bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal residues in linker domain of syntaxin 1A required for binding affinity to Ca2+/calmodulin‐dependent protein kinase II
Authors: Nomura Kazushige , Ohyama Akihiro , Komiya Yoshiaki , Igarashi Michihiro 
Published: March 2003

AbstractThe linker domain is important for the conformational change syntaxin 1A, which enables it to act as a SNARE for exocytosis. We found that when applied exogenously, the linker domain is a potent inhibitor of exocytosis through inhibiting interaction between autophosphorylated CaMKII and endogenous syntaxin 1A (Ohyama et al. [2002] J. Neurosci. 22:3342–3351). To identify the simplest and the most potent inhibitor for exocytosis, we further characterized the linker domain and determined the minimal number of residues required for CaMKII binding. The minimal length of the CaMKII‐binding site was 145–172 residues and a loss of G172 considerably weakened affinity for CaMKII. The basic amino acid clusters, R151 and K146, were indispensable for binding, whereas R148 was not. A comparison of the CaMKII‐binding in several syntaxin isoforms revealed that the substitution of S162 attenuated CaMKII‐binding activity. These results suggest that S162 is an important residue as well as the basic amino acid cluster within region 145–172 of the linker domain. © 2003 Wiley‐Liss, Inc.
Growth arrest of PC12 cells by nerve growth factor is dependent on the phosphatidylinositol 3‐kinase/Akt pathway via p75 neurotrophin receptor
Authors: Ito Hisanori , Nomoto Hiroshi , Furukawa Shoei 
Published: March 2003

AbstractWe recently isolated mutant PC12 cell clones (PC84 cells) by transfection of PC12 cells with nerve growth factor (NGF) cDNA. These cells secreted active NGF and extended short processes, but proliferated faster than the parental PC12 cells. Because the expression level of p75, a low‐affinity receptor for NGF, was significantly low, we suspected that NGF signaling via p75 was necessary for the growth arrest of the PC12 cells, and this was shown to be the case by repressing p75 function in PC12 cells. In this study, we examined the downstream signaling of p75, which would ultimately evoke the growth arrest. NGF is known to induce rapid phosphorylation of MAP kinase and Akt in PC12 cells, whereas in PC84 cells, MAP kinase was phosphorylated but the phosphorylation level of Akt was very low under the serum‐free condition. This finding suggested that the low expression level of p75 in PC84 cells was the reason for the low Akt activation. Because Akt is known to be activated via phosphatidylinositol (PI) 3‐kinase, we treated PC12 cells with a PI3‐kinase inhibitor, Wortmannin, and found these cells did not cease proliferation in the presence of NGF. Furthermore, anti‐p75 neutralizing antibody reduced NGF‐induced phosphorylation of Akt in PC12 cells under the serum‐free condition. Because we had already shown that PC12 cells treated with anti‐p75 neutralizing antibody did not cease proliferation in the presence of NGF, these results suggest that NGF activates Akt via p75, which is necessary for the NGF‐induced growth arrest of PC12 cells. © 2003 Wiley‐Liss, Inc.
Nerve growth factor regulates neuroectodermal tumor cell responses to mitogenic growth factors
Authors: Castellon Raquel , Mirkin Bernard L. 
Published: March 2003

AbstractPrevious studies showed that nerve growth factor (NGF) decreases the proliferation of neuroectodermal tumor (NET) cells (C‐1300 and Neuro2A murine neuroblastoma, PC12 rat pheochromocytoma) within 5–7 days in a dose‐dependent manner. This effect is regulated by the concentration of serum in the culture medium. Therefore, we hypothesized that NGF exerts its antimitogenic activities by interfering with the proliferative action of other growth factors. We studied the effects of short‐term vs. long‐term as well as endogenous vs. exogenous NGF on NET cell proliferation in response to various mitogenic growth factors. Retrovirus‐mediated transfer of the β‐NGF gene into NET cells activated TrkA and consistently decreased their proliferative responses to insulin‐like growth factor (IGF)‐I, IGF‐II, fibroblast growth factor‐2, and epidermal growth factor (EGF), down‐regulating EGF and IGF‐I binding sites. It also decreased tyrosine phosphorylation of ERK‐1, STAT3, and EGF or IGF receptors after treatment with IGF‐I or EGF. Long‐term incubation of NET cells with NGF mimicked the responses induced by β‐NGF gene transfer, albeit in a reversible manner. Short‐term NGF treatment augmented the proliferative responses to IGF‐I or EGF by enhancing cell survival. It also increased tyrosine phosphorylation of signal transducing proteins after exposure to IGF or EGF, an effect opposite to that of long‐term NGF treatments. Hence, long‐term NGF exposure in vitro might better reproduce the effects of NGF in vivo than short‐term treatments. Only long‐term exposure to NGF decreased the responses of NET cells to mitogenic growth factors by down‐regulating their receptors and attenuating signal transduction events required for cell proliferation. These results suggest that NGF could exert similar actions on cellular responses to growth factors in vivo. © 2003 Wiley‐Liss, Inc.
TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress
Authors: Hewett Jeffrey , Ziefer Philipp , Bergeron Daniele , Naismith Teri , Boston Heather , Slater Damien , Wilbur Jeremy , Schuback Deborah , Kamm Christoph , Smith Nicole , Camp Sara , Ozelius Laurie J. , Ramesh Vijaya , Hanson Phyllis I. , Breakefield Xandra O. 
Published: March 2003

