bluuebunny/crossref_metadata_2025 huggingface dataset:
PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells
Authors: Nishimoto Mika , Furuta Akiko , Aoki Shunsuke , Kudo Yoshihisa , Miyakawa Hiroyoshi , Wada Keiji
Published: November 2006

The Pituitary adenylate cyclase‐activating peptide (PACAP) ligand/type 1 receptor (PAC1) system regulates neurogenesis and gliogenesis. It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs‐mediated cAMP‐dependent signaling pathway. However, it is unknown whether this ligand/receptor system has a function in proliferation of NPCs. In this study, we identified that PACAP and PAC1 were highly expressed and co‐localized in NPCs of mouse cortex at embryonic day 14.5 (E14.5) and found that the PACAP/PAC1 system potentiated growth factor‐induced proliferation of mouse cortical NPCs at E14.5 via Gq‐, but not Gs‐, mediated PLC/IP3‐dependent signaling pathway in an autocrine manner. Moreover, PAC1 activation induced elongation of cellular processes and a stellate morphology in astrocytes that had the bromodeoxyuridine (BrdU)‐incorporating ability of NPCs. Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling. These results suggest that the PACAP/PAC1 system may play a dual role in neural/glial progenitor cells not only differentiation but also proliferation in the cortical astrocyte lineage via Ca2+‐dependent signaling pathways through PAC1. © 2006 Wiley‐Liss, Inc.
Usefulness of MRI volumetric evaluation in patients with squamous cell cancer of the head and neck treated with neoadjuvant chemotherapy
Authors: Baghi Mehran , Mack Martin G. , Hambek Markus , Bisdas Sotirios , Muerthel Ramona , Wagenblast Jens , Gstoettner Wolfgang , Vogl Thomas , Knecht Rainald
Published: November 2006

Background.

The purpose was to evaluate the efficacy of tumor volumetry on MRI as predictive of response to treatment with induction chemotherapy, comparing the results with endoscopy.

Methods:

Fifty patients with advanced squamous cell carcinoma of the head and neck (SSCHN) who underwent MRI volumetry before and after neoadjuvant chemotherapy consisting of docetaxel, cisplatin, and 5‐fluorouracil (TPF) were included in this study. The tumor volume was calculated by a slice‐by‐slice evaluation. With the standard software of a workstation, the area of the tumor was measured slice by slice using manual segmentation. To evaluate the efficacy of MRI volumetry, pretreatment volume was compared with pretreatment remission status as evaluated with endoscopy.

Results.

Forty‐five (90%) patients demonstrated a tumor downstaging after chemotherapy. Fourteen (28%) patients showed a complete histologic remission (CR), 31 (62%) patients showed a partial remission (PR). Pretreatment tumor volume was significantly different between patients whose tumor completely responded (CR) and those whose tumor did not completely respond or whose disease was stable or was progressive (p = .00023). We defined a threshold for the pretreatment tumor volume in patients with CR, which was equal to 29.71 cc.

Conclusion.

We propose that MRI tumor volume analyses can be a useful parameter to predict the response to neoadjuvant chemotherapy in SCCHN. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Acceleration of hyperfractionated chemoradiation regimen for advanced head and neck cancer
Authors: Allen Aaron M. , Elshaikh Mohamed , Worden Francis P. , Bradford Carol R. , Teknos Theodoros N. , Chepeha Douglas B. , Tsien Christina , Dawson Laura A. , Urba Susan , Wolf Gregory T. , Normolle Daniel , Eisbruch Avraham
Published: November 2006

Background.

Our aim was to evaluate the acceleration of a hyperfractionated, concurrent chemoradiation regimen (HxCRT) for advanced head and neck squamous cell carcinoma (HNSCC).

Methods.

Patients with unresectable HNSCC were treated based on a previously published HxCRT regimen: 1.25 Gy twice daily to 70 Gy concurrent with cisplatin 12 mg/m2/day and5‐fluorouracil 600 mg/m2/day for 5 days, weeks 1, 5. This regimen was accelerated in this series by shortening the treatment from 7 to 6 weeks by omitting the planned mid‐treatment 1‐week break.

Results.

Forty‐six patients with T3‐4/N3 disease were treated. The main acute toxicity was pharyngeal. Median weight change during therapy in patients with and without enteral feeding tubes was −3.8% and −7.9%, respectively (p = .08). Fifteen percent had late grade III pharyngeal toxicity. Local/regional and distant failure rates were 28% and 17%, respectively; 52% are alive without evidence of disease.

Conclusions.

In nonresectable HNSCC, acceleration of the HxCRT regimen is feasible, requiring enteral feeding tubes during therapy in most patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Influence of social support on health‐related quality of life outcomes in head and neck cancer
Authors: Karnell Lucy Hynds , Christensen Alan J. , Rosenthal Eben L. , Magnuson J. Scott , Funk Gerry F.
Published: November 2006

Background.

Evidence that social support influences health‐related quality of life (HRQOL) in oncologic patients could be particularly important for head and neck cancer because this disease can affect speech, eating, and facial aesthetics.

Methods.

Multiple regression analyses were used in this prospective, observational study to determine the association between 394 patients' ratings of perceived post‐treatment social support and HRQOL outcomes while controlling for possible confounding variables.

Results.

Higher social support scores were significantly associated with higher scores in speech (p = .007), aesthetics (p = .015), social disruption (p = .045), and general mental health (p = .016) and with fewer depressive symptoms (p = .023) but not with general physical health (p = .191) or eating (p = .114). The magnitude of differences in the HRQOL outcomes for patients whose social support scores fell in the lowest and highest quartiles were clinically meaningful.

