bluuebunny/crossref_metadata_2025 huggingface dataset:
C. elegans dysferlin homologfer-1is expressed in muscle, andfer-1mutations initiate altered gene expression of muscle enriched genes
Authors: Krajacic Predrag , Hermanowski Jane , Lozynska Olga , Khurana Tejvir S. , Lamitina Todd
Published: September 2009

Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms development but is not known to be expressed in or have a functional roles outside of the male germline. Using several approaches, we show that fer-1 mRNA is present in C. elegans muscle cells but is absent from neurons. In mammals, loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle expressed genes. To determine if similar alterations in gene expression are initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both mutants gave rise to highly similar changes in gene expression and altered the expression of 337 genes. Using multiple analysis methods, we show that this gene set is enriched for genes known to regulate the structure and function of muscle. However, these transcriptional changes do not appear to be in response to gross sarcomeric damage, since genetically sensitized fer-1 mutants exhibit normal thin filament organization. Our data suggest that processes other than sarcomere stability may be affected by loss of fer-1 in C. elegans muscle. Therefore, C. elegans may be an attractive model system in which to explore new muscle-specific functions of the dysferlin protein and gain insights into the molecular pathogenesis of LGMD2B.
Effect of Poly (Sodium 4‐Styrene Sulfonate) on the Morphology of Hydroxyapatite Particles
Authors: Esmaeilian Tari Nesa , Kashani Motlagh Mohammad Mahdi
Published: September 2009

Nanorods hydroxyapatite, (HAP) is successfully prepared by water in oil microemulsion using, CaCL2
and H3PO4
(water phase), poly(sodium 4‐styrene sulfonate) (PSSS) as template and cyclohexane as oil phase. The nano‐structure of the product was studied by means of X‐ray diffraction (XRD), Fourier transmission infrared spectrometer (FT‐IR), scanning electron microscopy (SEM), and atomic force microscope (AFM). With this system, we could synthesize nano‐particles of hydroxyapatite with high crystallinity and least agglomeration.
Progressive Multifocal Leukoencephalopathy in HIV-Infected Children: A Case Report and Literature Review
Authors: Oberdorfer Peninnah , Washington Charles H. , Katanyuwong Kamornwan , Jittamala Podjanee
Published: September 2009

We report a case of a perinatally HIV-infected patient aged 9 years, who presented with right-sided hemiplegia. His initial CD4 T-cell was of 0.21% (4 cells/μL) and plasma HIV RNA virus of 185 976 copies/mL (log 5.27). Plasma and CSF samples were subsequently positive for JCV. Twelve days after the initiation of highly active antiretroviral therapy (HAART), the MRI showed progressive white matter lesions with asymmetrical deep and subcortical white matter lesions over the left frontotemporoparietal region and the right frontal lobe. Immune Reconstitution Inflammatory Syndrome (IRIS) was suspected, and the patient was treated with methylprednisolone. His clinical symptoms worsened and despite therapy the patient deteriorated.
Trajectory Sensitivity Method and Master‐Slave Synchronization to Estimate Parameters of Nonlinear Systems
Authors: Cari Elmer P. T. , Theodoro Edson A. R. , Mijolaro Ana P. , Bretas Newton G. , Alberto Luis F. C.
Published: September 2009

A combination of trajectory sensitivity method and master‐slave synchronization was proposed to parameter estimation of nonlinear systems. It was shown that master‐slave coupling increases the robustness of the trajectory sensitivity algorithm with respect to the initial guess of parameters. Since synchronization is not a guarantee that the estimation process converges to the correct parameters, a conditional test that guarantees that the new combined methodology estimates the true values of parameters was proposed. This conditional test was successfully applied to Lorenz′s and Chua′s systems, and the proposed parameter estimation algorithm has shown to be very robust with respect to parameter initial guesses and measurement noise for these examples.
DNA Loci Cross‐Talk through Thermodynamics
Authors: Scialdone Antonio , Nicodemi Mario
Published: September 2009

The recognition and pairing of specific DNA loci, though crucial for a plenty of important cellular processes, are produced by still mysterious physical mechanisms. We propose the first quantitative model from Statistical Mechanics, able to clarify the interaction allowing such “DNA cross‐talk” events. Soluble molecules, which bind some DNA recognition sequences, produce an effective attraction between distant DNA loci; if their affinity, their concentration, and the relative DNA binding
sites number exceed given thresholds, DNA colocalization occurs as a result of a thermodynamic phase transition. In this paper, after a concise report on some of the most recent experimental results, we introduce our model and carry out a detailed “in silico” analysis of it, by means of Monte Carlo simulations. Our studies, while rationalize several experimental observations, result in very interesting and testable predictions.
Alterations in Adenylate Kinase Activity in Human PBMCs after In Vitro Exposure to Electromagnetic Field: Comparison between Extremely Low Frequency Electromagnetic Field (ELF) and Therapeutic Application of a Musically Modulated Electromagnetic Field (TAMMEF)
Authors: Albanese Antonietta , Battisti Emilio , Vannoni Daniela , Aceto Emilia , Galassi Gianmichele , Giglioni Stefania , Tommassini Valentina , Giordano Nicola
Published: September 2009

