bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of immunosuppressive drugs in islet xenotransplantation: A study in the pig‐to‐rat model
Authors: Wennberg L. , Wallgren A.C. , Sundberg B. , Rafael E. , Zhu S. , Tibell A. , Karisson‐Parra A. , Groth C.G. , Korsgren O.
Published: November 2008

Abstract:Several immunosuppressive regime's were used in a pig‐to‐rat islet transplant model, with porcine islet‐like cell clusters placed under the kidney capsule of Lewis rats. The animals were killed 12 days after the implantation. In untreated control rats, a massive infiltration of mononuclear cells occured in the xenograft and no morphologically intact endocrine cells could be seen. Most of the infiltrating cells were large, polygonal, macrophage‐like cells. T‐lymphocytes were found mainly in the peripheral parts of the xenografts. Some NK‐cells were also observed. Treatment with cyclosporin A (CyA, 20 mg/kg BW, p.o.), cyclophosphamide (CYP, 20 mg/kg BW, p.o.), prednisolone (PRED, 20 mg/kg BW, p.o.) and mycophenolate mofetil (MMF, 40 mg/kg BW, p.o.) had little inhibitory effect on the xenograft rejection. In animals given cyclosporin and cyclophosphamide in combination with plasmapheresis there were only occasional infiltrating cells, still only endocrine cells were morphologically intact. Immunosuppression with CyA in combination with rapamycin (RPM, 5 mg/kg BW, i.p.) also had an inhibitory effect on xenograft rejection and there were only a few or a moderate number of cells infiltrating the grafts. However, in this treatment group many morphologically intact endocrine cells were present. The most effective treatment was CyA in combination with 15‐deoxyspergualine (DSG, 10 mg/kg BW, i.m.). The animals so treated had hardly any infiltrating mononuclear cells and the islet xenograft revealed a morphological appearance similar to that observed after transplantation to nude mice‐i.e., intact endocrine tissue, organized in duct‐like structures or cell clusters. All rats had preformed, xenoreactive antibodies in serum directed against membrane antigens on pig ICC. In control animals and animals treated with CyA, a marked rise in antibody levels was found after transplantation. Treatment with CyA and DSG (10 mg/kg BW), CyA and CYP, and protocols including plasmapheresis, resulted in a significant decrease in antibody levels. With the other treatment protocols, the antibody levels remained unchanged.
Islet Isolation from the porcine pancreas, using a continuous digestion method
Authors: Polo F. , Monroy B. , Maria S. Di , Ruiu G. , Darquy S. , Petruzzo P. , Arbet‐Engels C. , Cappai A. , Brotzu G. , Reach G.
Published: November 2008

Abstract: This paper describes a method for pig islet isolation with the following original features: first, we set up a reproducible, rapid, sterile, and simple method for pancreas procurement and preparation with double duct incannulation. Second, we demonstrated that UW solution can be used for pancreas digestion; third, we designed an original method for pancreas digestion, derived from the method originally described by Ricordi, except that a double digestion circuit made it possible to digest continuously, within one step, the pancreas, which makes the method operator‐independent; finally we designed a simple method for islet purification based on a two‐layer Histopaque/ UW density gradient and the use of the COBE 2991 cell processor.
Identification of porcine membrane antigens involved in the cytotoxic response mediated by human xenoreactive antibodies
Authors: Aspeslet Launa J. , Chackowsky Patricia , Sekhon Harbuksh , Malcolm Andrew J. , Mosleh Zina , Koshal Arvind , Yatscoff Randall W.
Published: November 2008

Abstract: The identification of xenoantigens on the surface of endothelial cells is important for understanding the mechanism of hyperacute rejection and development of abrogating methods. The objective of our study was to identify the porcine antigens that, when bound by xenoreactive antibodies in human serum, result in cytotoxicity of porcine cells. Human AB and O sera were adsorbed with porcine aortae, erythrocytes, platelets, and a broad spectrum of immobilized carbohydrate moieties (Synsorbs). Aortae and erythrocytes were able to adsorb the xenoreactive antibodies that were cytotoxic to porcine cells (LLC‐PK1), determined using an MTT cytotoxicity assay. Only carbohydrates having the αGal(1–3)βGal(1–4) moieties (Synsorbs 90, 115) were able to significantly reduce cytotoxicity with both types of sera. Western blots of porcine aortic endothelial cells (PAEC) and LLC‐PK1 cell membrane extracts probed with unadsorbed sera indicate the binding of xenoreactive IgM to approximately 17 and 11 antigen bands, respectively, having molecular weights ranging from 20–133 kDa. Anti‐IgG development showed 8 and 11 antigen bands on PAEC and LLC‐PK1 membrane preparations, respectively. When blots were performed using adsorbed AB sera, the binding to all antigens was still observed. When Synsorb 90 bound antibodies were used to probe the blots, the majority of antigens were still detected. This suggests that the binding of xenoantibodies to the most prominent antigens, as detected by Western blot procedures may not be the ones to which cytotoxic xenoreactive antibodies bind. Alternative approaches are required to identify such antigens.
Human anti‐pig cell‐mediated cytotoxicity in vitro involves non‐T as well as T cell components
Authors: Chan Derek V. , Auchincloss Hugh
Published: November 2008

