bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals
Authors: Houser Dorian S. , Champagne Cory D. , Crocker Daniel E.
Published: October 2007

Adult female elephant seals ( Mirounga angustirostris) combine long-term fasting with lactation and molting. Glycerol gluconeogenesis has been hypothesized as potentially meeting all of the glucose requirements of the seals during these fasts. To test this hypothesis, a primed constant infusion of [2-14C]glycerol was administered to 10 ten adult female elephant seals at 5 and 21–22 days postpartum and to 10 additional adult females immediately after the molt. Glycerol kinetics, rates of lipolysis, and the contribution of glycerol to glucose production were determined for each period. Plasma metabolite levels as well as insulin, glucagon, and cortisol were also measured. Glycerol rate of appearance was not significantly correlated with mass ( P = 0.14, r2= 0.33) but was significantly related to the percentage of glucose derived from glycerol ( P < 0.01, r2= 0.81) during late lactation. The contribution of glycerol to glucose production was <3% during each fasting period, suggesting a lower contribution to gluconeogenesis than is observed in other long-term fasting mammals. Because of a high rate of endogenous glucose production in fasting elephant seals, it is likely that glycerol gluconeogenesis still makes a substantial contribution to the substrate needs of glucose-dependent tissues. The lack of a relationship between glucoregulatory hormones and glycerol kinetics, glycerol gluconeogenesis, and metabolites supports the proposition that fasting elephant seals do not conform to the traditional insulin-glucagon model of substrate metabolism.
IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men
Authors: Devries Michaela C. , Lowther Stuart A. , Glover Alexander W. , Hamadeh Mazen J. , Tarnopolsky Mark A.
Published: October 2007

Women use more fat during endurance exercise as evidenced by a lower respiratory exchange ratio (RER). The contribution of intramyocellular lipid (IMCL) to lipid oxidation during endurance exercise is controversial, and studies investigating sex differences in IMCL utilization have found conflicting results. We determined the effect of sex on net IMCL use during an endurance exercise bout using an ultrastructural evaluation. Men ( n = 17) and women ( n = 19) completed 90-min cycling at 63% V̇o2peak. Biopsies were taken before and after exercise and fixed for electron microscopy to determine IMCL size, # IMCL/area, IMCL area density, and the % IMCL touching mitochondria. Women had a lower RER and carbohydrate oxidation rate and a higher lipid oxidation rate during exercise ( P < 0.05), compared with men. Women had a higher # IMCL/area and IMCL area density ( P < 0.05), compared with men. Women, but not men, had a higher % IMCL touching mitochondria postexercise ( P = 0.03). Exercise decreased IMCL area density ( P = 0.01), due to a decrease in the # IMCL/area ( P = 0.02). There was no sex difference in IMCL size or net use. In conclusion, women have higher IMCL area density compared with men, due to an increased # IMCL and not an increased IMCL size, as well as an increased % IMCL touching mitochondria postexercise. Endurance exercise resulted in a net decrease in IMCL density due to decreased number of IMCL, not decreased IMCL size, in both sexes.
Vasopressin receptor subtype 2 activation increases cell proliferation in the renal medulla of AQP1 null mice
Authors: Cai Qi , McReynolds Matthew R. , Keck Maggie , Greer Kevin A. , Hoying James B. , Brooks Heddwen L.
Published: October 2007

Aquaporin (AQP) 1 null mice have a defect in the renal concentrating gradient because of their inability to generate a hyperosmotic medullary interstitium. To determine the effect of vasopressin on renal medullary gene expression, in the absence of high local osmolarity, we infused 1-deamino-8-d-arginine vasopressin (dDAVP), a V2 receptor (V2R)-specific agonist, in AQP1 null mice for 7 days. cDNA microarray analysis was performed on the renal medullary tissue, and 5,140 genes of the possible 12,000 genes on the array were included in the analysis. In the renal medulla of AQP1 null mice, 245 transcripts were identified as increased by dDAVP infusion and 200 transcripts as decreased (1.5-fold or more). Quantitative real-time PCR measurements confirmed the increases seen for cyclin D1, early growth response gene 1, and activating transcription factor 3, genes associated with changes in cell cycle/growth. Changes in mRNA expression were correlated with changes in protein expression by semiquantitative immunoblotting; cyclin D1 and ATF3 were increased significantly in abundance following dDAVP infusion in the renal medulla of AQP1 null mice (161 and 461%, respectively). A significant increase in proliferation of medullary collecting ducts cells, following V2R activation, was identified by proliferating cell nuclear antigen immunohistochemistry; colocalization studies with AQP2 indicated that the increase in proliferation was primarily observed in principal cells of the inner medullary collecting duct (IMCD). V2R activation, via dDAVP, increased AQP2 and AQP3 protein abundance in the cortical collecting ducts of AQP1 null mice. However, V2R activation did not increase AQP2 protein abundance in the IMCD of AQP1 null mice.
Role of endogenously secreted angiotensin II in the CO2-induced stimulation of HCO3reabsorption by renal proximal tubules
Authors: Zhou Yuehan , Boron Walter F.
Published: October 2007

