bluuebunny/crossref_metadata_2025 huggingface dataset:
Epinephrine enhances lysosomal enzyme delivery across the blood–brain barrier by up-regulation of the mannose 6-phosphate receptor
Authors: Urayama Akihiko , Grubb Jeffrey H. , Banks William A. , Sly William S.
Published: July 2007

Delivering therapeutic levels of lysosomal enzymes across the blood–brain barrier (BBB) has been a pivotal issue in treating CNS storage diseases, including the mucopolysaccharidoses. An inherited deficiency of β-glucuronidase (GUS) causes mucopolysaccharidosis type VII that is characterized by increased systemic and CNS storage of glycosaminoglycans. We previously showed that the neonate uses the mannose 6-phosphate (M6P) receptor to transport phosphorylated GUS (P-GUS) across the BBB and that this transporter is lost with maturation. Induction of expression of this BBB transporter would make enzyme replacement therapy in the adult possible. Here, we tested pharmacological manipulation with epinephrine to restore functional transport of P-GUS across the adult BBB. Epinephrine (40 nmol) coinjected i.v. with
131
I-P-GUS induced the transport across the BBB in 8-week-old mice. The brain influx rate of
131
I-P-GUS (0.29 μl/g per min) returned to the level seen in neonates. Capillary depletion showed that 49% of the
131
I-P-GUS in brain was in brain parenchyma. No increases of influx rate or the vascular space for
125
I-albumin, a vascular marker, was observed with epinephrine (40 nmol), showing that enhanced passage was not caused by disruption of the BBB. Brain uptake of
131
I-P-GUS was significantly inhibited by M6P in a dose-dependent manner, whereas epinephrine failed to increase brain uptake of nonphosphorylated GUS. Thus, the effect of epinephrine on the transport of
131
I-P-GUS was ligand specific. These results indicate that epinephrine restores the M6P receptor-mediated functional transport of
131
I-P-GUS across the BBB in adults to levels seen in the neonate.
Comparison of Olanzapine to Risperidone in Substance‐Abusing Individuals with Schizophrenia
Authors: Akerele Evaristo , Levin Frances R.
Published: July 2007

A 14‐week double blind study compared the efficacy of olanzapine to risperidone in reducing marijuana/cocaine craving and use in individuals with schizophrenia. The study consisted of three phases: a two‐week assessment phase, a two‐week cross‐taper phase onto olanzapine/risperidone, and a ten‐week period of maintenance on olanzapine/risperidone. The proportion of cocaine‐positive urines decreases over time for both groups with a trend for a greater reduction for the olanzapine group compared to risperidone group. In the last six weeks, marijuana craving was more likely for the risperidone group compared to the olanzapine group, although there was no group difference in the proportion of negative marijuana urines. The data suggest some potential for the utility of olanzapine for the treatment of cocaine dependence in individuals with schizophrenia.
Schizophrenia and Pathological Gambling
Authors: Borras Laurence , Huguelet Philippe
Published: July 2007

High rates of pathological gambling are found in psychiatric populations, including those with mood or substance use disorders. The extent to which individuals with schizophrenia exhibit the symptoms of pathological gambling has not been adequately investigated. This paper examines the case of a 40‐year‐old schizophrenic female with a four‐year history of gambling. The characteristics of possible interactions between pathological gambling and schizophrenic symptom profiles are outlined in order to propose better treatments for this group of patients.
Concurrent and Predictive Validity of the Addiction Severity Index in Pathological Gamblers
Authors: Petry Nancy M.
Published: July 2007

This study evaluated psychometric properties of the Addiction Severity Index (ASI) in 231 pathological gamblers. Internal consistency was similar to that reported in substance abusers, temporal stability was good, and convergent and discriminant validity was established with other indices of patient, collateral, and interviewer‐rated reports. Predictive validity of most subscales was excellent when baseline composite scores were used to predict the utilization of relevant services or unemployment, probation/parole status, and bankruptcy one year later. Thus, the ASI may be a useful tool for assessing gambling and psychosocial problems in the growing population of treatment‐seeking gamblers.
Phorbol Esters: Structure, Biological Activity, and Toxicity in Animals
Authors: Goel Gunjan , Makkar Harinder P. S. , Francis George , Becker Klaus
Published: July 2007

Phorbol esters are the tetracyclic diterpenoids generally known for their tumor promoting activity. The phorbol esters mimic the action of diacyl glycerol (DAG), activator of protein kinase C, which regulates different signal transduction pathways and other cellular metabolic activities. They occur naturally in many plants of the family Euphorbiacaeae and Thymelaeaceae. The biological activities of the phorbol esters are highly structure specific. The phorbol esters, even at very low concentrations, show toxicological manifestations in animals fed diets containing them. This toxicity limits the use of many nutritive plants and agricultural by-products containing phorbol esters to be used as animal feed. Therefore, various chemical and physical treatments have been evaluated to extract or inactivate phorbol esters so that seed meals rich in proteins could be used as feed resources. However, not much progress has been reported so far. The detoxifying ability has also been reported in some molluscs and in liver homogenate of mice. Besides, possessing antinutritional and toxic effects, few derivatives of the phorbol esters are also known for their antimicrobial and antitumor activities. The molluscicidal and insecticidal properties of phorbol esters indicate its potential to be used as an effective biopesticide and insecticide.
Vitamin E Protection from Testicular Damage Caused by Intraperitoneal Aluminium
Authors: Kutlubay Recep , Oğuz Emin Oğuzhan , Can Belgin , Güven M. Cengiz , Sinik Zafer , Tuncay Ömer Levent
Published: July 2007

