bluuebunny/crossref_metadata_2025 huggingface dataset:
Anagrelide for thrombocytosis in myeloproliferative disorders
Authors: Steurer Michael , Gastl Guenther , Jedrzejczak Wieslaw‐Wiktor , Pytlik Robert , Lin Werner , Schlögl Ernst , Gisslinger Heinz
Published: October 2004

BACKGROUND

Although the platelet count does not correlate with the rate of thrombosis, there is evidence that a strict control of the platelet count decreases the incidence of thromboembolic complications in essential thrombocythemia. In the current study, the authors evaluated the efficacy and tolerability of anagrelide in thrombocytosis associated with myeloproliferative disorders.

METHODS

The study cohort comprised 97 patients (n = 69 females, n = 28 males) with a median age of 59 years (range, 21–80 years). Patients with essential thrombocythemia (n = 79) or with thrombocytosis due to polycythemia vera (n = 16) or to chronic idiopathic myelofibrosis (n = 2) were enrolled in the multicenter, prospective study. Patients received anagrelide at a starting dose of 0.5 mg twice per day, which was then adjusted for each patient.

RESULTS

Treatment with anagrelide resulted in a rapid decrease in the platelet count, from a median baseline platelet count of 743 × 109/L to a median platelet count of 441 × 109/L after 6 months (P < 0.0001). The proportion of patients with a platelet count < 600 × 109/L increased from 30% at baseline to 77% after the 6‐month study period. The rate of major thrombotic complications significantly decreased from 5% to 2% (P = 0.2568). For patients with essential thrombocythemia, the reduction of major thromboembolic complications was significant (P = 0.0455). The rate of minor thromboembolic complications decreased from 25% before anagrelide treatment to 14% during anagrelide treatment (P = 0.0278). No severe side effects were observed during the study period. There was, however, evidence that concomitant administration of acetylsalicylic acid may increase bleeding tendency.

CONCLUSIONS

Anagrelide was an effective and well tolerated treatment modality for reducing platelet counts in both newly diagnosed and pretreated patients with thrombocytosis due to myeloproliferative disorders. Cancer 2004. © 2004 American Cancer Society.
A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors
Authors: Ohuchida Kenoki , Mizumoto Kazuhiro , Ishikawa Nami , Sato Norihiro , Nagai Eishi , Yamaguchi Koji , Takaishi Hideki , Ide Toshinori , Tanaka Masao
Published: October 2004

BACKGROUND

Early detection of pancreatic carcinoma is difficult even with current diagnostic tools. Novel biomarkers and detection techniques are urgently needed. Telomerase activity is a promising diagnostic marker. However, the conventional telomeric repeat amplification protocol (TRAP) assay is not suitable for clinical application because of its complexity, time‐consuming nature, and the effects of polymerase chain reaction (PCR) inhibitors in samples leading to difficulties in quantification.

METHODS

The authors used a hybridization protection assay in combination with TRAP (TRAP/HPA) to investigate the effects of PCR inhibitors in pancreatic juice on quantification of telomerase activity. They analyzed 117 consecutive samples of pancreatic juice to determine the feasibility of TRAP/HPA for diagnosis of pancreatic carcinoma.

RESULTS

The authors found that TRAP/HPA was 1000‐fold more sensitive than the conventional TRAP assay, and that the effects of PCR inhibitors could be avoided by diluting samples. In a large analysis of pancreatic juice samples with TRAP/HPA, 17 samples were excluded from the final analysis because of insufficient follow‐up periods or inadequate treatment of the samples. Relative telomerase activity (RTA) in samples from patients with pancreatic carcinoma was significantly higher in comparison to samples from patients with pancreatitis and 13 (61.9%) of 21 samples from patients with pancreatic carcinoma showed high RTA (> 4 U). Meanwhile, high RTAs were observed in 4 of 35 (11.4%) samples from patients with intraductal papillary mucinous tumor and in 1 of 40 samples (2.5%) fom patients without malignant disease.

CONCLUSIONS

TRAP/HPA accurately evaluated weak telomerase activity in pancreatic juice samples without the problem due to PCR inhibitors. This large analysis of nonselected pancreatic juice samples suggested that TRAP/HPA is a promising approach for the diagnosis of pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society.
Treatment of breast carcinoma in patients with clinically negative axillary lymph nodes using radiotherapy versus axillary dissection
Authors: Fujimoto Naoko , Amemiya Atsushi , Kondo Makoto , Takeda Atsuya , Shigematsu Naoyuki
Published: October 2004

BACKGROUND

The role of axillary lymph node dissection (AxD) for patients with breast carcinoma who have clinically negative lymph nodes (cN0) and undergo breast‐conserving therapy has been controversial. If patients do not undergo AxD, then it is uncertain whether specific lymph node irradiation should be given. The authors compared the results obtained from patients w ho underwent AxD with the results from patients who received axillary irradiation (AxR) using one of two radiotherapy techniques.

METHODS

Patients with T1–T2cN0 breast carcinoma were treated from 1983 to 2002 with either AxD (80 patients) or AxR (1134 patients received tangential‐field [2‐field] irradiation, and 303 patients received 3‐field irradiation). The median follow‐up was 161 months for the AxD group and 66 months for the AxR group (55 months for patients who received tangential‐field irradiation, and 122 months for patients who received 3‐field irradiation).