AbstractMost cases of early‐onset torsion dystonia are caused by deletion of GAG in the coding region of the DYT1 gene encoding torsinA. This autosomal dominant neurologic disorder is characterized by abnormal movements, believed to originate from neuronal dysfunction in the basal ganglia of the human brain. The torsins (torsinA and torsinB) are members of the “ATPases associated with a variety of cellular activities” (AAA+) superfamily of proteins that mediate chaperone and other functions involved in conformational modeling of proteins, protection from stress, and targeting of proteins to cellular organelles. In this study, the intracellular localization and levels of endogenous torsin were evaluated in rat pheochromocytoma PC12 cells following differentiation and stress. TorsinA, apparent MW 37 kDa, cofractionates with markers for the microsomal/endoplasmic reticulum (ER) compartment and appears to reside primarily within the ER lumen based on protease resistance. TorsinA immunoreactivity colocalizes with the lumenal ER protein protein disulfide isomerase (PDI) and extends throughout neurites. Levels of torsinA did not increase notably in response to nerve growth factor‐induced differentiation. None of the stress conditions tested, including heat shock and the unfolded protein response, affected torsinA, except for oxidative stress, which resulted in an increase in the apparent MW of torsinA and redistribution to protrusions from the cell surface. These findings are consistent with a relatively rapid covalent modification of torsinA in response to oxidative stress causing a change in state. Mutant torsinA may interfere with and/or compromise ER functions, especially in dopaminergic neurons, which have high levels of torsinA and are intrinsically vulnerable to oxidative stress. © 2003 Wiley‐Liss, Inc.
Poly(L‐Lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions
Authors: Ngo Teri‐T B. , Waggoner Paula J. , Romero Andres A. , Nelson Kevin D. , Eberhart Robert C. , Smith George M. 
Published: March 2003

AbstractAfter injury, axonal regeneration occurs across short gaps in the peripheral nervous system, but regeneration across larger gaps remains a challenge. To improve regeneration across extended nerve defects, we have fabricated novel microfilaments with the capability for drug release to support cellular migration and guide axonal growth across a lesion. In this study, we examine the nerve repair parameters of non‐loaded filaments. To examine the influence of packing density on nerve repair, wet‐spun poly(L‐Lactide) (PLLA) microfilaments were bundled at densities of 3.75, 7.5, 15, and 30% to bridge a 1.0‐cm gap lesion in the rat sciatic nerve. After 10 weeks, nerve cable formation increased significantly in the filament bundled groups when compared to empty‐tube controls. At lower packing densities, the number of myelinated axons was more than twice that of controls or the highest packing density. In a consecutive experiment, PLLA bundles with lower filament‐packing density were examined for nerve repair across 1.4‐ and 1.8‐cm gaps. After 10 weeks, the number of successful regenerated nerves receiving filaments was more than twice that of controls. In addition, nerve cable areas for control groups were significantly less than those observed for filament groups. Axonal growth across 1.4‐ and 1.8‐cm gaps was more consistent for the filament groups than for controls. These initial results demonstrate that PLLA microfilaments enhance nerve repair and regeneration across large nerve defects, even in the absence of drug release. Ongoing studies are examining nerve regeneration using microfilaments designed to release neurotrophins or cyclic AMP. © 2003 Wiley‐Liss, Inc.
Impact of adjuvant chemotherapy in the long‐term outcome of patients with resected gastric cancer
Authors: Grau Juan J. , Martín Marta , Fuster José , Pera Manuel , García‐Valdecasas Juan C. , Bombí Josep A. , Bordas José M. , Alcobendas Felipe , Grande Luis , Estapé Jordi 
Published: March 2003