Conclusions.

Given the association between social support and HRQOL outcomes in this patient population, modification of perceived social support through clinical interventions could improve the survivorship of these patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Use of integrated 18F‐FDG PET/CT to improve the accuracy of initial cervical nodal evaluation in patients with head and neck squamous cell carcinoma
Authors: Jeong Han‐Sin , Baek Chung‐Hwan , Son Young‐Ik , Ki Chung Man , Kyung Lee Dong , Young Choi Joon , Kim Byung‐Tae , Kim Hyung‐Jin
Published: November 2006

Background.

We investigated the accuracy of performing cervical nodal evaluation with using integrated 18F‐fluoro deoxyglucose positron emission tomography (PET)/CT for squamous cell carcinoma (SCC) of the head and neck as compared with using PET and contrast‐enhanced CT (CECT) alone.

Methods.

The presence of metastatic lymphadenopathy in each cervical nodal group (level I–VI) and the nodal (N) classification of 47 patients with SCC of the head and neck were determined by using PET, CECT, and PET/CT, respectively, and the results were verified according to the histopathologic findings.

Results.

Among the 91 foci that had abnormal uptake on PET, the combined PET/CT images provided additional information over PET for the anatomical localization and lesion characterization of 18 sites (19.8%) in 17 patients (36.2%). PET/CT also showed the best results among the three imaging modalities for the sensitivity, specificity, and accuracy (91.8, 98.9, and 97.1%, respectively) for predicting metastatic nodes on a level‐by‐level analysis, and PET/CT had a higher accuracy (85.1%) for the pathologic nodal classification over the clinical examinations (68.1%) or PET (70.2%).

Conclusions.

Combined PET/CT images are more accurate than the PET or CECT images alone for conducting cervical node evaluation in the patients suffering with head and neck SCC. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Successful implant of long‐term cryopreserved parathyroid glands after total parathyroidectomy
Authors: de Menezes Montenegro Fábio Luiz , Custódio Melani Ribeiro , Arap Sérgio Samir , Reis Luciene Machado dos , Sonohara Shigueko , Castro Inês Vieira , Jorgetti Vanda , Cordeiro Anói Castro , Ferraz Alberto Rosseti
Published: November 2006

Background.

Parathyroid cryopreservation is essential in some cases of parathyroid surgery. The fate of autografted tissue after long‐term cryopreservation is not fully discussed in the literature.

Methods.

The successful experience with the use of parathyroid tissues preserved for 21 months and 30 months is reported.

Results.

Both patients were women with renal hyperparathyroidism who underwent total parathyroidectomy without autotransplantation. Patient 1 was a 40‐year‐old woman. At 21 months of follow‐up, her parathyroid hormone (PTH) level was undetectable, and despite oral calcium supplements, she was hypocalcemic. Forty‐five cryopreserved fragments were thawed and implanted in her forearm. Calcium levels improved, and PTH steadily increased in both arms. PTH levels at 18 months after the autograft were 37.0 pg/mL in the contralateral arm and 1150.0 pg/mL in the implant arm. Patient 2 was a 44‐year‐old woman. After 30 months, her PTH was undetectable, and she underwent cryopreserved tissue implantation.

Conclusion.

These cases show that parathyroid tissue may remain viable even after long‐term storage. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck
Authors: Hoffmann Thomas K. , Sonkoly Eniko , Homey Bernhard , Scheckenbach Katrin , Gwosdz Christian , Bas Murat , Chaker Adam , Schirlau Kerstin , Whiteside Theresa L.
Published: November 2006

Background.

Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) represent 2 clinically important subtypes of head and neck cancer. Our objective was to characterize and compare cytokine profiles in the systemic circulation of patients with SCC and ACC.

Methods.

Multiplex analysis of 10 different cytokines (interleukin [IL]‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF], interferon [IFN]‐γ, and tumor necrosis factor [TNF]‐α) in the serum of patients with SCC (n = 20) and ACC (n = 20) and healthy controls (n = 20) was performed using the Luminex fluorescent‐bead technology.

Results.

Patients with SCC as well as patients with ACC showed an altered cytokine profile compared with healthy individuals. In patients with SCC, significantly elevated serum levels of the proinflammatory cytokines, IL‐6 and IL‐8, were observed. In patients with ACC, IL‐8 serum levels were significantly elevated, and IL‐6 serum levels were only increased in a subset of patients.

Conclusions.

A similar serum cytokine profile, with the predominance of proinflammatory cytokines, was observed in patients with SCC and ACC. The newly defined cytokine profile in ACC patients may form the basis for future investigations to explore the role of cytokines in ACC tumor progression and their potential value as predictive biomarkers. © 2006 Wiley Periodicals, Inc. Head Neck, 2007
Impaired maze performance in aged rats is accompanied by increased density of NMDA, 5‐HT1A, and α‐adrenoceptor binding in hippocampus
Authors: Topic B. , Willuhn I. , Palomero‐Gallagher N. , Zilles K. , Huston J.P. , Hasenöhrl R.U.
Published: November 2006