Previous studies demonstrated that the proximal tubule (PT) responds to isolated increases in basolateral ([CO2]BL) or “bath” CO2concentration by increasing the HCO3−reabsorption rate ( J[Formula: see text]). Blockade of the rabbit apical AT1receptor or knockout of the mouse AT1Areceptor eliminates these effects, demonstrating a requirement for luminal ANG II that the PT itself synthesizes. In the present study, we examined the effects of the ACE inhibitor lisinopril on J[Formula: see text] in isolated perfused rabbit PTs (S2 segment), using out-of-equilibrium solutions to make isolated changes in [CO2]BLat a fixed baseline HCO3−concentration of 22 mM and fixed baseline pH of 7.4. Adding 60 or 240 nM lisinopril (in vitro Ki: 0.5 or 1.2 nM) to the lumen had no effect. These results are not consistent with the hypothesis that the PT secretes either angiotensinogen or ANG I. However, adding 60 nM basolateral lisinopril significantly decreased J[Formula: see text] at a [CO2]BLof 20%. Moreover, 240 nM basolateral lisinopril decreased baseline (i.e., at 5% CO2) J[Formula: see text] by one-half and completely eliminated the response to altering [CO2]BLfrom 0 to 20%, but left intact the stimulatory effect of 10−11M basolateral ANG II. At extremely high concentrations (i.e., 100 μM), luminal lisinopril replicated the effects of 240 nM basolateral lisinopril. Our data are consistent with the hypothesis that lisinopril readily crosses the basolateral (but not apical) membrane to block ACE in a vesicular compartment. We conclude that the isolated PT predominantly secretes preformed ANG II, rather than angiotensinogen or ANG I.
Bleomycin-induced pulmonary fibrosis is attenuated by a monoclonal antibody targeting HER2
Authors: Faress Jihane A. , Nethery David E. , Kern Elizabeth F. O. , Eisenberg Rosana , Jacono Frank J. , Allen Chris L. , Kern Jeffrey A.
Published: October 2007

The importance of HER2/HER3 signaling in decreasing the effects of lung injury was recently demonstrated. Transgenic mice unable to signal through HER2/HER3 had significantly less bleomycin-induced pulmonary fibrosis and showed a survival benefit. Based on these data, we hypothesized that pharmacological blockade of HER2/HER3 in vivo in wild-type mice would have the same beneficial effects. We tested this hypothesis in a bleomycin lung injury model using 2C4, a monoclonal antibody directed against HER2 that blocks HER2/HER3 signaling. The administration of 2C4 before injury decreased the effects of bleomycin at days 15 and 21 after injury. HER2/HER3 blockade resulted in less collagen deposition (362.8 ± 37.9 compared with 610.5 ± 27.1 μg/mg; P = 0.03) and less lung morphological changes (injury score of 1.99 ± 1.55 vs. 3.90 ± 0.76; P < 0.04). In addition, HER2/HER3 blockade resulted in a significant survival advantage with 50% vs. 25% survival at 30 days ( P = 0.04). These results confirm that HER2 signaling can be pharmacologically targeted to reduce lung fibrosis and remodeling after injury.
Separate Adaptive Mechanisms for Controlling Trajectory and Final Position in Reaching
Authors: Scheidt Robert A. , Ghez Claude
Published: October 2007

We examined control of the hand's trajectory (direction and shape) and final equilibrium position in horizontal planar arm movements by quantifying transfer of learned visuomotor rotations between two tasks that required aiming the hand to the same spatial targets. In a trajectory-reversal task (“slicing”), the hand reversed direction within the target and returned to the origin. In a positioning task (“reaching”), subjects moved the hand to the target and held it there; cursor feedback was provided only after movement ended to isolate learning of final position from trajectory direction. We asked whether learning acquired in one task would transfer to the other. Transfer would suggest that the hand's entire trajectory, including its endpoint, was controlled using a common spatial plan. Instead we found minimal transfer, suggesting that the brain used different representations of target position to specify the hand's initial trajectory and its final stabilized position. We also observed asymmetrical practice effects on hand trajectory, including systematic curvature of reaches made after rotation training and hypermetria of untrained slice reversals after reach training. These are difficult to explain with a unified control model, but were replicated in computer simulations that specified the hand's initial trajectory and its final equilibrium position. Our results suggest that the brain uses different mechanisms to plan the hand's initial trajectory and final position in point-to-point movements, that it implements these control actions sequentially, and that trajectory planning does not account for specific impedance values to be implemented about the final stabilized posture.
Effects of Dopaminergic Modulation on the Integrative Properties of the Ventral Striatal Medium Spiny Neuron
Authors: Moyer Jason T. , Wolf John A. , Finkel Leif H.
Published: October 2007

Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor–mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.
Modulation of Soleus H-Reflexes During Gait in Children With Cerebral Palsy
Authors: Hodapp Maike , Klisch Cornelia , Mall Volker , Vry Julia , Berger Wiltrud , Faist Michael
Published: October 2007

In healthy adults, soleus H-reflexes are rhythmically modulated and generally depressed during gait compared with rest. From ages 6 to 13 yr, there is a progressive increase in the tonic inhibition of H-reflexes during walking, especially during the stance phase of the step cycle. In adults, rhythmic modulation and tonic depression are severely disturbed after bilateral spinal lesions but remain partly preserved after unilateral cerebral lesions. Children with diplegic cerebral palsy (CP) suffer from a bilateral supraspinal lesion of the corticospinal tract that occurs before the maturation of the CNS is complete. If supraspinal structures are involved in the tonic, but not rhythmic, age-dependent reflex depression, it could be hypothesized that the tonic reflex depression with age is disturbed in CP, whereas the rhythmic part of the modulation remains unaffected. To test this hypothesis, soleus H-reflexes were assessed during gait in 16 CP children aged 5–11 and 15–16 and compared with 25 age-matched healthy children walking at similar velocities. Although the rhythmic part of the modulation pattern was present in CP, there was no significant tonic reflex depression with age, thus reflecting a lack of maturation of the corticospinal tract. It is argued the rhythmic part of the modulation may be generated on a spinal or brain stem level and is therefore not affected by the bilateral supraspinal lesion, whereas the tonic depression that occurs with maturation of the CNS is under supraspinal control. In conclusion, the supraspinal structures affected in CP are therefore likely involved in this age-dependent tonic depression.
Variability in Responses and Temporal Coding of Tastants of Similar Quality in the Nucleus of the Solitary Tract of the Rat
Authors: Roussin Andre T. , Victor Jonathan D. , Chen Jen-Yung , Di Lorenzo Patricia M.
Published: October 2007

In the nucleus of the solitary tract (NTS), electrophysiological responses to taste stimuli representing four basic taste qualities (sweet, sour, salty, or bitter) can often be discriminated by spike count, although in units for which the number of spikes is variable across identical stimulus presentations, spike timing (i.e., temporal coding) can also support reliable discrimination. The present study examined the contribution of spike count and spike timing to the discrimination of stimuli that evoke the same taste quality but are of different chemical composition. Responses to between 3 and 21 repeated presentations of two pairs of quality-matched tastants were recorded from 38 single cells in the NTS of urethane-anesthetized rats. Temporal coding was assessed in 24 cells, most of which were tested with salty and sour tastants, using an information-theoretic approach. Within a given cell, responses to tastants of similar quality were generally closer in magnitude than responses to dissimilar tastants; however, tastants of similar quality often reversed their order of effectiveness across replicate sets of trials. Typically, discrimination between tastants of dissimilar qualities could be made by spike count. Responses to tastants of similar quality typically evoked more similar response magnitudes but were more frequently, and to a proportionally greater degree, distinguishable based on temporal information. Results showed that nearly every taste-responsive NTS cell has the capacity to generate temporal features in evoked spike trains that can be used to distinguish between stimuli of different qualities and chemical compositions.
Synchronization Measurement of Multiple Neuronal Populations
Authors: Li Xiaoli , Cui Dong , Jiruska Premysl , Fox John E. , Yao Xin , Jefferys John G. R.
Published: October 2007

The purpose of the present paper is to develop a method, based on equal-time correlation, correlation matrix analysis and surrogate resampling, that is able to quantify and describe properties of synchronization of population neuronal activity recorded simultaneously from multiple sites. Initially, Lorenz-type oscillators were used to model multiple time series with different patterns of synchronization. Eigenvalue and eigenvector decomposition was then applied to identify “clusters” of locally synchronized activity and to calculate a “global synchronization index.” This method was then applied to multichannel data recorded from an in vitro model of epileptic seizures. The results demonstrate that this novel method can be successfully used to analyze synchronization between multiple neuronal population series.
Effects of Initial Eye Position on Saccade-Related Behavior of Abducens Nucleus Neurons in the Primate
Authors: Ling Leo , Fuchs Albert , Siebold Christoph , Dean Paul
Published: October 2007