Abstract:Human anti‐pig cell‐mediated cytotoxicity was studied in vitro. Unprimed human peripheral blood lymphocytes (PBL) were able to lyse pig targets but not human targets when the assay was performed in human serum (HS). Much less, but still detectable, lysis was obtained using fetal calf serum (FCS). Human PBLs cultured for 6 days in FCS without stimulating cells showed substantial lysis of pig targets. This lysis was increased by the addition of human IL‐2. Unseparated human PBLs stimulated for 6 days with pig cells in serum‐free media lysed pig targets expressing the same or different SLA antigens as the stimulating cells. This lysis could not be significantly inhibited by anti‐CD3 or anti‐CD8 blocking antibodies during the effector phase of the assay. T cell‐enriched human PBLs treated with anti‐CD 16 and anti‐CD56 antibodies plus complement also lysed pig targets. These effector cells were significantly inhibited by anti‐CD3 and anti‐CD8 antibodies but not by anti‐CD4 antibodies. Furthermore, these primed T cell effectors could only lyse pig targets that shared the same MHC class I antigens as the sensitizing stimulators.

These results suggest that human anti‐pig cell‐mediated cytotoxicity in vitro has at least three different components in bulk culture: 1) an ADCC component depending on natural antibodies from human serum, 2) an NK and/or a LAK cell component that is enriched by in vitro culture and interleukin‐2 (IL‐2), and (3) an allospecific T cell component, involving CD3+, CD8+, class I‐specific effector cells.
Effect of DSG on xenogeneic immune reactivity with special emphasis on human anti‐pig cellular reactions in vitro
Authors: Borg Anette Johansson , Kumagai‐Braesch Makiko , Möller Erna
Published: November 2008

Abstract:The effect of the immunosuppressive drug 15‐deoxyspergualin (DSG) on xenogeneic human anti‐porcine cellular reactivity in vitro, including MLR induced proliferation, interleukin‐2 (II‐2) production, generation of cytotoxic cells, and the effect on antibody‐dependent cellular cytotoxicity (ADCC), were compared with the effects of cyclosporin A (CsA) and/or FK506. The cytotoxic response was evaluated for both direct and indirect pathways for antigen presentation. In addition, the effects of DSG and CsA on antibody production to pig peripheral blood lymphocytes (PBL) in mice was studied. The degree of immunosuppression of xenogeneic and allogeneic cellular responses was compared. CsA and FK506 effectively inhibited proliferation and II‐2 production induced by allogeneic human PBL or xenogeneic porcine PBL, whereas DSG did not have any effect on these responses. However, DSG suppressed both the allogeneic and xenogeneic in vitro induced cytotoxic responses, to the same level whether induced via the direct or indirect pathways of immune activation. In contrast, CsA inhibited cytotoxicity induced by xenogeneic cells via the direct but not via the indirect pathway. No effect of FK506 and DSG on ADCC was demonstrated.

A 5‐day treatment with DSG or CsA of mice immunized with pig PBL partly suppressed antibody production. In DSG treated mice anti‐pig PBL antibodies were produced, but titers were lower than in nontreated or CsA treated mice. The results indicate that DSG may be more effective than CsA/FK506 in inhibiting cytotoxic responses and antibody production induced by xenogeneic pig cells. A possible explanation could be that cytotoxicity induced via the indirect activation pathway of xenoreactivity is mediated to a high degree by CD3‐CD16+(natural killer) NK‐like cells, and that stimulation of these cells may be more sensitive to DSG than to CsA/FK506.
Natural human antibody‐mediated destruction of porcine neonatal islet cell grafts
Authors: Korbutt G. S. , Aspeslet L. J. , Rajotte R. V. , Warnock G. L. , Ao Z. , Ezekowitz J. , Malcolm A. J. , Koshal A. , Yatscoff R. W.
Published: November 2008

Abstract:Porcine pancreata may be considered a potential source of islets for transplantation into diabetic recipients; however, whether porcine islet grafts will be susceptible to damage by natural antibody‐mediated hyperacute rejection remains unknown. In this study, we performed Western blots to determine whether membrane proteins present on porcine neonatal islet cells (NIC) are recognized by xenoreactive antibodies present in human sera. Western blots of freshly isolated porcine NICs with AB sera detected the presence of 14 antigens (MW 24–164 kDa) and 4 antigens (MW 101–150 kDa) to which antiserum against human IgM and IgG bound, respectively. The most prominent antigens with IgM reactivity had MWs of 36, 63, and 120 kDa, whereas for IgG, the most intensely reactive antigen had a MW of 120 kDa. When membrane fractions prepared from purified porcine aortic endothelial cells and LLC‐PK1 cells were analyzed, the major antigens had molecular weights comparable to those seen for NICs. After culturing the NICs for 5 days, the number of detected xenoreactive antigens binding IgM or IgG decreased and the antigens present at 36, 63, and 120 kDa with IgM reactivity were shown to have a decreased intensity of binding. Incubation of cultured porcine NICs for 18 hr in the presence of human AB serum containing complement resulted in a 55% loss of cellular insulin content (P< 0.0001), a 45% reduction in recoverable DNA (P< 0.0001), and a marked reduction in insulin secretory response to an in vitro glucose challenge. Recovery and viability of porcine NICs was not affected when incubated with AB serum depleted of anti‐Gal antibodies with Synsorb 90. These results demonstrate that natural human antibodies of both IgM and IgG subtypes bind to antigens present on Department of Laboratory Medicine and complement reduces islet cell survival and functional viability. Adsorbing serum with the αGal(1–3)βGal(1–4)βGlc carbohydrate removes natural human antibody‐mediated destruction of porcine neonatal islet cell grafts.
Extracorporeal (“ex vivo”) connection of pig kidneys to humans. II. The anti‐pig antibody response
Authors: Rydberg Lennart , Björck Staffan , Hallberg Eva , Magnusson Stefan , Sumitran Suchitra , Samuelsson Bo E. , Strokan Valeri , Svalander Christian T. , Breimer Michael E.
Published: November 2008