Using quantitative receptor autoradiography, we assessed binding site densities and distribution patterns of glutamate, GABAA, acetylcholine (ACh), and monoamine receptors in the hippocampus of 32‐month‐old Fischer 344/Brown Norway rats. Prior to autoradiography, the rats were divided into two groups according to their retention performance in a water maze reference memory task, which was assessed 1 week after 8 days of daily maze training. The animals of the inferior group showed less long‐term retention of the hidden‐platform task but did not differ from superior rats in their navigation performance during place training and cued trials. The decreased retention performance in the group of inferior learners was primarily accompanied by increased α1‐adrenoceptors in all hippocampal subregions under inspection (CA1‐CA4 and dentate gyrus), while elevated α2‐adrenoceptor binding was observed in the CA1 region and DG. Furthermore, inferior learners had higher NMDA binding in the CA2 and CA4 and increased 5‐HT1A binding sites in the CA2, CA3, and CA4 region. No significant differences between inferior and superior learners were evident with regard to AMPA, kainate, GABAA, muscarinergic M1, dopamine D1, and 5‐HT2 binding densities in any hippocampal region analyzed. These results show that increased NMDA, 5‐HT1A, and α‐adrenoceptor binding in the hippocampus is associated with a decline in spatial memory. The increased receptor binding observed in the group of old rats with inferior maze performance might be the result of neural adaptation triggered by age‐related changes in synaptic connectivity and/or synaptic activity. © 2006 Wiley‐Liss, Inc.
Risk factors for intrahepatic cholangiocarcinoma in a low‐risk population: A nationwide case‐control study
Authors: Welzel Tania M. , Mellemkjaer Lene , Gloria Gridley , Sakoda Lori C. , Hsing Ann W. , Ghormli Laure El , Olsen Jorgen H. , McGlynn Katherine A.
Published: November 2006

Recently, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing in a number of developed (Western) countries. However, risk factors in these low‐risk populations are poorly understood. In this nationwide population based case‐control study in Denmark, we examined the relationship between selected medical conditions and subsequent ICC risk to provide additional clues to etiopathogenesis. All histologically confirmed ICC cases diagnosed in Denmark between 1978 and 1991 were identified from the Danish cancer registry. Population controls were selected from the central population registry and were matched 4:1 to cases on sex and year of birth. Cases and controls were linked to the Danish hospital discharge registry to obtain information on prior hospital diagnoses. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived using conditional logistic regression. A total of 764 ICC cases and 3,056 population controls were included in the study. Chronic liver diseases were significantly related to ICC: alcoholic liver disease (OR = 19.22, 95% CI = 5.55–66.54), unspecified cirrhosis (OR = 75.9, 95% CI 10.2–565.7). Bile duct diseases were also associated with risk: cholangitis (OR = 6.3, 95% CI = 2.3–17.5), choledocholithiasis (OR = 23.97, 95% CI = 2.9–198.9), cholecystolithiasis (OR = 4.0, 95% CI = 2.0–7.99), though gallbladder removal did not change risk (OR = 1.6, 95% CI = 0.65–3.7). Among other conditions, chronic inflammatory bowel disease (OR = 4.7, 95% CI = 1.65–13.9) was significantly associated with ICC. Diabetes was associated with risk in the year prior to diagnosis of ICC (OR = 3.02, 95% CI = 1.05–8.69). Obesity was unrelated to risk. These results confirm that prior bile duct diseases increase risk of ICC and suggest that alcoholic liver disease and diabetes may also increase risk. © 2006 Wiley‐Liss, Inc.
A novel ordered nano hydroxyapatite coating electrochemically deposited on titanium substrate
Authors: Hu Ren , Lin Chang‐Jian , Shi Hai‐Yan
Published: November 2006

A novel porous nano hydroxyapatite (HA) coating has been prepared on commercially pure titanium substrate by a modified electrochemical deposition method. The physico‐chemical and biological properties of the coating were characterized by SEM, XRD, FTIR, Raman, and in vitro cell culture test respectively. The SEM patterns show a uniform microporous morphology consisting of wirelike crystals at nanometer scale. It is suggested that under controlled deposition conditions, the primary HA nanowires grow and self‐assemble to construct an ordered microporous nest‐like morphology, thus to form a nano‐micro two‐level structure. The XRD results demonstrate that the HA nanowires are orderly arranged with their c‐axis preferentially perpendicular to the substrate surface. The Raman and IR spectra affirm that the main component of the coating is well crystallized HA. An interdigitation phenomenon of the MG63 human osteosarcoma cells with the HA nanowires is observed in the in vitro test, indicating excellent biocompatibility and bioactivity for the prepared coating. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Plasma deposition of tetraglyme inside small diameter tubing: Optimization and characterization
Authors: Cao Lan , Ratner Buddy D. , Horbett Thomas A.
Published: November 2006

In this study, a glow discharge plasma deposition system previously used for treating flat substrates was successfully modified and optimized to produce a PEO‐like coating on the inner surface of 1–3 mm ID polyethylene tubing by deposition of tetra ethylene glycol dimethyl ether (tetraglyme). The plasma treatment conditions were varied in order to find operating values that would produce coatings with the ultralow (<5 ng/cm2) fibrinogen adsorption (ΓFg) previously shown necessary to significantly reduce platelet adhesion. The flow rate of gaseous tetraglyme monomer, pressure, and plasma generating power were found to be the most important parameters affecting the uniformity and chemical structure of the coating. The coating uniformity and quality were assessed by measuring ΓFg at positions 1 cm apart along the entire tube and the fraction of C1s carbon that was in an ether bond (ether–carbon ratio) by electron spectroscopy of chemical analysis. Under optimized conditions, tetraglyme plasma‐coated tubes of up to 20 cm in length had ultralow ΓFg. The region of the tube that had ultralow ΓFg also had C1s ether–carbon ratios that are greater than 50%. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Investigation ofin vitrobiocompatibility of novel pentablock copolymers for gene delivery
Authors: Agarwal Ankit , Unfer Robert , Mallapragada Surya K.
Published: November 2006