AbstractBackground and ObjectivesWe analyzed in a retrospective analysis whether adjuvant chemotherapy with mitomycin (MMC) alone or with Tegafur (TG) is associated with long‐term survival benefit in resected gastric cancer. Other prognostic factors are compared.MethodsFrom 1977 to 1998, 314 consecutive totally resected gastric adenocarcinoma patients have been included in a survival study. In 151 patients no adjuvant therapy was given. In 163 patients, four courses of adjuvant chemotherapy was given, 109 of them with MMC, 10–20 mg/m2 i.v. every 6 weeks and the other 54 with MMC plus TG, 500 mg/m2 p.o. day for 42 consecutive days. Univariate and multivariate survival analyses were performed.ResultsSurvival benefit was seen in patients who had received adjuvant chemotherapy compared with the controls (52% vs. 30% alive at the end of the study, relative risk = 0.46, 95% CI: 0.33–0.62, P < 0.0001), women (52% vs. 35%, RR = 0.83, 95% CI: 0.71–0.98, P = 0.0342) and increment of staging IB, II, IIIA, or IIIB (80, 56, 24 vs. 13%, respectively, RR = 1.83, 95% CI: 1.42–2.35, P < 0.0001). Better prognosis of node‐negative patients was observed only in univariate analysis.ConclusionsAfter curative surgery, adjuvant chemotherapy with mitomycin C, both alone or combined with Tegafur, improved the long‐term cure rate over no postoperative chemotherapy in locally advanced gastric cancer patients. This benefit was not influenced by other prognostic factors. J. Surg. Oncol. 2003;82:234–240. © 2003 Wiley‐Liss, Inc.
Role of skip metastasis to mediastinal lymph nodes in non‐small cell lung cancer
Authors: Prenzel Klaus L. , Mönig Stefan P. , Sinning Jan M. , Baldus Stefan E. , Gutschow Christian A. , Grass Guido , Schneider Paul M. , Hölscher Arnulf H. 
Published: March 2003

AbstractBackgroundSkip metastasis to mediastinal lymph nodes is a well‐known phenomenon in non‐small cell lung cancer (NSCLC). Little is reported in the literature about its clinical importance. It is still under discussion whether any prognostic differences exist between resected NSCLC with either skip metastases or continuous mediastinal lymph node metastases (N2).Patients and MethodsWe analyzed retrospectively the data of 45 patients with a pN2‐stage, who underwent resection for NSCLC. Seventeen of these patients (37.8%), showing no metastatic involvement of hilar (N1) lymph nodes, were compared to the remaining 28 patients with infiltration of hilar nodes (N1) as well as N2 nodes.ResultsMultivariate analysis showed no statistically significant difference between the skip metastasis and the continuous N2 group regarding sex, age, histology, T‐ or M‐status. The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe (n = 12, 71%) compared to the lower lobe (n = 5, 29%). This difference was not statistically significant. In patients with a non‐continuous lymph node spread, 29 out of 119 resected mediastinal lymph nodes were infiltrated (1.7 per patient, range: 1–10). Compared to 83 metastatic involved lymph nodes out of 198 resected mediastinal nodes (three per patient, range: 1–10) in patients with involvement of N1 and N2 nodes (P = 0.034, Mann–Whitney test). The 5‐year survival rate of pN2 patients with skip metastasis was 41% compared to 14% in patients with involvement of N1 and N2 nodes (P = 0.019).ConclusionspN2 patients with mediastinal lymph node skip metastasis have a more favorable prognosis compared to pN2 patients with continuous infiltration of the regional lymph nodes. Patients with a continuous lymph node involvement show an increased number of infiltrated mediastinal lymph nodes per patient compared to patients with a non‐continuous spread. Skip metastasis is an independent prognostic factor of survival. The presence of skip metastasis seems to be a unique subgroup of pN2 disease in NSCLC. J. Surg. Oncol. 2003;82:256–260. © 2003 Wiley‐Liss, Inc.
Surgery‐related shedding of breast cancer cells as determined by RT‐PCR assay
Authors: Hu Xi‐Chun , Loo Wings T.Y. , Chow Louis W.C. 
Published: March 2003