RESULTS

One patient in the AxD group and 35 patients in the AxR group had axillary recurrences. The 10‐year cumulative axillary recurrence rates were 1.3% and 4.6% for the AxD group and the AxR group, respectively (P= 0.21). For patients with T1 tumors, the 10‐year overall survival rates for the two groups were 94.7% and 92.7%, respectively (P= 0.34); and, for patients with T2 tumors, the 10‐year overall survival rates were 92.5% and 89.1%, respectively (P= 0.34). In the AxR group, the 5‐year axillary recurrence rates were 2.5% for patients who received tangential‐field irradiation and 1.7% for patients who received 3‐field irradiation (P= 0.18), and the 5‐year regional recurrence rates for the two groups were 4.8% and 2.4%, respectively (P= 0.048). On multivariate analysis, positive lymphovascular invasion, outer tumor location, and larger tumor size were significant risk factors for regional failure.

CONCLUSIONS

For patients with cN0 breast carcinoma, AxD and AxR yielded the same overall survival rates. Most patients can be treated safely with tangential‐field irradiation alone. Patients who are at increased risk of regional failure may benefit from three‐field irradiation. Cancer 2004. © 2004 American Cancer Society.
Flow cytometric detection of complement‐activating HLA antibodies
Authors: Schönemann Constanze , Lachmann Nils , Kiesewetter Holger , Salama Abdulgabar
Published: October 2004

Background

Antibodies to HLA are implicated in allograft rejection; as a consequence, tests to identify them are indicated in organ transplantation. Flow cytometry (FC) may improve the outcome of organ transplantation. Although increasingly used, most of the available FC techniques do not discriminate between complement and noncomplement‐activating antibodies. However, the clinical relevance of noncomplement‐activating antibodies is controversial. Therefore, many laboratories still use the conventional complement‐dependent microlymphocytotoxicity crossmatch (CDC‐XM) alone or in combination with FC.

Methods

We describe a novel flow cytometric complement‐dependent cytotoxicity crossmatch assay (FC‐CDC‐XM) that clearly identifies complement‐binding HLA antibodies. With the aid of a three‐color FACScan flow cytometer with a standard argon ion laser, we used fluorescence‐conjugated anti‐CD3 for the identification of T lymphocytes, anti‐CD19 antibodies for the identification of B lymphocytes, and propidium iodide (PI) for the identification of damaged cells. Fluorescence‐conjugated anti‐CD3 and anti‐CD19 antibodies were detected in the green (FL1) and orange (FL2) ranges of the spectrum. PI fluorescence was measured with the red (FL3) fluorescence channel. Gating of lymphocytes was performed using side scatter versus FL1 or FL2 dot plots for the identification of T and B lymphocytes, respectively.

Results

FC‐CDC‐XM was able to correctly identify all antibodies tested as specific to HLA class I (n = 18) or II (n = 4).

Conclusions

The new FC‐CDC‐XM is more sensitive and more objective than the standard CDC‐XM and can be used for pre‐ and posttransplant diagnoses and for the detection of other antibody‐mediated cytotoxic reactions. © 2004 Wiley‐Liss, Inc.
BDNF protects against stress‐induced impairments in spatial learning and memory and LTP
Authors: Radecki Daniel T. , Brown Laurie M. , Martinez James , Teyler Timothy J.
Published: October 2004

The present study investigated whether infusion of brain‐derived neurotrophic factor (BDNF) could ameliorate stress‐induced impairments in spatial learning and memory as well as hippocampal long‐term potentiation (LTP) of rats. Chronic immobilization stress (2 h/day × 7 days) significantly impaired spatial performance in the Morris water maze, elevated plasma corticosterone, and attenuated LTP in hippocampal slices from these animals as compared with normal control subjects. BDNF was infused into the left hippocampus (0.5 μl/h) for 14 days, beginning 7 days before the stress exposure. The BDNF group was protected from the deleterious effects of stress and performed at a level indistinguishable from normal control animals despite the presence of elevated corticosterone. BDNF alone and sham infusions had no effect on performance or LTP. These results demonstrate that spatial learning and memory, and LTP, a candidate neural substrate of learning and memory, are compromised during chronic stress, and may be protected by BDNF administration. © 2004 Wiley‐Liss, Inc.
Tonic modulation of inhibition by dopamine D4 receptors in the rat hippocampus
Authors: Romo‐Parra Héctor , Aceves Jorge , Gutiérrez Rafael
Published: October 2004

Dopaminergic pathways have been recognized to play a critical role in cognition and emotion. Dopamine D2 and D4 receptors are the target for most common antipsychotics and their activation, particularly those in the medial temporal lobe structures, has been associated with their beneficial actions. The entorhinal cortex, which is the cortical area most consistently and severely affected in schizophrenia constitutes the main input to the hippocampus. Since the D4 receptor is highly concentrated in the hippocampus, and the effects of the selective activation of D4 receptors on the input/output function of the hippocampal formation are poorly understood, we sought to investigate the role of these receptors in the synaptic transmission and paired‐pulse inhibition from the perforant path to area CA1 and the dentate gyrus. The D4 receptor antagonist, clozapine, translated paired‐pulse inhibition into paired‐pulse potentiation in both perforant path targets. By contrast, the D2/D3 antagonist quinpirole had no effect. The blockade of the D2/3 receptors with sulpiride, and of D1/5 receptors with SCH‐23390, has no effect on paired‐pulse inhibition, suggesting that these receptors are not involved in feedforward inhibition in these hippocampal areas. Interestingly, the perfusion of the D4 selective antagonist, L‐745,870 (Patel et al., 1997: J Pharmacol Exp Ther 283:636–647) during the blockade of D2/3 and D1/5 receptors produces a reversible decrease in paired‐pulse inhibition in CA1, but not in the DG. Our results show that endogenous DA tonically modulates feedforward inhibition in area CA1 and the dentate gyrus through the activation of D4 receptors located in the interneuronal population of these hippocampal regions. Since activation of the D4 receptor inhibits GABA release and GABAergic synaptic transmission, we suggest that the perforant path stimulates interneurons that have the D4 receptor and that, in turn, contact other interneurons that synapse onto pyramidal cells. © 2004 Wiley‐Liss, Inc.
Frequency and resolution dependence of the anisotropic impedance estimation in cortical bone using time‐resolved scanning acoustic microscopy
Authors: Raum Kay , Reißhauer Jan , Brandt Jörg
Published: October 2004