Different forms of Aluminium (Al) are environmental xenobiotics that induce free radical–mediated cytotoxicity and reproductive toxicity. Vitamin E ( α-tocopherol) is an antioxidative agent that has been reported to be important for detoxification pathways. This study was thus aimed at elucidating the protective effects of vitamin E towards aluminium toxicity on the histology of the rat testis. Al (5 mg/kg body weight) was administered intraperitoneally in 2 ml saline, either alone or immediately before vitamin E (500 mg/kg body weight), at a different point of abdomen, and the alterations in the testis tissue were analyaed histologically. Seven treated animals were sacrificed for each group, with the testes removed and examined histologically. In the Al-treated group, the germinal epithelium of the seminiferous tubules was thinner in places and spermatids were almost absent; sperm numbers were low and there were no sperm in the lumen. In the Al plus vitamin E rats, there were large numbers of spermatids and sperm in the seminiferous tubule lumen. In the vitamin E alone group, a normal histology was seen. Electron microscopically, in the Al-treated group there were irregularities in the nuclear membrane, some damaged mitochondria, a decrease in the number of ribosomes, and an increase in the number of lysosomes in the sertoli cell cytoplasm. In the primary spermatocyte cytoplasm, there was an increase in the rough endoplasmic reticulum. In the Al plus vitamin E group, the spermatogeneic cells and the sertoli cell cytoplasm showed an almost normal appearance. The ultrastructure of the testis in the vitamin E alone group showed a normal appearance. In conclusion, vitamin E antagonizes the toxic effects of Al at the histological level, thus potentially contributing to an amelioration of the testis histology in the Al-treated rats. The associated biochemical parameters merit further investigation.
An Updated Review of Inhalation Studies with Cigarette Smoke in Laboratory Animals
Authors: Coggins Christopher R. E.
Published: July 2007

Until recently, the published literature on inhalation studies with laboratory animals and cigarette smoke consisted entirely of negative findings, as far as neoplastic disease is concerned. This paper brings readers up to date, with analyses of recent studies that do indeed appear to report success after so many years of failure. The paper consists of a brief analysis of the literature up until a couple of years ago, giving brief, representative examples of inhalation studies with the five main species of laboratory animals that have been used: rat, mouse, hamster, dog, and nonhuman primate. A brief examination of the various technologies used to expose laboratory animals is given, along with an analysis of the histopathology and related toxicology data (specifically, biomarkers of exposure) that have been reported. The paper concludes by briefly mentioning the most recent studies, where positive results have been reported.
Treatment of Experimental Nephrotic Syndrome with Artesunate
Authors: Razavi Alireza , Nouri Hamid R. , Mehrabian Farhad , Mirshafiey Abbas
Published: July 2007

The present study was designed to test the therapeutic effect of a new antimalarial drug, artesunate in experimental model of nephrotic syndrome. To induce this experimental model, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (IP) administration of 5 mg/kg artesunate (ARS). Total of IP injections were 14, of which 5 injections were made every day and 9 injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 49. The results showed that treatment with ARS caused a significant reduction in the level of proteinuria, urine urea and urine sodium compared with nontreated controls. In addition, decrease in serum triglyceride and increase in the level of serum albumin was significant in treated group with ARS compared with nontreated controls. Moreover, treatment with ARS significantly reduced glomerular polymorphonuclear (PMN) and mononuclear cells infiltration, hypercellularity, karyorrhexis, wire loops, and hydropic change in capillary network within the renal cortex, as well as decreased hyalin casts. On the other hand, healthy controls receiving ARS showed a significant decrease in amounts of serum triglyceride, urine urea, and urine sodium and potassium compared with normal group. These data suggest that artesunate therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrotic syndrome; it may also be recommended as a lipid-lowering drug.
Cell size and invasion in TGF-β–induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway
Authors: Lamouille Samy , Derynck Rik
Published: July 2007

Epithelial to mesenchymal transition (EMT) occurs during development and cancer progression to metastasis and results in enhanced cell motility and invasion. Transforming growth factor-β (TGF-β) induces EMT through Smads, leading to transcriptional regulation, and through non-Smad pathways. We observe that TGF-β induces increased cell size and protein content during EMT. This translational regulation results from activation by TGF-β of mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt, leading to the phosphorylation of S6 kinase 1 and eukaryotic initiation factor 4E–binding protein 1, which are direct regulators of translation initiation. Rapamycin, a specific inhibitor of mTOR complex 1, inhibits the TGF-β–induced translation pathway and increase in cell size without affecting the EMT phenotype. Additionally, rapamycin decreases the migratory and invasive behavior of cells that accompany TGF-β–induced EMT. The TGF-β–induced translation pathway through mTOR complements the transcription pathway through Smads. Activation of mTOR by TGF-β, which leads to increased cell size and invasion, adds to the role of TGF-β–induced EMT in cancer progression and may represent a therapeutic opportunity for rapamycin analogues in cancer.
Localized zones of Rho and Rac activities drive initiation and expansion of epithelial cell–cell adhesion
Authors: Yamada Soichiro , Nelson W. James
Published: July 2007

