bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Metal‐Ion Composition in the Synthesis of Ternary II‐II′‐VI Nanoparticles by Using a Mixed‐Metal Cluster Precursor Approach.
Authors: DeGroot Marty W. , Roesner Harald , Corrigan John F.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Nearly Monodisperse Cu2O and CuO Nanospheres: Preparation and Applications for Sensitive Gas Sensors.
Authors: Zhang Jiatao , Liu Junfeng , Peng Qing , Wang Xun , Li Yadong
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Interplay of Magnetism, Structure and Superconductivity in Heavy‐Fermion Systems CeMIn5 and PuMGa5
Authors: Thompson J. D. , Nicklas M. , Sidorov V. A. , Bauer E. D. , Movskovich R. , Curro N. J. , Sarrao J. L.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Magnetoresistance of Nanoscale Molecular Devices
Authors: Hod Oded , Rabani Eran , Baer Roi
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Improvement of High Frequency Properties of Nickel—Zinc—Copper Ferrites
Authors: Lebourgeois R. , Ganne J.‐P. , Peyresoubes G. , Rebernak W.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Rare‐Earth Metal‐Rich Tellurides — A Spectrum of Solid‐State Chemistry, Metal—Metal Bonding, and Principles
Authors: Corbett John D.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Processing and Properties of Nanocomposite Nd2Fe14B‐Based Permanent Magnets
Authors: Hirosawa Satoshi
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Fine Tuning of Structure and Reactivity of Copper Complexes Using Pyridylalkylamine Ligands — Active Site Models for Copper Proteins
Authors: Itoh Shinobu
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Gold‐Catalyzed Cyclization of Enynes
Authors: Ma Shengming , Yu Shichao , Gu Zhenhua
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthetic Chemistry of Halichlorine and the Pinnaic Acids
Authors: Clive Derrick L. J. , Yu Maolin , Wang Jian , Yeh Vince S. C. , Kang Shunzhen
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Total Synthesis of Natural tert‐Alkylamino Hydroxy Carboxylic Acids
Authors: Kang Sung Ho , Kang Suk Youn , Lee Hee‐Seung , Buglass Alan J.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Total Synthesis of α‐Pyrone Meroterpenoids, Novel Bioactive Microbial Metabolites
Authors: Sunazuka Toshiaki , Omura Satoshi
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
A Case Study in Biomimetic Total Synthesis: Polyolefin Carbocyclizations to Terpenes and Steroids
Authors: Yoder Ryan A. , Johnston Jeffrey N.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Metal Complexes of Monocarbon Carboranes: A Neglected Area of Study?
Authors: Mcgrath Thomas D. , Stone F. Gordon A.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Biochemistry of Human Skin — Our Brain on the Outside
Authors: Tobin Desmond J.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Magnetoresistive Sensors and Magnetic Nanoparticles for Biotechnology
Authors: Reiss Guenter , Brueckl Hubert , Huetten Andreas , Schotter Joerg , Brzeska Monika , Panhorst Michael , Sudfeld Daniela , Becker Anke , Kamp Paul B. , Puehler Alfred , et al. et al.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synchroton Radiation Circular Dichroism Spectroscopy of Proteins and Applications in Structural and Functional Genomics
Authors: Miles Andrew J. , Wallace B. A.
Published: April 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Circulating levels and clinical significance of soluble CD40 in patients with hematologic malignancies
Authors: Hock Barry D. , McKenzie Judith L. , Patton Nigel W. , Drayson Mark , Taylor Karen , Wakeman Chris , Kantarjian Hagop , Giles Francis , Albitar Maher
Published: April 2006

BACKGROUND

CD40 plays a critical role in immunoregulation, and CD40 ligation is being investigated as a therapy for hematologic malignancies. Although soluble CD40 (sCD40) is a potential modulator of both antitumor responses and CD40‐based therapies, the levels and significance of sCD40 in patients with hematologic malignancies are unknown.