This study investigated the effects of electromagnetic fields on enzymes involved in purine metabolism in human peripheral blood mononuclear cells in vitro. Cells were obtained from 20 volunteers. We tested both low‐energy, extremely low frequency (ELF; 100‐Hz) electromagnetic fields and the Therapeutic Application of Musically Modulated Electromagnetic Fields
(TAMMEFs); the latter is characterized by variable frequencies, intensities, and wave shapes. Adenylate kinase activity was increased after ELF field exposure but decreased slightly after TAMMEF exposure. Neither of the two electromagnetic field affected the activities of the purine metabolism enzymes ecto‐5′‐nucleotidase, adenosine deaminase, and adenosine kinase. We concluded that ELF fields may influence cellular electrical charge stability; stimulation of adenylate kinase activity could restore the cell to a state of equilibrium. In contrast, TAMMEF fields may be useful for maintaining and regulating the cellular electrical charge.
The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity
Authors: Hanbauer Ingeborg , Rivero-Covelo Ignacio , Maloku Ekrem , Baca Adam , Hu Qiaoyan , Hibbeln Joseph R. , Davis John M.
Published: September 2009

Feeding mice, over 3 generations, an equicaloric diet in whichα-linolenic acid, the dietary precursor of n-3 polyunsaturated fatty acids, was substituted by linoleic acid, the dietary precursor of n-6 polyunsaturated fatty acids, significantly increased body weight throughout life when compared with standard diet-fed mice. Adipogenesis observed in the low n-3 fatty acid mice was accompanied by a 6-fold upregulation of stearyl-coenzyme A desaturase 1 (Scd1), whose activity is correlated to plasma triglyceride levels. In total liver lipid and phospholipid extracts, the sum of n-3 fatty acids and the individual longer carbon chain acids, eicosapentaenoic acid (20:5n3), docosapentaenoic acid (22:5n3), and docosahexaenoic acid (22:6n3) were significantly decreased whereas arachidonic acid (20:4n6) was significantly increased. In addition, low n-3 fatty acid-fed mice had liver steatosis, heart, and kidney hypertrophy. Hence, reducing dietaryα-linolenic acid, from 1.02 energy% to 0.16 energy% combined with raising linoleic acid intake resulted in obesity and had detrimental consequences on organ function.
HBX‐Mediated Migration of HBV‐Replicating HepG2 Cells: Insights on Development of Hepatocellular Carcinoma
Authors: Feng Huixing , Zhang Jianhua , Li Xi , Chen Wei Ning
Published: September 2009

Hepatitus B virus (HBV) is a major cause of the development of hepatpcellular carcinoma (HCC). One of the significant characteristics of tumor progression is cell migration which is reflective of cytoskeletal dynamics. The Rho GTPases contribute to a multiple cellular processes, including the cellular cytoskeletal reorganization and motility. It has been found that some Rho GTPases have oncogenic activity and can promote cancer cell invasion. Here we discuss one of the Rho GTPases, Rac1 can be activated by HBV replication and such activation results in the high motility of HBV‐replicating cells. The enhanced cell motility can be interestingly alleviated by the mutation at the sites of proline rich domain located in HBX. Our findings may provide new insights on the mechanism of HCC development associated with chronic HBV infection.
Probabilities as Values of Modular Forms and Continued Fractions
Authors: Masri Riad , Ono Ken
Published: September 2009

We consider certain probability problems which are naturally related to
integer partitions. We show that the corresponding probabilities are values of classical
modular forms. Thanks to this connection, we then show that certain ratios of
probabilities are specializations of the Rogers‐Ramanujan and Ramanujan‐ Selberg‐
Gordon‐Göllnitz continued fractions. One particular evaluation depends on a result
from Ramanujan′s famous first letter to Hardy.
Tumor Spreading to the Contralateral Ovary in Bilateral Ovarian Carcinoma Is a Late Event in Clonal Evolution
Authors: Micci Francesca , Haugom Lisbeth , Ahlquist Terje , Abeler Vera M. , Trope Claes G. , Lothe Ragnhild A. , Heim Sverre
Published: September 2009

Cancer of the ovary is bilateral in 25%. Cytogenetic analysis could determine whether the disease in bilateral cases is metastatic or two separately occurring primary tumors, but karyotypic information comparing the two cancerous ovaries is limited to a single report with 11 informative cases. We present a series of 32 bilateral ovarian carcinoma cases, analyzed by karyotyping and high-resolution CGH. Our karyotypic findings showed that spreading to the contralateral ovary had occurred in bilateral ovarian cancer cases and that it was a late event in the clonal evolution of the tumors. This was confirmed by the large number of similar changes detected by HR-CGH in the different lesions from the same patient. The chromosomal bands most frequently involved in structural rearrangements were 19p13 (n=12) and 19q13 (n=11). The chromosomal bands most frequently gained by both tumorous ovaries were 5p14 (70%), 8q23-24 (65%), 1q23-24 (57%), and 12p12 (48%), whereas the most frequently lost bands were 17p11 (78%), 17p13 (74%), 17p12 (70%), 22q13 (61%), 8p21 and 19q13 (52%), and 8p22-23 (48%). This is the first time that 5p14 is seen gained at such a high frequency in cancer of the ovary; possibly oncogene(s) involved in bilateral ovarian carcinogenesis or tumor progression may reside in this band.
Down-regulation of ZIP4 by RNA Interference Inhibits Pancreatic Cancer Growth and Increases the Survival of Nude Mice with Pancreatic Cancer Xenografts
Authors: Li Min , Zhang Yuqing , Bharadwaj Uddalak , Zhai Qihui (Jim) , Ahern Charlotte H. , Fisher William E. , Brunicardi F. Charles , Logsdon Craig D. , Chen Changyi , Yao Qizhi
Published: September 2009

Purpose: Zinc levels have been correlated with cancer risk, although the role of zinc and zinc transporters in cancer progression is largely unknown. We recently found that a zinc transporter, ZIP4, is overexpressed in pancreatic cancer. In this study, we further deciphered the role that ZIP4 plays in a pancreatic cancer mouse model by silencing ZIP4.