Abstract: Pig kidneys were extracorporeally “ex vivo” connected to the circulation of two volunteer male dialysis patients (Breimer et al., this issue). The patients were pretreated by daily plasmapheresis for 3 consecutive days, which reduced the anti‐pig lymphocytotoxic titer from 8 to 2 in the first patient and from 8 to 1 in the second patient. The anti‐pig hemagglutinating titers were reduced from 32 to 4 in the first patient and from 2 to 1 in the second patient. No drugs, except heparin, were given. The perfusion lasted for 65 min in patient 1 and the experiment was terminated due to increased vascular resistance in the pig kidney. Ultrastructural investigation showed a picture similar to a hyperacute vascular rejection. Immunohistochemical studies showed a weak staining of IgM antibodies, but no IgG in the small arteries and glomeruli.

The pig kidney of patient 2 was perfused for 15 min and the experiment terminated due to serious side effects of the patient. Light and electron microscopical investigation showed virtually no structural changes of the kidney tissue and immunostaining for human antibodies was negative.

In both patients, serum samples collected 2–5 weeks postperfusion showed a strong anti‐pig antibody titer rise (up to 512) which thereafter declined but stabilized on a higher level than before the experiment. The antibody response in the two patients was different. In patient 1, the major anti‐pig antibodies directed to carbohydrate antigens were of IgG (IgG1 and IgG2 subclasses) type, while the IgM response was less prominent and virtually no IgA antibodies were produced. Despite the short duration of the perfusion in patient 2, a humoral immune response was seen that was mainly confined to the IgA immunoglobulin class (IgA1 subclass). Blood group glycospingolipid fractions, prepared from the contralateral kidney of the donor pigs, were used for immunostaining with patient serum samples. In both patients, the antibodies produced after the perfusion, mainly recognized the Galα1–3Gal epitope both as part of the “linear B” pentasaccharide but also on more complex carbohydrate structures.

Patient 1 was HLA‐immunized before the experiment due to a kidney allograft and had a panel reactivity of 85% before the perfusion. No change in the panel reactivity of HLA‐antibodies was found after the perfusion experiments. Patient 2 had no HLA antibodies before and remained negative after the perfusion.

Patient serum samples collected before and after the perfusion were tested for reactivity against human endothelial cell lines. No antibodies were generated.
Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model
Authors: Tango Margaret J. , Safaris Evelyn , Romanella Margarita , Aminian Atousa , Katerelos Marina , Somerwille Christine , Tearle RIek G. , Pearse Martin J. , D'Apice Anthony J.E
Published: November 2008

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2‐Kb promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.
The acceptability of pig organ xenografts to patients awaiting a transplant
Authors: Arundeii M.A. , McKenzie I.F.C.
Published: November 2008

Abstract: As the waiting lists for allotransplants of heart, kidney, and liver continue to grow, alternative sources of organs for transplantation are being sought: xenografts from pigs to humans could be a solution. However, is this solution acceptable to patients? To answer this question, we sought opinions, using a questionnaire, from 277 patients on a waiting list for a cadaver transplant for either a kidney (207), heart, or heart/lung transplant (70); there was a 65% (188) response rate. Approximately 75% of respondents had heard of xenografting; 50% would accept a xenograft for themselves and 43% for a relative; and 10% found a xenograft to be unacceptable and 40% were unsure and wanted more information. The most acceptable donor animal was the pig (27%), but 24% would accept organs from any animal; 68% had no objection to breeding animals as a source of organs and considered that the most appropriate use of animal tissue to be when no human organs were available. Thus, a minimum of 50% and a maximum of 90% of patients awaiting an allograft would accept a xenograft, although most would prefer a human rather than an animal donor.
Characteristics of direct and indirect activation of human T cells against allogeneic and porcine xenogeneic cells/peptides
Authors: Kumagai‐Braesch Makiko , Borg Anetfe Johansson , Satake Masahiro , Möller Erna
Published: November 2008