Spatiotemporal coordination of cell–cell adhesion involving lamellipodial interactions, cadherin engagement, and the lateral expansion of the contact is poorly understood. Using high-resolution live-cell imaging, biosensors, and small molecule inhibitors, we investigate how Rac1 and RhoA regulate actin dynamics during de novo contact formation between pairs of epithelial cells. Active Rac1, the Arp2/3 complex, and lamellipodia are initially localized to de novo contacts but rapidly diminish as E-cadherin accumulates; further rounds of activation and down-regulation of Rac1 and Arp2/3 occur at the contacting membrane periphery, and this cycle repeats as a restricted membrane zone that moves outward with the expanding contact. The cortical bundle of actin filaments dissolves beneath the expanding contacts, leaving actin bundles at the contact edges. RhoA and actomyosin contractility are activated at the contact edges and are required to drive expansion and completion of cell–cell adhesion. We show that zones of Rac1 and lamellipodia activity and of RhoA and actomyosin contractility are restricted to the periphery of contacting membranes and together drive initiation, expansion, and completion of cell–cell adhesion.
The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease
Authors: Gentry Matthew S. , Dowen Robert H. , Worby Carolyn A. , Mattoo Seema , Ecker Joseph R. , Dixon Jack E.
Published: July 2007

Lafora disease (LD) is a progressive myoclonic epilepsy resulting in severe neurodegeneration followed by death. A hallmark of LD is the accumulation of insoluble polyglucosans called Lafora bodies (LBs). LD is caused by mutations in the gene encoding the phosphatase laforin, which reportedly exists solely in vertebrates. We utilized a bioinformatics screen to identify laforin orthologues in five protists. These protists evolved from a progenitor red alga and synthesize an insoluble carbohydrate whose composition closely resembles LBs. Furthermore, we show that the kingdom Plantae, which lacks laforin, possesses a protein with laforin-like properties called starch excess 4 (SEX4). Mutations in the Arabidopsis thaliana SEX4 gene results in a starch excess phenotype reminiscent of LD. We demonstrate that Homo sapiens laforin complements the sex4 phenotype and propose that laforin and SEX4 are functional equivalents. Finally, we show that laforins and SEX4 dephosphorylate a complex carbohydrate and form the only family of phosphatases with this activity. These results provide a molecular explanation for the etiology of LD.
The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells
Authors: Egawa Takeshi , Tillman Robert E. , Naoe Yoshinori , Taniuchi Ichiro , Littman Dan R.
Published: July 2007

Members of the Runx family of transcriptional regulators are required for the appropriate expression of CD4 and CD8 at discrete stages of T cell development. The roles of these factors in other aspects of T cell development are unknown. We used a strategy to conditionally inactivate the genes encoding Runx1 or Runx3 at different stages of thymocyte development, demonstrating that Runx1 regulates the transitions of developing thymocytes from the CD4−CD8− double-negative stage to the CD4+CD8+ double-positive (DP) stage and from the DP stage to the mature single-positive stage. Runx1 and Runx3 deficiencies caused marked reductions in mature thymocytes and T cells of the CD4+ helper and CD8+ cytotoxic T cell lineages, respectively. Runx1-deficient CD4+ T cells had markedly reduced expression of the interleukin 7 receptor and exhibited shorter survival. In addition, inactivation of both Runx1 and Runx3 at the DP stages resulted in a severe block in development of CD8+ mature thymocytes. These results indicate that Runx proteins have important roles at multiple stages of T cell development and in the homeostasis of mature T cells.
Inflammatory arthritis can be reined in by CpG-induced DC–NK cell cross talk
Authors: Wu Hsin-Jung , Sawaya Heloisa , Binstadt Bryce , Brickelmaier Margot , Blasius Amanda , Gorelik Leonid , Mahmood Umar , Weissleder Ralph , Carulli John , Benoist Christophe , Mathis Diane
Published: July 2007

Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the inhibitory influence did not depend on the adaptive immune system cells mobilized in an immunostimulatory context. Instead, they relied on cells of the innate immune system, specifically on cross talk between CD8α+ dendritic cells and natural killer cells, resulting in suppression of neutrophil recruitment to the joint, orchestrated through interleukin-12 and interferon-γ. These findings highlight potential applications of CpG-ODNs and downstream molecules as antiinflammatory agents.
FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors
Authors: O'Neil Jennifer , Grim Jonathan , Strack Peter , Rao Sudhir , Tibbitts Deanne , Winter Christopher , Hardwick James , Welcker Markus , Meijerink Jules P. , Pieters Rob , Draetta Giulio , Sears Rosalie , Clurman Bruce E. , Look A. Thomas
Published: July 2007