Experimental Design: ZIP4 stable silencing was established in pancreatic cancer cell lines ASPC-1 (ASPC-shZIP4) and BxPC-3 (BxPC-shZIP4) by short hairpin RNA using retrovirus vectors. The stable cells were characterized in vitro and in vivo using a nude mouse xenograft model.

Results: Silencing of ZIP4 was associated with decreased cell proliferation, migration, and invasion. Both ASPC-shZIP4 and BxPC-shZIP4 cells showed a significant reduction in tumor volume and weight in the s.c. model, and decreased primary tumor weight in the orthotopic model compared with the vector control cells (ASPC-shV and BxPC-shV). Silencing of ZIP4 also caused reduced incidence of tumor metastasis in the mice and downsized the tumor grade. More importantly, silencing of ZIP4 significantly increased the survival rate of nude mice with orthotopic xenografts (P = 0.005). All ASPC-shZIP4–injected mice (100%) remained alive up to 32 days after tumor implantation, whereas only 30% of the ASPC-shV mice were alive at the same time point. CyclinD1 expression was decreased in the ASPC-shZIP4 xenografts.

Conclusions: These results identify a previously uncharacterized role of ZIP4 in pancreatic cancer progression, and indicate that knocking down ZIP4 by short hairpin RNA might be a novel treatment strategy for pancreatic cancers with ZIP4 overexpression. (Clin Cancer Res 2009;15(19):5993–6001)
Src Tyrosine Kinase Regulates Adhesion and Chemotaxis in Waldenstrom Macroglobulinemia
Authors: Ngo Hai T. , Azab Abdel Kareem , Farag Mena , Jia Xiaoying , Melhem Molly M. , Runnels Judith , Roccaro Aldo M. , Azab Feda , Sacco Antonio , Leleu Xavier , Anderson Kenneth C. , Ghobrial Irene M.
Published: September 2009

Purpose: Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma characterized by widespread involvement of the bone marrow. Despite different options of therapy, Waldenstrom macroglobulinemia is still incurable. Src tyrosine kinase has been shown to play a central role in the regulation of a variety of biological processes, such as cell proliferation, migration, adhesion, and survival in solid tumors. We sought to determine whether the protein tyrosine kinase Src regulates adhesion, migration, and survival in Waldenstrom macroglobulinemia.

Experimental Design: We tested the expression of Src tyrosine kinase in Waldenstrom macroglobulinemia and normal cells, and the effect of the specific Src inhibitor AZD0530 on the adhesion, migration, cell cycle, and survival of a Waldenstrom macroglobulinemia cell line and patient samples. Moreover, we tested the effect of AZD0530 on cytoskeletal and cell cycle signaling in Waldenstrom macroglobulinemia.

Results: We show that Src is overexpressed in Waldenstrom macroglobulinemia cells compared with control B cells, and that the use of the Src inhibitor AZD0530 led to significant inhibition of adhesion, migration, and cytoskeletal signaling induced by SDF1. Moreover, inhibition of Src activity induced G1 cell cycle arrest; however, it had minimal effect on survival of Waldenstrom macroglobulinemia cells, and no significant effect on survival of normal cells.

Conclusions: Taken together, these results delineate the role of Src kinase activity in Waldenstrom macroglobulinemia and provide the framework for future clinical trials using Src inhibitors in combination with other drugs to improve the outcome of patients with Waldenstrom macroglobulinemia. (Clin Cancer Res 2009;15(19):6035–41)
A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis
Authors: Huesca Mario , Lock Lisa S. , Khine Aye Aye , Viau Stéphane , Peralta Robert , Cukier I. Howard , Jin Hongnan , Al-Qawasmeh Raed A. , Lee Yoon , Wright Jim , Young Aiping
Published: September 2009

ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G1-S phase arrest of cell proliferation. The antiproliferative and antitumor activity of ML-133 described in the present study suggests modulation of intracellular zinc homeostasis as a potential strategy for the treatment of several cancer types, and ML-133 represents a promising new class of antitumor agents that deserves further development. [Mol Cancer Ther 2009;8(9):2586–96]
Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells
Authors: Yoon Young-Kwang , Kim Hwang-Phill , Han Sae-Won , Hur Hyung-Seok , Oh Do Youn , Im Seock-Ah , Bang Yung-Jue , Kim Tae-You
Published: September 2009