The influences of frequency and spatial resolution on the anisotropic impedance estimation of cortical bone was investigated in the frequency range 25–100 MHz. A set of spherically focused transducers provided a spatial resolution in the range from 150 down to about 20 μm. Four embedded cortical bone samples (two male, two female, two donors aged <30 years, two donors aged >70 years) were cut with different orientations relative to the long axis of the femur (0–90°). From each section, impedance maps were acquired in the C‐scan mode. Histogram evaluations showed a similar angular dependence with a characteristic off‐axis maximum of the estimated impedance for all samples and frequencies. The impedance values obtained with the 25‐MHz transducer were significantly lower than those obtained with the 50‐ and 100‐MHz transducers. Morphological parameters of the macrostructure, for example, size and distribution of the haversian channels and the resulting porosity, were estimated from the high‐resolution acoustic images. These structures appeared to have a significant influence on the measured properties of the bone matrix for the low‐frequency and low‐aperture measurements. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 430–438, 2004
Surface chemistry mediates adhesive structure, cytoskeletal organization, and fusion of macrophages
Authors: Dadsetan Mahrokh , Jones Jacqueline A. , Hiltner Anne , Anderson James M.
Published: October 2004

Surface chemistry modulates many critical functions of monocyte/macrophages such as adhesion, fusion, spreading, phagocytosis, and secretion. In this study, we investigated the effect of silicone modification on adhesive structure development and cytoskeletal reorganization of adherent macrophages on polyurethanes. Confocal scanning laser microscopy (CSLM) was used for qualitative and quantitative evaluation of cytoskeletal reorganization of adherent macrophages. Data presented here showed less spreading for adherent cells on silicone‐modified materials due to the higher hydrophobicity and protein adsorption profile. This decrease in spreading was accompanied by less F‐actin content in adherent cells on silicone‐modified polyurethanes and PDMS control, indicating that silicone modification reduces the strength of adhesion. With the addition of interleukin‐4 (IL‐4) at days 3 and 7 to our culture, adherent cell morphology dramatically changed. The change in morphology led to higher macrophage fusion and foreign body giant cell (FBGC) formation on silicone modified materials after 10 days. In addition, mannose receptor (MR) expression was up‐regulated on the silicone‐modified polyurethanes and PDMS control in the presence of IL‐4. Up‐regulation of MR expression suggests an alternatively activated phenotype for adherent macrophages, which is accompanied with an attenuated proinflammatory cytokine production and reactive oxygen secretion. It appears that silicone modification accelerates acquisition of an alternative macrophage and FBGC phenotype, which may then result in increased polyurethane biostability. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 439–448, 2004
Analysis of immobilized L‐cysteine on polymers
Authors: Gappa‐Fahlenkamp H. , Duan X. , Lewis R. S.
Published: October 2004

Recently, we reported that L‐cysteine attached to polymeric biomaterials, without prior nitrosation, enhances the hemocompatibility of biomaterials via exploiting endogenous nitric oxide (NO). As part of the polymer optimization process to further enhance platelet inhibition, a kinetic model is being developed to predict the release rate of NO. A key model parameter is the immobilized concentration of L‐cysteine. This article demonstrates how several chemiluminescence‐based assays, previously utilized for measuring thiols in solution, were successfully adapted to quantify immobilized L‐cysteine. The assays showed that the immobilized L‐cysteine on the modified PET sample is within the range of 4.1 to 6.5 nmol/cm2. An advantage of using the more successful chemiluminescence‐based assay is that it can accurately measure molar concentrations of any thiol‐containing compound with a detection limit in the pmol range. The major disadvantage is that L‐cysteine must first be broken off of the polymer and released into solution prior to measurement, therefore leaving the sample unable to be reused. Other thiol‐measuring techniques, such as fluorescence microscopy and X‐ray photoelectron spectroscopy (XPS), were used to provide qualitative and semiquantitative analysis to substantiate the polymer development. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 519–527, 2004
Integrin α2β1 modulates EGF stimulation of Rho GTPase‐dependent morphological changes in adherent human rhabdomyosarcoma RD cells
Authors: Leabu M. , Uniyal S. , Xie J. , Xu Y.Q. , Vladau C. , Morris V.L. , Chan B.M.C.
Published: October 2004