γ-secretase inhibitors (GSIs) can block NOTCH receptor signaling in vitro and therefore offer an attractive targeted therapy for tumors dependent on deregulated NOTCH activity. To clarify the basis for GSI resistance in T cell acute lymphoblastic leukemia (T-ALL), we studied T-ALL cell lines with constitutive expression of the NOTCH intracellular domain (NICD), but that lacked C-terminal truncating mutations in NOTCH1. Each of the seven cell lines examined and 7 of 81 (8.6%) primary T-ALL samples harbored either a mutation or homozygous deletion of the gene FBW7, a ubiquitin ligase implicated in NICD turnover. Indeed, we show that FBW7 mutants cannot bind to the NICD and define the phosphodegron region of the NICD required for FBW7 binding. Although the mutant forms of FBW7 were still able to bind to MYC, they do not target it for degradation, suggesting that stabilization of both NICD and its principle downstream target, MYC, may contribute to transformation in leukemias with FBW7 mutations. In addition, we show that all seven leukemic cell lines with FBW7 mutations were resistant to the MRK-003 GSI. Most of these resistant lines also failed to down-regulate the mRNA levels of the NOTCH targets MYC and DELTEX1 after treatment with MRK-003, implying that residual NOTCH signaling in T-ALLs with FBW7 mutations contributes to GSI resistance.
Selection and validation of normalization methods for c-DNA microarrays using within-array replications
Authors: Fan Jianqing , Niu Yue
Published: July 2007

Motivation: Normalization of microarray data is essential for multiple-array analyses. Several normalization protocols have been proposed based on different biological or statistical assumptions. A fundamental problem arises whether they have effectively normalized arrays. In addition, for a given array, the question arises how to choose a method to most effectively normalize the microarray data.

Results: We propose several techniques to compare the effectiveness of different normalization methods. We approach the problem by constructing statistics to test whether there are any systematic biases in the expression profiles among duplicated spots within an array. The test statistics involve estimating the genewise variances. This is accomplished by using several novel methods, including empirical Bayes methods for moderating the genewise variances and the smoothing methods for aggregating variance information. P-values are estimated based on a normal or χ approximation. With estimated P-values, we can choose a most appropriate method to normalize a specific array and assess the extent to which the systematic biases due to the variations of experimental conditions have been removed. The effectiveness and validity of the proposed methods are convincingly illustrated by a carefully designed simulation study. The method is further illustrated by an application to human placenta cDNAs comprising a large number of clones with replications, a customized microarray experiment carrying just a few hundred genes on the study of the molecular roles of Interferons on tumor, and the Agilent microarrays carrying tens of thousands of total RNA samples in the MAQC project on the study of reproducibility, sensitivity and specificity of the data.

Availability: Code to implement the method in the statistical package R is available from the authors.

Contact:  jqfan@princeton.edu
Robustness analysis and tuning of synthetic gene networks
Authors: Batt Grégory , Yordanov Boyan , Weiss Ron , Belta Calin
Published: July 2007

Motivation: The goal of synthetic biology is to design and construct biological systems that present a desired behavior. The construction of synthetic gene networks implementing simple functions has demonstrated the feasibility of this approach. However, the design of these networks is difficult, notably because existing techniques and tools are not adapted to deal with uncertainties on molecular concentrations and parameter values.

Results: We propose an approach for the analysis of a class of uncertain piecewise-multiaffine differential equation models. This modeling framework is well adapted to the experimental data currently available. Moreover, these models present interesting mathematical properties that allow the development of efficient algorithms for solving robustness analyses and tuning problems. These algorithms are implemented in the tool RoVerGeNe, and their practical applicability and biological relevance are demonstrated on the analysis of the tuning of a synthetic transcriptional cascade built in Escherichia coli.

Availability: RoVerGeNe and the transcriptional cascade model are available at http://iasi.bu.edu/%7Ebatt/rovergene/rovergene.htm

Contact:  gregory.batt@imag.fr
Quality estimation of multiple sequence alignments by Bayesian hypothesis testing
Authors: Tomovic Andrija , Oakeley Edward J.
Published: July 2007

Summary: In this work we present a web-based tool for estimating multiple alignment quality using Bayesian hypothesis testing. The proposed method is very simple, easily implemented and not time consuming with a linear complexity. We evaluated method against a series of different alignments (a set of random and biologically derived alignments) and compared the results with tools based on classical statistical methods (such as sFFT and csFFT). Taking correlation coefficient as an objective criterion of the true quality, we found that Bayesian hypothesis testing performed better on average than the classical methods we tested. This approach may be used independently or as a component of any tool in computational biology which is based on the statistical estimation of alignment quality.

Availability:  http://www.fmi.ch/groups/functional.genomics/tool.htm

Contact:  edward.oakeley@fmi.ch

Supplementary information: Supplementary data are available from http://www.fmi.ch/groups/functional.genomics/tool-Supp.htm
Comparative modeling without implicit sequence alignments
Authors: Kolinski Andrzej , Gront Dominik
Published: July 2007

Motivation: The number of known protein sequences is about thousand times larger than the number of experimentally solved 3D structures. For more than half of the protein sequences a close or distant structural analog could be identified. The key starting point in a classical comparative modeling is to generate the best possible sequence alignment with a template or templates. With decreasing sequence similarity, the number of errors in the alignments increases and these errors are the main causes of the decreasing accuracy of the molecular models generated. Here we propose a new approach to comparative modeling, which does not require the implicit alignment — the model building phase explores geometric, evolutionary and physical properties of a template (or templates).

Results: The proposed method requires prior identification of a template, although the initial sequence alignment is ignored. The model is built using a very efficient reduced representation search engine CABS to find the best possible superposition of the query protein onto the template represented as a 3D multi-featured scaffold. The criteria used include: sequence similarity, predicted secondary structure consistency, local geometric features and hydrophobicity profile. For more difficult cases, the new method qualitatively outperforms existing schemes of comparative modeling. The algorithm unifies de novo modeling, 3D threading and sequence-based methods. The main idea is general and could be easily combined with other efficient modeling tools as Rosetta, UNRES and others.

