bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional characteristics of S1P receptors
Authors: Sanchez Teresa , Hla Timothy 
Published: May 2004

AbstractThe sphingosine‐1‐phosphate (S1P) family of G protein‐coupled receptors (GPCR) regulates essential cellular processes such as proliferation, migration, cytoskeletal organization, adherens junction assembly, and morphogenesis. S1P, a product from the breakdown of sphingomyelin, binds to the five members of this receptor family, S1P1, S1P2, S1P3, S1P4, and S1P5, previously referred to as endothelial differentiation gene (EDG)‐1, ‐5, ‐3, ‐6, and ‐8. S1P receptors are widely expressed in different tissues, so it is not surprising that the S1P receptor family regulates many physiological processes, such as vascular maturation, cardiac development, lymphocyte trafficking, and vascular permeability. FTY720, a new S1P receptor agonist, is undergoing clinical trials as an immunosuppressor. Understanding the physiological role of these receptors and the basics of the ligand‐receptor interaction will potentially provide new therapies to control a variety of diseases. © 2004 Wiley‐Liss, Inc.
A 32 kDa protein—whose phosphorylation correlates with oncogenic Ras‐induced cell cycle arrest in activated Xenopus egg extracts—is identified as ribosomal protein S6
Authors: Pian Jerry Pinghwa , Huang Tun‐Lan , Tsai Pei‐Chi , Shi Jian‐Peng , Cu Hong , Pan Bin‐Tao 
Published: May 2004

AbstractOncogenic Ras induces cell‐cycle arrest in mammalian cells and in fertilized Xenopus eggs. How oncogenic Ras induces cell‐cycle arrest remains unclear. We previously showed that oncogenic Ras induces cell‐cycle arrest in activated Xenopus egg extracts (cycling extracts) and that the induced cell‐cycle arrest correlates with hyperphosphorylation of a 32 kDa protein. However, the identity of the 32 kDa protein was not known. By using a sucrose density‐gradient centrifugation, Triton X‐100–acetic acid–urea (TAU)‐gel electrophoresis, composite agarose‐polyacrylamide gel electrophoresis (CAPAGE), SDS–PAGE, and partial tryptic peptide sequence analysis, the 32 kDa protein has now been identified as S6, a 40S subunit ribosomal protein. Hence, our results indicate that the oncogenic Ras‐induced cell‐cycle arrest is correlated with hyperphosphorylation of S6, suggesting that phosphorylation of S6 plays an important role in the induced cell‐cycle arrest. It has been shown that conditional deletion of gene encoding S6 in mammalian cells prevents proliferation, demonstrating the importance of S6 in cell proliferation. The exact role S6 plays in cell proliferation is unclear. However, phosphorylation of S6 has been implicated in the regulation of protein synthesis. Thus, our results are consistent with the concept that oncogenic Ras induces S6 phosphorylation to influence protein synthesis, thereby contributing to the cell‐cycle arrest. In addition, our results also demonstrate that composite agarose‐polyacrylamide gel electrophoresis is suitable for the separation of large molecular complexes. © 2004 Wiley‐Liss, Inc.
Hepatitis C virus replication in stably transfected HepG2 cells promotes hepatocellular growth and tumorigenesis
Authors: Sun Bill S. , Pan Jingbo , Clayton Marcy M. , Liu Jie , Yan Xiaoping , Matskevich Alexey A. , Strayer David S. , Gerber Michael , Feitelson Mark A. 
Published: May 2004

AbstractHepG2 cells stably transfected with a full‐length, infectious hepatitis C virus (HCV) cDNA demonstrated consistent replication of HCV for more than 3 years. Intracellular minus strand HCV RNA was present. Minus strand synthesis was NS5B dependent, and was sensitive to interferon alpha (IFNα) treatment. NS5B and HCV core protein were detectable. HCV stimulated HepG2 cell growth and survival in culture, in soft agar, and accelerated tumor growth in SCID mice. These mice became HCV RNA positive in blood, where the virus was also sensitive to IFNα. The RNA banded at the density of HCV, and was resistant to RNase prior to extraction. Hence, HCV stably replicates in HepG2 cells, stimulates hepatocellular growth and tumorigenesis, and is susceptible to IFNα both in vitro and in vivo. © 2004 Wiley‐Liss, Inc.
Adenosine stimulation of proliferation of breast carcinoma cell lines: Evaluation of the [3H]thymidine assay system and modulatory effects of the cellular microenvironment in vitro
Authors: Mujoomdar Michelle , Bennett Amy , Hoskin David , Blay Jonathan 
Published: May 2004