Abstract:The immunological consequences of direct versus indirect activation of T lymphocytes is of considerable interest both in allogeneic and in xenogeneic transplantation. In this paper, the activation of human T cells by allogeneic and xenogeneic porcine antigen‐presenting cells (APC) (direct activation), or by donor‐derived peptides presented on autologous APC (indirect activation) was studied in vitro. The direct activation of purified human T lymphocytes by allogeneic and xenogeneic porcine stimulator cells led to marked proliferative responses, IL‐2 and IFN‐γ production. The ratio of CD4/CD8 of responsive cells upon direct activation was the same for allogeneic and xenogeneic stimulation. Also, the CD25 expression on total and on CD8+ lymphoblasts was similar in allogeneic and xenogeneic responses. The frequency of alloreactive and xenoreactive CTLp following direct activation was 7.7 ± 1.4 / 104and 3.7 ± 1.3 / 104, respectively. Direct activation of proliferation and IL‐2 and IFN‐γ production in both experimental situations was completely blocked by Cyclosporin A (CsA). 15‐deoxyspergualin (DSG), which is thought to prevent antigen processing, had little effect. Thus, when it comes to direct activation of T lymphocytes xeno‐ and allospecific responses were qualitatively and quantitatively comparable.

However, some differences between allogeneic and xenogeneic responses were observed when indirect activation was studied using stimulator cells from peripheral blood depleted of both adherent cells and of SLA class II positive cells or when human allogeneic or xenogeneic fibroblasts were used as stimulators. Indirect activation following recognition of alio‐ or xenogeneic peptides in a responder HLA‐restricted fashion resulted in proliferation, IL‐2 and IFN‐y production, albeit lower than in direct combinations. Indirect activation also induced a lower proportion of CD25+ lymphoblasts than direct activation. Furthermore, indirect xenoactivation resulted preferentially in proliferation and CD25 expression in the CD4+ cell population, and in contrast to direct activation, not only CsA but also DSG inhibited activation. Thus, our findings indicate that direct and indirect activation of human responder T cells stimulated by allogeneic and/or xenogeneic porcine cells/peptides results in immune responses with similar characteristics. Only the proliferation of CD8+ cells and their expression of CD25 and of functional IL‐2 receptors was weaker following xeno‐ than alloactivation, reasons for which are discussed. We conclude that indirect activation of T cell reactivity against xenogeneic peptides leads to an efficient immune response, likely to be of clinical importance for rejection of xenogeneic transplants devoid of professional antigen‐presenting cells.
Engraftment of discordant xenogeneic swine bone marrow cells in immunodeficient mice
Authors: Yang Yong‐Guang , Sergio Justin J. , Sykes Megan
Published: November 2008

Abstract:We have recently demonstrated that swine bone marrow cells (BMC) can engraft in C.B‐17 scid mice. While engraftment is enhanced by providing donor‐specific porcine cytokines, the level of swine hematopoiesis declines between 3 and 6 weeks post‐transplant. In the present study, the utility of several strains of immunodeficient mice as recipients of swine hematopoietic cells has been determined by comparing levels of swine bone marrow engraftment at 3 weeks after bone marrow transplant. Irradiated recipients were injected with lxlO8 swine BMC and were treated daily with porcine cytokines. The presence of swine cells in BMT recipients was detected by flow cytometry and marrow colony‐forming assays. Recombination activating gene‐1 (RAG‐1)‐deficient mice were not permissive for the engraftment of swine BMC, even with administration of increased doses of whole body irradiation, or with depleting anti‐NK cell antibody. In contrast, NOD‐scid mice showed improved swine BMC engraftment compared to C.B‐17 scid mice. Levels of swine class I+, myeloid, and CD2+ cells in bone marrow, spleen, and peripheral blood, and the number of porcine myeloid progenitor cells was significantly higher in NOD‐scid recipients than in simultaneous C.B‐17 scid recipients. In addition, the sera from C.B‐17 scid mice markedly inhibited the proliferation of swine BMC in vitro. A weaker inhibitory effect was also mediated by sera from RAG‐1‐deficient mice, but not by sera from NOD‐scid mice. Together, our results indicate that multiple host elements resist xenogeneic hematopoietic engraftment and function, some of which are clearly independent of host T, B, or NK cells. Understanding the basis for the advantage of NODscid mice as recipients of discordant xenogeneic porcine BMC will help to identify these elements.
Amplification of Bovine Viral Diarrhoea Virus Introduced into an In Vitro Embryo Production System Via Oocytes from Persistently Infected Cattle
Authors: Marley MSD , Givens MD , Galik PK , Riddell KP , Stringfellow DA
Published: November 2008

Contents

The purpose of this study was to determine whether or not embryos derived from in vitro fertilization of oocytes from persistently infected (PI) cattle would contain infectious virus. Three in vitro embryo production treatment groups were assessed: 1) oocytes and uterine tubal cells (UTC) free of bovine viral diarrhoea virus (BVDV) (negative control), 2) oocytes free of BVDV fertilized and cultured in media containing UTC obtained from PI heifers, and 3) oocytes from PI heifers fertilized and cultured in media containing UTC free of BVDV. The developmental media, UTC and embryos (individual or groups of five) were assayed for virus. Virus was not isolated from any samples in treatment group 1. As shown in previous studies, a proportion of embryo samples were positive for BVDV in treatment group 2. In treatment group 3, the virus associated with the oocytes contaminated the developmental media and infected susceptible co‐culture cells used during fertilization and culture. In addition, 65% (11/17) of the degenerated ova from treatment group 3 had infectious virus associated with them. While none of the ova developed into transferable embryos, the study did confirm that use of oocytes from PI cows could lead to amplification of BVDV and cross contamination during in vitro embryo production.
Recurrent postpartum urinary retention: A case report
Authors: Humburg Joerg , Ladewig Ariane , Hoesli Irene , Holzgreve Wolfgang
Published: November 2008

Postpartum urinary retention (PUR) is a clinical condition that is neither well‐recognized nor defined by standardized means but normally has a good prognosis. We present the case of a woman with a history of PUR who demonstrated recurrent PUR.