Contact:  dgront@chem.uw.edu.pl
Polyketide synthase genes and the natural products potential ofDictyostelium discoideum
Authors: Zucko J. , Skunca N. , Curk T. , Zupan B. , Long P.F. , Cullum J. , Kessin R.H. , Hranueli D.
Published: July 2007

Motivation: The genome of the social amoeba Dictyostelium discoideum contains an unusually large number of polyketide synthase (PKS) genes. An analysis of the genes is a first step towards understanding the biological roles of their products and exploiting novel products.

Results: A total of 45 Type I iterative PKS genes were found, 5 of which are probably pseudogenes. Catalytic domains that are homologous with known PKS sequences as well as possible novel domains were identified. The genes often occurred in clusters of 2–5 genes, where members of the cluster had very similar sequences. The D.discoideum PKS genes formed a clade distinct from fungal and bacterial genes. All nine genes examined by RT–PCR were expressed, although at different developmental stages. The promoters of PKS genes were much more divergent than the structural genes, although we have identified motifs that are unique to some PKS gene promoters.

Contact:  dhranueli@pbf.hr

Supplementary information: Supplementary data are available at Bioinformatics online.
PRESEMO—a predictive model of codend selectivity—a tool for fishery managers
Authors: O'Neill F. G. , Herrmann B.
Published: July 2007

O'Neill, F. G., and Herrmann, B. 2007. PRESEMO—a predictive model of codend selectivity—a tool for fishery managers. – ICES Journal of Marine Science, 64: 1558–1568. The codend selectivity simulation model PRESEMO is a predictive model based on an understanding of the physical, biological, and behavioural mechanisms that underpin codend selection. In this paper, PRESEMO is used to predict the selectivity of a large range of codends of varying design. In particular, the selectivity of codends with mesh sizes in the range 80–160 mm, number of meshes around in the range 60–140, and netting twine thickness in the range 3–6 mm are predicted and, where possible, the predictions are validated with experimental data. Using the simulated data, the codend selectivity parameters are expressed in terms of the gear design parameters and in terms of both catch size and gear design parameters. The potential use of these results in a management context and for the development of more selective gears is highlighted by plotting iso-l50 and iso-sr curves used to identify gear design parameters that give equal estimates of the 50% retention length and the selection range, respectively. It is emphasized that this approach can be extended to consider the influence of other design parameters and, if sufficient relevant quantitative information exists, biological and behavioural parameters. As such, the model presented here will provide a better understanding of the selection process, permit a more targeted approach to codend selectivity experiments, and assist fishery managers to assess the impact of proposed technical measures that are introduced to reduce the catch of undersized fish and unwanted bycatch.
Seasonal variation in the trawl codend selectivity of picarel (Spicare smaris)
Authors: Özbilgin Hüseyin , Tosunoğlu Zafer , Tokaç Adnan , Metin Gülnur
Published: July 2007

Özbilgin, H., Tosunoğlu, Z., Tokaç, A., and Metin, G. 2007. Seasonal variation in the trawl codend selectivity of picarel (Spicare smaris). – ICES Journal of Marine Science, 64: 1569–1572. Seasonal selectivity of commercial 40 mm polyethylene codend was tested for picarel (Spicara smaris) in spring (4–18 April 2002), summer (10–25 July 2002), autumn (26 September–2 October 2002), and winter (22–23 January 2003) in the Aegean Sea. Data were collected using the covered codend technique and analysed using the logistic equation with the maximum likelihood method. Four sets of selection curves were analysed and compared using the model developed by Fryer (1991). Highest L50 is in autumn (13.82 cm; s.e. 0.62), when water temperature is highest and the fish are expected to be in their best condition after summer feeding. Lowest L50 is in spring (11.09 cm; s.e. 0.51), when water temperature is lowest and the fish are at their spawning stage. However, there is not sufficient evidence to say that the seasonal variation in the selectivity of 40 mm polyethylene codend for picarel is statistically significant (p > 0.05).
Pediatric Short Bowel Syndrome: Adaptation After Massive Small Bowel Resection
Authors: Rossi Ljubomir , Kadamba Padmalatha , Hugosson Claes , De Vol Edward B , Habib Zakaria , Al‐Nassar Saleh
Published: July 2007

Background:

Short bowel syndrome (SBS) develops after massive small bowel resections. Patients with less than 12 cm of jejunoileum have a slim possibility of being weaned from parenteral nutrition (PN).

Patients and Methods:

In a retrospective review of records of consecutive patients with SBS, 8 patients were evaluated for treatment by adaptation and weaning from PN. These included 4 patients with class I SBS (0–10 cm of small bowel), one with class II SBS (>10–25 cm), one with class III SBS (>25–50 cm), and 2 with class IV SBS (>50–75 cm). Adaptation was assessed by measuring growth in the small bowel and the ability to be weaned from PN.

Results:

Adaptation was achieved primarily by extending the length of jejunoileum by approximately 450% over the first 2.5 years after resection and by increasing the degree of colonic fermentation and absorption of nutrients. As of July 1, 2005, all of the patients were off PN, with the exception of 2 patients with class I‐A SBS: patient 3 had a remaining jejunoileum of only 2.5 cm and patient 4 had a remaining jejunoileum of 9 cm but developed eosinophilic enterocolitis. These 2 patients continued with PN on alternate months.

