bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of electrophysiological and morphological characteristics of enteric neurons in the mouse colon
Authors: Nurgali Kulmira , Stebbing Martin J. , Furness John B. 
Published: November 2003

AbstractWe report on the first correlative study of the electrophysiological properties, shapes, and projections of enteric neurons in the mouse. Neurons in the myenteric plexus of the mouse colon were impaled with microelectrodes containing biocytin, their passive and active electrophysiological properties determined, and their responses to activation of synaptic inputs investigated. Biocytin, injected into the neurons from which recordings were made, was converted to an optically dense product and used to determine the shapes of neurons. By electrophysiological properties, almost all neurons belonged to one of two classes, AH neurons or S neurons. AH neurons had a biphasic repolarization of the action potential, and slow afterhyperpolarizing potentials usually followed the action potentials. S neurons had monophasic repolarizations, no slow afterhyperpolarization, and fast excitatory postsynaptic potentials in response to fibre tract stimulation. By shape, neurons were divided into Dogiel type II (28/136 neurons) and uniaxonal neurons. Dogiel type II neurons had large, smooth‐surfaced cell bodies and several long processes that supplied branches within myenteric ganglia. All Dogiel type II neurons had AH electrophysiology; conversely, most AH neurons had Dogiel type II morphology. The majority of uniaxonal neurons had lamellar dendrites, i.e., Dogiel type I morphology. They projected to the circular muscle (circular muscle motor neurons), to the longitudinal muscle (longitudinal muscle motor neurons), and to other myenteric ganglia (interneurons) and in some cases could not be traced to target cells. All S neurons were uniaxonal. A small proportion of uniaxonal neurons (3/70) had AH electrophysiology. Fast excitatory synaptic potentials were only recorded from uniaxonal neurons and were in most cases blocked by nicotinic receptor antagonists. A small component of fast excitatory transmission in some neurons was antagonized by the purine receptor antagonist PPADS. Slow excitatory postsynaptic potentials were observed in both AH and S neurons. Slow inhibitory postsynaptic potentials were recorded from S neurons. We conclude that the major classes of neurons are Dogiel type II neurons with AH electrophysiological properties and Dogiel type I neurons with S electrophysiological properties. The S/Dogiel type I neurons include circular muscle motor neurons, longitudinal muscle motor neurons, and interneurons. J. Comp. Neurol. 468:112–124, 2004. © 2003 Wiley‐Liss, Inc.
Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP‐43 mRNA in the adult rat
Authors: Feig Sherry L. 
Published: November 2003

AbstractThe expression of a presynaptic phosphoprotein, growth‐associated protein (GAP)‐43, is associated with synaptogenesis during development and synaptic remodeling in the adult. This study examined GAP‐43 mRNA expression and distribution in primary and secondary areas of visual, auditory, and somatosensory cortex of the adult rat, by in situ hybridization with a digoxigenin‐coupled mRNA probe, focusing particularly on the corticothalamic cells in layers 5 and 6. In the six cortical areas studied, GAP‐43 mRNA was expressed predominantly in layers 5 and 6 and was greater in secondary than primary areas. There were densely labeled cells in layers 5 and 6 of all areas, which showed a restricted sublaminar distribution in primary areas and more even distribution in secondary areas. Combining retrograde transport of rhodamine beads with in situ hybridization in visual and auditory cortex showed that corticothalamic cells in layers 5 and 6 express GAP‐43 mRNA. There are more of these GAP‐43 mRNA positive corticothalamic cells in layer 5 of secondary areas than in primary areas. The evidence suggests that in the adult rat, plasticity related to GAP‐43 is present in primary and secondary sensory cortex and more so in secondary areas. J. Comp. Neurol. 468:96–111, 2004. © 2003 Wiley‐Liss, Inc.
CHEK2 1100delC is not a risk factor for male breast cancer population
Authors: Syrjäkoski Kirsi , Kuukasjärvi Tuula , Auvinen Anssi , Kallioniemi Olli‐P 
Published: November 2003