AbstractBackground and ObjectivesSurgery could result in the shedding of cancer cells into the circulation. These cells were investigated with reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay for cytokeratin 19 (CK19) and β‐subunit of human chorionic gonadotropin (β‐hCG).Patients and MethodsPeripheral blood was sampled from 49 patients with breast cancer before operation (d−1), 1 day after operation (d1), and 7 days after operation (d7). Total RNA was extracted from peripheral blood mononuclear cells, followed by RT‐PCR assay. The products for β‐hCG were digested with Sty I endonuclease. The patients were followed up for a median of 33 months for signs of recurrence and metastasis.ResultsThe results for CK19 at d−1, d1, and d7 were 8.2, 20.4, and 10.2%, respectively. For β‐hCG, the corresponding results were 12.2, 26.5, and 16.3%, respectively. There was a higher positive rate in d1 samples than in d−1 samples for CK19 and β‐hCG (P < 0.05 and P = 0.092, respectively). Conversions of signals from being negative to positive were found in all stages. These did not demonstrate a statistical correlation with prognostic factors associated with a poor prognosis. Only two of the five recurrence occurred in the 15 patients with the signal conversions, while the other three occurred in the patients showing no signals in all samples.ConclusionsCancerous breast cells that enter into the blood circulation as a result of an operation are unlikely to be involved in the formation of metastatic deposits. J. Surg. Oncol. 2003;82:228–232. © 2003 Wiley‐Liss, Inc.
Detection of disseminated tumour cells in bone marrow of patients with isolated liver metastases from colorectal cancer
Authors: Bjørnland Kristin , Flatmark Kjersti , Mala Tom , Mathisen Øystein , Bakka Arne , Aasen Ansgar O. , Bergan Anstein , Søreide Odd , Fodstad Øystein 
Published: March 2003

AbstractBackground and ObjectivesIn colorectal cancer (CRC) patients, tumour recurrence is common following potentially curative surgery for liver metastases. This may be caused by occult tumour cells present at the time of surgery. Dissemination of micrometastatic cells may occur early in patients with solid cancer, and micrometastases may signify a poor prognosis. The aim of the present study was to evaluate the frequency of micrometastatic cells in the bone marrow of patients with potentially resectable liver metastases.MethodsTwenty millilitres of bone marrow was aspirated from both anterior iliac crests from 48 patients. Mononuclear cells were isolated and incubated with superparamagnetic Dynabeads® coated with an anti‐epithelial monoclonal antibody (MOC31). Magnetically selected cells were identified by light microscopy as cells with bead rosettes (>5 beads/cell).ResultsMicrometastatic tumour cells were identified in four of 48 (8%) patients who all had their liver metastases surgically removed. Two of the four died after 17 and 18 months, respectively, whereas two are alive after 10 and 12 months. None of the 19 inoperable patients had micrometastases.ConclusionsThe frequency of bone marrow micrometastases in patients with clinically isolated liver metastases from CRC was low. This is biologically interesting, but bone marrow status should not affect current treatment protocols. J. Surg. Oncol. 2003;82:224–227. © 2003 Wiley‐Liss, Inc.
Metastatic pattern of lymph node and surgery for gastric stump cancer
Authors: Han Shao‐Liang , Hua Ya‐Wei , Wang Cheng‐Hu , Ji She‐Qing , Zhuang Jing 
Published: March 2003

AbstractBackground and ObjectivesMetastatic pattern of lymph node (LN) and surgery options for gastric stump cancer (GSC) remain controversial. The aim of this study was to investigate LN metastasis and lymphadenectomy for GSC for curative purposes.MethodsSixty‐seven patients with GSC were analyzed retrospectively.ResultsThe metastatic rates of LN were as follows: 63.3% in right cardia (No. 1), 33.3% in left cardia (No. 2), 75.0% in lesser curvature (No. 3), 53.3% in greater curvature (No. 4), 40.0% in celiac artery (No. 9), 60.0% in splenic hilus (No. 10), 72.7% in splenic artery (No. 11), 36.1% in hepatoduodenal ligament (No. 12), 8.3% in retropancreatic (No. 13), 21.4% in para‐aortic (No. 16), 50% in supra‐diaphragm (No. 111), 16.7% in LN within jejunal mesentery, respectively. All nine patients who only received simple laparotomy died within 1 year. The overall 5‐year survival rate of GSC was 17.9% (12/67), including 100% for stage I, 80.0% for stage II, 12.1% for stage III, and 0% for stage IV. Moreover, the 5‐year survival rate (36.7%, 11/30) for curative patients was significantly better than that (3.6%, 1/28) of non‐curative patients (χ2 = 7.76, P < 0.01).ConclusionsOur results imply that GSC has a wide range of LN metastases, including LN within jejunal mesentery in B‐II reconstruction cases, and curable resection may obtain better results. Therefore, we suggest that radical operation for B‐I patients needs removal of gastroduodenectomy anastomosis and the above LNs, and that B‐II patients need removal of 10 cm of jejunum besides gastrojejunostomy anastomosis, and clearance of LN within its mesentery, in addition to B‐I GSC. J. Surg. Oncol. 2003;82:241–246. © 2003 Wiley‐Liss, Inc.
Control of Biodegradability of Polylactide via Nanocomposite Technology
Authors: Ray Suprakas Sinha , Yamada Kazunobu , Okamoto Masami , Ueda Kazue 
Published: March 2003