Prolonged first and second stage of labor, isolated prolonged second stage of labor, forceps delivery or vacuum extraction, perineal laceration, nulliparity and epidural anesthesia can act as independent risk factors for the development of PUR.

In this case, epidural anesthesia, which was administered in both deliveries, was the only risk factor, suggesting that its application in a woman with a history of PUR should be carefully considered and discussed with the patient.

Bladder drainage resolves PUR, after which there seems to be no cumulative risk for voiding dysfunction. An initial smaller post‐void residual bladder volume may have a predictive value concerning the time to resolution of PUR.
The dendritically targeted protein Dendrin is induced by acute nicotine in cortical regions of adolescent rat brain
Authors: Schochet Terri L. , Bremer Quentin Z. , Brownfield Mark S. , Kelley Ann E. , Landry Charles F.
Published: November 2008

The response of the brain to addictive substances such as nicotine includes the rapid induction of genes that influence synaptic events. This response is different in adolescent brain, which continues to undergo synaptic remodeling in regions that include reward‐associated corticolimbic areas. We report here that acute nicotine (0.4 mg/kg), but not cocaine or exposure to a novel environment, induces the expression of the dendritically targeted, corticolimbic mRNA Dendrin in specific regions of adolescent brain. Acute nicotine resulted in an increase in Dendrin mRNA levels in the adolescent prefrontal cortex that was not evident in adult animals. The induction in Dendrin mRNA was a rapid, short‐lived transcriptional event that resulted in changes in Dendrin protein. For example, an increase in Dendrin protein levels following nicotine treatment paralleled enhanced Dendrin immunoreactivity in the dendrites of pyramidal neurons of somatosensory cortex. As Dendrin is an important component of cytoskeletal modifications at the synapse, these results suggest that nicotine influences unique plasticity‐related changes in the adolescent forebrain that differ from the adult.
The role of single subunits of the DNA transport machinery of Thermus thermophilus HB27 in DNA binding and transport
Authors: Schwarzenlander Cornelia , Haase Winfried , Averhoff Beate
Published: November 2008

Thermus thermophilus HB27 is well known for its extraordinary trait of high frequencies of natural transformation, which is considered a major mechanism of horizontal gene transfer. We show that the DNA translocator of T. thermophilus binds and transports DNA from members of all three domains. These results, together with the data obtained from genome comparisons, suggest that the DNA translocator of T. thermophilus has a major impact in adaptation of Thermus to thermal stress conditions and interdomain DNA transfer in extreme hot environments. DNA transport in T. thermophilus is mediated by a macromolecular transport machinery that consists of at least 16 subunits and spans the cytoplasmic membrane and the entire cell periphery. Here, we have addressed the role of single subunits in DNA binding and transport. PilQ is involved in DNA binding, ComEA, PilF and PilA4 are involved in transport of DNA through the outer membrane and PilM, PilN, PilO, PilA1–3, PilC and ComEC are essential for the transport of DNA through the thick cell wall layers and/or through the inner membrane. These data are discussed in the light of the subcellular localization of the proteins. A topological model for DNA transport across the cell wall is presented.
Is losing sleep making us obese?
Authors: Jones K. E. , Johnson R. K. , Harvey‐Berino J. R.
Published: November 2008

Obesity has become pandemic. In America, as obesity has increased, the amount of sleep Americans get per night has decreased, and studies are now showing an association. Epidemiological studies on short sleep duration (SSD) and obesity have been conducted in children and adults, and show an overall positive association. Leptin and ghrelin, two hormones that control appetite, have been studied as a mechanism for SSD causing obesity. Low leptin and high ghrelin levels have been seen in sleep deprivation, the effect of which is an increase in appetite that could be linked to obesity. Decreasing media use, namely television and computers, could be one way to increase nightly sleep and potentially help people lose weight. Paediatric studies have shown an association with bedroom media use and shorter sleep duration. Adult studies are lacking in this area. Limitations in the literature include self‐report in a majority of sleep studies and only a suggested causal link between SSD and obesity among all of the epidemiological studies. In conclusion, obesity is a global problem with great complexity. Encouraging people to get more sleep could be one part of the solution to help them lose weight and gain health.
α‐priori versus α‐posterior methods in dietary pattern analysis: a review in nutrition epidemiology
Authors: Panagiotakos D.
Published: November 2008