Novel pentablock copolymers of poly(diethylaminoethylmethacrylate) (PDEAEM), poly(ethylene oxide) (PEO), and poly(propylene oxide) (PPO), (PDEAEM‐b‐PEO‐b‐PPO‐b‐PEO‐b‐PDEAEM), were synthesized as vectors for gene delivery, and were tested for their biocompatibility on SKOV3 (human ovarian carcinoma) and A431 (human epidermoid cancer) cell lines under differentin vitroconditions using various assays to elucidate the mechanism of cell death. These copolymers form micelles in aqueous solutions and can be tuned for their cytotoxicity by tailoring the weight percentage of their cationic component, PDEAEM. Copolymers with higher PDEAEM content were found to be more cytotoxic, though their polyplexes were less toxic than the polycations alone. Pentablock copolymers displayed higher cell viability than commercially available ExGen 500® at similar N:P ratios. While cell death with ExGen was found to be accompanied by an early loss of cell membrane integrity, pentablock copolymers caused very little membrane leakage. Caspase‐3/7 assay confirmed that none of these polymers induced apoptosis in the cells. These pentablock copolymers form thermo‐reversible gels at physiological temperatures, thereby enabling controlled gene delivery. Toxicity of the polymer gels was tested using an agarose‐matrix, simulating anin vivotumor model where injected polyplex gels would dissolve to release polyplexes, diffusing through tumor mass to reach the target cells. Twenty five weight percent of copolymer gels were found to be nontoxic or mildly cytotoxic after 24 h incubation. Transfection efficiency of the copolymers was found to be critically correlated to cytotoxicity and depended on DNA dose, polymer concentration, and N:P ratios. Transgene expression obtained was comparable to that of ExGen, but ExGen exhibited greater cell death. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Three‐dimensional growth behavior of osteoblasts on biomimetic hydroxylapatite scaffolds
Authors: Rumpler M. , Woesz A. , Varga F. , Manjubala I. , Klaushofer K. , Fratzl P.
Published: November 2006

The authors used rapid prototyping to produce three‐dimensional hydroxylapatite scaffolds with controlled, fully interconnected porosity. The purpose of this study was to illuminate the effect of hormones on the osteogenic differentiation and to investigate how osteoblasts colonize the three‐dimensional scaffold focusing on the formation of the cellular network. Preosteoblasts were seeded onto scaffolds, were optionally treated with the osteogenic hormones triiodo‐L‐thyronine (T3) and 1,25‐dihydroxyvitamin‐D3 (D3), and the expression of osteoblastic marker genes was investigated. Confocal laser scanning microscopy was used to investigate the three‐dimensional growth behavior. Culturing cells on scaffolds strongly increased the expression of osteocalcin, osteoprotegerin, Runx2, and receptor activator of NFkB‐ligand (RANKL). Treatment with T3 increased the expression of osteocalcin but did not change that of osteoprotegerin and Runx2. Treatment with D3 inhibited the expression of osteocalcin, Runx2, and osteoprotegerin. Both hormones had similar effects in the three‐dimensional system as found in two‐dimensional cultures although more accentuated, indicating that preosteoblasts behave more naturally on three‐dimensional structures. The osteoblasts colonized the three‐dimensional squared pores of scaffolds by forming a cellular network with a round central channel keeping it into the depth and depositing collagen fibrils. These results provide insight how osteoblasts colonize a three‐dimensional system and underline the importance of this environment in osteoblastic differentiation studies. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Direct encapsulation of BSA and DNA into silica microcapsules (hollow spheres)
Authors: Fujiwara Masahiro , Shiokawa Kumi , Hayashi Kaoru , Morigaki Kenichi , Nakahara Yoshiko
Published: November 2006

We reported before that silica hollow spheres (microcapsules) are prepared by interfacial reaction method that W/O emulsion with the aqueous solution of sodium silicate and n‐hexane solution of Tween 80 and Span 80 is combined with another aqueous solution of silica precipitant such as NH4HCO3 and NH4Cl. This procedure using W/O/W emulsion fabricates the hollow structures of silica particles directly, and additional steps such as the removal of core parts, that are often essential for the preparation of hollow particles via core‐shell materials, are not required. When biomacromolecules such as protein and nucleic acid are mixed in the aqueous solution of sodium silicate, these macromolecules can be encapsulated into the microcapsules. We succeeded the direct encapsulation of bovine serum albumin (BSA) and duplex DNA. Most of encapsulated BSA and DNA cannot be released from the microcapsules without the destruction of microcapsule shell. These microcapsule materials encapsulating biomacromolecules will be applied to biotechnologies such as immobilized enzyme and so on. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Adhesion of MC3T3‐E1 cells to RGD peptides of different flanking residues: Detachment strength and correlation with long‐term cellular function
Authors: Lee Mark H. , Adams Christopher S. , Boettiger David , DeGrado William F. , Shapiro Irving M. , Composto Russell J. , Ducheyne Paul
Published: November 2006