METHODS

The authors evaluated serum/plasma sCD40 levels using an enzyme‐linked immunoassay in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and multiple myeloma (MM).

RESULTS

Levels of sCD40 were elevated in serum (>1.697 ng/mL) or plasma (>0.649 ng/mL) from 73% of patients with CLL, 80% of patients with MCL, 40% of patients with AML, 43% of patients with MDS, and 33% of patients with MM. Multivariate analysis of patients with MM demonstrated that elevated sCD40 was a significant, independent predictor of poor survival. In multivariate analysis of patients with AML, sCD40 was a significant prognostic factor when the interaction of age and sCD40 was included as a variable. Further analysis demonstrated that elevated sCD86 levels were associated with significantly shorter survival only in AML patients younger than age 64 years. Release of sCD40 by CLL cells was induced by cross‐linking with CD40 monoclonal antibody.

CONCLUSIONS

Many patients with hematologic malignancies have elevated circulating levels of sCD40, and these elevated levels are associated with a poor prognosis at least in patients with MM and AML, suggesting that sCD40 may have a role in modulating antitumor responses and also may be a useful prognostic marker. In addition, the findings suggested that further studies will be required to determine the effect of circulating sCD40 on the clinical effectiveness of CD40‐ligating reagents used in the treatment of hematologic malignancies. Cancer 2006. © 2006 American Cancer Society.
Maintenance therapy with thalidomide improves overall survival after autologous hematopoietic progenitor cell transplantation for multiple myeloma
Authors: Brinker Brett T. , Waller Edmund K. , Leong Traci , Heffner, Jr. Leonard T. , Redei Istvan , Langston Amelia A. , Lonial Sagar
Published: April 2006

BACKGROUND

High‐dose chemotherapy with autologous hematopoietic progenitor cell (HPC) transplantation improves survival for patients with multiple myeloma (MM); however, most patients develop recurrent disease after undergoing transplantation, and new treatment approaches are needed. The objective of this retrospective review of autologous HPC transplantation for patients with MM was to evaluate the impact of conditioning regimens and posttransplantation therapy on survival.

METHODS

The authors reviewed 112 patients with MM who received autologous HPC grafts at their institution. Between June 1992 and August 2001, 54 patients received busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP‐16), and 58 patients received high‐dose melphalan (MEL‐200) followed by autologous HPC transplantation. After transplantation, 36 patients received thalidomide for maintenance or salvage therapy, and 76 patients received no posttransplantation thalidomide.

RESULTS

At a median follow‐up of 58 months, the median survival was 54 months. There was no statistically significant difference noted with regard to response to conditioning regimen, progression‐free survival, or overall survival between the Bu/Cy/VP‐16 and MEL‐200 cohorts. Patients who received thalidomide after transplantation had improved median survival (65.5 months) compared with patients who did not receive thalidomide (44.5 months; P = .09). When they were separated according to reasons for thalidomide use, patients who received thalidomide as maintenance had improved overall survival compared with patients who received thalidomide as salvage (65 months vs. 54 months; P = .05).

CONCLUSIONS

Combination chemotherapy provided no advantage over high‐dose melphalan in patients with MM who underwent autologous HPC transplantation. The posttransplantation use of thalidomide seemed to improve the survival of patients compared with historical controls from the prethalidomide era. Further prospective trials are underway to confirm the benefit of thalidomide in the posttransplantation setting. Cancer 2006. © 2006 American Cancer Society.
Exclusive mutation in epidermal growth factor receptor gene, HER‐2, and KRAS, and synchronous methylation of nonsmall cell lung cancer
Authors: Suzuki Makoto , Shigematsu Hisayuki , Iizasa Toshihiko , Hiroshima Kenzo , Nakatani Yukio , Minna John D. , Gazdar Adi F. , Fujisawa Takehiko
Published: April 2006

BACKGROUND

Both genetic and epigenetic changes in nonsmall cell lung cancer (NSCLC) are known to be a common event.