AbstractGenetic risk factors for male breast cancer (MBC) are poorly understood. High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of the disease. A 1100delC mutation in CHEK2 (previously known as CHK2), a cell‐cycle checkpoint kinase, has been implicated in predisposition of Li‐Fraumeni syndrome (LFS) and breast cancer in families suggestive of LFS. This 1100delC mutation has also been shown to confer a 2‐fold increase of breast cancer risk in women and a 10‐fold increase of risk in men. It was estimated to account for 1% of breast cancers in women and as much as 9% of breast cancers in men at the population level based on analysis of breast cancer families without BRCA1 or BRCA2 mutations. We wanted to evaluate the significance of CHEK2 1100delC in predisposition to MBC by assessing its frequency in a population‐based material of 114 Finnish MBC patients. Two patients (1.8%) carried the 1100delC mutation. The mutation frequency among MBC cases was similar to that seen in population controls (26/1885, 1.4%). Our results indicate that CHEK2 1100delC variant does not substantially increase the risk of male breast cancer at the population level. We cannot exclude the fact that a small fraction of hereditary, family‐positive male breast cancers could be attributable to CHEK2 mutations. © 2003 Wiley‐Liss, Inc.
Human agmatinase is diminished in the clear cell type of renal cell carcinoma
Authors: Dallmann Kerstin , Junker Heike , Balabanov Stefan , Zimmermann Uwe , Giebel Jürgen , Walther Reinhard 
Published: November 2003

AbstractThe proteome of RCC was analyzed by 2D PAGE to search for tumor‐associated proteins. Agmatinase, which hydrolyzes agmatine to putrescine and urea, was identified by mass spectrometry and database searches and shown to be downregulated in tumor cells. Additionally, RT‐PCR and Northern blot analyses demonstrated a clearly decreased amount of agmatinase mRNA in tumor cells. The differential expression of agmatinase mRNA was confirmed at the protein level. Western blot analysis showed almost no detectable agmatinase protein in tumor cells compared to corresponding normal renal tissue. Agmatinase mRNA is most abundant in human liver and kidney but expressed to a lesser extent in several other tissues, including skeletal muscle and small intestine. The human agmatinase gene encodes a 352‐residue protein with a putative mitochondrial targeting sequence at the N‐terminus. Using transfection and immunohistochemical studies, we show that agmatinase is localized in the mitochondria. Immunohistochemical studies revealed that agmatinase in the normal kidney is restricted to tubulus epithelial cells, while in tumors staining was low and heterogeneous. Thus, expression of human agmatinase is altered in RCC. We discuss the consequences of these findings in terms of polyamine, NO metabolism and macrophage function. © 2003 Wiley‐Liss, Inc.
Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women
Authors: Lukanova Annekatrin , Lundin Eva , Micheli Andrea , Arslan Alan , Ferrari Pietro , Rinaldi Sabina , Krogh Vittorio , Lenner Per , Shore Roy E. , Biessy Carine , Muti Paola , Riboli Elio , Koenig Karen L. , Levitz Mortimer , Stattin Pär , Berrino Franco , Hallmans Göran , Kaaks Rudolf , Toniolo Paolo , Zeleniuch‐Jacquotte Anne 
Published: November 2003

AbstractExperimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre‐diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case‐control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76–9.72), ptrend = 0.0008 for estradiol, 3.67 (1.71–7.88), ptrend = 0.0007 for estrone, 2.15 (1.05–4.40), ptrend = 0.04 for androstenedione, 1.74 (0.88–3.46), ptrend = 0.06 for testosterone, 2.90 (1.42–5.90), ptrend = 0.002 for DHEAS and 0.46 (0.20–1.05), ptrend = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis. © 2003 Wiley‐Liss, Inc.
Intake of beer inhibits azoxymethane‐induced colonic carcinogenesis in male Fischer 344 rats
Authors: Nozawa Hajime , Yoshida Aruto , Tajima Osamu , Katayama Mikio , Sonobe Hiromi , Wakabayashi Keiji , Kondo Keiji 
Published: November 2003

