cancer
Authors: Tsunoda A. , Yasuda N. , Nakao K. , Narita K. , Watanabe M. , Matsui N. , Kusano M.
Published: September 2009

Objective: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. Methods: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. Results: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5–77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7–9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. Conclusion: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.
Do Recurrent and Metastatic Pancreatic Cancer Patients Have the Same Outcomes with Gemcitabine Treatment?
Authors: Hashimoto Kenji , Ueno Hideki , Ikeda Masafumi , Kojima Yasushi , Hagihara Atsushi , Kondo Shunsuke , Morizane Chigusa , Okusaka Takuji
Published: September 2009

Background: Whether recurrence after surgery and primary metastatic pancreatic cancer should be included in the same category when conducting gemcitabine-based clinical trials remains controversial. Objective: To clarify the outcomes of recurrent and metastatic pancreatic cancers. Methods: 326 patients who received gemcitabine monotherapy as a first-line treatment for advanced pancreatic cancer between 2001 and 2007 were reviewed. Multivariate analysis was performed to determine the prognostic relevance of recurrence or metastasis in relation to other factors possibly influencing treatment outcomes with respect to overall survival. Differences in response to chemotherapy, drug delivery and adverse events were also analyzed. Results: There were 65 recurrent and 261 metastatic cancer patients. Recurrent cancer patients had a significantly longer time to treatment failure and survival (respective medians 138 and 77 days, p = 0.017) than the metastatic patients (respective medians 270 and 185 days, p = 0.0003). Multivariate analysis revealed poor Karnofsky performance status (<80), presence of liver or peritoneal metastasis, elevated lactate dehydrogenase (>220 U/l), elevated alkaline phosphatase (>330 U/l) and elevated C-reactive protein (>1.0 mg/dl) to be significantly correlated with short survival, while neither recurrent nor metastatic status were related to survival (hazard ratio 0.76, 95% CI 0.53–1.09, p = 0.14). The response rates and dose intensities of gemcitabine were similar in these groups, although leukopenia was more frequently observed in the recurrence group (p = 0.008). Conclusion: When conducting clinical trials, it appears to be acceptable to treat recurrent pancreatic cancer after surgery and pancreatic cancer with primary metastasis under the same category.
Sox17 Expression Patterns during Gastrulation and Early Neurulation in the Rabbit Suggest Two Sources of Endoderm Formation
Authors: Hassoun Romia , Püschel Bernd , Viebahn Christoph
Published: September 2009

Most gastrointestinal tract and associated gland epithelia originate from the endoderm germ layer discovered by Pander in 1817. The recent surge in stem cell concepts revived interest in the findings of 30 years ago that the endoderm layer itself originates from the epiblast (which since Pander’s time had been held to be the forerunner of the ectoderm and mesoderm germ layers only). However, the question as to which parts of the mammalian gastrulation-stage embryonic disc generate endoderm cells is still unresolved. Therefore, the expression of the gene coding for the transcription factor Sox17, a key transcription factor involved in endoderm formation in mouse, chick, frog, and zebrafish, was analyzed in the rabbit, a model organism for mammalian gastrulation morphology, using whole-mount in situ hybridization and high-resolution histological analysis of embryos at gastrulation and early neurulation stages. Sox17 mRNA in the mesoderm and lower layer (hypoblast) compartments within and adjacent to Hensen’s node and the anterior segment of the primitive streak confirmed the validity of this approach, as this region had previously been shown to form endoderm in mouse and chick. However, Sox17 expression in central and posterior epiblast at pregastrulation stages together with a transient expression at the posterior extremity of the primitive streak suggest that endoderm (possibly hindgut) may be formed close to the emerging cloacal membrane, as well.
The Hedgehog Transcription Factor Gli3 Modulates Angiogenesis
Authors: Renault Marie-Ange , Roncalli Jérôme , Tongers Jörn , Misener Sol , Thorne Tina , Jujo Kentaro , Ito Aiko , Clarke Trevor , Fung Chris , Millay Meredith , Kamide Christine , Scarpelli Andrew , Klyachko Ekaterina , Losordo Douglas W.
Published: September 2009