Previous work suggests that when the eye starts at different orbital initial positions (IPs), the saccade control system is faced with significant nonlinearities. Here we studied the effects of IP on saccade-related firing of monkey abducens neurons by either isolating saccade variables behaviorally or applying a multiple linear regression analysis. Over a 50° range of IPs, we could select 10° horizontal saccades with identical velocity profiles, which would require identical control signals in a linear system. The bursts accompanying ipsiversive saccades for IPs above the threshold for steady firing were quite similar. The excess burst rate above steady firing was either constant or decreased with ipsiversive IP, and both the number of excess spikes in the burst and burst duration were nearly constant. However, for ipsiversive saccades from IPs below threshold, both peak burst rate (6.82 ± 1.38 spikes·s−1·deg−1) and burst duration (0.67 ± 0.28 ms/deg) increased substantially with ipsiversive IPs. Moreover, the pause associated with contraversive saccades shortened considerably with ipsiversive IPs (mean 1.2 ms/deg). This pattern of results for pauses and for bursts below threshold suggests the presence of a significant nonlinearity. Abducting saccades are produced by the net force of agonist lateral rectus (LR) and antagonist medial rectus (MR) muscles. We suggest that the decreasing force in the MR muscle with IPs in the abducting direction requires a more vigorous burst in LR motoneurons, which appears to be generated by a combination of saturating and nonsaturating burst commands and the recruitment of additional abducens neurons.
Local Pixel Value Collection Algorithm for Spot Segmentation in Two-Dimensional Gel Electrophoresis Research
Authors: Peer Peter , Corzo Luis Galo
Published: October 2007

Two-dimensional gel-electrophoresis (2-DE) images show the expression levels of several hundreds of proteins where each protein is represented as a blob-shaped spot of grey level values. The spot detection, that is, the segmentation process has to be efficient as it is the first step in the gel processing. Such extraction of information is a very complex task. In this paper, we propose a novel spot detector that is basically a morphology-based method with the use of a seeded region growing as a central paradigm and which relies on the spot correlation information. The method is tested on our synthetic as well as on real gels with human samples from SWISS-2DPAGE (two-dimensional polyacrylamide gel electrophoresis) database. A comparison of results is done with a method called pixel value collection (PVC). Since our algorithm efficiently uses local spot information, segments the spot by collecting pixel values and its affinity with PVC, we named it local pixel value collection (LPVC). The results show that LPVC achieves similar segmentation results as PVC, but is much faster than PVC.
Management of the Hepatic Lymph Nodes during Resection of Liver Metastases from Colorectal Cancer: A Systematic Review
Authors: Gurusamy Kurinchi S. , Imber Charles , Davidson Brian R.
Published: October 2007

Background. Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. Methods. Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. Results. A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or “selective” lymphadenectomy. Conclusion. Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required.
Synthesis and Cytotoxicity Studies of Titanocene C Analogues
Authors: Hogan Megan , Claffey James , Fitzpatrick Eoin , Hickey Thomas , Pampillón Clara , Tacke Matthias
Published: October 2007

From the carbolithiation of 6-N,N-dimethylamino fulvene (3) and 2,4[bis(N,N-dimethylamino)methyl]-N-methylpyrrolyl lithium (2a), N-(N′,N′-dimethylaminomethyl)benzimidazolyl lithium (2b)' or p-(N,N-dimethylamino)methylphenyl lithium (2c), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4' resulting in N,N-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the IC50 values obtained were of 23, and 52 μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene in this paper, 5c with an IC50 value of 13 μM, was found to be approximately two times less cytotoxic than its analogue Titanocene C (IC50=5.5 μM) and almost four times less cytotoxic than cisplatin, which showed an IC50 value of 3.3 μM when tested on the LLC-PK cell line.
Transient Burning Rate Model for Solid Rocket Motor Internal Ballistic Simulations
Authors: Greatrix David R.
Published: October 2007

A general numerical model based on the Zeldovich-Novozhilov solid-phase energy conservation result for unsteady solid-propellant burning is presented in this paper. Unlike past models, the integrated temperature distribution in the solid phase is utilized directly for estimating instantaneous burning rate (rather than the thermal gradient at the burning surface). The burning model is general in the sense that the model may be incorporated for various propellant burning-rate mechanisms. Given the availability of pressure-related experimental data in the open literature, varying static pressure is the principal mechanism of interest in this study. The example predicted results presented in this paper are to a substantial extent consistent with the corresponding experimental firing response data.
Inhibitory activity of cetuximab on epidermal growth factor receptor mutations in non–small cell lung cancers
Authors: Doody Jacqueline F. , Wang Ying , Patel Sheetal N. , Joynes Christopher , Lee Sui Ping , Gerlak Jason , Rolser Robin L. , Li Yanxia , Steiner Philipp , Bassi Rajiv , Hicklin Dan J. , Hadari Yaron R.
Published: October 2007