We synthesized a series of RGD peptides and immobilized them to an amine‐functional self‐assembled monolayer using a modified maleimide‐based conjugate technique that minimizes nonspecific interactions. Using a spinning disc apparatus, a trend in the detachment strength (τ50) of RGD peptides of different flanking residues was found: RGDSPK > RGDSVVYGLR ≈ RGDS > RGES. Using blocking monoclonal antibodies, cellular adhesion to the peptides was shown to be primarily αv‐integrin‐mediated. In contrast, the τ50 value of the cells on fibronectin (Fn)‐coated substrates of similar surface density was 6–7 times higher and involved both α5β1 and αvβ3 integrins. Cellular spreading was enhanced on RGD peptides after 1 h when compared to RGE and unmodified substrates. However, no significant differences were observed between the different RGD peptides. Long‐term function of MC3T3‐E1 cells was also evaluated by measuring alkaline phosphatase (ALP) activity and mineral deposition. Among the four peptides, RGDSPK exhibited the highest level of ALP activity after 11 days and mineralization after 15 days and reached comparable levels as Fn substrates after 15 and 24 days, respectively. These findings collectively illustrate both the advantages and limitations of enhancing cellular adhesion and function by the design of RGD peptides. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Microstructure and macroscopic properties of bioactive CaO–SiO2–PDMS hybrids
Authors: Salinas A. J. , Merino J. M. , Babonneau F. , Gil F. J. , Vallet‐Regí M.
Published: November 2006

CaO–SiO2–PDMS (polydimethylsiloxane) hybrid materials were synthesized as crack‐free monoliths presenting in vitro bioactivity, i.e. able to be coated with a calcium phosphate‐rich layer after having been soaked in simulated body fluid (SBF). A wide physical–chemical characterization of these materials was carried out to relate their microscopic structure and macroscopic properties. The effect of PDMS and the amounts of water used for the tetraethoxysilane (TEOS) hydrolysis on the mechanical properties of hybrid materials was investigated by three‐point bending tests. For a given amount of water, as PDMS content in hybrids increased, the elastic modulus decreased. Furthermore, keeping the PDMS content constant, when the amount of H2O decreased, the elastic modulus increased. Regarding in vitro bioactivity and mechanical properties, the hybrid material obtained with molar ratios H2O/TEOS = 2 and TEOS/PDMS = 3.5 proved to be the best candidate for either soft tissue substitution or metallic implant coating since the hybrid material would promote bond to bone formation, simultaneously dampening the mechanical charges. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
An active wound dressing for controlled convective mass transfer with the wound bed
Authors: Cabodi Mario , Cross Valerie L. , Qu Zheng , Havenstrite Karen L. , Schwartz Suzanne , Stroock Abraham D.
Published: November 2006

Conventional wound dressings—gauze, plastic films, foams, and gels—do not allow for spatial and temporal control of the soluble chemistry within the wound bed, and are thus limited to a passive role in wound healing. Here, we present an active wound dressing (AWD) designed to control convective mass transfer with the wound bed; this mass transfer provides a means to tailor and monitor the chemical state of a wound and, potentially, to aid the healing process. We form this AWD as a bilayer of porous poly(hydroxyethyl methacrylate) (pHEMA) and silicone; the pHEMA acts as the interface with the wound bed, and a layer of silicone provides a vapor barrier and a support for connecting to external reservoirs and pumps. We measure the convective permeability of the pHEMA sponge, and use this value to design a device with a spatially uniform flow profile. We quantify the global coefficient of mass transfer of the AWD on a dissolvable synthetic surface, and compare it to existing theories of mass transfer in porous media. We also operate the AWD on model wound beds made of calcium alginate gel to demonstrate extraction and delivery of low molecular weight solutes and a model protein. Using this system, we demonstrate both uniform mass transfer over the entire wound bed and patterned mass transfer in three spatially distinct regions. Finally, we discuss opportunities and challenges for the clinical application of this design of an AWD. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Severe citrate toxicity complicating volunteer apheresis platelet donation
Authors: Bell A.M. , Nolen J.D.L. , Knudson C.M. , Raife T.J.
Published: November 2006

We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40‐year‐old female, first‐time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre‐procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors. J. Clin. Apheresis. © 2006 Wiley‐Liss, Inc.
Approach to systematic analysis of serine/threonine phosphoproteome using Beta elimination and subsequent side effects: Intramolecular linkage and/or racemisation
Authors: Tinette Sylvette , Feyereisen René , Robichon Alain
Published: November 2006

Complete analysis of the phosphorylation of serine and threonine residues directly from biological extracts is still at an early stage and will remain a challenging goal for many years. Analysis of phosphorylated proteins and identification of the phosphorylated sites in a crude biological extract is a major topic in proteomics, since phosphorylation plays a dominant role in post‐translational protein modification. Beta elimination of the serine/threonine‐bound phosphate by alkali action generates (methyl)dehydroalanine. The reactivity of this group susceptible of nucleophilic attacks might be used as a tool for phosphoproteome analysis. Most of the known serine/threonine kinases recognize motifs in protein targets that are rich in lysine(s) and/or arginine(s). The (methyl)dehydroalanine resulting from beta elimination of the serine/threonine‐bound phosphate by alkali action is likely to react with the amino groups of these neighboring amino acids. Furthermore, the addition reaction of dehydroalanine‐peptides with a nucleophilic group more likely generates diastereoisomers derivatives. The internal cyclic bonds and/or the stereoisomer peptide derivatives thus generated confer resistance to trypsin cleavage and/or constitute stop signals for exopeptidases such as carboxypeptidase. This might form the basis of a method to facilitate the systematic identification of phosphorylated peptides. J. Cell. Biochem. 100: 875–882, 2007. © 2006 Wiley‐Liss, Inc.
Vascular permeability induced by VEGF family members in vivo: Role of endogenous PAF and NO synthesis
Authors: Brkovic Alexandre , Sirois Martin G.
Published: November 2006