Rationale
:

The Gli transcription factors are mediators of Hedgehog (Hh) signaling and have been shown to play critical roles during embryogenesis. Previously, we have demonstrated that the Hh pathway is reactivated by ischemia in adult mammals, and that this pathway can be stimulated for therapeutic benefit; however, the specific roles of the Gli transcription factors during ischemia-induced Hh signaling have not been elucidated.

Objective
:

To investigate the role of Gli3 in ischemic tissue repair.

Methods and Results
:

Gli3-haploinsufficient (Gli3
+/−
) mice and their wild-type littermates were physiologically similar in the absence of ischemia; however, histological assessments of capillary density and echocardiographic measurements of left ventricular ejection fractions were reduced in Gli3
+/−
mice compared to wild-type mice after surgically induced myocardial infarction, and fibrosis was increased. Gli3-deficient mice also displayed reduced capillary density after induction of hindlimb ischemia and an impaired angiogenic response to vascular endothelial growth factor in the corneal angiogenesis model. In endothelial cells, adenovirus-mediated overexpression of Gli3 promoted migration (modified Boyden chamber), small interfering RNA–mediated downregulation of Gli3 delayed tube formation (Matrigel), and Western analyses identified increases in Akt phosphorylation, extracellular signal-regulated kinase (ERK)1/2 activation, and c-Fos expression; however, promoter–reporter assays indicated that Gli3 overexpression does not modulate Gli-dependent transcription. Furthermore, the induction of endothelial cell migration by Gli3 was dependent on Akt and ERK1/2 activation.

Conclusions
:

Collectively, these observations indicate that Gli3 contributes to vessel growth under both ischemic and nonischemic conditions and provide the first evidence that Gli3 regulates angiogenesis and endothelial cell activity in adult mammals.
Dynamical Analysis of the Boundary Layer and Surface Wind Responses to Mesoscale SST Perturbations
Authors: O’Neill Larry W. , Esbensen Steven K. , Thum Nicolai , Samelson Roger M. , Chelton Dudley B.
Published: August 2009

The dynamical response of the marine atmospheric boundary layer (MABL) to mesoscale sea surface temperature (SST) perturbations is investigated over the Agulhas Return Current during winter from a 1-month, high-resolution, three-dimensional simulation using the Weather Research and Forecasting (WRF) mesoscale model. A steady lower boundary condition for July 2002 is obtained using SST measurements from the Advanced Microwave Scanning Radiometer on the Earth Observing System (EOS)–Aqua satellite (AMSR-E). The WRF models’ ability to accurately simulate the SST-induced surface wind response is demonstrated from a comparison with satellite surface wind observations from the SeaWinds scatterometer on the Quick Scatterometer (QuikSCAT) satellite. Relevant features of this simulation include a quasi-periodic distribution of mesoscale SST perturbations with spatial scales ∼200 km and strong winds that lead to a large surface sensible heat flux response, whose broad range of 80–100 W m−2 between warm and cool SST perturbations is much larger than seen in most previous simulations of mesoscale wind–SST coupling.

This simulation provides the first realistic example of vertical turbulent redistribution of momentum driven by the SST-induced surface heating perturbations acting in concert with the SST-induced pressure gradients to accelerate near-surface flow toward warm water and decelerate near-surface flow toward cool water. This simulation is also the first example of a near-surface wind speed response to mesoscale SST perturbations that differs qualitatively and substantially from the vertically averaged MABL wind response. In the vertically averaged MABL momentum budget, the surface wind stress acts as a drag on the SST-induced perturbation flow as it is being accelerated by SST-induced pressure gradients. However, only in the middle and upper reaches of the MABL does the turbulent stress divergence act as a drag on the SST-induced winds perturbations in this simulation.