METHODS

Mutations in the epidermal growth factor receptor gene (EGFR), HER‐2, and KRAS and the methylation profile of 9 genes for NSCLC were analyzed and correlated with clinical and histologic data.

RESULTS

Thirty‐nine EGFR, 4 HER‐2, and 6 KRAS mutations were found in 150 NSCLC cases, with the methylation percentages of the genes ranging from 13% to 54%. Most mutations were present in adenocarcinomas, but mutations of the 3 genes were never found to be present in individual tumors. The frequency of methylation for all the genes was correlated with the Methylation Index, a reflection of the overall methylation pattern (all genes, P≤.01), supporting the presence of the CpG island methylator phenotype (CIMP) in NSCLC. On the basis of the methylation profile, CRBP1 and CDH13 methylation were good indicators of CIMP in NSCLC, and were correlated with a poorer prognosis in adenocarcinomas. Mutations in EGFR, HER‐2, and KRAS were found to be present exclusively, whereas methylation tended to be present synchronously. A comparison of mutation and methylation demonstrated that the EGFR mutation had an inverse correlation with methylation of SPARC (secreted protein acidic and rich in cysteine), an extracellular Ca2+‐binding matricellular glycoprotein associated with the regulation of cell adhesion and growth, and the p16INK4A gene.

CONCLUSIONS

The findings of the current study suggest that adenocarcinoma cases with CIMP have a poorer prognosis than adenocarcinoma cases without CIMP, and the EGFR mutation was shown to have an inverse correlation with methylation of SPARC and the p16INK4A gene in NSCLC. Cancer 2006. © 2006 American Cancer Society.
The methylation status and protein expression of CDH1, p16INK4A, and fragile histidine triad in nonsmall cell lung carcinoma
Authors: Nakata Shoji , Sugio Kenji , Uramoto Hidetaka , Oyama Tsunehiro , Hanagiri Takeshi , Morita Masaru , Yasumoto Kosei
Published: April 2006

BACKGROUND

Aberrant methylation of the promoter CpG island (methylation) is known as a major inactivation mechanism of tumor suppressor and tumor‐related genes. In this study, the authors studied the presence of methylation by investigated the inactivation of genes and prognostic factors in patients with nonsmall cell lung carcinoma (NSCLC) by examining resection samples for the presence of methylation.

METHODS

Samples were obtained from 224 patients who underwent pulmonary resection for NSCLC. The authors used those samples to study methylation status with methylation‐specific polymerase chain reaction analysis and to study protein expression with immunohistochemistry for 3 different genes: CDH1, p16INK4A, and fragile histidine triad (FHIT).

RESULTS

The frequency of methylation in NSCLC was determined as 58.0% for CDH1, 21.9% for p16INK4A, and 52.2% for FHIT. The methylation of p16INK4A was observed significantly in heavy smokers compared either with nonsmokers or with patients who had smoked for <20 pack‐years (P = .0420); it also was more significant in squamous cell carcinomas than in adenocarcinomas (P = .0343). FHIT methylation also was correlated significantly with lymph node metastasis (P = .0361). Patients who had tumors with both methylation and reduced expression of CDH1 had a significantly poorer prognosis compared with patients who had tumors both without methylation and with positive expression of CDH1 (P = .0259 and P = .0369, respectively; multivariate Cox analysis). For p16INK4A methylation, 63.3% of tumors showed reduced expression; whereas, in p16INK4A‐unmethylated tumors, 33.7% showed reduced expression (P = .0002). However, for CDH1 and FHIT, no significant correlation was found for either methylation or reduced expression.