We previously reported that vascular endothelial growth factor (VEGF) increases vascular permeability through the synthesis of endothelial platelet‐activating factor (PAF), while others reported the contribution of nitric oxide (NO). Herein, we addressed the contribution of VEGF receptors and the role played by PAF and NO in VEGF‐induced plasma protein extravasation. Using a modified Miles assay, intradermal injection in mice ears of VEGF‐A165, VEGF‐A121, and VEGF‐C (1 µM) which activate VEGFR‐2 (Flk‐1) receptor increased vascular permeability, whereas a treatment with VEGFR‐1 (Flt‐1) analogs; PlGF and VEGF‐B (1 µM) had no such effect. Pretreatment of mice with PAF receptor antagonist (LAU8080) or endothelial nitric oxide synthase (eNOS) inhibitor (L‐NAME) abrogated protein extravasation mediated by VEGF‐A165. As opposed to PAF (0.01‐1 µM), treatment with acetylcholine (ACh; up to 100 µM; inducer of NO synthesis) or sodium nitroprusside (SNP; up to 1 µM; NO donor) did not induce protein leakage. Simultaneous pretreatment of mice with eNOS and protein kinase A (PKA) inhibitors restored VEGF‐A165 vascular hyperpermeability suggesting that endogenous NO synthesis leads to PKA inhibition, which support maintenance of vascular integrity. Our data demonstrate that VEGF analogs increase vascular permeability through VEGFR‐2 activation, and that both endogenous PAF and NO synthesis contribute to VEGF‐A165‐mediated vascular permeability. However, PAF but not NO directly increases vascular permeability per se, thereby, suggesting that PAF is a direct inflammatory mediator, whereas NO serves as a cofactor in VEGF‐A165 proinflammatory activities. J. Cell. Biochem. 100: 727–737, 2007. © 2006 Wiley‐Liss, Inc.
VDR‐mediated gene expression patterns in resting human coronary artery smooth muscle cells
Authors: Wu‐Wong J. Ruth , Nakane Masaki , Ma Junli , Ruan Xiaoan , Kroeger Paul E.
Published: November 2006

Vitamin D analogs such as paricalcitol and calcitriol that activate the vitamin D receptor (VDR) provide survival benefit for Stage 5 chronic kidney disease (CKD) patients, possibly associated with a decrease in cardiovascular (CV)‐related incidents. Phenotypic changes of smooth muscle cells play an important role in CV disease. The role of vitamin D analogs in modulating gene expression in smooth muscle cells is still not well understood. In this study, DNA microarray analysis of ∼22,000 different human genes was used to characterize the VDR‐mediated gene expression profile in human coronary artery smooth muscle cells (CASMC) at rest. Cells in serum free medium were treated with 0.1 µM calcitriol (1α,25‐dihydroxyvitamin D3) or paricalcitol (19‐nor‐1α,25‐(OH)2D2) for 30 h. A total of 181 target genes were identified, with 103 genes upregulated and 78 downregulated (>two fold changes in either drug treatment group with P < 0.01). No significant difference was observed between calcitriol and paricalcitol. Target genes fell into various categories with the top five in cellular process, cell communication, signal transduction, development, and morphogenesis. Twenty‐two selected genes linked to the CV system were also impacted. Real‐time RT‐PCR and/or Western blotting analysis were employed to confirm the expression patterns of selected genes such as 25‐hydroxyvitamin D‐24‐hydroxylase, Wilms' tumor gene 1, transforming growth factorβ3, plasminogen activator inhibitor‐1, thrombospondin‐1 (THBS1), and thrombomodulin (TM). This study provides insight into understanding the role of VDR in regulating gene expression in resting smooth muscle cells. J. Cell. Biochem. 100: 1395–1405, 2007. © 2006 Wiley‐Liss, Inc.
Comprehensive analysis of chemical bonding in boron clusters
Authors: Zubarev Dmitry Yu. , Boldyrev Alexander I.
Published: November 2006

We present a comprehensive analysis of chemical bonding in pure boron clusters. It is now established in joint experimental and theoretical studies that pure boron clusters are planar or quasi‐planar at least up to twenty atoms. Their planarity or quasi‐planarity was usually discussed in terms of π‐delocalization or π‐aromaticity. In the current article, we demonstrated that one cannot ignore σ‐electrons and that the presence of two‐center two‐electron (2c2e) peripheral BB bonds together with the globally delocalized σ‐electrons must be taken into consideration when the shape of pure boron cluster is discussed. The global aromaticity (or global antiaromaticity) can be assigned on the basis of the 4n + 2 (or 4n) electron counting rule for either π‐ or σ‐electrons in the planar structures. We showed that pure boron clusters could have double (σ‐ and π‐) aromaticity (B, B4, B, B, B, B, B8, B, B, B10, B, B12, and B), double (σ‐ and π‐) antiaromaticity (B, B15), or conflicting aromaticity (B5−,σ‐antiaromatic and π‐aromatic and B14, σ‐aromatic and π‐antiaromatic). Appropriate geometric fit is also an essential factor, which determines the shape of the most stable structures. In all the boron clusters considered here, the peripheral atoms form planar cycles. Peripheral 2c2e BB bonds are built up from s to p hybrid atomic orbitals and this enforces the planarity of the cycle. If the given number of central atoms (1, 2, 3, or 4) can perfectly fit the central cavity then the overall structure is planar. Otherwise, central atoms come out of the plane of the cycle and the overall structure is quasi‐planar. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2007
σ and π contributions to the induced magnetic field: Indicators for the mobility of electrons in molecules
Authors: Heine Thomas , Islas Rafael , Merino Gabriel
Published: November 2006