AbstractThe purine nucleoside adenosine is produced at increased levels in the tissues of solid cancers as a result of local hypoxia. Adenosine inhibits the cell‐mediated anti‐tumor immune response, promotes tumor cell migration and angiogenesis, and stimulates the proliferation of tumor cells. We examined the stimulatory effect of adenosine on DNA synthesis, cell cycle progression, and cell proliferation in MCF7 and T‐47D breast carcinoma cell lines in culture, and identified factors that modulate the growth response. The ability of adenosine to stimulate DNA synthesis, as measured by the incorporation of [3H]thymidine, was independent of the total radioactivity of the [3H]thymidine up to 10 μCi/ml, total thymidine concentrations up to 100 μM, and the labeling interval. It was also not affected by the presence of low‐molecular‐weight compounds (such as thymidine and adenosine) in the serum used to supplement the medium. Adenosine stimulated DNA synthesis and cell proliferation with an EC50 of 4–6 μM and a maximum response at 30–100 μM, when given as a single addition. The stimulatory effect of adenosine involved progression through the cell cycle and a genuine increase in cell number, in the absence of significant apoptotic or necrotic cell death. The mitogenic effect of adenosine was dependent upon the culture cell density, with an optimum adenosine response at around 50% of confluent density. The response was also highly dependent upon the form of the serum addition to the growth medium, with the best response elicited in the presence of low concentrations of nonfetal bovine serum, although adenosine was mitogenic under standard culture conditions. The effects of serum supplementation and cell density were not due to differences in the rate of adenosine metabolism by either serum or cellular enzymes, but appeared to result from changes in the sensitivity to adenosine of the cell population in response to environmental cues. We, therefore, find that adenosine is consistently mitogenic for human breast carcinoma cells, and that the [3H]thymidine incorporation assay is a valid measure of this response. The data are consistent with the stimulatory effect of adenosine on cell proliferation being modulated by the local cellular environment. © 2004 Wiley‐Liss, Inc.
Margins in extra‐abdominal desmoid tumors: A comparative analysis
Authors: Leithner Andreas , Gapp Markus , Leithner Katharina , Radl Roman , Krippl Peter , Beham Alfred , Windhager Reinhard 
Published: May 2004

AbstractBackground and ObjectivesThe main treatment of extra‐abdominal desmoid tumors remains surgery, but recurrence rates up to 80% are reported. The impact of microscopic surgical margin status according to the Enneking classification system is discussed controversially.MethodsTherefore, the authors screened the published literature for reliable data on the importance of a wide or radical excision of extra‐abdominal desmoid tumors. All studies with more than ten patients, a surgical treatment only, and margin status stated were included.ResultsOnly 12 out of 49 identified studies fulfilled the inclusion criteria. One hundred fifty‐two primary tumors were excised with wide or radical microscopic surgical margins, while in 260 cases a marginal or intralesional excision was performed. In the first group 41 patients (27%) and in the second one 187 patients (72%) developed a recurrence. Therefore, microscopic surgical margin status according to the Enneking classification system is a significant prognostic factor (P < 0.001).ConclusionsThe data of this review underline the strategy of a wide or radical local excision as the treatment of choice. Furthermore, as a large number of studies had to be excluded from this analysis, exact microscopic surgical margin status should be provided in future studies in order to allow comparability. J. Surg. Oncol. 2004;86:152–156. © 2004 Wiley‐Liss, Inc.
Groin soft tissue tumors—a challenge for local control and reconstruction: A prospective cohort analysis
Authors: Mack L.A. , Temple Walley J. , DeHaas W.G. , Schachar N. , Morris D.G. , Kurien E. 
Published: May 2004