The ability of cells to undergo shape changes is essential for diverse cellular functions including cell growth, differentiation, and movement. The present study examines how an integration of the function of α2β1 integrin with that of the receptor for epidermal growth factor (EGFR) modulates EGF‐stimulated morphological changes in human rhabdomyosarcoma RD transfectant cells. Upon EGF stimulation, RD transfectant cells that lacked α2β1 integrin expression (RDpF) underwent contraction; in contrast, expression of α2β1 on RD cells (RDX2C2) resulted in transient cell spreading. Integrin α2 cytoplasmic domain played a critical role in the observed α2β1‐mediated conversion from a cell rounding to a cell spreading phenotype. Thus, the expression of an α2 cytoplasmic domain deletion variant (X2C0) or a chimeric α2β1 containing the cytoplasmic domain of α4 (X2C4) or α5 (X2C5), instead of α2, failed to mediate spreading upon EGF stimulation. Using dominant negative (DN) mutants of RhoGTPases, results revealed that RhoA activation was required for both EGF‐stimulated responses of cell rounding and spreading, Cdc42 functioned in the re‐spreading of cells after undergoing EGF‐stimulated contraction, and Rac1 was required in α2β1‐mediated RD cell spreading. Therefore, α2β1 integrin function can switch the Rho GTPase‐dependent cell shape changes in RD cells from an EGF‐stimulated cell contraction to a spreading morphology. Together, results show that integrin α2 cytoplasmic domain plays an indispensable role in the ability of integrin α2β1 to modulate EGF stimulation of Rho‐GTPase‐dependent morphological changes in RD cells. © 2004 Wiley‐Liss, Inc.
Pretreatment of barley husk for bioethanol production
Authors: Palmarola‐Adrados Beatriz , Galbe Mats , Zacchi Guido
Published: October 2004

This paper reports on the optimization of steam pretreatment of barley husk for high pentose and hexose recovery in the subsequent enzymatic hydrolysis step, as well as high ethanol yield, following simultaneous saccharification and fermentation. The parameters optimized in the steam pretreatment step were residence time (5–15 min), temperature (190–215 °C), and concentration of the acid catalyst (0 or 0.5% H2SO4). A microwave oven was employed for screening of the optimal conditions to obtain the highest sugar yield following combined pretreatment and enzymatic hydrolysis. The final optimization of the pretreatment prior to enzymatic hydrolysis was performed on a larger scale, in a steam pretreatment unit. Simultaneous saccharification and fermentation was carried out following steam pretreatment on 5 and 10% dry matter steam‐pretreated slurries. Fermentability tests were performed to determine the effect of by‐products (ie furfural and 5‐hydroxymethyl furfural) in the bioconversion of glucose to ethanol by baker's yeast. The maximum glucose yield, 88% of the theoretical, was obtained following steam pretreatment with 0.5% H2SO4 at 200 °C for 10 min. Under these conditions, a sugar to ethanol conversion of 81% was attained in simultaneous saccharification and fermentation. Copyright © 2004 Society of Chemical Industry
A biological method for synthesizing 14C‐vinyl chloride
Authors: Walker Christopher B. , Gu April Z. , Stensel H. David , Strand Stuart E.
Published: October 2004

14C‐labeled vinyl chloride (VC) was produced from 14C‐labeled trichloroethylene by an enriched, halorespiring culture, and purified using a hydrophobic column. This technically simple and economical method generated high yields of high‐purity radiolabeled VC. Copyright © 2004 John Wiley & Sons, Ltd.
Radiosynthesis and in vivo evaluation of [11C]Ro‐647312: a novel NR1/2B subtype selective NMDA receptor radioligand
Authors: Dollé Frédéric , Valette Héric , Demphel Stéphane , Coulon Christine , Ottaviani Michelle , Bottlaender Michel , Kassiou Michael
Published: October 2004

[2‐(3,4‐Dihydro‐1H‐isoquinolin‐2‐yl)‐pyridin‐4‐yl]‐dimethylamine, Ro‐647312 (1) represents a new novel class of NR1/2B subtype selective NMDA ligand. Ro‐647312 has been radiolabelled with carbon‐11 using [11C]methyl triflate from the nor‐methyl compound 2. The reaction was performed in acetone as solvent using aqueous NaOH as base. Following HPLC purification [11C]Ro‐647312 ([11C]‐1) was obtained in 6.9–9.2% (n = 3) radiochemical yield decay‐corrected based on starting [11C]CO2, with specific radioactivity measured at the end of the radiosynthesis ranging from 1.0 to 3.5 Ci/µmol (37–129 GBq/µmol). Radiochemical and chemical purities were assessed as >99 and >95%, respectively. Following i.v. injection of [11C]‐1 in rat, the distribution of radioactivity was homogeneous in all brain structures and did not correlate with the known distribution of NR2B subunits. The radioactivity observed in plasma was also higher than any brain structure throughout the time course of the experiment. [11C]‐1 does not possess the required properties for imaging NMDA receptors using positron emission tomography. Copyright © 2004 John Wiley & Sons, Ltd.
Deuterated analogues of 4,8‐dimethyldecanal, the aggregation pheromone of Tribolium castaneum: synthesis and pheromonal activity
Authors: Kim Junheon , Matsuyama Shigeru , Suzuki Takahisa
Published: October 2004

To elucidate the deuterium isotope effect (DIE) in pheromonal activity and to investigate the biosynthetic pathway of 4,8‐dimethyldecanal (4,8‐DMD; 1), the aggregation pheromone of the red flour beetle (Tribolium castaneum), deuterated analogues of 4,8‐DMDs (2, 3, 4, and 5), were synthesized and their pheromonal activities were tested using a two‐hole pitfall olfactometer. Although no apparent DIE was observed in their pheromonal activities, 4,8‐DMD‐1‐d1 (2) was less attractive than other analogues, which suggested that the bond distance between the formyl group of 1 and its receptor was critical in pheromone recognition by T. castaneum. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and separation of tritiated inhibitors of aminopeptidase A and their prodrugs
Authors: Inguimbert Nicolas , Coric Pascale , Dhotel Hélène , Llorens‐Cortes Catherine , Fournié‐Zaluski Marie‐Claude , Roques Bernard P.
Published: October 2004