EGFR tyrosine kinase inhibitors have shown promising efficacy in the treatment of tumors with EGFR mutations and amplifications. However, tyrosine kinase inhibitors have also proven ineffective against most tumors with EGFR wild-type (WT) alleles. Although some genetic changes, including the KRAS mutation, have been shown to confer resistance to tyrosine kinase inhibitors, novel strategies for the treatment of cancer patients with tumors harboring EGFR WT alleles have yet to be thoroughly delineated. The principal objective of this study was to improve our current understanding of drug interactions between EGFR and MAP/ERK kinase (MEK) inhibitors in an effort to gain insight into a novel therapeutic strategy against EGFR WT tumors. Using a panel of human EGFR WT gastric cancer cell lines, we showed that gastric cancer cells harboring the KRAS mutation were selectively sensitive to MEK inhibition as compared with those cells harboring KRAS and PI3K mutations and KRAS WT alleles. However, all cell lines were found to be resistant to EGFR inhibition. The results from Western blots and phosphoprotein arrays showed that, in MEK inhibitor resistant cell lines, AKT was activated through the EGFR/HER3/PI3K pathway following AZD6244 (ARRY-142886) treatment. Blockade of this feedback mechanism through the targeting of MEK and EGFR resulted in detectable synergistic effects in some cell lines in vitro and in vivo. Our results provide the basis for a rational combination strategy against human EGFR WT gastric cancers, predicated on the understanding of cross-talk between the MEK and EGFR pathways. [Mol Cancer Ther 2009;8(9):2526–36]
Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines
Authors: Morelli M. Pia , Brown Amy M. , Pitts Todd M. , Tentler John J. , Ciardiello Fortunato , Ryan Anderson , Jürgensmeier Juliane M. , Eckhardt S. Gail
Published: September 2009

The effect of vascular endothelial growth factor (VEGF) ligands and cediranib on tumor cell proliferation, migration, and invasion was determined. It has recently been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway may play a role in tumor cell survival, invasion, and migration. The purpose of the present study was to determine the expression of VEGFRs and VEGFR ligands in a panel of gastrointestinal carcinoma cells. Additionally, we evaluated the effects of VEGF autocrine signaling on tumor cell proliferation, migration, and invasion utilizing cediranib (AZD2171), a pan-VEGFR inhibitor. Five colorectal, three pancreatic, and two hepatocellular carcinoma cell lines were screened for VEGFR and VEGF expression by several methods. Expression of VEGFR-1 and VEGFR-3 was cell line–dependent, whereas VEGFR-2 was not detected. Secretion of VEGF-A was detected in the supernatants of all cell lines whereas VEGF-C secretion was detected in the Panc-1, MiaPaca2, and Hep1 cells only. Tumor cells showed increased migratory activity, but not proliferation, when stimulated with VEGFs. The pan-VEGFR inhibitor cediranib (100 nmol/L) inhibited tumor cell migration and invasion, with no effects on proliferation. Cediranib decreased VEGFR-1 and VEGFR-3 phosphorylation as well as activation of downstream effectors. VEGFR-1 and VEGFR-3 expression was detected in all the gastrointestinal carcinoma cells evaluated. Although activation of the VEGF pathway did not affect cell proliferation, our data indicate that this pathway seems to play a role in tumor cell migration and invasion in these cell lines. Therefore, inhibition of VEGFR by cediranib may represent a clinically relevant treatment option for gastrointestinal tumors. [Mol Cancer Ther 2009;8(9):2546–58]
Diagnostic and Therapeutic Double-Balloon Enteroscopy after Small Bowel Roux-en-Y Reconstructive Surgery
Authors: Moreels Tom G. , Hubens Guy J. , Ysebaert Dirk K. , Op de Beeck Bart , Pelckmans Paul A.
Published: September 2009

Background: Roux-en-Y reconstruction excludes the afferent limb and the biliopancreatic system from conventional endoscopic access. Postoperative problems in these excluded gastrointestinal systems are therefore often dealt with surgically. We investigated the usefulness of the therapeutic double-balloon enteroscope to perform interventional endoscopic procedures in the excluded segment of the gastrointestinal tract after Roux-en-Y reconstruction. Methods: 30 procedures were performed in 22 patients with Roux-en-Y reconstruction after enterobiliary anastomosis, gastrectomy or bariatric gastric bypass. All procedures were performed with the therapeutic double-balloon enteroscope, under general anesthesia and with fluoroscopic control. Results: ERCP at the enterobiliary anastomosis was successful in 90% (n = 10) of the procedures. ERCP at the intact papilla was successful in 60% (n = 5). Enterocutaneous fistula closure after (sub)total gastrectomy was performed in 2 procedures. Successful diagnostic procedures encompassed intubation of the excluded stomach after bariatric gastric bypass (89%, n = 9) or the afferent limb after Roux-en-Y reconstruction (75%, n = 4). The overall success rate in accessing the aimed excluded segment with the double-balloon enteroscope was 87%. Interventional procedures were able to avoid surgery in 65%. One retroperitoneal perforation occurred during ERCP which was conservatively treated. Conclusions: Excluded gastrointestinal segments after Roux-en-Y reconstruction can be accessed with a substantial success rate using double-balloon enteroscopy. Therapeutic interventions like ERCP can prevent surgery in the majority of patients.
Limitations of PET/CT in Determining Need for Neck Dissection after Primary Chemoradiation for Advanced Head and Neck Squamous Cell Carcinoma
Authors: Lyford-Pike Sofia , Ha Patrick K. , Jacene Heather A. , Saunders John R. , Tufano Ralph P.
Published: September 2009

Objective: The purpose of our study was to evaluate PET/CT in predicting residual nodal disease after primary chemoradiation (CRT) for head and neck cancer (HNSCC) with N2 disease or greater. Design: A retrospective cohort analysis was conducted. Thirty-eight patients received primary CRT for HNSCC with N2 or greater disease, PET/CT after treatment and neck dissection from January 2003 to December 2006. PET/CT results were correlated with pathology results from neck dissection specimens for each respective side. Results: Forty-six neck regions were analyzed. Nine were determined to have either PET/CT result reports (n = 5) or pathology reports (n = 4) that were indeterminate. PET/CT demonstrated a sensitivity and specificity of 57.1 and 73.9%, respectively, an accuracy of 67.5%, a positive predictive value of 57.1% and a negative predictive value of 73.9% when compared to the final pathology. Conclusion: PET/CT is neither highly sensitive nor highly specific for identifying residual nodal metastases after CRT for advanced-stage HNSCC. Physicians should not rely solely on PET/CT to determine interventions on the neck after CRT. A standardization of language for reporting findings and risk of residual disease is needed.
Carotid and Basilar Artery Wall Shear Stress in Alzheimer’s Disease and Mild Cognitive Impairment
Authors: van Es A.C.G.M. , van der Flier W.M. , Box F.M.A. , Middelkoop H.A.M. , Westendorp R.G.J. , van Buchem M.A. , van der Grond J.
Published: September 2009