AbstractBackground and ObjectivesGroin soft tissue tumors are associated with high local recurrence rates of 16–48% and postoperative complications in 40–68%. Neoadjuvant chemoradiation and aggressive reconstructive techniques were utilized to improve local control and complication rates in this challenging area.MethodsNine patients in this prospective series were treated with neoadjuvant chemoradiation (30 mg IV doxorubicin × 3d followed by 300 cGy/d × 10d) followed by surgery and two patients received radiation (5,000 cGy with tissue spacer) followed by surgery for tumors with a pelvic/retroperitoneal component. Surgery included resection plus reconstruction of the abdominal wall, myocutaneous flaps for large defects, and vascular reconstruction as necessary.ResultsThe 11 consecutive patients presented with Stage I (30%), II (40%), or III (30%) disease. Four patients (36%) were operated on for possible incarcerated hernia prior to referral and two (18%) presented with recurrent tumors. Pathology included 10 sarcomas and 1 desmoid tumor; tumor grade was low (30%), moderate (40%), or high (30%). Local control (mean follow‐up 55 months; minimum follow‐up 36 months) and limb salvage rate was 100%. Minor wound complications not requiring re‐operation occurred in three patients, lymphedema in two, and there were no postoperative hernias.ConclusionsPreoperative therapy provides excellent local control of groin soft tissue tumors. Current surgical techniques allow extensive resection with limb salvage, dependable primary wound healing and long‐term integrity of the abdominal wall. J. Surg. Oncol. 2004;86:147–151. © 2004 Wiley‐Liss, Inc.
Improving the physical status and quality of life of women treated for breast cancer: A pilot study of a structured exercise intervention
Authors: Turner Jane , Hayes Sandi , Reul‐Hirche Hildegard 
Published: May 2004

AbstractBackground and ObjectivesThis pilot project assessed the acceptability of a mixed‐type, moderate‐intensity exercise programme following breast cancer treatment, and the impact on presence of lymphoedema, fitness, body composition, fatigue, mood and quality of life.MethodsTen women completed the programme and measures of fitness (sub‐maximal ergometer test), body composition (bio‐electrical impedance), lympoedema (bio‐electrical impedance and arm circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety and Depression Scale), quality of life (FACT‐B) and general well‐being, at baseline, completion of the programme, and 6‐week and 3‐month follow‐up.ResultsParticipation in the programme caused no adverse effect on the presence of lymphoedema. There was a trend towards reduction in fatigue and improved quality of life across the testing phases. Women rated the programme extremely favourably, citing benefits of the support of other women, trained guidance, and the opportunity to experience different types of exercise.ConclusionsA mixed‐type, moderate‐intensity exercise program in a group format is acceptable to women following breast cancer treatment, with the potential to reduce fatigue and improve quality of life, without exacerbating or precipitating lymphoedema. This pilot work needs to be confirmed in larger randomised studies. J. Surg. Oncol. 2004;86:141–146. © 2004 Wiley‐Liss, Inc.
Kinetics and mechanism of the pyridinolysis of aryl dithiobenzoates in acetonitrile
Authors: Oh Hyuck Keun , Lee Jae Myon , Lee Hai Whang , Lee Ikchoon 
Published: May 2004

AbstractThe kinetics and mechanism of the aminolysis of aryl dithiobenzoates (RC(S)SC6H4Z; R = Ph) with pyridines (XC5H4N) in acetonitrile at 60.0°C have been studied. A biphasic Brönsted plot is obtained with a change in slope from a large value (βX ≅ 0.7–0.8) to a small value (βX ≅ 0.2) at pKa° = 5.2, which is interpreted to indicate a change of the rate‐determining step from breakdown to formation of the zwitterionic tetrahedral intermediate, T±, at pKa = 5.2 as the pyridine basicity is increased. Rates are compared with those corresponding values for aryl dithioacetates (R = Me). The faster rates for R = Me than for R = Ph, for the rate‐limiting formation of T±, can be attributed to the hyperconjugative charge transfer effect of the Me group, pseudo‐πMe → π*C=S. Clear‐cut change in the cross‐interaction constants, ρXZ, from +1.47 to −0.20 supports the proposed mechanistic change. The breakpoint at pKa° = 5.2 for R = Ph in the present work is in agreement with those for the pyridinolysis of R = Me and 2‐furyl, and attests to the insignificant effect of acyl group, R, on the breakpoint. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 434–440, 2004
Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism
Authors: Foltynie Thomas , Goldberg Terry E. , Lewis Simon G.J. , Blackwell Andrew D. , Kolachana Bhaskar S. , Weinberger Daniel R. , Robbins Trevor W. , Barker Roger A. 
Published: May 2004