CONCLUSIONS

Although protein expression was not inactivated by methylation alone, p16 expression was inactivated strongly by methylation. In addition, the analysis of methylation and expression of CDH1 played a clinically important role in treatment strategies for patients with NSCLC. Cancer 2006. © 2006 American Cancer Society.
Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor‐positive breast cancer
Authors: Cataliotti Luigi , Buzdar Aman U. , Noguchi Shinzaburo , Bines Jose , Takatsuka Yuichi , Petrakova Katarina , Dube Pierre , Tosello de Oliveira Celia
Published: April 2006

BACKGROUND

The Pre‐Operative “Arimidex” Compared to Tamoxifen (PROACT) study was a randomized, multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large, operable (T2/3, N0‐2, M0), or potentially operable (T4b, N0‐2, M0) breast cancer. The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated.

METHODS

Patients with hormone receptor‐positive breast cancer received anastrozole (n = 228) or tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary surgery.

RESULTS

Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0% and 46.2% of patients, respectively (caliper measurements). In hormonal therapy‐only patients (n = 314), feasible surgery at baseline improved after 3 months in 43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04). In the intent‐to‐treat population, improvement in feasible surgery at baseline to actual surgery at 3 months was found to be numerically higher in the anastrozole group compared with the tamoxifen group, although this difference did not reach significance. Drug‐related adverse events were reported in 20.2% and 18.1% of patients, respectively, in the anastrozole and tamoxifen groups.

CONCLUSIONS

Anastrozole is an effective and well‐tolerated preoperative therapy, producing clinically beneficial tumor downstaging and reductions in tumor volume. These effects enable more minimal surgical interventions in patients scheduled for mastectomy, and mastectomy in patients with previously inoperable tumors. Anastrozole appears to be at least as effective as tamoxifen in this setting, and more effective than tamoxifen in certain clinically relevant subgroups. Cancer 2006. © 2006 American Cancer Society.
Phase II trial of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer
Authors: Hoff Paulo M. , Wolff Robert A. , Xiong Henry , Jones Dennie , Lin Edward , Eng Cathy , Dutta Ankhi , Bogaard Karla R. , Abbruzzese James L.
Published: April 2006

BACKGROUND

Both irinotecan and oxaliplatin are active agents in the treatment of patients with metastatic colorectal cancer, and there is a strong preclinical rationale for combining these 2 agents. Therefore, a Phase II trial was designed and conducted to determine the efficacy and tolerability of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer.

METHODS

Patients with previously untreated metastatic colorectal cancer received irinotecan at a dose of 175 mg/m2 and oxaliplatin at a dose of 130 mg/m2, both given intravenously every 3 weeks. Objective responses were evaluated every 2 courses and were confirmed at least 4 weeks after the initial determination.

RESULTS

Fifty‐five patients were enrolled and treated in the current trial. Of the 53 patients whose responses were evaluable, 18 (34%) achieved a partial response, 27 (51%) had stable disease, and 8 (15%) developed disease progression as their best response to the treatment. The intent‐to‐treat median survival for all patients was 16.4 months and the time to progression was 4.8 months. All 55 patients were available for toxicity analysis (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria). The most common Grade 3‐4 toxic effect was neutropenia, which was reported to occur in 22 patients (40%).

CONCLUSIONS

The combination of irinotecan and oxaliplatin appears to be safe and active when used to treat patients with metastatic colorectal cancer. Treatment results with this regimen were similar to those reported for other combined frontline chemotherapy regimens for colorectal cancer. When this particular regimen wa used, neutropenia was found to be the predominant toxicity. Cancer 2006. © 2006 American Cancer Society.
Molecular genetic cascades for external genitalia formation: An emerging organogenesis program
Authors: Yamada G. , Suzuki K. , Haraguchi R. , Miyagawa S. , Satoh Y. , Kamimura M. , Nakagata N. , Kataoka H. , Kuroiwa A. , Chen Y.
Published: April 2006