With the aim of studying the bioavailability of two related aminopeptidase A (APA) inhibitors, we have synthesized tritiated disulfide prodrugs. These molecules, 4,4′‐dithiobis‐(3,3′‐amino)‐1,1′‐butanesulfonic acid (RB 150) and its 2,2‐dimethylpropyl ester(RB 151) bearing one tritium atom per monomer in position 2 were obtained with high purity and a final specific activity of about 30 Ci/mmol. The active radiolabeled inhibitor EC 33, Ki=270 nM for APA was obtained by reduction of the disulfide bond of RB 150. Copyright © 2004 John Wiley & Sons, Ltd.
Effect of polyglycerol esters of fatty acids on physicochemical properties and stability of β‐carotene nanodispersions prepared by emulsification/evaporation method
Authors: Tan Chin Ping , Nakajima Mitsutoshi
Published: October 2004

The effects of six different polyglycerol esters of fatty acids (PGEs) as nonionic emulsifiers on the physicochemical properties and stability of β‐carotene nanoparticles in oil‐in‐water dispersions produced by an emulsification/evaporation technique were examined. The β‐carotene particle size was measured by a laser diffraction technique, and the stability and retention of β‐carotene during various preparation steps and storage were determined by HPLC. In the prepared nanodispersions the β‐carotene particle size decreased with increasing degree of glycerol polymerisation and decreasing carbon number of the fatty acid group in the PGE. The particle size of β‐carotene in nanodispersions containing polyglycerol monooleate was generally larger than that in the presence of polyglycerol monolaurate. During storage at 4 °C, although the β‐carotene content in the nanodispersions showed a significant (P < 0.05) decrease with increasing storage period, the size distribution of β‐carotene was almost unchanged in all prepared nanodispersions. In general, the mean diameter of β‐carotene nanoparticles ranged from 85 to 132 nm. In the light of their ability to physically stabilise β‐carotene particle formation, it is suggested that PGEs with a high degree of glycerol polymerisation may be useful in the preparation of β‐carotene nanodispersions. The best stabilisation was obtained using 10 g kg−1 decaglycerol monolaurate. Copyright © 2004 Society of Chemical Industry
Fixed point theory for generalized contractive maps of Meir–Keeler type
Authors: Agarwal Ravi P. , O'Regan Donal , Shahzad Naseer
Published: October 2004

Fixed point, domain invariance and coincidence results are presented for single‐valued generalized contractive maps of Meir–Keeler type defined on complete metric spaces (or more generally complete gauge spaces). The maps of Caristi type are also considered. In addition the random analogue of some of these fixed point results will be presented. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Characteristic exponents of semialgebraic singularities
Authors: Birbrair Lev , Cano Felipe
Published: October 2004

Let X be a semialgebraic (or algebraic) set and let x0 ∈ X be a singular point. There are some topological cycles of different dimensions contained in a small neighbourhood of x0 in X. All these cycles vanish in x0. The paper is devoted to “vanishing rates” of these cycles, which we call “characteristic exponents”. We prove that the characteristic exponents are invariant under bi‐Lipschitz transformations. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Coefficients with unbounded derivatives in hyperbolic equations
Authors: Cicognani Massimo
Published: October 2004

We are concerned with the problem of determining the sharp regularity of the coefficients with respect to the time variable t in order to have a well‐posed Cauchy problem in H∞ or in Gevrey classes for linear or quasilinear hyperbolic operators of higher order. We use and mix two different scales of regularity of global and local type: the modulus of Hölder continuity and/or the behaviour with respect to |t − t1|−q, q ≥ 1, of the first derivative as t tends to a point t1. Both are ways to weaken the Lipschitz regularity. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fourier type 2 operators with respect to locally compact abelian groups
Authors: Hinrichs Aicke , Piotrowski Mariusz
Published: October 2004

A linear and bounded operator T between Banach spaces X and Y has Fourier type 2 with respect to a locally compact abelian group G if there exists a constant c > 0 such that∥T$\hat f$∥2 ≤ c∥f∥2 holds for all X‐valued functions f ∈ LX2(G) where $\hat f$ is the Fourier transform of f. We show that any Fourier type 2 operator with respect to the classical groups has Fourier type 2 with respect to any locally compact abelian group. This generalizes previous special results for the Cantor group and for closed subgroups of ℝn. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Bilinear estimates in homogeneous Triebel‐Lizorkin spaces and the Navier‐Stokes equations
Authors: Kozono Hideo , Shimada Yukihiro
Published: October 2004

We shall show that every strong solution u(t) of the Navier‐Stokes equations on (0, T) can be continued beyond t > T provided u ∈ $L^{{{2} \over {1 - \alpha}}}$ (0, T; $\dot F^{- \alpha}_{\infty ,\infty}$ for 0 < α < 1, where $\dot F^{s}_{p,q}$ denotes the homogeneous Triebel‐Lizorkin space. As a byproduct of our continuation theorem, we shall generalize a well‐known criterion due to Serrin on regularity of weak solutions. Such a bilinear estimate $\dot F^{- \alpha}_{p_1 , q_1} \cap \dot F^{s + \alpha}_{p_2 , q_2} \subset \dot F^{s}_{p, q}$, 1/p = 1/p1 + 1/p2, 1/q = 1/q1 + 1/q2 as the Hölder type inequality plays an important role for our results. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
CBMO estimates for commutators and multilinear singular integrals
Authors: Lu Shanzhen , Wu Qiang
Published: October 2004

In this paper, the authors establish the CBMO estimates for the commutators and multilinear singular integrals with rough kernels. Their endpoint estimates are also disposed. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Unboundedness of the large solutions of some asymmetric oscillators at resonance
Authors: Yang Xiaojing
Published: October 2004

In this paper, we consider the unboundedness of solutions of the following differential equation