The authors discuss the role of the σ and π contributions to the induced magnetic field for simple hydrocarbons containing a double or a triple bond, as well as for benzene and cyclobutadiene. While the magnetic field induced by the σ electrons is short‐ranged, the π system is responsible for the formation of long‐range cones. These cones influence the chemical shift of atoms by additional shielding (for aromatic) or deshielding (for antiaromatic molecules) contributions. While the hydrogen atoms of benzene are found to lie within the deshielded region of the magnetic field induced by the π electrons, they are shielded by the total induced magnetic field. The induced magnetic field of the π electrons support Pople's model on the basis of first‐principles calculations. © 2006 Wiley Periodicals, Inc. J Comput Chem 2007
HIV‐1 negatively affects the survival/maturation of cord blood CD34+ hematopoietic progenitor cells differentiated towards megakaryocytic lineage by HIV‐1 gp120/CD4 membrane interaction
Authors: Gibellini Davide , Vitone Francesca , Buzzi Marina , Schiavone Pasqua , De Crignis Elisa , Cicola Ronny , Conte Roberto , Ponti Cristina , Re Maria Carla
Published: November 2006

To investigate the mechanisms involved in the human immunodeficiency virus type 1 (HIV‐1)‐related thrombocytopenia (TP), human umbilical cord blood (UCB) CD34+ hematopoietic progenitor cells (HPCs) were challenged with HIV‐1IIIb and then differentiated by thrombopoietin (TPO) towards megakaryocytic lineage. This study showed that HIV‐1, heat‐inactivated HIV‐1, and HIV‐1 recombinant gp120 (rgp120) activated apoptotic process of megakaryocyte (MK) progenitors/precursors and decreased higher ploidy MK cell fraction. All these inhibitory effects on MK survival/maturation and platelets formation were elicited by the interaction between gp120 and CD4 receptor on the cell membrane in the absence of HIV‐1 productive infection. In fact, in our experimental conditions, HPCs were resistant to HIV‐1 infection and no detectable productive infection was observed. We also evaluated whether the expression of specific cytokines, such as TGF‐β1 and APRIL, involved in the regulation of HPCs and MKs proliferation, was modulated by HIV‐1. The specific protein and mRNA detection analysis, during TPO‐induced differentiation, demonstrated that HIV‐1 upregulates TGF‐β1 and downregulates APRIL expression through the CD4 engagement by gp120. Altogether, these data suggest that survival/differentiation of HPCs committed to MK lineage is negatively affected by HIV‐1 gp120/CD4 interaction. This long‐term inhibitory effect is also correlated to specific cytokines regulation and it may represent an additional mechanism to explain the TP occurring in HIV‐1 patients. J. Cell. Physiol. 210: 315–324, 2007. © 2006 Wiley‐Liss, Inc.
Identification of differentially expressed microRNAs by microarray: A possible role for microRNA genes in pituitary adenomas
Authors: Bottoni Arianna , Zatelli Maria Chiara , Ferracin Manuela , Tagliati Federico , Piccin Daniela , Vignali Cristina , Calin George A. , Negrini Massimo , Croce Carlo M. , degli Uberti Ettore C.
Published: November 2006

MicroRNAs (miRNAs) are small non‐coding RNAs that control gene expression by targeting mRNA. It has been demonstrated that miRNA expression is altered in many human cancers, suggesting that they may play a role in human neoplasia. To determine whether miRNA expression is altered in pituitary adenomas, we analyzed the entire miRNAome in 32 pituitary adenomas and in 6 normal pituitary samples by microarray and by Real‐Time PCR. Here, we show that 30 miRNAs are differentially expressed between normal pituitary and pituitary adenomas. Moreover, 24 miRNAs were identified as a predictive signature of pituitary adenoma and 29 miRNAs were able to predict pituitary adenoma histotype. miRNA expression could differentiate micro‐ from macro‐adenomas and treated from non‐treated patient samples. Several of the identified miRNAs are involved in cell proliferation and apoptosis, suggesting that their deregulated expression may be involved in pituitary tumorigenesis. Predictive miRNAs could be potentially useful diagnostic markers, improving the classification of pituitary adenomas. J. Cell. Physiol. 210: 370–377, 2007. © 2006 Wiley‐Liss, Inc.
Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF‐β1 to induce mesenchymal cell condensation
Authors: Song Jason J. , Aswad Rulla , Kanaan Reem A. , Rico Mario C. , Owen Thomas A. , Barbe Mary F. , Safadi Fayez F. , Popoff Steven N.
Published: November 2006