External genitalia are anatomical structures located at the posterior embryonic region as part of several urogenital/reproductive organs. The embryonic anlage of the external genitalia, the genital tubercle (GT) develops as a bud‐shaped structure with an initial urethral plate and later urethra. Embryonic external genitalia are considered to be one of the appendages. Recent experiments suggest that essential regulatory genes possess similar functions for the outgrowth regulation of the GT and limb appendages. The transient embryonic epithelia located in the distal GT are called the distal urethral epithelium (DUE) regulating, at least in part, the (distal) GT development. This review covers the available data about early patterning of GT and discusses the molecular developmental similarities and points of divergence between the different appendages. Development of the male and female external genitalia is also reviewed. Developmental Dynamics 235:1738–1752, 2006. © 2006 Wiley‐Liss, Inc.
No evidence for dualism in function and receptors: PD‐L2/B7‐DC is an inhibitory regulator of human T cell activation
Authors: Pfistershammer Katharina , Klauser Christoph , Pickl Winfried F. , Stöckl Johannes , Leitner Judith , Zlabinger Gerhard , Majdic Otto , Steinberger Peter
Published: April 2006

The B7 family member programmed‐death‐1‐ligand 2 (PD‐L2/B7‐DC) is a ligand for programmed‐death‐receptor 1 (PD‐1), a receptor involved in negative regulation of T cell activation. Several independent studies have reported that PD‐L2, however, can also potently costimulate murine T cells via an additional yet unidentified receptor. In this study, we evaluated the contribution of PD‐L2 to the activation of human T cells using a novel system of engineered T cell stimulators that expresses membrane‐bound anti‐CD3 antibodies. Analyzing early activation markers, cytokine production and proliferation, we found PD‐L2 to consistently inhibit T cell activation. PD‐L2 inhibition affected CD4+ and CD8+ T cells and was not abrogated by costimulation via CD28. Blocking PD‐1 reverted the inhibitory effect of PD‐L2, demonstrating involvement of this pathway. In human T cells, we found no evidence for any of the costimulatory effects described for PD‐L2 in murine systems. In line with our functional data that do not point to stimulatory PD‐L2‐ligands, we show that binding of PD‐L2‐immunoglobulin to activated human T cells is abrogated by PD‐1 antibodies. Our results demonstrate that PD‐L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses.
Priming of CD8+ T cell responses following immunization with heat‐killed Plasmodium sporozoites
Authors: Hafalla Julius C. R. , Rai Urvashi , Morrot Alexandre , Bernal‐Rubio Dabeiba , Zavala Fidel , Rodriguez Ana
Published: April 2006

Protective immune responses against malaria are induced by immunization with radiation‐attenuated Plasmodium sporozoites. In contrast, non‐viable, heat‐killed sporozoites do not induce protection, emphasizing the requirement for live parasites to achieve effective immune responses. Using an experimental system with CD8+ T cells from T cell receptor‐transgenic mice, we analyzed the primary CD8+ T cell responses elicited by heat‐killed inactivated sporozoites. We found that the numbers of specific CD8+ T cells induced were much lower compared to when immunizing with attenuated sporozoites; however, the kinetics of activation and the phenotype of these T cells were similar in both groups. Despite their low frequency after priming, high numbers of specific CD8+ T cells were observed after boosting with a recombinant vaccinia virus. Upon induction of the recall response, the same level of protection was observed when either heat‐killed or attenuated sporozoites were used for priming. We propose that live parasites are not critical for the induction of memory T cell populations against the malaria liver stages.
Grass ley set‐aside and soil organic matter dynamics on sandy soils in Shropshire, UK
Authors: Fullen Michael A. , Booth Colin A.
Published: April 2006