Dietary patterns are a set of habits regarding consumption of foods and beverages. They are often influenced by environmental or cultural particularities, and by religion. Examples of dietary patterns include the Mediterranean, Asian and Western diets, and the prudent diet. The majority of these dietary patterns suggest portion sizes for different food items, as well as giving information on the number of servings from each food group to be consumed on a daily, weekly or monthly basis. In the past, many epidemiological studies assessing the role that diet plays in health have focused upon single nutrients or food items. However, people do not eat isolated nutrients; instead they consume meals consisting of a variety of foods, with complex combinations of micro‐ and macronutrients. Therefore, it is becoming apparent that dietary pattern analysis may be a useful tool to use in research of this nature. In this review, two methodologies used to assess dietary patterns are described: α‐posterior and α‐priori pattern analysis.
Gender Differences in Formal On‐the‐Job Training: Incidence, Duration, and Intensity
Authors: O'Halloran Patrick Lee
Published: November 2008

This paper explores whether there is a gender gap in the incidence, duration, intensity, and number of events of on‐the‐job training. Overall, women appear to receive a higher incidence of on‐the‐job training whereas men receive on‐the‐job training of longer duration. Including measures intended to capture the extent of labor force attachment and expected tenure fails to reduce the gender gap in the duration of on‐the‐job training. Therefore, the gender gap in the duration of on‐the‐job training must be attributed to differences in unobserved worker characteristics that differ by gender or discrimination.
Trade Unions, Wage Bargaining Coordination, and Foreign Direct Investment
Authors: Radulescu Roxana , Robson Martin
Published: November 2008

Conventional wisdom is that a high trade union bargaining strength and a system of coordinated wage bargaining reduce the attractiveness of an economy as a location for foreign direct investment, although there is limited evidence for this. The paper takes panel data for 19 OECD economies to examine the relationship between trade union bargaining strength, bargaining coordi nation, and a range of incentives for inward foreign direct investment. It finds a strong negative effect of trade union density on inward foreign direct investment, which is dependent on the degree of wage bargaining coordination. A high degree of coordination weakens the deterrent effect of high union density, which is consistent with the notion that under certain circumstances a coordinated increase in wages can increase profits of the multinationals by hurting domestic firms.
CRITICAL STUDY
Authors: MILBANK JOHN
Published: November 2008

Stanley Hauerwas, Character and the Christian Life: a Study in Theological Ethics, with a new introduction by the author, Trinity University Monograph Series in Religion

Stanley Hauerwas, Against the Nations: War and Survival in a Liberal Society. Winston
ASYNDETON: SYNTAX AND INSANITY. A STUDY OF THE REVISION OF THE NICENE CREED
Authors: Pickstock Catherine
Published: November 2008

Let not the wise man glory in his wisdom, neither let the mighty man glory in his might, let not the rich man glory in his riches: But let him that glorieth glory in this, that he understandeth and knoweth me, that I am the Lord which exercise lovingkindness, judgement, and righteousness in the earth: for in these things I delight, saith the Lord (Jer. 9:23–at)
Effects of peer‐assisted training during the neurology clerkship: a randomized controlled study
Authors: Heckmann J. G. , Dütsch M. , Rauch C. , Lang C. , Weih M. , Schwab S.
Published: November 2008

Objective:  To determine the efficacy of peer‐assisted clinical skills training for students during their neurology clerkship.

Methods:  Students (n = 122) were randomized to get clinical skills training from either student (peer) instructors (experimental group) or from experienced clinical staff (control group). The remaining schedule during the clerkship did not differ between both groups. Primary endpoint was students’ practical skills and knowledge tested at the end of the course by a written test and objective structured clinical examination (OSCE). Secondary endpoints were evaluation of the practical training and self‐estimated gain in theoretical and practical competence.

Results:  In the written test, the peer‐trained group (n = 66) scored 69.5 ± 10.2 (95% CI 67–72) points of 100 and the postgraduates‐trained group (n = 56) 66.7 ± 11.4 (95% CI 63.6–69.8) (P = 0.15). In the OSCE the peer‐trained group scored 93.7 ± 6.3 (95% CI 92.1 to 95.2) points of 100 and the postgraduates‐trained group 92 ± 5.1 (95% CI 90.6 to 93.4) (P = 0.11). In the evaluation and self‐assessment items, there was no significant difference between the two groups except for the postgraduates’ higher competence (P = 0.004).

Conclusion:  Peer‐trained students pass written exam and OSCE as efficient as postgraduates‐trained students. Self‐assessed learning success is equally rated in both groups.
Chronic acquired sensory neuron diseases
Authors: Damasceno A. , França Jr M. C. , Nucci A.
Published: November 2008

Background and purpose:  Sensory neuron diseases (SND) represent a specific subgroup of peripheral nervous system disorders that are becoming increasingly recognized. We aimed to analyze clinical, neurophysiological, and MRI features in patients with SND.

Methods:  We reviewed clinical and electrophysiological data of 20 individuals fulfilling SND criteria. Patients underwent an additional neurological evaluation and cervical spine MRI.

Results:  Sensory neuron diseases was associated with dysimmune conditions in six, hepatitis C in one, B12 deficiency in another, and in one patient SND was related to organophosphate intoxication. In the remaining eleven, it was considered as idiopathic. Nineteen patients experienced sensory symptoms. Worse ataxia was related with longer disease duration (P = 0.02). Early CSF assessment was related to higher protein level (P = 0.008). All patients showed widespread impairment in sensory nerve action potential amplitudes. High signal intensity in the posterior columns was observed in most patients when MRI was performed more than 3 years after disease onset.