Conclusions:

Bowel growth after massive small bowel resection provides an objective parameter of adaptation and a means of predicting ability to be weaned from PN. Aggressive nutritional support makes even patients with class I SBS, whose disease was previously considered hopeless, likely candidates to achieve freedom from PN.
Infant Feeding Patterns in the First 6 Months: An Assessment in Full‐term Infants
Authors: Nevo Neta , Rubin Lisa , Tamir Ada , Levine Arie , Shaoul Ron
Published: July 2007

Background:

The infant formula market has grown significantly and offers a wide range of products for the different stages of healthy infant growth. Healthy infants often go through a series of unnecessary changes of formulas. The present study aimed to identify the factors leading to switches to alternative formulas. We studied the feeding patterns in the first 6 months of babies born at term, particularly changes in infant formulas. We also investigated the reasons for choosing the first formula, infant formula changes, the addition of formulas to supplement breast‐feeding, and various aspects related to formula thickening.

Patients and Methods:

Two hundred parents of babies ages 6 to 18 months were interviewed. The interviews included a detailed questionnaire and were conducted in child and maternal health care centers.

Results:

Forty‐seven percent of these infants underwent changes in their formula in the first 6 months of life, most of which (67%) were to another cow's milk–based formula. The main reasons for switching a formula were regurgitation or vomiting (24%) followed by restlessness (18%). Lower z scores at birth and a higher Δz2 (z score at the time of the questionnaire minus z score at birth) were associated with significantly more formula changes. The impact of pediatricians and other health care professionals on the choice of infant nutrition was surprisingly negligible.

Conclusions:

The most common reason for switching a formula was concern regarding common infantile symptoms or behavior patterns perceived by parents to be related to formula intolerance. The decision to switch formula was usually made by the parents without consulting a health professional.
Lack of Effect of Lactobacillus GG in Breast‐fed Infants With Rectal Bleeding: A Pilot Double‐blind Randomized Controlled Trial
Authors: Szajewska H , Gawrońska A , Woś H , Banaszkiewicz A , Grzybowska‐Chlebowczyk U
Published: July 2007

Objectives:

For breast‐fed infants with rectal bleeding, maternal restriction of dietary protein such as cow's milk proteins is often recommended; however, poor response to dietary protein restriction is of concern. This pilot study was designed to assess the effectiveness of Lactobacillus GG (LGG) in breast‐fed infants with rectal bleeding.

Patients and Methods:

Breast‐fed infants <6 months of age with rectal bleeding (defined as the presence of visible specks or streaks of blood mixed with mucus in the stool in otherwise healthy infants) were enrolled in a double‐blind randomized controlled trial in which they received LGG 3 × 109 colony‐forming units (n = 14) or placebo (n = 15) twice daily for 4 weeks as an adjunct to cow's milk restriction in the mother's diet. Analyses were based on allocated treatment and included data from 26 infants.

Results:

Mean duration of rectal bleeding was similar in the LGG and control groups (17.3 ± 10.6 vs 15.4 ± 11 days; mean difference −1.9 (95% confidence interval [CI] −4 to 7). No difference was found in the number of infants with clinical resolution of rectal bleeding within 72 hours and no relapse afterward (2/11 vs 3/15, relative risk [RR] 0.9, 95% CI 0.2–3.9) and the number of infants with clinical resolution of rectal bleeding within 72 hours followed by relapse of symptoms (5/11 vs 5/15, RR 1.4, 95% CI 0.5–3.5). Breast‐feeding cessation was not needed in any infant.

Conclusions:

These results do not support the use of LGG as an adjunct to maternal cow's milk restriction in breast‐fed infants with rectal bleeding.
Disaccharidase Activity in Infants and Comparison Based on Symptoms and Histological Changes
Authors: Tori Alvaro J , Carroll Aaron E , Gupta Sandeep K
Published: July 2007

Objectives:

There is uncertainty regarding disaccharidase activity (DA) in infants. In this study, values for DA in infants were established and compared with symptoms and intestinal mucosal histological appearance.

Patients and Methods:

Disaccharidase activity and histological appearance of endoscopically obtained intestinal mucosal biopsy specimens from 131 infants (75 males; mean age 180 days; range 20–364 days) obtained during an 8‐year period were reviewed. Patients were divided into 2 groups on the basis of absence (group 1; n = 56) or presence (group 2; n = 75) of failure to thrive (FTT) and/or diarrhea. These groups were subdivided into 3 subgroups on the basis of histological findings: normal histological appearance (A), mild histological abnormalities (B), and moderate to severe histological abnormalities (C).

Results:

The DA from patients in group 1A represent values in infants who were free of diarrhea/FTT and who had normal intestinal mucosal histological appearance. The geometric means (95% CI) in units of DA were as follows: lactase 33.7 (normal range 29.0–39.1), sucrase 48.9 (normal range 44.2–54.1), maltase 160.5 (normal range 144.4–178.3), and palatinase 11.2 (normal range 9.7–12.9). Differences in DA were not related to symptoms, in the absence of histological abnormalities (1A vs 2A), but rather on the presence of histological abnormalities even in the absence of symptoms (1A vs 1B). Differences were also found when patients with FTT and/or diarrhea with abnormal histological appearance (2B and 2C) were compared with patients with no FTT and/or diarrhea with a normal brush border (1A).