These mesoscale SST perturbations are also shown to modify the wind direction within the MABL. Dynamically, this is accomplished through SST-induced perturbations to the crosswind components of the pressure gradient, turbulent stress divergence, and the Coriolis force.
The Role of Rossby Wave Breaking in Shaping the Equilibrium Atmospheric Circulation Response to North Atlantic Boundary Forcing
Authors: Strong Courtenay , Magnusdottir Gudrun
Published: August 2009

The role of Rossby wave breaking (RWB) is explored in the transient response of an atmospheric general circulation model to boundary forcing by sea ice anomalies related to the North Atlantic Oscillation (NAO). When the NCAR Community Climate Model, version 3, was forced by an exaggerated sea ice extent anomaly corresponding to one arising from a positive NAO, a localized baroclinic response developed and evolved into a larger-scale equivalent barotropic pattern resembling the negative polarity of the NAO. The initial baroclinic response shifted the phase speeds of the dominant eddies away from a critical value equal to the background zonal flow speed, resulting in significant changes in the spatial distribution of RWB. The forcing of the background zonal flow by the changes in RWB accounts for 88% of the temporal pattern of the response and 80% of the spatial pattern of the zonally averaged response. Although results here focus on one experiment, this “RWB critical line mechanism” appears to be relevant to understanding the equilibrium response in a broad class of boundary forcing experiments given increasingly clear connections among the northern annular mode, jet latitude shifts, and RWB.
The Source of the Midwinter Suppression in Storminess over the North Pacific
Authors: Penny Sandra , Roe Gerard H. , Battisti David S.
Published: August 2009

Feature-tracking techniques are employed to investigate why there is a relative minimum in storminess during winter within the Pacific storm track (the midwinter suppression). It is found that the frequency and amplitude of disturbances entering the Pacific storm track from midlatitude Asia are substantially reduced during winter relative to fall and spring and that the magnitude of this reduction is more than sufficient to account for the midwinter supression. Growth rates of individual disturbances are calculated and compared to expectations from linear theory for several regions of interest. Although there are discrepancies between linear expectations and observed growth rates over the Pacific, the growth of disturbances within the Pacific storm track cannot explain why the midwinter suppression exists. Furthermore, it is determined that the development of a wintertime reduction in storminess over midlatitude Asia is consistent with linear expectations, which predict a wintertime minimum in Eady growth rates in this region, mainly because of increased static stability. Several other mechanisms that may contribute to the initiation of the midwinter suppression over midlatitude Asia are discussed, including the interaction between upper-level waves and topography, the behavior of waves upwind of the Tibetan Plateau, and the initiation of lee cyclones.
On the Madden–Julian Oscillation–Atlantic Hurricane Relationship
Authors: Klotzbach Philip J.
Published: August 2009

The large-scale equatorial circulation known as the Madden–Julian oscillation (MJO) has been shown to impact tropical cyclone activity in several basins around the globe. In this paper, the author utilizes an MJO index created by Wheeler and Hendon to examine its impacts on tropical genesis and intensification in the Atlantic. Large differences in frequency and intensity of tropical cyclone activity are seen, both in the tropical Atlantic as well as in the northwest Caribbean and Gulf of Mexico depending on the MJO phase. Coherent changes in upper- and lower-level winds and relative humidity are likely responsible for these differences. Since the MJO shows potential predictability out to about two weeks, the relationships discussed in this paper may be useful for short-term predictions of the probability of tropical cyclone activity in the Atlantic as a complement to the already available longer-term seasonal predictions.
Simulation of Present-Day and Twenty-First-Century Energy Budgets of the Southern Oceans
Authors: Trenberth Kevin E. , Fasullo John T.
Published: August 2009