AbstractParkinson's disease (PD) patients show a range of executive deficits involving dopaminergic transmission in the prefrontal cortex. In this study, we have investigated the impact of catechol‐O‐methyl‐transferase (COMT) val158met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. Motor and cognitive assessments were performed on 288 patients as part of a population‐based study of PD. These patients were subsequently genotyped for the COMT val158met polymorphism. Patients with high activity COMT genotypes performed significantly better at the TOL task than those with low activity genotypes. Subgroup analyses suggest that this effect is greatest in patients exposed to dopaminergic agents. We hypothesise that the inferior performance in patients with the low activity COMT genotype is attributable to a state of relative hyperdopaminergic activity in the dorsolateral prefrontal cortex compared with that in the striatum. We suggest that polymorphisms of common genes, which regulate central nervous system dopaminergic transmission, can influence some of the phenotypic manifestations of PD. © 2004 Movement Disorder Society
Alien limb syndrome and moya–moya disease
Authors: Rabbani Omid , Bowen Lennon E. , Watson Robert T. , Valenstein Edward , Okun Michael S. 
Published: May 2004

AbstractWe present the case of a 29‐year‐old woman with an alien limb and callosal disconnection syndrome who was diagnosed with moya–moya disease. We discuss the potential mechanisms responsible for the alien limb syndrome. © 2004 Movement Disorder Society
Myositis in a patient with large granular leukocyte leukemia
Authors: Rosche Berit , Jacobsen Marc , Cepok Sabine , Barth Peter , Sommer Norbert , Hemmer Bernhard 
Published: May 2004

AbstractWe describe the case of a 58‐year‐old patient with subacute progressive weakness in both legs accompanied by recurrent opportunistic infections. White cell count was normal, but immunophenotyping revealed an increased number of CD8+ T cells and deficiency of natural killer cells, B cells, and CD4+ T cells in the peripheral blood. Large granular leukocyte (LGL) leukemia was diagnosed based on a clonal T‐cell receptor rearrangement. Muscle biopsy demonstrated severe myositis with extensive CD8+ T‐cell infiltrates. Since no evidence of microbial muscle infection was found, autoimmune myositis was diagnosed. Immunosuppressive treatment resulted in clinical improvement and normalization of creatine kinase (CK) serum levels. The immunological phenotype of the patient and the positive response to treatment adds further to the concept that CD8+ T cells mediate disease in autoimmune myositis. Muscle Nerve 29: 873–877, 2004
Functional activity and expression of inducible nitric oxide synthase (iNOS) in muscle of the isolated distal colon of mdx mice
Authors: Vannucchi Maria Giuliana , Corsani Letizia , Azzena Gian Battista , Faussone‐Pellegrini Maria Simonetta , Mancinelli Rino 
Published: May 2004

AbstractThe inducible isoform of nitric oxide (NO) synthase (iNOS), expressed in endothelium, epithelium, and inflammatory cells, produces a large amount of NO. Previous studies on mouse intestine indicate that a muscular iNOS may have a role in the storage of intraluminal content. In this study we investigated the presence and function of iNOS in the colonic smooth muscle cells of 2‐ and 12‐month‐old dystrophic (mdx) mice. By using an in vitro isovolumic technique, and immunohistochemical and Western blot analysis, we demonstrated that iNOS is expressed and active in the smooth muscle cells of normal mouse and defective in young adult (2‐month‐old) mdx mice. Therefore, an altered activity of the muscle iNOS might explain the motility disorders observed in the colon of mdx mice and, from a clinical point of view, the impairment of intestinal function in dystrophic patients. Muscle Nerve 29: 795–803, 2004
A novel central motor conduction abnormality in D90A‐homozygous patients with amyotrophic lateral sclerosis
Authors: Osei‐Lah Abena D. , Turner Martin R. , Andersen Peter M. , Leigh P. Nigel , Mills Kerry R. 
Published: May 2004