AbstractModulatory effects of beer consumption on azoxymethane (AOM)‐induced rat colonic carcinogenesis in male Fischer 344 rats were investigated. Single cell gel electrophoresis assay indicated that DNA damage of colonocytes, induced by a single AOM injection (15 mg/kg body weight), was significantly reduced in rats fed beer or malt extract for 2 weeks. Examination of aberrant crypt foci (ACF) formation in colonic mucosa, induced by AOM (15 mg/kg body weight; twice weekly), revealed that feeding of beer during the whole experimental period of 5 weeks significantly reduced the number of ACF by 35%. In the post‐initiation protocol, a reduction in ACF formation by 26% was not significant. The efficacy in inhibition of ACF formation varied with the brand of beer. ACF formation was significantly reduced in rats treated with freeze‐dried beer (FD Beer), but not with ethanol, suggesting that nonvolatile components of beer are responsible for the reduction. Significant suppression of ACF formation was observed in groups treated with hot water extract of malt, especially with extracts of colored malts, although no reduction was observed by feeding with hops extract. A long‐term experiment of 42 weeks indicated that intake of beer decreased tumor incidence by 22% and decreased the number of neoplastic lesions, including adenocarcinomas and adenomas, by 44%. These results suggest that components of beer have chemopreventive effects on colonic carcinogenesis induced by AOM and that intake of beer may contribute to a reduction in the risk of cancer susceptibility. © 2003 Wiley‐Liss, Inc.
Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids
Authors: Hoevel Thorsten , Macek Robert , Swisshelm Karen , Kubbies Manfred 
Published: November 2003

AbstractMembers of the claudin family together with occludin are the major constituents of the tight junction (TJ) complex. The human homologue of the murine CLDN1, previously called SEMP1, was identified by differential expression analysis, and the CLDN1 mRNA was found to be downregulated or completely lost in human breast cancer cells in vitro. Retroviral‐induced CLDN1 reexpression in breast cancer cells results in plasma membrane homing of the protein and reconstitution of paracellular flux inhibition, which is not dependent on the presence of occludin protein. In this report, we investigated the physiologic role of CLDN1 in CLDN1‐transduced MDA‐MB 361 breast tumor cells in adherent 2D and suspension 3D spheroid cell cultures. Retroviral‐transduced bulk cultures were FACS‐sorted to enrich for 100% CLDN1‐positive clonal derivatives with similar expression levels of CLDN1 mRNA and protein. There was no difference in proliferation and cell death characteristics in 2D adherent cell cultures of CLDN1‐positive compared to control CLDN1‐negative and mock‐transduced cell cultures. In contrast, the majority of the CLDN1‐transduced derivatives displayed a significant elevation of apoptosis that became evident as early as 2 days after 3D spheroid culture onset. This elevated apoptosis was independent of the volume of established spheroids. The cellular immunofluorescence analysis of CLDN1 protein expression in transduced bulk cultures revealed a CLDN1‐positive subfraction with a heterogeneous pattern of membrane and cytosolic immunostaining. In the clonal MDA‐MB 361 CLDN1‐positive cultures, we found that a more prominent cell membrane localization correlated with a pronounced increase of apoptosis in tumor spheroids. In parallel, inhibition of the paracellular flux rate was observed. These findings support a potential role of the TJ protein CLDN1 in restricting nutrient and growth factor supplies in breast cancer cells, and they indicate that the loss of the cell membrane localization of the TJ protein CLDN1 in carcinomas may be a crucial step during tumor progression. © 2003 Wiley‐Liss, Inc.
High levels of circulating testosterone are not associated with increased prostate cancer risk: A pooled prospective study
Authors: Stattin Pär , Lumme Sonja , Tenkanen Leena , Alfthan Henrik , Jellum Egil , Hallmans Göran , Thoresen Steinar , Hakulinen Timo , Luostarinen Tapio , Lehtinen Matti , Dillner Joakim , Stenman Ulf‐Håkan , Hakama Matti 
Published: November 2003