Background/Aims: Vascular pathology is increasingly seen as a factor contributing to the development of Alzheimer’s disease (AD). With this in mind we hypothesized that this vascular pathology could be directly detected in the arteries contributing to the cerebral circulation of mild cognitive impairment (MCI) and AD patients by means of wall shear stress (WSS) measurements. Methods: In this study we investigated the mean wall shear stress (MWSS), diastolic wall shear stress (DWSS) and systolic wall shear stress (SWSS) in the carotid and basilar arteries of control subjects (mean age: 72; SD: 8.8), patients suffering from MCI (mean age: 76; SD: 6.7), and patients suffering from AD (mean age: 72; SD: 8.2) that were consecutively referred to our outpatient memory clinic using in-house developed software on gradient echo phase-contrast MRI sequences. Results: We found that all these parameters were significantly lower in the carotid arteries of patients suffering from AD or MCI when compared to control subjects. In the basilar artery only DWSS was lower in MCI or AD patients compared to control subjects. In none of the arteries a difference was found for any WSS parameter between MCI and AD patients. WSS parameters were significantly associated (corrected for age and sex) with the degree of cognitive impairment. Conclusion: Increased vascular pathology, as expressed by lower WSS measures, was found in patients suffering from MCI and AD compared to normal controls. This might point to the involvement of vascular pathology in the development of AD.
Time between Symptom Onset and Assessment in Age-Related Macular Degeneration with Subfoveal Choroidal Neovascularization
Authors: Schalnus Rainer , Meyer Carsten H. , Kuhli-Hattenbach Claudia , Lüchtenberg Marc
Published: September 2009

Background: Therapy delay in neovascular age-related macular degeneration (NV-AMD) is associated with risk of visual deterioration. Methods: Retrospective cross section analysis including patients with NV-AMD who received fluorescein angiography (FA). The time elapsed from symptom onset to assessment was analysed in relation to different factors. Inclusion criteria were: age >50 years, symptom onset within 6 months before assessment, no previous AMD therapy, indication for vascular endothelial growth factor inhibitor treatment. Results: Mean duration of symptoms was 2.272 ± 1.683 months (n = 220); percentiles 25, 50, 75 and 90 corresponded to 1, 2, 3 and 5.383 months. A significant increase (p = 0.033) in mean symptom duration was found between age groups 65–74, 75–84 and over 84 years. Privately insured persons (assessment 1.242 ± 1.060 months after symptom onset; n = 14) received FA 1.083 months earlier (p = 0.0089) than patients with a statutory health insurance (assessment 2.325 ± 1.661 months after symptom onset; n = 194). Conclusion: In order to avoid progressive visual deterioration in patients with NV-AMD earlier assessment of these individuals should be aimed for.
Effects of Flossing and Rinsing with a Fluoridated Mouthwash after Brushing with a Fluoridated Toothpaste on Salivary Fluoride Clearance
Authors: Duckworth R.M. , Horay C. , Huntington E. , Mehta V.
Published: September 2009

The aims of this study were to test the hypothesis that flossing after brushing with a fluoridated toothpaste may lower salivary fluoride (F), and to evaluate the consequence of subsequent F mouthwash use. Twenty adults used 3 oral hygiene regimes in a randomised order: A, brushing with an NaF toothpaste; B, as A but followed by professional flossing; C, as B followed by rinsing with an NaF mouthwash. Saliva samples were collected up to 120 min after each regime and analysed for F. The mean area under the clearance curve value for regime C was statistically significantly greater than the corresponding values for A and B (p < 0.0001), which differed little. The regime that included the mouthwash may provide better anticaries protection.
Validity and Reliability of Laser-Induced Fluorescence Measurements on Carious Root Surfaces in vitro
Authors: Karlsson L. , Johansson E. , Tranæus S.
Published: September 2009

The aim was to assess the validity of laser fluorescence (LF), visual inspection and surface texture on root caries lesions in vitro, related to histological lesion depths. Agreement on interdevice, interexaminer and intra-examiner levels as well as the influence of discolouration and surface texture on LF readings were investigated. Calibrated examiners assessed lesion colour and surface texture and performed measurements with 2 LF devices in 3 separate series at intervals of 1 week. Sections (300 μm thick) of 64 out of 93 teeth were obtained and examined under the microscope. Lesion depth was assessed with 2 references: from the delineated borderline of the original exposed root surface (ref. I), or if loss of surface continuity, the absolute lesion depth (ref. II). The correlation (Spearman ρ) between LF readings and histological depth was low with values ranging from 0.22 (p > 0.05) to 0.31 (p < 0.05). LF 1 and LF 2 were significantly correlated with discolouration (ρ = 0.52 and 0.46, respectively) and with surface texture denoted as hard (ρ = 0.34 and 0.33, respectively). A significant correlation between colour and histological depth ref. I (ρ = 0.51) and ref. II (ρ = 0.56) was found. No significant correlation between surface texture and histological depth was found. The reliability, evaluated as intraclass correlation coefficient was for intra-examiner 0.99, interexaminer 0.97 and interdevice level 0.98. Large differences were found between 2 consecutive measurements, and high measurement errors indicated considerable deviation of individual measurements. Based on these findings, the LF device is not suitable as a diagnostic tool for root caries.
Postural Balance and Self-Reported Balance Confidence in Older Adults with a Hip Fracture History
Authors: Sihvonen Sanna , Kulmala Jenni , Kallinen Mauri , Alén Markku , Kiviranta Ilkka , Sipilä Sarianna
Published: September 2009