(φp(x′))′ + (p − 1)[αφp(x+) − βφp(x−)] = f(x)x′ + g(x) + h(x) + e(t)

where φp(u) = |u|p− 2 u, p > 1, x± = max {±x, 0}, α and β are positive constants satisfying $\alpha ^{-{{1} \over {p}}} + \beta ^{-{{1} \over {p}}} = {{2m} \over {n}}$ with m, n ∈ N and (m, n) = 1, f and g are continuous and bounded functions such that limx→±∞g(x) ≕ g(±∞) exists and h has a sublinear primitive, e(t) is 2πp‐periodic and continuous. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relatively stable bundles over elliptic fibrations [Math. Nachr. 238, 23–36 (2002)]
Authors: Bartocci Claudio , Bruzzo Ugo , Hernández Ruipérez Daniel , Muñoz Porras José M.
Published: October 2004

See original Math. Nachr. 238, 23–36 (2002)
Development of an epitope‐specific analytical tool for the major peanut allergen Ara h 2 using a high‐density multiple‐antigenic peptide strategy
Authors: Gruber Patrick , Suhr Martin , Frey Andreas , Becker Wolf‐Meinhard , Hofmann Thomas
Published: October 2004

Using the major peanut allergen Ara h 2 as an example, an analytical tool enabling the determination of immunoglobulin E (IgE)‐epitopes in processed food allergens was developed. We synthesized a multiple‐antigenic peptide (MAP) of the IgE‐reactive linear epitope 3 (amino acid positions 27–36) of Ara h 2 and raised a monospecific antiserum against this epitope to obtain a positive control for future epitope resolved diagnostics. First, a MAP of epitope 3, having a molecular mass of 7770 Da, was synthesized, purified, and its structure confirmed by liquid chromatography‐mass spectrometry (electrospray ionization) (LC‐MS(ESI)), matrix assisted laser desorption/ionization‐time of flight (MALDI‐TOF), and Edman sequencing. The MAP was then used to raise high titer antibodies in rabbits using the adjuvant TitermaxTM and to characterize the specificity of IgE from allergenic patients sensitized to Ara h 2. The antiserum exclusively detects Ara h 2 in crude peanut extract with a titer of 107 by Western blot and reacts specifically with epitope 3 shown by epitope mapping for a library of solid‐phase‐bound synthetic 15‐mer peptides covering the entire sequence of Ara h 2. Such IgE‐reactive epitopes are of high analytical relevance as they could constitute the basis for epitope‐specific detection systems for use in quality control in the food industry or for forensic purposes in cases of fatal reactions to otherwise undetected peanut proteins.
The tautomerism of 1H‐pyrazole‐3(5)‐(N‐tert‐butyl)carboxamide in the solid state and in solution
Authors: Claramunt Rosa M. , García M. Ángeles , López Concepción , Trofimenko Swiatoslaw , Yap Glenn P. A. , Alkorta Ibon , Elguero José
Published: October 2004

The X‐ray crystal structure of 1H‐pyrazole‐3‐(N‐tert‐butyl)‐carboxamide was determined. In the solid state, the 13C and 15N CP/MAS NMR spectra correspond to this tautomer. In solution, both tautomers are present in a ratio that depends on the temperature (at 293 K, 90% 3‐substituted/10% 5‐substituted). Some unusual 1H, 1H couplings involving the NH proton were observed. DFT (GIAO) calculations were carried out. Copyright © 2004 John Wiley & Sons, Ltd.
Removal of dyes from water by conducting polymeric adsorbent
Authors: Chowdhury A.‐N. , Jesmeen S. R. , Hossain M. M.
Published: October 2004

Chemically synthesized conducting polyaniline (PANI) was investigated as adsorbent for its possible application in the removal of organic dyes, such as methylene blue (MB) and procion red (PR) from their aqueous solution. PANI adsorbent behaves as a charged surface upon post‐synthesis treatment of the polymer with acid and base. The adsorbent thus treated shows a high selectivity for the removal of dyes in the adsorption process. The Langmuir adsorption isotherm was used to represent the experimental adsorption data. The cationic dye, MB can be preferentially removed by the base‐treated PANI while the anionic dye, PR is predominately removed by the acid‐treated one. These observations were further evidenced from the measurements of molar conductance and pH of the dye solutions employed for adsorption. The finding can be explained considering the electrostatic nature of adsorption coupled with the morphology of the PANI surface thus treated. Copyright © 2004 John Wiley & Sons, Ltd.
The candidate oncogene ZNF217 is frequently amplified in colon cancer
Authors: Rooney Patrick H , Boonsong Attasit , McFadyen Morag CE , McLeod Howard L , Cassidy James , Curran Stephanie , Murray Graeme I
Published: October 2004

In this study we have defined the changes in gene copy number of the candidate oncogene ZNF217 during colon cancer development and progression. This gene is mapped to chromosome 20q and lies within 20q13.2, a region which we have previously shown to be highly amplified in colorectal cancer by comparative genomic hybridization. The gene copy number of ZNF217 was assessed in 100 colon carcinomas (19 Dukes' A, 42 Dukes' B and 39 Dukes' C), 13 colonic adenomas and 10 normal colon samples. DNA extracted from laser microdissected cells was amplified by multiplex real‐time PCR at two distinct gene loci—ZNF217 and β‐globin (control gene)—on an ABI7700 sequence detection system. Of the 100 colon cancers studied, 61 showed some level of amplification of ZNF217, 15 had loss of ZNF217, while 24 were diploid. All the adenomas except one were diploid. In this study we have found that ZNF217 amplification is a frequent event in colon cancer and that the extent of its amplification varies markedly between tumours (range 3–13 copies). There was a trend toward poorer survival in patients whose cancers had either gain or loss of ZNF217. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The prion protein in human neuromuscular diseases
Authors: Kovács Gábor G , Kalev Ognian , Gelpi Ellen , Haberler Christine , Wanschitz Julia , Strohschneider Michaela , Molnár Mária J , László Lajos , Budka Herbert
Published: October 2004