AbstractAndrogens stimulate prostate cancer in vitro and in vivo. However, evidence from epidemiologic studies of an association between circulating levels of androgens and prostate cancer risk has been inconsistent. We investigated the association of serum levels of testosterone, the principal androgen in circulation, and sex hormone‐binding globulin (SHBG) with risk in a case‐control study nested in cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate cancer after blood collection and among 2,242 men who were not. In conditional logistic regression analyses, modest but significant decreases in risk were seen for increasing levels of total testosterone down to odds ratio for top vs. bottom quintile of 0.80 (95% CI = 0.59–1.06; ptrend = 0.05); for SHBG, the corresponding odds ratio was 0.76 (95% CI = 0.57–1.01; ptrend = 0.07). For free testosterone, calculated from total testosterone and SHBG, a bell‐shaped risk pattern was seen with a decrease in odds ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60–1.14; ptrend = 0.44). No support was found for the hypothesis that high levels of circulating androgens within a physiologic range stimulate development and growth of prostate cancer. © 2003 Wiley‐Liss, Inc.
CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival
Authors: Palma Carla , Binaschi Monica , Bigioni Mario , Maggi Carlo Alberto , Goso Cristina 
Published: November 2003

AbstractCD137, a member of the tumor necrosis factor receptor family, provides expansion and survival signal to T cells. Its ligand, CD137L, in addition to its ability to costimulate T cells, signals back into antigen presenting cells promoting their activation and differentiation. Recently, CD137 has been proposed as a therapeutic target to improve and sustain anticancer immune response. Several activated T leukemia and B lymphoma cell lines expressed CD137 or CD137L, respectively, and soluble CD137L has been found in sera of leukemia patients. However, the functionality and role of these costimulatory molecules in hematologic malignancies are until now unknown. Interestingly, we observed constitutive CD137 and CD137L coexpression on both human T and B leukemia cell lines. The constitutive CD137 expression on unstimulated T or B leukemia cells presents some differences compared to CD137 expressed on PMA/ionomycin‐activated T leukemia cells. Surprisingly, in spite of the low expression level, both tumor CD137 and CD137L molecules signaled in T and B leukemia cells inducing proliferation and prolonging survival. In addition, CD137/CD137L system ligation opposed the anticancer drug cytotoxic effects, reducing the apoptotic DNA fragmentation and stimulating proliferation of doxorubicin‐escaped leukemia cells. Although the role of leukemia CD137/CD137L system in vivo is unknown, these data suggest that these costimulatory molecules might confer an advantage to hematologic tumors promoting survival, sustaining cellular growth and contributing to drug resistance. © 2003 Wiley‐Liss, Inc.
Quantification of cytokeratin 20, carcinoembryonic antigen and guanylyl cyclase C mRNA levels in lymph nodes may not predict treatment failure in colorectal cancer patients
Authors: Bustin Stephen A. , Siddiqi Shahab , Ahmed Shafi , Hands Rebecca , Dorudi Sina 
Published: November 2003

AbstractConventional histopathologic staging of primary colorectal cancers does not allow accurate prognostic stratification within a given tumour stage. Therefore, PCR‐based assays are increasingly used to try to predict more accurately the likelihood of disease progression for the individual patient. Real‐time reverse transcription PCR (RT‐PCR) assays were used to detect and quantitate cytokeratin 20 (ck20), carcinoembryonic antigen (CEA) and guanylyl cyclase C (GCC) mRNA in 149 lymph nodes (LN) from 17 patients with benign disease and 302 LN from 42 patients with colorectal cancer who had curative (R0) resections. None of the markers were specific, with ck20, CEA and GCC mRNA detected in 47%, 89% and 13% of 149 LN, respectively, from patients with benign disease. The sensitivity of all 3 markers was very high, with mRNA detected in 93%, 100% and 97% of 30 histologically involved LN, respectively. There was significant overlap in the mRNA levels of all 3 markers between histologically involved and uninvolved LN. There was no association between mRNA levels and distant recurrence (median follow‐up: 3.94 years, range 3.35–5.12). We conclude that the use of molecular techniques to detect occult disease in LN may suffer from the same limitations as conventional methods. Instead, accurate prognostic stratification requires careful assessment of the likely metastatic potential of the primary cancer. © 2003 Wiley‐Liss, Inc.
Nadir B cell counts are significantly correlated with the risk of Kaposi's sarcoma
Authors: Stebbing Justin , Gazzard Brian , Newsom‐Davis Tom , Nelson Mark , Patterson Steve , Gotch Frances , Mandalia Sundhiya , Bower Mark 
Published: November 2003