AbstractPolymer/layered silicate nanocomposite technology is not only suitable for the significant improvement of mechanical and various other materials properties of virgin polymers, it is also suitable to enhance the rate of biodegradation of biodegradable polymers such as polylactide. The biodegradability of polylactide in nanocomposites completely depends upon both the nature of pristine layered silicates and surfactants used for the modification of layered silicate, and we can control the biodegradability of polylactide via judicious choice of organically modified layered silicate.
Biodegradation of neat PLA and various PLA/OMLS nanocomposites recovered from compost with time.magnified imageBiodegradation of neat PLA and various PLA/OMLS nanocomposites recovered from compost with time.
Applicability of Frozen Gels from Ultra High Molecular Weight Polyethylene and Paraffin Waxes as Shape Persistent Solid/Liquid Phase Change Materials
Authors: Beginn Uwe 
Published: March 2003

AbstractUltra high molecular weight polyethylene (UHMW‐PE) physically gels molten paraffin waxes (PW) at concentrations exceeding 0.5 wt.‐%. In the composites the paraffin wax crystallises without destruction of the UHME‐PE gel network. Above the melting transition of the paraffin compound the capillary forces prevent the liquid wax from free flow. The composites can be processed by melt extrusion, and injection moulding above the melting temperature of the gel at 116 °C. The thermal and mechanical properties of these UHMW‐PE/paraffin composites have been characterised regarding their applicability as shape persistent phase change materials (PCM). The UHMW‐PE/PW gels can store, and release enthalpies up to 200 J/g at the melting temperature of the PW. In the gel state the liquid alkane can leave the gel when in direct contact to porous materials, and the gels mechanical strength are lower than that of standard polymers. These drawbacks are proposed to overcome by formation of PCM/polymer, or PCM/metal laminates.Schematic cross section of a proposed PCM laminate consisting of a polymer top‐ and bottom layer enclosing the UHMW‐PE/paraffin gel.magnified imageSchematic cross section of a proposed PCM laminate consisting of a polymer top‐ and bottom layer enclosing the UHMW‐PE/paraffin gel.
Effect of Soft Segment Length and Chain Extender Structure on Phase Separation and Morphology in Poly(urethane urea)s
Authors: Gisselfält Katrin , Helgee Bertil 
Published: March 2003

AbstractThe phase separation and morphology in poly(urethane urea)s were investigated as soft segment length and chain extender structure were varied. Increases in soft segment length led to increased phase separation that resulted in greater mobility of the soft segment. This was shown by lower soft segment glass transition temperatures in differential scanning calorimetry (DSC) as well as a shift of Emax″ and tan δmax to lower temperatures. Also the structure of the chain extender affected the degree of phase separation and mixing of the soft and the hard blocks in an interphase. Atomic force microscopy (AFM) was used to visualize the structure of the phase‐separated domains. The hard domains were in the form of spheres 5–10 nm, or long needles 5 nm thick and 50–300 nm long. As the soft segment length increased, there were more pure soft segment phase areas between the hard domains. At high hard segment content, a larger scale structure was found, consisting of both hard and soft segments.DSC thermograms of poly(urethane urea)s containing different soft segment lengths.magnified imageDSC thermograms of poly(urethane urea)s containing different soft segment lengths.
Oscillatory nature of human basal ganglia activity: Relationship to the pathophysiology of Parkinson's disease
Authors: Brown Peter 
Published: March 2003

AbstractAlterations of basal ganglia physiology in parkinsonism may consist of two elements, an increase in the firing rate of neurones and a change in the pattern of synchronisation of discharges between neurones. Recent findings suggest the presence of two principal modes of synchronised activity within the human subthalamo‐pallidal‐thalamo‐cortical circuit, at <30 Hz and >60 Hz. These oscillations are dynamically and systematically modulated by task, thereby suggesting a functional role in movement. More importantly, the two frequency modes are inversely affected by movement, consistent with opposing actions, and differentially expressed according to the prevailing level of dopaminergic activity. It is argued that the balance between these modes determines the effects of basal ganglia‐thalamocortical projections on the motor areas of the cortex. The lower frequency oscillations facilitate slow idling rhythms in the motor areas of the cortex, whereas synchronisation at high frequency restores dynamic task‐related cortical ensemble activity in the gamma band.© 2002 Movement Disorder Society