Background: Balance dysfunction and loss of balance confidence have been associated with functional limitations and loss of independency in daily tasks. This study examined various aspects of postural balance and balance confidence between older adults with a hip fracture history and their non-fractured counterparts. A comprehensive assessment of balance capacity in older adults with a hip fracture history may help to identify aspects of postural balance that play an important role in the mobility recovery and the avoidance of further falls. Methods: The present study comprised 79 community-dwelling older adults with a hip fracture history and 31 non-fractured subjects of the same age, who participated in balance tests including both force platform measures and functional balance testing (Berg Balance Scale, BBS). In addition, balance confidence was assessed with the Activities-Specific Balance Confidence (ABC) scale. Results: Persons with a hip fracture history had a markedly poorer balance control and were significantly less confident maintaining their balance during daily activities compared to the controls. Sixty percent of the subjects in the hip fracture group versus 87% of the non-fracture group (χ2 test, p = 0.003) were able to perform the semi-tandem standing with their eyes closed. Significantly lower scores in the BBS (hip fracture group 46.3 vs. non-fracture group 52.9) and ABC (hip fracture group 59.4 vs. non-fracture group 77.5%) tests were found among the hip fracture subjects compared to the controls. In addition, the performance time in the lateral weight-shifting task (hip fracture group 13.4 vs. non-fracture group 8.4 s) was significantly slower compared to the controls. Conclusions: Balance impairments along with the loss of balance confidence are persistent problems among community-dwelling older adults with a history of hip fracture and may contribute to mobility limitations and the risk of falling. These areas of function and behaviour in older adults with a hip fracture history should be taken into consideration when planning effective, well-targeted rehabilitation programs.
Metabolism of 35S-Methionine and 35S-Cystine in the Pregnant Rhesus Monkey
Authors: Sturman J.A. , Niemann W.H. , Gaull G.E.
Published: September 2009

Unlike the human fetus late in gestation, the fetal rhesus monkey may have considerable activity of hepatic cystathionase, and brain and renal cystathionase have attained mature activity. The term rhesus monkey fetus, like the human fetus, accumulates methionine, but does not accumulate cystine from the mother against a fetal: maternal concentration gradient. Studies with 35S-methionine and 35S-cystine measuring incorporation into various tissues confirm the ability of the fetus to metabolize methionine and cystine to inorganic sulfate. However, incorporation of 35S-methionine into 35S-cystathionine in the fetal liver suggests that the ability to cleave cystathionine is still diminished.
The Effect of Glucose in the Prenatal Treatment of Small-for-Date Fetuses
Authors: Šabata V. , Znamenáček K. , Přibylová H. , Melichar V.
Published: September 2009

Glucose infused to the parturient with a small-for-date fetus passes readily through the placental barrier and is retained and utilized by the fetus. The umbilical blood glucose levels are significantly increased, the arteriovenous differences show a greater retention and the FFA levels decrease. There are no signs of deterioration of fetal metabolic situation.In the small-for-date newborn the prenatal glucose infusion prevents neonatal hypoglycaemia and the enhanced FFA mobilization. Also this time metabolic changes in the newborn do not increase acidosis.The prenatal glucose infusion at a speed of 1 g glucose/min appears to be a useful tool in the treatment of small-for-date fetuses.
Insulin Secretion in the Fetal and Neonatal Sheep
Authors: Alexander D.P. , Britton H.G. , Cohen N.M. , Nixon D.A. , Parker R.A.
Published: September 2009

The effect on plasma insulin of elevating plasma glucose levels was studied in exteriorized sheep fetuses of 68 to 142 days conceptual age and in 2 lambs, 1 and 7 days old. Fetuses of less than 110 days showed, at most, only a very small and delayed rise in plasma insulin following an injection of glucose (1.67–3.45 g/kg body weight) into the umbilical vein. In 5 out of 6 fetuses of 110 days and older intravenous glucose (0.54–1.38 g/kg) was followed by a marked but delayed rise in plasma insulin reaching a peak 25–100 min after glucose administration. In the lambs intravenous glucose (1 g/kg) gave an immediate response in plasma insulin. Intraduodenal glucose was also seen to give a marked rise in plasma insulin in a 123 day fetus and 2 lambs. Intravenous fructose (0.65 and 0.55 g/kg) to two older fetuses caused no rise in plasma insulin although glucose given subsequently evoked a marked response. The onset of appearance of a marked response to glucose in the fetus was preceded by a proliferation of secondary islets in the pancreas. The changes in plasma insulin in the exteriorized fetuses and in 2 isolated fetuses suggest that the placenta must be relatively impermeable to insulin, fetal insulin must largely be derived from the fetal pancreas and fetal tissues must take up insulin.
Prenatal Development of Malformed Fetuses at 28–42 Weeks of Gestational Age (Anencephalus, Hydrocephalus, Down’s Syndrome, Cleft Lip and Palate, and Hypospadias)
Authors: Kučera J. , Doležalová Věra
Published: September 2009