Mutations in the kinase domain of the epidermal growth factor receptor (EGFR) were identified in ∼15% of all patients with non–small cell lung cancer (NSCLC). These mutations have been established as an indicator of superior response to gefitinib and erlotinib, small molecule inhibitors of the EGFR kinase domain. Whether these mutations would also render patients more susceptible to treatment with cetuximab (Erbitux), an EGFR-neutralizing antibody, is yet to be determined. In this study, we attempted to evaluate the effect of cetuximab on several NSCLC lines harboring some of the more common EGFR mutations (L858R and delL747-T753insS), as well as the recently identified kinase inhibitor–resistant mutation, T790M. We could show that the kinase activity of the abovementioned EGFR mutants was hindered by cetuximab, as detected by both cell-based phosphorylation and proliferation assays. Interestingly, cetuximab also induced enhanced degradation of the EGFR mutants as compared with the wild-type receptor. Most importantly, cetuximab successfully inhibited the growth of NSCLC lines in xenograft models. These results indicate the promising potential of cetuximab as a regimen for patients with NSCLC bearing these mutations. [Mol Cancer Ther 2007;6(10):2642–51]
The relevance of estrogen receptor-β expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment
Authors: Stettner Mark , Kaulfuß Silke , Burfeind Peter , Schweyer Stefan , Strauss Arne , Ringert Rolf-Hermann , Thelen Paul
Published: October 2007

In the prostate, estrogen receptor β (ERβ), the preferred receptor for phytoestrogens, has features of a tumor suppressor. To investigate the mechanisms underlying the beneficial effects on prostate cancer of histone deacetylase inhibitor valproic acid (VPA) and phytoestrogen tectorigenin, we analyzed the expression of ERβ after tectorigenin or VPA treatment. For further functional analysis, we knocked down ERβ expression by RNA interference. LNCaP prostate cancer cells were treated with 5 mmol/L VPA or 100 μmol/L tectorigenin and transfected with small interfering RNA (siRNA) against ERβ. Control transfections were done with luciferase (LUC) siRNA. Expression of ERβ was assessed by Western blot. mRNA expression was quantitated by real-time reverse transcription-PCR. Expression of ERβ mRNA and protein markedly increased after VPA or tectorigenin treatment. When ERβ was knocked down by siRNA, the expression of prostate-derived Ets factor, prostate-specific antigen, prostate cancer–specific indicator gene DD3PCA3, insulin-like growth factor-1 receptor, the catalytic subunit of the telomerase, and ERα was up-regulated and the tectorigenin effects were abrogated. ERβ levels were diminished in prostate cancer and loss of ERβ was associated with proliferation. Here, we show that siRNA-mediated knockdown of ERβ increases the expression of genes highly relevant to tumor cell proliferation. In addition, we show that one prominent result of treatment with VPA or tectorigenin is the up-regulation of ERβ resulting in antiproliferative effects. Thus, these drugs, by restoring the regulatory function of ERβ in tumor cells, could become useful in the intervention of prostate cancer. [Mol Cancer Ther 2007;6(10):2626–33]
Symptoms and Surgical Management of a Distal Choledochal Cyst in a Patient with Pancreas Divisum: Case Report and Review of the Literature
Authors: Hackert Thilo , Hartwig Werner , Werner Jens
Published: October 2007

We report the case of a 63-year-old woman who presented with the rare finding of a distal choledochocele in a pancreas divisum with recurrent abdominal pain and episodes of pancreatitis. She underwent successful resection with choledochectomy, papillectomy and reconstruction with a hepatico-jejunostomy and reinsertion of the uncinate pancreatic duct into the same jejunal loop. Comparable literature findings are discussed with regard to the presented case.
Molecular Basis for the Regenerative Properties of a Secretion of the Mollusk Cryptomphalus aspersa
Authors: Brieva A. , Philips N. , Tejedor R. , Guerrero A. , Pivel J.P. , Alonso-Lebrero J.L. , Gonzalez S.
Published: October 2007

A screen for natural products bearing pharmacological properties has yielded a secretion of the mollusk Cryptomphalus aspersa (SCA), which possesses skin-regenerative properties. In this report, we outline some of the cellular and molecular effects underlying this observation. First, we found that SCA contained antioxidant SOD and GST activities. In addition, SCA stimulated fibroblast proliferation and rearrangement of the actin cytoskeleton. Additional mechanisms involved in the regenerative effect of SCA included the stimulation of extracellular matrix assembly and the regulation of metalloproteinase activities. Together, these effects provide an array of molecular mechanisms underlying SCA-induced cellular regeneration and postulate its use in regeneration of wounded tissue.
Transdermal Penetration of UV Filters
Authors: Klinubol P. , Asawanonda P. , Wanichwecharungruang S.P.
Published: October 2007

A penetration study of 2-ethylhexyl-4-methoxycinnamate (EHMC), 4-methyl benzylidenecamphor (MBC), butyl methoxydibenzoylmethane (BMBM), 2-ethylhexyl-2,4,5-trimethoxycinnamate (EHTMC) and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate (TMB) through baby mouse skin (Mus musculus Linn.) was carried out using a vertical Franz diffusion cell. At 4.4 mg/cm2 coverage of UV filter on the skin, 2.98 ± 0.38, 1.15 ± 0.14 and 0.80 ± 0.28% of the applied EHMC, MBC and BMBM were detected in the receptor fluid at 24 h after application. Penetrations of UV filter in an ethanolic solution and lotion forms were comparable. EHTMC and TMB showed insignificant penetration across the baby mouse skins. Baby mouse skins kept at 4, –20 and –80°C gave similar EHMC penetration results. Penetrations of EHMC, BMBM, EHTMC and TMB across human epidermis were carried out upon 5 volunteers using the suction blister technique. The results also confirmed the significant penetrations of EHMC and BMBM and the insignificant penetrations of EHTMC and TMB.
Neuroimaging and APOE Genotype: A Systematic Qualitative Review
Authors: Cherbuin Nicolas , Leach Liana S. , Christensen Helen , Anstey Kaarin J.
Published: October 2007

Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer’s disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages. A search of Pubmed, Psycinfo, and Web of Science databases identified 64 articles available for qualitative review. The review found that presence of the APOE Ε4 allele is associated with (1) hippocampal, amygdalar and entorhinal cortex atrophy, (2) increased brain atrophy, (3) increased white matter hyperintensity volumes and (4) altered cerebral blood flow and glucose metabolism patterns. It is possible that there are critical age ranges when these effects are evident and that the APOE Ε2 genotype might present a risk. We conclude that structural brain change is associated with the APOE genotype and that it is more salient in younger ageing individuals.
Vulnerability to Proactive Semantic Interference and Progression to Dementia among Older Adults with Mild Cognitive Impairment
Authors: Loewenstein David A. , Acevedo Amarilis , Agron Joscelyn , Duara Ranjan
Published: October 2007

There is evidence that vulnerability to proactive semantic interference may be an early manifestation of early Alzheimer’s disease and other neurodegenerative disorders. At present, there is a paucity of data regarding the extent to which such deficits relate to the progression of cognitive deficits and to clinically significant endpoints such as dementia. In this study, we followed 76 older adults, initially diagnosed with mild cognitive impairment, for a period of up to 3 years. Twenty-seven of these individuals (35.5%) progressed from mild cognitive impairment to dementia. An examination of baseline neuropsychological performance indicated lower baseline scores for object memory among those progressing to dementia. However, baseline Mini-Mental State Examination scores, delayed memory for passages, delayed visual memory, letter fluency, category fluency, Trails B and Block Design did not differ among study groups. In contrast, the Semantic Interference Test, a measure susceptible to vulnerability to proactive semantic interference showed the greatest baseline differentiation between those who progressed and those who did not progress to dementia. Further, scores on this measure predicted future progression to dementia with high accuracy. Vulnerability to proactive interference may be an early manifestation of an early dementing process and may have utility in predicting future progression to dementia.
Uterine Activity after Oral Mifepristone Administration in Human Pregnancies beyond 41 Weeks’ Gestation
Authors: Fassett Michael J. , Wing Deborah A.
Published: October 2007

Background/Aim: To examine the effect of oral mifepristone on uterine activity in postterm human pregnancies. Methods: As part of a randomized, placebo-controlled trial comparing 200 mg oral mifepristone to placebo for preinduction cervical ripening in women with well-dated pregnancies beyond 41 weeks’ gestation with unfavorable cervices, uterine activity was continuously recorded with external tocodynamometry and contraction frequency tabulated. Results: Ninety-seven women received mifepristone and 83 women received placebo. Uterine activity (uterine contractions/hour) was greater in the mifepristone than in the placebo group between 7 h (8.03 ± 0.48 vs. 5.90 ± 0.39, p = 0.001) and 24 h (8.53 ± 0.68 vs. 6.61 ± 0.46, p = 0.02) after dosing. Conclusion: Oral mifepristone administration to women with pregnancies beyond 41 weeks increases uterine activity in the absence of externally administered uterotonic agents.
Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome
Authors: Englund Hillevi , Annerén Göran , Gustafsson Jan , Wester Ulrika , Wiltfang Jens , Lannfelt Lars , Blennow Kaj , Höglund Kina
Published: October 2007

Background: Individuals with Down syndrome (DS) invariably develop Alzheimer’s disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-β (Aβ) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20–40 and 54 months of age. Results: Individual levels of the Aβ peptides, as well as total Aβ levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of Aβ in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the Aβ precursor APP, which leads to an overproduction of Aβ. Despite the increased CSF concentrations of Aβ, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of Aβ pathology preceding tau pathology in AD.
Reactivity of Shrimp Allergy-Related IgE Antibodies to Krill Tropomyosin
Authors: Nakano Shigeru , Yoshinuma Toshio , Yamada Toshihiro
Published: October 2007