Discussion:  Sensory neuron diseases usually presents with sensory symptoms and ataxia. A high index of suspicion is important because inflammatory changes might be more prominent initially, a period when immunotherapy could be more valuable. Early diagnosis should be based mainly on electrophysiological and clinical grounds, as MRI may be normal initially.
Obstruction of cerebral venous sinus secondary to idiopathic intracranial hypertension
Authors: Stienen A. , Weinzierl M. , Ludolph A. , Tibussek D. , Häusler M.
Published: November 2008

Background:  Whether cerebral venous sinus obstruction is a cause or consequence of idiopathic intracranial hypertension (IIH) is uncertain.

Methods and results:  Among the nine children with IIH, five showed stenosis (n = 5) and occlusion (n = 1) of cerebral venous sinus on cranial magnetic resonance imaging (n = 4) or conventional angiography (n = 1), respectively. Follow‐up magnetic resonance imaging performed in four children showed complete regression of the venous pathology in one and partial regression in two of them.

Conclusions:  Our data demonstrate that cerebral venous sinus obstruction is frequent and frequently transient in pediatric IIH and suggest that stenoses may result from elevated intracranial pressure.
Prevention of embolic stroke by catheter ablation of atrial fibrillation
Authors: Stöllberger C. , Schneider B. , Winkler‐Dworak M. , Finsterer J.
Published: November 2008

Background and purpose:  Radiofrequency‐catheter‐ablation of atrial fibrillation is now commonly performed. Aim of this short review is to summarize questions and uncertainties concerning radiofrequency ablation of atrial fibrillation with respect to therapeutic mechanisms, long‐term efficacy and stroke‐prevention.

Results:  The majority of atrial fibrillation patients is too old for radiofrequency ablation. Candidates for radiofrequency ablation belong to a subgroup with a low embolic risk. The radiofrequency ablation procedure itself may increase the embolic risk, and at present it is uncertain how long this embolic risk persists after the procedure.

Conclusion:  We doubt if radiofrequency ablation prevents embolism in atrial fibrillation.
Muscular fatigue and decremental response to repetitive nerve stimulation in X‐linked spinobulbar muscular atrophy
Authors: Inoue K. , Hemmi S. , Miyaishi M. , Kutoku Y. , Murakami T. , Kurokawa K. , Sunada Y.
Published: November 2008

Background and Purpose:  We report decremental responses to repetitive nerve stimulation (RNS) in 11 patients diagnosed with X‐linked spinobulbar muscular atrophy (X‐SBMA).

Methods:  The compound muscle action potential (CMAP) of the right abductor digiti minimi (ADM) and trapezius (TZ) in response to a 3‐Hz stimulation of the ulnar nerve at the wrist and accessory nerve at the neck were recorded by surface electrodes.

Results:  A decremental response to RNS was observed in 90.9% of the TZ muscle and 27.2% in the ADM muscle of patients with X‐SBMA.

Conclusion:  These electrophysiological features of X‐SBMA are considered to be useful for diagnosis of X‐SBMA. Furthermore, the waning phenomena that mostly appeared in the TZ muscle and increment of CMAP in RNS after the exercise also suggest a unique manifestation in X‐SBMA.
Comorbidity of migraine and epilepsy in a Norwegian community
Authors: Brodtkorb E. , Bakken I. J. , Sjaastad O.
Published: November 2008

Background and purpose:  Studies on the comorbidity of migraine and epilepsy have shown conflicting results. We wanted to explore the epidemiological association between migraine and seizure disorders in a population‐based material where case ascertainment was enhanced by individual specialist assessments.

Methods:  Information concerning migraine and seizure disorders was collected from 1793 participants in an interview‐based survey in a circumscribed community. Mixed headache, with features both of migraine without aura and tension‐type headache, was excluded from further analyses because of its ambiguous character (n = 137). Thus, data from 1656 participants were included in the study.

Results:  The number of subjects with epilepsy was small, and a statistically significant association between migraine and the diagnosis of epilepsy was not found. There was a tendency to more active epilepsy in subjects with migraine (1.0%, 5/524), particularly for migraine with aura (1.8%, 3/168), compared with subjects without migraine (0.5%, 6/1132). Migraine was present in five of 11 subjects with active epilepsy (45%) and in four of 28 (14%) with epilepsy in remission (P = 0.09).

Conclusions:  An overall association between migraine and seizure disorders could not be demonstrated, but there was a tendency to more migraine in individuals with active epilepsy.
Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity
Authors: Pippucci T. , Panza E. , Pompilii E. , Donadio V. , Borreca A. , Babalini C. , Patrono C. , Zuntini R. , Kawarai T. , Bernardi G. , Liguori R. , Romeo G. , Montagna P. , Orlacchio A. , Seri M.
Published: November 2008

Background and purpose:  Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR‐HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR‐HSPTCC loci have been assigned to chromosome 15q13‐15 (SPG11) and chromosome 8p12‐p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12‐p11.21 loci was investigated in five Italian families, of which four consanguineous.

Methods:  Families were tested for linkage to the SPG11 or 8p12‐p11.21 loci and the SPG11 gene was screened in all the affected individuals.