Mean body sizes of 416 anencephalus, 504 hydrocephalus, 550 Down’s syndrome cases, 653 cases of cleft lip and/or palate and of 1,047 hypospadias were calculated for each week of prenatal life between 28 and 42 weeks of pregnancy. Except for anencephalus no considerable differences were found in comparison with standard growth. A tendency to undergrowth is most pronounced in the phase of reduced growth of fetuses with Down’s syndrome and hypospadias. The reduced growth in anencephalus, hydrocephalus and in cases withcleft lip and/or palate is absent.
Glia of Myelination and Fat Deposit during Early Myelogenesis
Authors: Larroche J.C. , Amakawa H.
Published: September 2009

An attempt at a semi-quantitative and morphological study of the fatty glia of myelination is presented. 71 brains ranging from 26 to 40 weeks of gestational age were selected. Different representative systems such as precentral gyrus and low pyramidal tract, corpus callosum and tapetum, chiasma and optic radiations were studied. Accumulation of lipid materials in the cytoplasm of glial cells precedes myelin sheath formation in corpus callosum, optic radiations, and precentral gyrus. This is not the case in the chiasma and low pyramidal tract. The amount of fat deposits and the speed of myelination differ from one system to another, according to their specific tempo of maturation.
Pretreatment of Pregnant Rabbits with Chlorpromazine – Assessment of any Enzyme-Inducing Effect on the Fetus
Authors: Krauer B. , Rosegger H. , Salloch R. , Scopes J.
Published: September 2009

Pretreatment of pregnant rabbit does with chlorpromazine during 10 days before delivery reduced the weight of the does. Their fetuses were lighter than the untreated control fetuses of the same gestational age. The occurrence of RDS in the prematurely delivered fetuses (gestational days 26, 27 or 28) was neither promoted nor prevented by the drug, but diminished with increasing gestational age in both pretreated and untreated fetuses. There was no statistically significant difference in the activity of intestinal lactase of the pretreated fetuses as compared to that of the untreated fetuses.
Plasma Renin Levels in the Normal and Anephric Fetus at Birth
Authors: Symonds E.M. , Furler I.
Published: September 2009

(1) Plasma renin activity (PRA), plasma renin concentration (PRC), and renin substrate (RS), have been measured in venous blood samples of 4 healthy women during the second stage of labour and the cord bloods of the 4 infants at delivery. (2) PRA and PRC show a similar range of values in both mothers and fetuses, but fetal renin substrate levels are approximately half the values seen in the maternal samples. (3) There was no plasma renin activity in the cord blood of the anephric fetus, suggesting that biologically active renin does not cross the placenta. Plasma renin concentration was approximately 10% of the level seen in normal infants.
Serum Zinc in the Newborn
Authors: Kurz Diann L. , Eyring Edward J. , Roach Jane E.
Published: September 2009

A sensitive, accurate flameless atomic absorption method, requiring only 1 μl of sample per determination, was used to investigate the serum zinc levels of newborns and to establish normal values. There were no significant differences due to race or sex. The mean zinc value for 115 normal newborns was 91.8 μg/l00 ml and not significantly different from the mean value for 25 normal adults, 94.6 μg/l00 ml.
Studies on Lipids of Brain, Kidneys and Liver of Mice during Postnatal Development
Authors: Pushpendran C.K. , Eapen Jacob
Published: September 2009

The postnatal changes in distribution and synthesis of lipids of mice liver, kidneys and brain have been studied. The hepatic lipids show greater variation in females than in males during postnatal development. Lipid levels of kidneys and brain increase with advancing age unlike in the case of liver. The major component of brain and kidney lipids is phospholipid. The incorporation of 14C-acetate into lipids of the tissues is highest within 5 days and lowest 10 days after parturition. Sex-dependent changes are discernible in the lipid synthesis.
Presence of the Complete Sorbitol Pathway in the Human Normal Umbilical Cord Tissue
Authors: Brachet E.A.
Published: September 2009

The sorbitol pathway was investigated in vitro on slices of umbilical cord tissue from normal full-term pregnancies. Glucose, sorbitol and fructose were shown to be present in this tissue at fairly constant levels. When added to the medium, these three substrates can be actively taken up by these preparations (in decreasing order: glucose > fructose > sorbitol). Incubation noticeably increases the sorbitol content of the tissue, especially when glucose is present in the medium, thus showing the presence of aldose reductase. Concentrated by ammonium sulphate fractionation, the proteins of this tissue showed a NAD+-linked sorbitol dehydrogenase activity, able to transform sorbitol into a ketose which, as shown by TLC, is probably fructose. Therefore, the complete polyol pathway is probably effective in this fetal vascular tissue.
Radioactivity in Reproductive Organs and the Liver of Neonatal and Adult Rats Following 3H-Testosterone Administration
Authors: Scott Jane Nicholson , Traurig Harold H.
Published: September 2009