Erosion plot studies at the Hilton Experimental Site, Shropshire, UK, evaluated the effects of set‐aside on runoff, erosion and soil organic matter (SOM) dynamics. Ten runoff plots (slope angles 7–15°) were put to a grass ley in April 1991. Runoff and erosion rates during nine years were low, despite the occurrence of potentially erosive rains. Mean runoff was 0·24 per cent of precipitation (SD = 0·20, n = 89 plot years), compared with a 15‐year mean value of 0·13 per cent (SD = 0·04) on permanent (control) grassland. The mean plot erosion rate was 0·21 t ha−1 a−1 (SD = 0·14, n = 69 plot years). Mean SOM content increased consistently and sign fi a tly on the set‐aside plots, by a mean value of 1·07 per cent by weight (i.e. 1·07 g per 100 g of soil) in ten ye rs, from 2·04 per cent (1991) to 3·11 per cent (2001). Soil erodibility after six years of set‐aside (sampling date 24 April 1997) was determined using a drip‐screen rainfall simulator. Soil aggregate stability was higher on the grassed soils, compared with set‐aside and bare arable soils. Despite no significant (P > 0·05) differences be w en grassland and set‐asid oils, both these treatments were s gnificantly (P < 0·001) diff rent from bare soils. Contrary to the usually strong relationship between SOM and clay content, the percentage silt (r = 0·52, P < 0·001, n = 50) exhibited a stronger correlation with SOM than percentage clay content (r = 0·37, P < 0·01, n = 50). Furthermore, there were equally strong correlations between SOM and cumulative particle size fractions of both clay and silt contents (r = 0·51, P < 0·001, n = 50). In the absence of significant quantities of clay in these sandy soils, silts assist binding of SOM, which has significance for assessing soil carbon sequestration potential. Finally, future SOM and soil organic carbon benchmark work at the Hilton Site will improve harmonization of global SOM databases and enhance international estimates of rates and potential for soil carbon sequestration. Copyright © 2006 John Wiley & Sons, Ltd.
Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine‐addicted mother: Beneficial effect of dextromethorphan
Authors: Yang San Nan , Liu Chieh‐An , Chung Mei‐Yung , Huang Hsin‐Chun , Yeh Geng‐Chang , Wong Chih‐Shung , Lin Wei‐Wen , Yang Chun‐Hua , Tao Pao‐Luh
Published: April 2006

Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD‐95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD‐95 expression at P14 followed by an age‐dependent improvement. In addition, prenatal morphine exposure reduced not only the expression ofnNOS and the phosphorylation of cAMP responsive element‐binding protein at serine 133 (CREBSerine‐133), but also the magnitude of long‐term depression (LTD) at P14. Subsequently, the morphine‐treated offspring exhibited impaired performance in long‐term learning and memory at later ages (P28–29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD‐95,nNOS, the phosphorylation of CREBSerine‐133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long‐term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine‐addicted mother and provide tentative therapeutic strategy. © 2006 Wiley‐Liss, Inc.
Skewed expression of natural‐killer (NK)‐associated antigens on lymphoproliferations of large granular lymphocytes (LGL)
Authors: Fischer Lars , Hummel Michael , Burmeister Thomas , Schwartz Stefan , Thiel Eckhard
Published: April 2006

Killer‐immunoglobulin‐like receptors (KIR) or C‐type lectin‐like receptors are heterogeneously expressed on NK cells and small subsets of T cells and might provide a new diagnostic tool for LGL lymphoproliferations (LGLL). We investigated the diagnostic impact of these cell surface molecules in T‐ and NK‐type LGLL. Using three‐color flow cytometry we examined the expression patterns of KIR (CD158a/b/e/i), CD85j, lectin‐like receptors (CD94, CD161, NKG2A/D) and natural cytotoxicity receptors (NKp30/44/46) in 13 patients with LGLL (10 T‐, 3 NK‐LGLL) and compared them to those of the corresponding lymphocyte subsets in 20 control subjects. The presence of clonal TCR‐gamma rearrangements and of Epstein Barr virus‐ (EBV) DNA were evaluated by PCR.