Conclusions:

We outline DA values in a large cohort of infants. DA in infants, as in children, relates to intestinal mucosal histological appearance rather than to symptoms.
Role of an Intestinal Rehabilitation Program in the Treatment of Advanced Intestinal Failure
Authors: Torres Clarivet , Sudan Debra , Vanderhoof Jon , Grant Wendy , Botha Jean , Raynor Stephen , Langnas Alan
Published: July 2007

Objective:

To analyze outcomes in children with intestinal failure treated by our Intestinal Rehabilitation Program (IRP) in a 4‐year period.

Patients and Methods:

A total of 51 parenteral nutrition (PN)–dependent patients (20 male) were enrolled in the IRP. Median age was 1.7 years, with the primary diagnoses being gastroschisis, necrotizing enterocolitis, volvulus, and congenital atresia. Median small bowel intestinal length was 35 cm, with the majority of patients having only jejunum as remaining bowel anatomy. Thirty‐six of the 51 patients had liver disease characterized by cirrhosis, advance bridging fibrosis, and portal and periportal fibrosis. Height, weight z score, platelet count, albumin, and bilirubin levels were measured at the beginning and end of the study.

Results:

Of the 51 patients, 29 had 46 different surgical intestinal repairs. Twenty‐nine of the 36 patients with hyperbilirubinemia had normalized serum bilirubin with treatment. Ten patients required transplantation. Five patients died of sepsis, influenza, or complications after intestinal transplantation. Of the remaining 37 patients in the IRP, 31 were weaned from parenteral nutrition (5 with cirrhosis); 6 patients are in the process of weaning. Survival rate of the patients in the IRP was 90%. Growth has continued along the same curve, and some patients have exhibited significant catch‐up.

Conclusions:

With an aggressive medical/surgical approach, even patients with intestinal failure and advanced liver disease can avoid transplantation. Patients in the IRP showed improved liver function and nutritional parameters with the ability to discontinue PN while maintaining growth. Early referral of these patients to specialized centers before the development of advanced liver disease is recommended.
Gastric Rupture and Necrosis in Prader‐Willi Syndrome
Authors: Stevenson David A , Heinemann Janalee , Angulo Moris , Butler Merlin G , Loker Jim , Rupe Norma , Kendell Patrick , Cassidy Suzanne B , Scheimann Ann
Published: July 2007

Hyperphagia and obesity are common features in individuals with Prader‐Willi syndrome (PWS). Demographic and cause‐of‐death data from individuals with PWS were obtained through a national support organization. Four reports of unexpected mortality due to gastric rupture and necrosis were found in 152 reported deaths, accounting for 3% of the causes of mortality. Four additional individuals were suspected to have gastric rupture. Vomiting and abdominal pain, although rare in PWS, were frequent findings in this cohort. The physician should consider an emergent evaluation for gastric rupture and necrosis in individuals with PWS who present with vomiting and abdominal pain.
Initial Experience With the Adjustable Gastric Band in Morbidly Obese US Adolescents and Recommendations for Further Investigation
Authors: Dillard Barney E , Gorodner Veronica , Galvani Carlos , Holterman Mark , Browne Allen , Gallo Alberto , Horgan Santiago , Le Holterman Ai‐Xuan
Published: July 2007

Background:

The public health crisis of obesity has spread to the pediatric population. In morbidly obese (MO) adolescents, early weight loss intervention can reduce and prevent obesity‐related comorbidities and mortality and improve quality of life. The present study was performed to evaluate weight loss efficacy and safety of “off‐label” laparoscopic adjustable gastric banding (LAGB) procedures performed in MO adolescents by our adult bariatric program.

Patients and Methods:

We retrospectively reviewed data from 716 LAGB procedures performed on an off‐label basis in adults and 24 adolescent patients ages 14 to 20 years by the adult bariatric program at our institution between 2001 and 2006.

Results:

There was no mortality. Average operative time was 45 minutes, length of stay for adolescents was 15 hours, and weight loss outcome and overall surgical complication rates are comparable between adolescents and adults. For adolescent subjects, baseline mean preoperative body mass index was 49 kg/m2 and average excess weight loss rates were 22%, 34%, 52%, 42%, and 42% at 3, 6, 12, 24, and 36 months, respectively. The overall complication rate was 29%, with a 25% incidence of pouch enlargement in adolescents (vs 18% in adult patients; P = ns). Two of 24 adolescent patients (8.4%) required laparoscopic band repositioning (vs 1.5% of adult patients; P = 0.06).