AbstractInfection with HIV‐1 is known to impair B cell function. To further elucidate the role of B cells during infection and tumorigenesis, we studied their numbers in cases of AIDS‐related Kaposi's sarcoma (KS) during the HAART era. Patients with AIDS‐related KS were identified from a database of 4,480 HIV‐1 positive individuals and the incidence of KS and rate ratio was stratified according to nadir number of B cells, measured as the CD19 count. In an unadjusted model, we observed that lower B cell counts were associated with a statistically significant increased risk of KS development (p < 0.001). We also observed a trend toward increased counts during KS resolution. When adjusted for nadir CD4 count in a multi‐variable model, higher B cell counts were protective against KS development (p = 0.015). These data highlight a potential role for B cells and therefore the humoral immune system in KS aetiopathogenesis. © 2003 Wiley‐Liss, Inc.
Theoretical study of ribonucleotide reductase mechanism‐based inhibition by 2′‐azido‐2′‐deoxyribonucleoside 5′‐diphosphates
Authors: Pereira Susana , Fernandes Pedro Alexandrino , Ramos Maria João 
Published: November 2003

Abstract2′‐Azido‐2′‐deoxyribonucleoside 5′‐diphosphates are mechanism‐based inhibitors of Ribonucleotide Reductase. Considerable effort has been made to elucidate their mechanism of inhibition, which is still controversial and not fully understood. Previous studies have detected the formation of a radical intermediate when the inhibitors interact with the enzyme, and several authors have proposed possible structures for this radical. We have conducted a theoretical study of the possible reactions involved, which allowed us to identify the structure of the new radical among the several proposals. A new reactional path is also proposed that is the most kinetically favored to yield this radical and ultimately inactivate the enzyme. The energetic involved in this mechanism, both for radical formation and radical decay, as well as the calculated Hyperfine Coupling Constants for the radical intermediate, are in agreement with the correspondent experimental values. This mechanistic alternative is fully coherent with remaining experimental data. © 2003 Wiley Periodicals, Inc. J Comput Chem 25: 227–237, 2004
Polymer‐solvent complexes and intercalates prepared under various conditions
Authors: Guenet Jean‐Michel 
Published: November 2003

AbstractThe relevancy of temperature‐composition phase diagrams for the study of polymer‐solvent complexes and intercalates is discussed. In particular the use of Tamman's diagrams for determining the stoichiometric composition is evaluated. Examples of the validity of this approach are taken from isotactic or syndiotactic polystyrene compounds. Also, the effect of the path followed for reaching a T, C coordinate is examined. It is shown that cooling hot, homogeneous solutions at composition C or allowing solvent to diffuse in a solid polymer matrix at temperature T yields basically the same thermal behaviour.
Highly conductive oriented PEO‐based polymer electrolytes
Authors: Golodnitsky D. , Livshits E. , Peled E. 
Published: November 2003

AbstractThis contribution presents an overview of the study of the effect of stretching on semicrystalline and amorphous complexes of poly(ethylene oxide) (PEO) with different salts, such as lithium iodide, lithium trifluoromethane‐sulfonate, lithium hexafluoroarsenate, lithium bis(oxalato)borate and lithium trifluoromethanesulfonimide. In spite of the conventional belief that ion transport in polymer electrolytes (PE) is mediated primarily by polymer segmental motion, we suggest that ion transport occurs preferentially along the PEO helical axis, at least in the crystalline phase. It was found that the more amorphous the PE, the less its lengthwise conductivity is influenced by stretching. It is suggested that the rate‐determining step of ion conduction in semicrystalline LiX:P(EO)20, polymer electrolytes below the melting point (Tm) is “interchain” hopping.
Water‐protein and ligand‐protein interactions as determined by selective NMR relaxation studies
Authors: Rossi Claudio , Martini Silvia , Ricci Maso , Picchi Maria Pia , Bonechi Claudia 
Published: November 2003

AbstractWater‐macromolecules and ligand‐macromolecules interactions were investigated considering the effects induced by the presence of a macromolecule on both the water and the ligand NMR selective (R1SE) and non‐selective (R1NS) spin‐lattice relaxation rates. The results obtained from the solvent studies were used to describe the solvent dynamics at the macromolecule‐solvent interface. On the other hand, ligand R1SE and (R1NS) analysis allowed the definition of the “affinity index”, [A]LT, an index related to the extent of the macromolecule‐ligand recognition process.