Background: Krill, which morphologically resembles small shrimp, represents small ocean crustaceans and has been used for human consumption in Japan and some other countries. The major allergen in crustaceans has been reported to be tropomyosin, but the allergenicity of krill tropomyosin remains uncertain. Methods: Amino acid sequences of tropomyosin in two species of krill (Euphausia superba and E. pacifica) were deduced. Recombinant krill tropomyosins were produced in Escherichiacoli using a pCold IV vector system, and the cross-reactivity of shrimp allergy-related IgE to the recombinant tropomyosins and several animal protein extracts was assessed by immunoblotting. Results: The deduced amino acid sequences of the E. superba and E. pacifica tropomyosins (designated as Eup s 1 and Eup p 1, respectively) were 284 residues and showed significant homology to those of shrimp, lobster and crab tropomyosins. Shrimp allergy-related IgE reacted to approximately 38-kDa protein bands in krill (E. superba), shrimp, lobster and crab protein extracts but did not react to protein extracts from either mollusks or vertebrates. Furthermore, the IgE recognized rEup s 1 and rEup p 1 as 38-kDa protein bands, and absorption of the IgE with rEup s 1 removed IgE reactivity to recombinant tropomyosins and protein extracts from krill and shrimp. Conclusions: Krill tropomyosins included highly homologous sequences to previously reported IgE-binding epitopes in Pen a 1 (tropomyosin of Penaeus aztecus). The cross-reactivity in shrimp allergy-related IgE binding among krill, shrimp, lobster and crab tropomyosins was revealed. These observations suggest the potential allergenicity of krill tropomyosin.
A Comparison of Inflammatory Mediators Released by Basophils of Asthmatic and Control Subjects in Response to High-Affinity IgE Receptor Aggregation
Authors: Gilmartin Laura , Tarleton Christy A. , Schuyler Mark , Wilson Bridget S. , Oliver Janet M.
Published: October 2007

Background: In human blood basophils, cross-linking the high-affinity IgE receptor FcΕRI with multivalent antigen activates a signaling pathway leading to secretion of inflammatory mediators and cytokine production. Basophils are known to play an important role in the pathogenesis of asthma but there has been no comprehensive examination of the effectors these cells produce. Here a study of the transcription and release of a selection of chemokines and cytokines from basophils was undertaken. Methods: A Cartesian antibody array provided an effective method of assaying for multiple cytokines and chemokines simultaneously. Results were verified by RT-PCR and ELISA assays. This allowed the comparison of freshly prepared peripheral blood basophil responses to cross-linking of the high-affinity IgE receptor, with and without preincubation with IL-3. Results: Evidence that human blood basophils produce the chemokines MIP-5, eotaxin and GM-CSF was provided by antibody array and RT-PCR analyses. Preincubation with IL-3 enhanced the expression and release of IL-13, IL-8 and mRNA transcripts encoding MIP-5 and GATA2 in basophils from both asthmatic and control subjects. Leptin mRNA transcription, storage and release in basophils are described for the first time. Conclusions: Surveying cytokine and chemokines stored and released by peripheral blood basophils shows that asthmatic and control subjects share similar profiles even when their degranulation responses are distinct. Evidence is provided for the production of leptin, GM-CSF, eotaxin and MIP-5 by peripheral blood basophils. IL-3 preincubation enhances the production and release of IL-8 upon IgE receptor cross-linking.
Characterization of a Hypoallergenic Recombinant Bet v 1 Variant as a Candidate for Allergen-Specific Immunotherapy
Authors: Kahlert H. , Suck R. , Weber B. , Nandy A. , Wald M. , Keller W. , Cromwell O. , Fiebig H.
Published: October 2007

Background: Recombinant allergens and especially their hypoallergenic variants are promising candidates for a more effective and safer specific immunotherapy. Methods: Physicochemical and immunological characteristics of a folding variant of recombinant Bet v 1 (rBet v 1-FV) were investigated in comparison to natural Bet v 1 (nBet v 1) and the correctly folded recombinant Bet v 1 (rBet v 1-WT) by SDS-PAGE, size exclusion chromatography, multi-angle light scattering, circular dichroism, immunoblotting and enzyme allergosorbent test inhibition assay for detection of IgE reactivity and ELISA with Bet v 1-specific monoclonal antibodies. The functional IgE reactivity of the different Bet v 1 proteins was investigated using basophil activation in terms of CD203c expression and histamine release. T cell reactivity was investigated using T cell lines raised from birch pollen-allergic subjects against nBet v 1. Immunogenicity was investigated in mice. Results: Physicochemical characterization revealed purity, homogeneity and monomeric properties of rBet v 1-FV. Unlike nBet v 1 and rBet v 1-WT, rBet v 1-FV showed almost no IgE binding in immunoblots. The reduction of allergenicity was further proved by IgE-binding inhibition assays, basophil activation and histamine release. T cell reactivity was completely conserved, as demonstrated by proliferation of Bet v 1-specific T cell lines with multiple epitope specificities. rBet v 1-FV showed strong immunogenicity in mice. Conclusions: Due to its reduced IgE reactivity and decreased capacity to activate basophils, but retained T cell reactivity and strong immunogenicity, rBet v 1-FV proved to be a very promising candidate for specific immunotherapy in birch pollen-allergic subjects.
Pollen Grains Induce a Rapid and Biphasic Eczematous Immune Response in Atopic Eczema Patients
Authors: Eyerich Kilian , Huss-Marp Johannes , Darsow Ulf , Wollenberg Andreas , Foerster Stefanie , Ring Johannes , Behrendt Heidrun , Traidl-Hoffmann Claudia
Published: October 2007