Mesenchymal cell (MC) condensation or the aggregation of MCs precedes chondrocyte differentiation and is required for subsequent cartilage formation during endochondral ossification. In this study, we used micromass cultures of C3H10T1/2 cells as an in vitro model system for studying MC condensation and the events important for this process. Transforming growth factor β1 (TGF‐β1) served as the initiator of MC condensation in our model system and we were interested in determining whether CTGF functions as a downstream mediator of TGF‐β1. CTGF is a matricellular protein that has been found to be expressed in MC condensations and in the perichondrium. Micromass cultures of C3H10T1/2 cells condensed under TGF‐β1 stimulation concomitant with dramatic up‐regulation of CTGF mRNA and protein levels. CTGF silencing by either CTGF siRNA or CTGF antisense oligonucleotide approaches showed that TGF‐β1‐induced condensation was CTGF dependent. Furthermore, silencing of CTGF expression resulted in significant reductions in cell proliferation and migration, events that are crucial during MC condensation. In addition, up‐regulation of Fibronectin (FN) and suppression of Sox9 expression by TGF‐β1 was also found to be mediated by CTGF. Immunofluorescence of developing mouse vertebrae showed that CTGF, TGF‐β1 and FN were co‐expressed in condensations of MCs, while Sox9 expression was low at this stage. During subsequent chondrogenesis, Sox9 expression was high in chondrocytes while CTGF expression was limited to the perichondrium. Thus, CTGF is an essential downstream mediator of TGF‐β1‐induced MC condensation through its effects on cell proliferation and migration. CTGF is also involved in up‐regulating FN and suppressing Sox9 expression during TGF‐β1 induced MC condensation. J. Cell. Physiol. 210: 398–410, 2007. © 2006 Wiley‐Liss, Inc.
Combinatorial treatment of non‐small‐cell lung cancers with gefitinib and Ad.mda‐7 enhances apoptosis‐induction and reverses resistance to a single therapy
Authors: Emdad Luni , Lebedeva Irina V. , Su Zao‐Zhong , Gupta Pankaj , Sarkar Devanand , Settleman Jeffrey , Fisher Paul B.
Published: November 2006

Activation of the epidermal growth factor receptor (EGFR) contributes to the pathogenesis of non‐small‐cell lung carcinomas (NSCLC) and gefitinib, a selective reversible EGFR inhibitor, is effective in treating patients with NSCLC. However, clinical resistance to gefitinib is a frequent occurrence highlighting the need for improved therapeutic strategies. Melanoma differentiation associated gene‐7 (mda‐7)/Interleukin‐24 (IL‐24) (mda‐7/IL‐24) displays cancer‐selective apoptosis induction when delivered via a replication‐incompetent adenovirus (Ad.mda‐7). In this study, the effect of Ad.mda‐7 infection, either alone or in combination with gefitinib, was analyzed in a panel of NSCLC cell lines carrying wild‐type EGFR (H‐460 and H‐2030) or mutant EGFR (H‐1650 and H‐1975). While H‐2030 and H‐1650 cells were sensitive, H‐460 and H‐1975 cells were resistance to growth inhibition by Ad.mda‐7, which was reversed by the combination of Ad.mda‐7 and gefitinib. This combination increased MDA‐7/IL‐24 and downstream effector double‐stranded RNA‐activated protein kinase (PKR) protein expression, promoting apoptosis induction of NSCLC cells. Inhibition of PKR significantly inhibited apoptosis induction by Ad.mda‐7 when administered alone but not when used in combination with gefitinib. The combination treatment also augmented inhibition of EGFR signaling. Our findings indicate that a combinatorial treatment with Ad.mda‐7 and gefitinib may provide benefit in the treatment of NSCLC, especially in patients displaying resistance to clinically used EGFR inhibitors. J. Cell. Physiol. 210: 549–559, 2007. © 2006 Wiley‐Liss, Inc.
PECAM‐1 modulates thrombin‐induced tissue factor expression on endothelial cells
Authors: Zhang Jenny J. , Kelm Robert J. , Biswas Purba , Kashgarian Michael , Madri Joseph A.
Published: November 2006

Platelet endothelial cell adhesion molecule‐1 (PECAM‐1) (CD31) is known to inhibit platelet function and thrombus formation. The mechanisms involved in PECAM‐1's roles as a modulator of hemostasis are still not completely understood. We examined the role of PECAM‐1 as a regulator of tissue factor (TF) expression, a known important inducer of thrombosis. Wildtype and CD31KO mice underwent transient (30 min) renal ischemia followed by 24 h re‐perfusion and their kidneys assessed for apoptosis, fibrin formation, and tissue factor expression. CD31KO mice exhibited increased tubular epithelial and endothelial apoptosis, increased fibrin deposition, and tissue factor expression. Human umbilical vein endothelial cells (HUVEC) transfected with antisense (AS) PECAM‐1 oligonucleotides to downregulate PECAM‐1 expression, exhibited greater induction of TF mRNA and protein expression as well as increased expression and nuclear localization of the transcription factor Egr‐1 compared to scrambled AS PECAM‐1 (Scr)‐treated HUVEC following thrombin stimulation. TF induction was found to be mediated through thrombin receptor PAR‐1 and the Gαi/o subunit of G‐protein, confirmed by PAR‐1 antagonist and pertussis toxin inhibition respectively. Thrombin‐mediated TF induction was dependent on Rho Kinase activity, phosphorylation of p38MAPK and p85 & Akt dephosphorylation. The inverse correlation of PI3K–Akt phosphorylation with p38 MAPK phosphorylation was confirmed by pharmacological inhibition. These studies suggest that PECAM‐1 is involved in regulating a signaling pathway, affecting PI3K and Akt activation, p38 MAPK phosphorylation, which in turn, affects Egr‐1 expression and nuclear translocation, ultimately affecting TF expression. These findings provide new insights into the action of PECAM‐1 as a modulator of thrombosis. J. Cell. Physiol. 210: 527–537, 2007. © 2006 Wiley‐Liss, Inc.