Results:  Linkage was excluded in the four consanguineous families. In the only SPG11‐linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene.

Discussion:  This collection of families contributes to highlight the intra and inter locus heterogeneity in AR‐HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.
The State‐by‐State Economic Impacts of the 2002 Shutdown of the Los Angeles–Long Beach Ports
Authors: PARK JIYOUNG , GORDON PETER , MOORE II JAMES E. , RICHARDSON HARRY W.
Published: November 2008

In previous research, the economic impacts of temporary shutdowns of the Los Angeles–Long Beach harbors were simulated after a hypothetical terrorist attack, applying the National Interstate Economic Model to estimate state‐by‐state as well as interindustry impacts. However, the unpredictable characteristic of terrorist attacks might not be applicable to the case of a ports shutdown such as the one caused by the lockout of September–October 2002. Market participants can be expected to have contingency plans based on anticipations of a strike or shutdown. Can we identify any of these in terms of the use of alternate ports, in terms of alternate modes or even alternate time periods? The purpose of this study is to examine these questions. The approach is elaborated by testing for the possible effects of trade diversion to other West Coast ports, transportation modes, and intertemporal substitutions. We use data from WISERTrade describing commodity‐specific trade for the major West Coast ports before, during, and after the 11‐day shutdown of the fall of 2002. Shippers’ ability to divert trade is a key ingredient in the economy's ability to withstand attacks and disruptions. The work estimates the impacts on 47 industrial sectors across 50 states (and the District of Columbia).
Critical Transport Infrastructure in Urban Areas: Impacts of Traffic Incidents Assessed Using Accessibility‐Based Network Vulnerability Analysis
Authors: TAYLOR MICHAEL A. P.
Published: November 2008

Incidents (vehicle breakdowns, crashes, roadworks, lane blockages, severe weather, etc.) are believed responsible for about 50 percent of traffic congestion in Australia's major cities, which is a similar situation to that found in cities in many other parts of the developed world. Incident‐based congestion is particularly disruptive because of its random occurrence in space and time, which maximises the operational impacts of the congestion on social and economic activities. This paper discusses a method for assessing critical locations—congestion “hot spots”—in urban road networks, and the development and application of diagnostic tools that will allow urban road system managers to anticipate potential vulnerabilities to incident‐related congestion and take proactive action to avoid congestion rather than react to it. The expected outcomes are then reduced congestion, delays, and pollution; significantly improved performance from the existing urban road system; and reduced pressure to build more roads. The method involves modelling of travel demand, network topology, capacity and road geometry, the identification and assessment of impacts of traffic incidents at specific locations in a road network, and the use of accessibility impact analysis to assess system‐wide effects. Accessibility impact analysis is undertaken using an accessibility framework, which can account for time of day, transport mode and destination choices by individuals, and level of traffic congestion among other factors. A case‐study application to a specific (potential) incident in a real‐world network indicates that the proposed method is feasible and demonstrates its power in identifying not just total impacts but the distribution of those impacts across a region or community. While current approaches to urban road network planning and management tend to be reactive—finding cures for problems as they arise or addressing locations of recurrent congestion or bad incident record—the vulnerability analysis method described in the paper should lend itself to a proactive approach that can anticipate structural weaknesses and vulnerabilities and help to avoid or at least temper potential adverse effects, rather than to react to them afterwards.
A Framework for Modeling Rail Transport Vulnerability
Authors: PETERSON STEVEN K. , CHURCH RICHARD L.
Published: November 2008

Railroads represent one of the most efficient methods of long‐haul transport for bulk commodities, from coal to agricultural products. Over the past 50 years, the rail network has contracted while tonnage has increased. Service, geographically, has been abandoned along short‐haul routes and increased along major long‐haul routes, resulting in a network that is more streamlined. The current rail network may be very vulnerable to disruptions, like the failure of a trestle. This paper proposes a framework to model rail network vulnerability and gives an application of this modeling framework in analyzing rail network vulnerability for the State of Washington. It concludes with a number of policy‐related issues that need to be addressed in order to identify, plan, and mitigate the risks associated with the sudden loss of a bridge or trestle.
Plant responses to photoperiod
Authors: Jackson Stephen D.
Published: November 2008

Photoperiod controls many developmental responses in animals, plants and even fungi. The response to photoperiod has evolved because daylength is a reliable indicator of the time of year, enabling developmental events to be scheduled to coincide with particular environmental conditions. Much progress has been made towards understanding the molecular mechanisms involved in the response to photoperiod in plants. These mechanisms include the detection of the light signal in the leaves, the entrainment of circadian rhythms, and the production of a mobile signal which is transmitted throughout the plant. Flowering, tuberization and bud set are just a few of the many different responses in plants that are under photoperiodic control. Comparison of what is known of the molecular mechanisms controlling these responses shows that, whilst common components exist, significant differences in the regulatory mechanisms have evolved between these responses.

Contents

Summary
517

I.
The importance of photoperiod
517

II.
The competence to respond to photoperiod
519

III.
The photoperiodic response pathway
521

IV.
Systemic signals
523

V.
Moderating factors
524

VI.
The flowering response to photoperiod in other species
525

VII.
Tuberization in potato
526

VIII.
Bud set and growth cessation in trees
527

References
528