The basis of human prion diseases affecting the nervous system is accumulation of a disease‐associated conformer (PrPSc) of the normal cellular prion protein (PrPC). Earlier studies demonstrated increased expression of PrPC in inclusion body myositis (IBM), dermato‐, and polymyositis, as well as neurogenic muscle atrophy. To define the spectrum and reliability of PrPC immunoreactivity, its expression was examined systematically in a series of pathologically characterized muscular disorders by means of immunohistochemistry, confocal laser microscopy, and immunogold electron microscopy. Anti‐PrPC immunolabelling of rimmed vacuoles was observed in IBM, inclusions of myofibrillary myopathy, targets, regenerating, and atrophic fibres, mononuclear cells, in addition to ragged red fibres in mitochondrial myopathies, and focal sarcolemmal immunostaining in non‐diseased controls. Quantitative analysis demonstrated that, in neurogenic muscle lesions, anti‐PrPC staining detects a significantly broader spectrum of fibres than anti‐vimentin or anti‐NCAM. In dystrophic muscle, PrPC expression was mainly restricted to regenerating fibres. In IBM, PrPC expression was not confined to rimmed vacuoles or vacuolated fibres and only a small percentage (7.1%) of rimmed vacuoles were PrPC positive. Ultrastructurally, PrPC was observed in the cytoplasm of lymphocytes, in the myofibrillar network of targets, and in rimmed vacuoles. Knowledge of disease circumstances with altered expression of PrPC is important in the setting of a potentially increased chance for extraneural PrPC–PrPSc conversion. In addition, our observations suggest that PrPC may have a general stress–response effect in various neuromuscular disorders. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Molecular cytogenetic analysis of human spermatocytic seminomas
Authors: Verdorfer Irmgard , Rogatsch Hermann , Tzankov Alexandar , Steiner Hannes , Mikuz Gregor
Published: October 2004

We performed comparative genomic hybridization (CGH) on 8 formalin‐fixed, paraffin wax‐embedded primary spermatocytic seminomas (SS) from 7 patients, one of whom developed metastatic disease. In general, this tumour type is not associated with development of metastases. Since there are only few reported cases of metastatic SS in the literature, this study is the first report of chromosomal constitution in a patient with metastatic disease. Chromosomal imbalances were observed in all 8 tumours analysed by CGH. Frequent copy number alterations were enh(9), dim(16 or 16p), enh(20) and enh(X), each in 6 samples, followed by dim(7) in 4, and enh(1), enh(18) and dim(15), each in 3 samples. In addition to the CGH analysis, interphase fluorescence in situ hybridisation (I‐FISH) was applied to evaluate the CGH results and to define the size of the aberrant cell population. Interphase cytogenetics showed gain of material on chromosomes 9 and X in all tumours analysed. Overall, the I‐FISH results were in agreement with the CGH data. In conclusion, gain of chromosome 9 seems to be restricted to SS and point to an important role for this aberration in the development of this tumour type. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase‐1 expression in intestinal inflammation: anti‐inflammatory effect of carbon monoxide
Authors: Dijkstra Gerard , Blokzijl Hans , Bok Lisette , Homan Manon , van Goor Harry , Nico Faber Klaas , Jansen Peter LM , Moshage Han
Published: October 2004

Inducible nitric oxide synthase (iNOS) is expressed in intestinal epithelial cells (IEC) of patients with active inflammatory bowel disease (IBD) and in IEC of endotoxaemic rats. The induction of iNOS in IEC is an element of the NF‐κB‐mediated survival pathway. Haem oxygenase‐1 (HO‐1) is an AP‐1‐regulated gene that is induced by oxidative stress. The enzyme produces carbon monoxide (CO), which may attenuate the inflammatory response. The aim of this study was to investigate the regulation and interaction of iNOS and HO‐1 in response to inflammation and oxidative stress. Male Wistar rats were treated with the thiol‐modifying agent diethylmaleate (DEM) to induce oxidative stress and rendered endotoxaemic by LPS injection. Human colonic biopsies and the human colon carcinoma cell line DLD‐1 were treated with DEM and the lipid peroxidation end‐product 4‐hydroxynonenal to induce oxidative stress and exposed to cytokine mix (CM) to mimic inflammation. In some experiments, cells were incubated with 250–400 ppm CO prior to and during stimulation with CM. HO‐1 and iNOS expression was evaluated by RT‐PCR, western blotting, and immunohistology. NF‐κB activation was evaluated by EMSA. LPS induced iNOS but not HO‐1 in epithelial cells of the ileum and colon. Oxidative stress strongly induced HO‐1 in epithelial and inflammatory cells. Combined oxidative stress and endotoxaemia decreased iNOS expression but strongly induced HO‐1 expression. Similarly, CM induced iNOS but not HO‐1 in colonic biopsies and DLD‐1 cells. Oxidative stress prevented iNOS induction in an NF‐κB‐dependent manner but increased HO‐1 expression in CM‐exposed DLD‐1 cells. CO inhibited iNOS mRNA induction in CM‐stimulated DLD‐1 cells. These data demonstrate opposite regulation of iNOS and HO‐1 in intestinal epithelial cells in response to cytokine exposure and oxidative stress. These findings suggest that iNOS (NF‐κB driven) and HO‐1 (AP‐1 driven) represent mutually exclusive survival mechanisms in intestinal epithelial cells. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma
Authors: Kammerer Robert , Riesenberg Rainer , Weiler Christoph , Lohrmann Jens , Schleypen Julia , Zimmermann Wolfgang
Published: October 2004