Conclusions:

LAGB is an effective and safe surgical weight loss modality for MO adolescent subjects. Vigilant follow‐up for LAGB‐related complications and intensive postoperative behavioral management are important for improving long‐term success. We recommend continued investigation of long‐term efficacy and safety of LAGB in this population.
Effects of Refrigeration on the Bactericidal Activity of Human Milk: A Preliminary Study
Authors: Martínez‐Costa Cecilia , Silvestre María Dolores , López María Carmen , Plaza Auxiliadora , Miranda María , Guijarro Raquel
Published: July 2007

This study analyzed the bactericidal activity of human milk and how it is influenced by refrigerated storage. Nine samples of mature human milk were collected and divided into 3 aliquots. One was analyzed immediately, and the other 2 were refrigerated at 4°C to 6°C for 48 and 72 hours, respectively. All of the fresh samples exhibited bactericidal activity with an average value of 83.47% ± 18.37%. Refrigeration for 48 hours did not cause significant modifications, whereas storage beyond 72 hours significantly lowered the degree of bacteriolysis versus fresh milk. In conclusion, human milk possesses bactericidal activity that remains stable during the first 48 hours of refrigerated storage, but it is significantly reduced beyond 72 hours.
Rotavirus Infections and Development of Type 1 Diabetes: An Evasive Conundrum
Authors: Ballotti Serena , de Martino Maurizio
Published: July 2007

Type 1 diabetes (T1D) is an organ‐specific autoimmune disease caused by altered immune tolerance to specific proteins leading to a selective destruction of insulin‐producing β cells in genetically predisposed individuals. T1D is likely to be triggered by environmental factors, including virus infections in genetically predisposed individuals. Rotaviruses are the main cause of severe diarrhea among children worldwide, but they seem to have a role also in T1D induction. Epidemiological data may be consistent with a similar hypothesis. Mechanisms hypothesized include molecular mimicry, bystander activation (with or without epitope spreading), and viral persistence. In this review the authors analyze the factors accounting for rotavirus ability to prime islet autoimmunity and cause T1D. A thorough comprehension of their potential pathogenetic mechanisms may allow preventive strategies to be designed.
Analysis of Candidate Genes on Chromosomes 5q and 19p in Celiac Disease
Authors: Latiano Anna , Mora Barbara , Bonamico Margherita , Megiorni Francesca , Mazzilli Maria Cristina , Cucchiara Salvatore , Palmieri Orazio , Valvano Maria Rosa , Annese Vito
Published: July 2007

Background and Aim:

Celiac disease (CD) is a multifactorial disease with involvement of both environmental and genetic susceptibility factors. The HLA‐DQ loci account for <40% of CD heritability, but linkage studies have delineated other loci at the 5q31–33 (CELIAC2), and 19p13 regions (CELIAC4), similarly as in inflammatory bowel diseases. However, data in association studies are contradictory. To evaluate whether single nucleotide polymorphisms (SNPs) tagging the MYO9B susceptibility haplotype and the IBD5 locus (5q31–33) are involved in CD predisposition, we performed case‐control and family‐based analyses. Additionally, any possible correlation with the HLA‐DQ status was investigated. Finally, our data were pooled with the results of other studies by a meta‐analysis.

Patients and Methods:

In all, 337 unrelated patients with CD, 424 parents (212 sets), and 452 healthy individuals were genotyped for the IGR2198a_1, rs12521868, rs1050152, and rs2631367 SNPs (IBD5 locus) and the rs962917, rs2305764, and rs1545620 SNPs of the MYO9B gene by the restriction enzyme method and the TaqMan system ABI PRISM 7700, respectively.

Results:

In comparison with healthy control individuals, the allele, genotype, and haplotype frequencies of all investigated SNPs were not different in the CD patients, nor was any correlation observed with the HLA‐DQ status or clinical presentation. The transmission disequilibrium test did not show a transmission distortion. Five other studies were available for meta‐analysis on MYO9B variants; by pooling of data, no significant association was demonstrated by the random effect model. A significant heterogeneity (P < 0.002) among the studies was present, mainly explained by a single study in the Dutch population.

Conclusions:

Our results and those of the meta‐analysis (>2000 CD patients and 4000 control individuals) question the role of MYO9B at the CELIAC4 locus as a disease‐causing gene. Moreover, none of the investigated SNPs explain the linkage at the CELIAC2 locus.
Subacute Nonsuppurative Cholangitis (Cholangitis Lenta) in Pediatric Liver Transplant Patients
Authors: Lin Chieh‐Chung , Sundaram Shikha S , Hart John , Whitington Peter F
Published: July 2007

Background:

Subacute nonsuppurative cholangitis (cholangitis lenta) is an uncommon yet important histological finding in liver biopsies from pediatric liver transplant recipients. The histopathological features include proliferation of bile ductules at the edges of portal tracts, inspissated bile within dilated bile ductules, absence of acute inflammation within ducts or ductules, and normal structure of interlobular bile ducts.

Objective:

To describe the histopathology and clinical outcomes of pediatric liver transplant recipients with subacute nonsuppurative cholangitis.

Materials and Methods:

This is a retrospective analysis involving review of medical records and analysis of liver‐biopsy specimens by a pathologist blinded to clinical diagnosis. We identified 9 pediatric patients meeting the criteria for nonsuppurative cholangitis. These patients were compared with a control group of patients with biliary obstruction.

Results:

Liver histopathology clearly distinguishes subacute nonsuppurative cholangitis from biliary obstruction and other causes of posttransplant cholestasis. Clinical biochemistry cannot reliably distinguish between the 2, although statistically significant differences existed in levels of serum total and direct bilirubin, alanine aminotransferase, and alkaline phosphatase. The rate of proven bacterial or fungal infection in the study group was 100% in contrast to a rate of 54.5% in the control group (P< .05). Graft and patient survival were similarly poor.

Conclusions:

Finding subacute nonsuppurative cholangitis suggests the presence of severe local or systemic infection in liver‐transplant recipients, and its recognition is important for clinical management.