The uptake of radioactivity by the reproductive organs and livers of neonatal, prepuberal, puberal and adult male and female rats 1 h after intraperitoneal administration of 3H-testosterone was measured by liquid scintillation quantification. Tissue homogenates of the testes, vasa deferentia-epididymides, ovaries, uteri, livers, muscle, cerebrum and thymuses were fractionated and aqueous, lipid and protein-nucleoprotein fractions separated for analysis. Accumulation of radioactivity above control levels was found in all fractions of the tissues, particularly in the fractions containing the protein-nucleoprotein residues of the reproductive organs and livers. The radioactivities associated with the tissue residues of reproductive organs were highest during the first postnatal days and subsequently declined while the radioactivities associated with the livers were lowest 2 days after birth and increased markedly by day 10. These observations suggest that the alterations in sexual physiology and behavior observed in adult female rats subsequent to administration of androgens during their neonatal critical period of sex development may be due to immaturity of steroid degradative mechanisms in the neonatal liver.
Impermeability of the Sheep Placenta to Glucagon
Authors: Alexander Pauline , Assan R. , Britton H.G. , Nixon D.A.
Published: September 2009

The permeability of the placenta to glucagon was studied in sheep of gestational ages of 99–143 days. Administration of large doses of glucagon to the mother was associated with little or no change in fetal plasma glucagon in the acute exteriorized fetal preparation and no change in the in situ perfused placental preparation. Glucagon administered to the fetal or placental circulation did not affect the maternal levels. The exteriorized fetus rapidly removed glucagon from its circulation although little was taken up by the perfused placenta. We conclude that the sheep placenta is effectively impermeable to glucagon and that the sheep fetus is autonomous with respect to this hormone.
Intrauterine Dystrophy in Rats Due to Placental Insufficiency Caused by Hormonally Induced Prolonged Gestation
Authors: Bührdel P. , Willgerodt H. , Keller E. , Theile H. , Emmrich P.
Published: September 2009

The duration of pregnancy in rats can be prolonged beyond day 26 after conception by administration of synthetic gestagens. The fetal mortality increased with prolonged duration of gestation to 24.8% on day 24 and 54.6% on day 25. Nearly all the fetuses were dead on day 26. On day 24 some of the litter mates and on day 25 all of the living ones were markedly hypotrophic. A placental insufficiency is suggested as causing the increasing mortality and the hypotrophy of the fetuses. The placental weight increases up to the 20th day of gestation, decreases slightly thereafter and does so markedly beyond the 24th day. An increase of water content is characteristic for the postmature litter mates.
Time of Onset of Effective Ventilation at Birth
Authors: Chou Paula J. , Ullrich J.R. , Ackerman B.D.
Published: September 2009

A method for serial sampling of umbilical artery blood was described in a previous report. Another study using this method demonstrated that the umbilical artery blood becomes more asphyxial over the first 20 sec after birth, even though up to 5 breaths occurred over this time. In the present study, serial samples of umbilical artery blood were function obtained at slightly later intervals; the first samplings occurred at 11–41 sec and the second samplings at 22–59 sec. From 3 to 11 breaths occurred between birth and the second sampling. Unlike the results in the prior study, many infants showed a rising pH, a falling PCO2, and a rising oxygen saturation from the first to the second sampling. When the results of one of the prior studies are combined with the present study, it appears that the fifth breath represents the approximate point of reversal of the trend from one of increasing asphyxia to one of improvement in blood gas values. The fifth breath usually occurred at 20–30 sec. It may be advantageous to allow the placental respiration to continue until the pulmonary respiration becomes effective by delaying cord clamping until 5 breaths have occurred or until 30 sec have elapsed.
Influence of Asphyxia and of Dexamethasone on ATP Concentrations in the Immature Rat Brain
Authors: Adlard B.P.F. , De Souza S.W.
Published: September 2009

Five-day-old rats subjected to prolonged asphyxia (at 37 °C) to the point of death showed an approximately 50-percent loss of brain ATP and a rise in ADP and AMP. Brain energy charge was reduced from 0.86 to 0.64. Recovery of ATP levels to normal was virtually complete 20 min after beginning resuscitation. Rats treated with dexamethasone (20 mg/kg body weight) showed, during asphyxia, a fall in brain ATP which was significantly less than in those animals asphyxiated without steroid. Possible implications for the use of glucocorticoid therapy in asphyxia neonatorum are discussed.
Pituitary and Plasma Concentrations of Adrenocorticotrophin, Growth Hormone, Vasopressin and Oxytocin in Fetal and Maternal Sheep during the Latter Half of Gestation and the Response to Haemorrhage
Authors: Alexander Pauline , Britton H.G. , Forsling Mary L. , Nixon † D.A. , Ratcliffe J.G.
Published: September 2009

Fetal haemorrhage in exteriorized fetuses of 90 to 143 days conceptual age caused marked increases in fetal plasma ACTH and AVP with maximal values for ACTH at about 40% blood loss and maximal values for AVP with somewhat smaller losses. The rates of rise of ACTH and the maximal values of ACTH were similar to those found in a non-pregnant adult female subjected to haemorrhage. Fetal plasma growth hormones rose in 2 out of 5 animals with no consistent trend in the remainder. In 2 out of 5 animals traces of oxytocin appeared. In two older fetuses in which fetal plasma corticosteroids were determined there was a moderate rise. There was no correlation between maternal and fetal plasma levels with any of the hormones. Fetal ACTH, AVP and growth hormones levels were greatly in excess of those of the mother. Fetal pituitary concentrations of ACTH, oxytocin and neurophysin at all ages were similar to those found in the adult; AVP concentrations were somewhat less. No arginine vasotocin was detected. The high hormone content of the fetal pituitary contrasted with the appearance by light microscopy in the younger animals which showed little evidence for hormone storage. The experiments indicate that the fetal pituitary in the sheep by 90 days is able to synthesize, store and increase several hormones and that haemorrhage is a potent stimulus for the release of ACTH and AVP.