The energy budget of the modern-day Southern Hemisphere is poorly simulated in both state-of-the-art reanalyses and coupled global climate models. The ocean-dominated Southern Hemisphere has low surface reflectivity and therefore its albedo is particularly sensitive to cloud cover. In modern-day climates, mainly because of systematic deficiencies in cloud and albedo at mid- and high latitudes, too much solar radiation enters the ocean. Along with too little radiation absorbed at lower latitudes because of clouds that are too bright, unrealistically weak poleward transports of energy by both the ocean and atmosphere are generally simulated in the Southern Hemisphere. This implies too little baroclinic eddy development and deficient activity in storm tracks. However, projections into the future by coupled climate models indicate that the Southern Ocean features a robust and unique increase in albedo, related to clouds, in association with an intensification and poleward shift in storm tracks that is not observed at any other latitude. Such an increase in cloud may be untenable in nature, as it is likely precluded by the present-day ubiquitous cloud cover that models fail to capture. There is also a remarkably strong relationship between the projected changes in clouds and the simulated current-day cloud errors. The model equilibrium climate sensitivity is also significantly negatively correlated with the Southern Hemisphere energy errors, and only the more sensitive models are in the range of observations. As a result, questions loom large about how the Southern Hemisphere will actually change as global warming progresses, and a better simulation of the modern-day climate is an essential first step.
The Relationships between Climatic and Hydrological Changes in the Upper Mississippi River Basin: A SWAT and Multi-GCM Study
Authors: Lu Er , Takle Eugene S. , Manoj Jha
Published: August 2009

Changes in major climatic and hydrological quantities in the upper Mississippi River basin and their interrelationships are studied with the Soil and Water Assessment Tool being driven by the contemporary climate and future scenario simulations of 10 global models in the Intergovernmental Panel on Climate Change (IPCC) Data Archive. Although the seasonal cycles of climate and hydrological quantities simulated by the 10 models have differences, the ensemble is very close to the observation. Ensemble predictions show that with warming in all months, precipitation decreases in summer but increases in all other seasons. Correspondingly, streamflow decreases in all seasons except winter, evapotranspiration decreases in July–September and increases in all other months, and snowmelt increases in winter but decreases in spring and fall. To understand the linkages between the cross-century changes of climate and hydrological quantities and the relative importance of the changes of temperature and precipitation to the changes of hydrological quantities, relationships between interannual variations of these quantities are investigated. It is shown that the change rates of the hydrological quantities with respect to temperature and precipitation obtained from regressions of interannual variations can vary greatly from month to month; however, on a monthly basis, they do not change much from the current to the future periods. Evaluations with these change rates indicate that for interannual variations of hydrological quantities, both variations of temperature and precipitation are important, and their relative importance depends on the month of the year. However, the changes of hydrological quantities from the means of the current years to the means of the future are dominated by warming in all months, and the influence from change of precipitation is much smaller. The changes of the hydrological quantities can be well predicted with the change rates from the warming alone.
Risk Factors in First Presentation Acute Coronary Syndromes (ACS): How Do We Move From Population to Individualized Risk Prediction?
Authors: Saab Fadi , Mukherjee Debabrata , Gurm Hitinder , Motivala Apurva , Montgomery Daniel , Kline-Rogers Eva , Rubenfire Melvyn , Eagle Kim
Published: September 2009

Patients with acute coronary syndromes (ACS) have a poor short- and long-term prognosis. We sought to examine the presence of established coronary risk factors in contemporary patients presenting with an ACS for the first time and no known coronary artery disease (CAD) in the past. The study was conducted in 3171 consecutive patients admitted with the diagnosis of ACS. Of these, 941 patients (30%) had the admission as the first occurrence of ACS and no prior history of CAD. We studied the degree to which these first presenters with ACS had 1 or more established risk factors. We found that 98% of patients presenting with an ACS for the first time and no previous CAD had at least 1 established risk factor. Current population-based screening efforts must be improved to allow more effective prevention strategies and more individualized risk prediction.