All patients exhibited an altered expression of NK‐associated markers. KIR were either lacking (6/13) or overexpressed (7/13). CD94 expression was significantly higher in all LGLL. NKG2A expression was significantly higher in NK‐LGLL. Absence or overexpression was observed for NKG2A in T‐LGLL and CD161 in most T/NK‐LGLL. In NK‐LGLL expression of NKp30 and NKp46 was significantly decreased, whereas CD85j was overexpressed.

We consistently found a skewed expression pattern of novel NK markers as a pathological feature of LGLL. These antigens should be included in the diagnostic workup of this rare disease. Copyright © 2006 John Wiley & Sons, Ltd.
Bacteria and cell cytocompatibility studies on coated medical grade titanium surfaces
Authors: Harris L. G. , Mead L. , Müller‐Oberländer E. , Richards R. G.
Published: April 2006

Acute and chronic osteomyelitis caused by staphylococci can be difficult to treat by conventional means and often has marked consequences for the patient. Current methods of treatment involve the use of systemic antibiotics, the local implantation of nondegradable drug carriers, and surgical debridement. A possible solution that could prevent initial bacterial adhesion could be to modify the implant surface with an antimicrobial coating while maintaining biocompatibility to host cells. This study describes the cytocompatibility evaluation of different coatings (poly(D,L‐lactide) (PDLLA), politerefate (PTF), calcium phosphate/anodic plasma‐chemical treatment (CaP/APC), polyurethane (PU), and polyvinylpyrollidone (PVP) on titanium surfaces with and without chlorhexidine diacetate (CHA) to Staphylococcus aureus, Staphylococcus epidermidis, and hTERT human fibroblasts. Surface characterization of the coatings showed no significant variation in the roughness or hydrophobicity of the coated surfaces, except the CaP/APC surface that was porous yet the smoothest, and PVP, PVP + CHA, and CaP/APC + CHA that were more hydrophilic in nature than the others. On the surfaces without CHA, both staphylococcal strains and spread fibroblasts were observed, but on the CHA impregnated surfaces few bacteria and no intact fibroblasts were seen. Flow cytometry found fewer bacteria in the media and on the surfaces containing CHA in comparison to the surfaces without CHA. The release kinetics varied from slow (over 200 h) to burst release: PDLLA > PTF > PU > CaP/APC = PVP. This study showed that PDLLA and PTF have the best potential as coatings on implants for drug delivery, as they were cytocompatible to hTERT fibroblasts, eluted CHA effectively, and passed mechanical testing. The actual release kinetics of PDLLA and PTF are important, as the amount of CHA present should remain above the minimal inhibitory concentration value for a limited time before disappearing completely. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Covalent modification of porous implants using extracellular matrix proteins to accelerate neovascularization
Authors: Williams Stuart K. , Kleinert Leigh B. , Hagen Kris M. , Clapper David L.
Published: April 2006

Healing associated with many polymeric biomedical implants commonly involves the formation of an avascular fibrous capsule. The lack of either formation or persistence of blood vessels in formed fibrous capsules, as well as a lack of new blood vessels within porous polymeric implants, often results in poor performance of the implant. The current study evaluated the use of extracellular matrix protein modification of a commonly used biomedical implant material, expanded polytetrafluoroethylene (ePTFE), as a mechanism to increase the neovascularization both within these porous implants and in tissue that forms in the peri‐implant area. Discs of ePTFE were covalently modified with different extracellular matrix proteins including collagen type IV, fibronectin, and laminin type I. Discs were implanted into the adipose tissue of adult rats, and following a 5‐week implant phase, histologic analysis of peri‐implant tissue angiogenesis and implant neovascularization was performed. Striking differences were observed in angiogenic and neovascularization responses to matrix‐modified ePTFE when compared with control, untreated ePTFE. Fibronectin treatment resulted in an extensive inflammatory response but, relative to the degree of inflammation, limited evidence of tissue angiogenesis or polymer neovascularization. Collagen type IV treatment groups exhibited a significant increase in angiogenesis in the peri‐implant tissue with minimal evidence of implant neovascularization. In contrast to all other implant modifications, laminin type 1‐treated ePTFE samples stimulated an extensive peri‐implant tissue angiogenic response and a coordinate neovascularization of the porous interstices of the biomaterial. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Growth behavior of rat bone marrow cells on RF magnetron sputtered hydroxyapatite and dicalcium pyrophosphate coatings
Authors: Yan Yonggang , Wolke J.G.C. , De Ruijter A. , Yubao Li , Jansen J.A.
Published: April 2006