AbstractPatients with amyotrophic lateral sclerosis (ALS) who are homozygous for the D90A SOD1 mutation have been noted to have central motor abnormalities distinct from those of patients with idiopathic ALS. We stimulated the motor cortex of ten patients homozygous for the D90A SOD1 mutation, using transcranial magnetic stimulation (TMS), and recorded the response evoked in the right first dorsal interosseous muscle when the muscle was at rest and when voluntarily active. A subgroup of patients had two distinct evoked responses when the cortex was stimulated at high intensity with the muscle at rest. When the muscle was modestly contracted, the first of these responses disappeared, whereas the second response was facilitated. Both fast and slow components of the corticospinal tract were usually intact and excited by TMS in these patients. We propose that there is an abnormality of intracortical or intraspinal inhibition in a subgroup of D90A SOD1 ALS patients, which suppresses fast‐conducted activity when the muscle is active. Apart from further defining the phenotype of familial ALS, these findings may have importance in understanding the pathogenesis of central motor abnormalities in these patients. Muscle Nerve 29: 790–794, 2004
Influence of repetitive hand movements on intracortical inhibition
Authors: Schubert Margot , Kretzschmar Elke , Waldmann Guido , Hummelsheim Horst 
Published: May 2004

AbstractRepetitive movements have been reported to induce task‐specific changes of intracortical inhibition and facilitation, but the mechanism operating shortly after hand movement is unclear. Transcranial magnetic single and paired stimuli (2 ms) were applied to 15 healthy subjects at rest and 1 s after repetitive (every 6 s) active and passive hand extensions. Motor evoked potentials (MEPs) were recorded from hand extensors (agonists) and flexors (antagonists). A strong overall inhibitory effect was observed after applying paired stimuli. In agonists only, active movements produced significantly larger MEPs. Inhibition, however, did not differ between active or passive movements and rest. This suggests that MEP increases produced by active movements in agonists are not caused by disinhibition, but are rather due to excitation (facilitation). This finding may also have implications for future studies evaluating the preferential activation of target muscles in physiotherapy. Muscle Nerve 29: 804–811, 2004
Functional relationships of central and peripheral muscle alterations in multiple sclerosis
Authors: Ng A. V. , Miller R. G. , Gelinas D. , Kent‐Braun J. A. 
Published: May 2004

AbstractThe functional implications of central motor impairment and peripheral muscle alterations in multiple sclerosis are unclear. Muscle strength, central and peripheral activation, and symptomatic fatigue were investigated in 16 patients with multiple sclerosis (MS) and 18 control subjects. Voluntary and electrically stimulated isometric contractions were obtained from the ankle dorsiflexor muscles. Maximal voluntary contraction (MVC) was 27% lower in MS patients than controls, although electrically stimulated force was similar. Muscle fat‐free cross‐sectional area (CSA) was similar in both groups. These data indicate central activation impairment in MS. Such impairment in MS was further demonstrated by decreased foot‐tap speed, rate of voluntary force development, and central activation ratio. Peripheral activation changes in MS patients were modest. Although stimulated tetanic force was similar, force relaxation was slower in MS patients compared to controls, resulting in a left‐shifted force–frequency relationship in MS. Motor function changes were not associated with fatigue but were associated with impaired ambulation. Thus, weakness and walking impairment, but not fatigue, were related to impaired central activation in MS. These findings may help optimize rehabilitation strategies designed to improve function in persons with MS. Muscle Nerve 29: 843–852, 2004
Receptor for advanced glycation endproduct (RAGE)–mediated nuclear factor‐κB activation in vasculitic neuropathy
Authors: Haslbeck Karl‐Matthias , Bierhaus Angelika , Erwin Schliecher , Kirchner Annette , Nawroth Peter , Schlötzer Ursula , Neundörfer Bernhard , Heuss Dieter 
Published: May 2004

AbstractBinding of ligands to the receptor for advanced glycation endproducts (RAGE) results in activation of the proinflammatory transcription factor nuclear factor‐kappaB (NF‐κB) and subsequent expression of NF‐κB–regulated cytokines. In order to determine whether engagement of RAGE contributes to the pathogenesis of vasculitic neuropathy, we studied the presence of the RAGE ligand Nϵ‐(carboxymethyl)lysine (CML), the receptor itself, NF‐κB, and interleukin‐6 (IL‐6) in sural nerve biopsies of 12 patients with vasculitic neuropathies and 12 controls. In the patients, CML, RAGE, NF‐κB, and IL‐6 were localized in mononuclear cells, epineurial and endoneurial vessels and the perineurium. CML, RAGE, NF‐κB, and IL‐6 were expressed by CD4+, CD8+, and CD68+ cells invading the nerves. Controls showed only weak staining. These data suggest that the RAGE pathway plays a critical proinflammatory role in vasculitic neuropathy. Muscle Nerve 29: 853–860, 2004