Introduction: Eczematous reactions to type I allergy-inducing antigens are documented in a subgroup of patients with atopic eczema. Yet, the underlying immunological mechanisms are not well understood. Material and Methods: To delineate the effect of native pollen grains on human skin of healthy and atopic individuals we performed patch tests (atopy patch test with native pollen grains, PPT). Nickel patch tests (NPT) served as an established model of contact dermatitis. Skin site biopsies were taken 6–96 h after allergen application and investigated immunohistochemically. Results: Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, CD45RO+). This influx was detected earlier in the PPT reaction than in the immune response to nickel. A biphasic cytokine response could be detected in the PPT: IL-5 dominated in the early, IFN-γ in the late phase. The NPT was continuously dominated by IFN-γ. Dendritic cell subpopulations imitated the earlier kinetics of the mononuclear infiltrate. Discussion: Thus, pollen grains induce eczematous reactions in susceptible individuals. This reaction appears clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: Th2 and IgE in the early (24 h) and Th1 predominance in the late (96 h) phase.
Date Palm Pollen Allergoid: Characterization of Its Chemical-Physical and Immunological Properties
Authors: Mistrello G. , Harfi H. , Roncarolo D. , Kwaasi A. , Zanoni D. , Falagiani P. , Panzani R.
Published: October 2007

Background: Date palm (DP) pollen can cause allergic symptoms in people living in different countries. Specific immunotherapy with allergenic extracts by subcutaneous route is effective to cure allergic people. However, the risk of side effects has led to explore safer therapeutic modalities. The aim of our work was to evaluate IgE cross-reactivity between DP and autochthonous palm (European fan palm, EFP) pollen extracts, to chemically modify DP extract with potassium cyanate in order to obtain an allergoid, and to characterize it. Methods: By radioallergosorbent test inhibition, immunoblotting (IB) and skin prick test, in vitro and in vivo allergenic activities of native and modified DP extracts were compared. By SDS-PAGE and IB, we compared the protein profile and IgE-binding capacity of both native and modified DP, as well as of EFP extracts. By IB inhibition, IgE cross-reactivity of native DP and EFP extracts was evaluated. By ELISA, the capacity of modified DP-induced IgG to react with native DP extract was determined. Results: Radioallergosorbent test inhibition, IB and skin prick test results demonstrated that modified DP was significantly less allergenic than native DP extract. The SDS-PAGE profile showed that potassium cyanate treatment of DP extract did not alter the molecular weight of its components. In addition, no difference was observed between native DP and EFP extracts. Subsequent IB inhibition data evidenced the existence of a strong IgE cross-reactivity between native DP and EFP extracts. ELISA results indicated that the administration of modified DP in mice was able to induce specific IgG also recognizing native DP extract. Conclusions: Modified DP extract (allergoid) seems to be a good candidate for immunotherapy of patients affected by specific allergy.
Accumulation of Regulatory T Cells in Local Draining Lymph Nodes of the Lung Correlates with Spontaneous Resolution of Chronic Asthma in a Murine Model
Authors: Carson IV William F. , Guernsey Linda A. , Singh Anurag , Vella Anthony T. , Schramm Craig M. , Thrall Roger S.
Published: October 2007

Background: Mice sensitized to ovalbumin develop allergic airway disease (AAD) with short-term aerosol challenge; however, airway inflammation resolves with long-term aerosol challenge, referred to as local inhalational tolerance (LIT). Methods: We sought to determine if resolution of airway inflammation correlated with increases in lymphocyte subsets in local lung compartments, including putative regulatory T cells. Results: At the AAD stage, total numbers of T and B lymphocytes in bronchoalveolar lavage (BAL) were significantly increased above controls; however, at LIT, T and B lymphocytes were significantly reduced compared to AAD. In the lung tissue, the only alteration was a significant increase in CD4+ CD25+ T cells at AAD. In the hilar lymph node (HLN), CD4+ and CD4+ CD25+ T cells were significantly increased at AAD and LIT. In addition, CD8+ T cells were significantly elevated in the HLN at LIT, and CD19+ B cells were significantly increased at AAD. Adoptive transfer of HLN lymphocytes to lymphopenic mice confirmed that AAD lymphocytes could induce airway inflammation in response to aerosol challenge, whereas LIT lymphocytes were unable to do so. Depletion of CD4+ CD25+ T cells in vivo resulted in exacerbation of inflammation at AAD and LIT. CD4+ CD25+ T cells in the HLN also displayed suppressive activity in vitro. Additionally, T cells expressing Foxp3 were increased in the BAL and HLN during LIT. Conclusions: These results indicate that lymphocytes with regulatory functions are increased and sustained in local lung compartments at LIT and that their appearance correlates with the resolution of lung inflammation.