CEACAM1 acts as a tumour suppressor in various epithelial tumours. On the other hand, de novo expression of CEACAM1 is strongly associated with reduced disease‐free survival of melanoma and non‐small cell lung carcinoma patients. Since effector functions of natural killer and T cells are inhibited by homophilic CEACAM1 interaction, immune escape could be responsible for the poor prognosis of these patients. Here, we describe CEACAM1 expression in normal kidney, renal adenomas and renal cell carcinomas (RCC) using a novel antibody generated by genetic immunization. In normal kidney, CEACAM1 was found in epithelial cells of proximal tubules and in endothelial cells. In contrast, tumour cells of 30 clear cell, three chromophobic, and two chromophilic RCCs were completely devoid of CEACAM1. Renal adenomas also lacked CEACAM1 expression. Similarly, RCC cell lines CaKi1, CaKi2, A498, and RCC26 exhibited no or low‐level CEACAM1 expression. However, CEACAM1 expression was transiently induced in A498 cells upon contact with allogeneic CD8+ T cells, mediated at least in part by interferon‐γ. Furthermore, the majority of tumour‐infiltrating T and NK cells expressed CEACAM1 upon stimulation. Thus, transient expression of the tumour suppressor CEACAM1 by tumour cells and subsequent homophilic interaction with CEACAM1 on tumour‐infiltrating lymphocytes could represent a novel immune escape mechanism in RCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Type I collagen synthesis parallels the conversion of keratinocytic intraepidermal neoplasia to cutaneous squamous cell carcinoma
Authors: van Kempen Léon CLT , Rijntjes Jos , Claes An , Blokx Willeke AM , Gerritsen Marie‐Jeanne P , Ruiter Dirk J , van Muijen Goos NP
Published: October 2004

Neoplastic progression of solid tumours is often characterized by a simultaneous increase in matrix protein (eg collagen) synthesis and degradation, and results in the formation of a tumour stroma. At the tumour periphery, this process is believed to facilitate angiogenesis and invasive growth of tumour cells. In various types of carcinoma, differentiation of fibroblasts towards myofibroblasts is thought to play an important role in extracellular matrix remodelling as their emergence coincides with architectural changes in the tumour stroma. Here, distinct architectural changes in collagen fibres are reported in cutaneous squamous cell carcinomas (cSCC) with respect to normal skin and precursor lesions, ie keratinocytic intraepidermal neoplasia (KIN). Simultaneously, type I collagen mRNA was observed in fibroblasts in close proximity to cSCC lesions (19/19) but only in 2 of 10 KIN lesions tested. Interestingly, whereas emerging of myofibroblasts correlated with reduced differentiation of cSCCs, it was not a prerequisite for type I collagen synthesis. These data indicate that type I collagen synthesis by fibroblasts parallels the malignant transformation of human KIN to cSCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Early recruitment of phagocytes contributes to the vascular inflammation of giant cell arteritis
Authors: Foell Dirk , Hernández‐Rodríguez José , Sánchez Montse , Vogl Thomas , Cid Maria C , Roth Johannes
Published: October 2004

Vascular inflammation in giant cell arteritis is generally described as a process involving dendritic cells, T‐lymphocytes, and effector tissue macrophages. Less is known about the contribution of phagocytes that are recruited early, such as monocytes and neutrophils. These cells express and secrete pro‐inflammatory S100 proteins which directly activate endothelial cells. In this study the expression of S100A8/S100A9 and S100A12, pro‐inflammatory proteins specific for early recruited phagocytes, was studied in biopsies from 36 patients with giant cell arteritis. In addition, serum concentrations of these proteins were analysed in serum samples from 42 patients and 35 healthy controls. The S100A8/S100A9 complex was found to be abundant in the adventitia and media in affected arteries. Besides neutrophils, cells expressing these proteins belonged to a pro‐inflammatory subtype of CD68‐positive monocytes. In contrast, S100A12 expression was restricted to neutrophils that were found around the vasa vasorum within the adventitial layer. Both S100A8/S100A9 and S100A12 serum concentrations were significantly higher in patients with giant cell arteritis than in healthy controls. In conclusion, recently recruited phagocytes expressing pro‐inflammatory S100 proteins take part in the vascular inflammation of giant cell arteritis. They may play important roles at the vasa vasorum of affected vessels, which represent sites of entry for recruited inflammatory cells. These data indicate that phagocytes within the adventitia and media contribute to the process of inflammation via release of the pro‐inflammatory S100 proteins S100A8, S100A9, and S100A12. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Successful engraftment following unrelated donor transplant in an alloimmunized patient with Kostmann syndrome
Authors: Myers Scott N. , Zeevi Adriana , Zorich G. Phil , Pillage Gina , Martel Joan , Goyal Rakesh K.
Published: October 2004

Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial infections during infancy. Blood or marrow transplantation (BMT) is the only curative option for patients with refractory disease. This report describes the case of a 4‐year‐old girl with refractory SCN, who received a bone marrow transplant from a highly matched donor after becoming HLA sensitized to multiple granulocyte transfusions. She is clinically well with normal blood counts and stable mixed chimerism 3 years after BMT. She experienced no graft rejection or graft versus host disease. © 2004 Wiley‐Liss, Inc.