The aim of this study was to evaluate the osteogenic properties of magnetron sputtered dicalcium pyrophaosphate (DCPP) and hydroxylapatite (HA) coatings. Therefore, DCPP and HA coatings were deposited on grit‐blasted titanium discs. The substrates were used as‐prepared or received an additional heat treatment which changed the amorphous coating structure to a crystalline structure. Subsequently, rat bone marrow stromal cells were cultured for 1–24 days on the various substrates. DNA and alkaline phosphatase activity was determined after 1, 3, 5, 8, and 12 days of incubation. Osteocalcin expression was evaluated after 8, 12, 16, and 24 days of incubation. Scanning electron microscopical analysis of cell morphology and coating characteristics was done after 8 and 16 days of incubation. All assays were done in duplicate and in each assay all specimens were present in fourfold. Results demonstrated that the cells did not proliferate and differentiate on all amorphous coatings. SEM revealed that the amorphous coatings showed significant dissolution. On the crystalline DCPP and HA coatings an increase in DNA and alkaline phosphatase activity was seen starting at day 8 of incubation. Osteocalcin expression on the crystalline coatings started to increase at day 16 of incubation. SEM showed that the growth and differentiation of the cells was associated with extensive collagen fiber formation and surface mineralization in the form of globular accretions. Further, statistical testing revealed that proliferation and differentiation of the rat bone marrow stromal cells started significantly earlier on the crystalline HA coatings than that on the crystalline DCPP coatings. These results demonstrate that the rat bone marrow stromal cells proliferated and differentiated only on crystalline magnetron sputtered DCPP as well as HA coatings, which warrants the further in vivo analysis of the bone healing supporting properties of these coatings. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
In vivo effects of BISGMA—a component of dental composite—on male mouse reproduction and fertility
Authors: Al‐Hiyasat Ahmad S. , Darmani Homa
Published: April 2006

The aim of this study is to investigate the effects of the resin monomer bisphenol A glycerolate dimethacrylate (BISGMA) on adult male mouse fertility. Male Swiss mice were administered various concentrations of BISGMA (0, 25, and 100 μg/kg) for a period of 28 days, and the effects on fertility was assessed by breeding these males with untreated female mice after the exposure periods. The results showed that fertility was significantly reduced when male mice were exposed to BISGMA, in comparison with their control counterparts. In females mated with males exposed to BISGMA, there was a significant reduction in the pregnancy rates as well as the number of viable fetuses. The number of resorptions out of the total number of implantations was significantly increased in females mated with males that had been exposed to BISGMA. Furthermore, the number of females with resorptions was also significantly increased. Significant reductions in bodyweight and weights of the testis and preputial glands were also observed. The weights of the seminal vesicles were significantly increased in males exposed to BISGMA in comparison with their control counterparts. There were significant reductions in testicular sperm counts, epididymal sperm counts and in the efficiency of sperm production. In conclusion, exposure of male mice to BISGMA results in an impairment of the reproductive system and fertility. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes
Authors: Oh Seunghan , Daraio Chiara , Chen Li‐Han , Pisanic Thomas R. , Fiñones Rita R. , Jin Sungho
Published: April 2006

Vertically aligned yet laterally spaced nanoscale TiO2 nanotubes have been grown on Ti by anodization, and the growth of MC3T3‐E1 osteoblast cells on such nanotubes has been investigated. The adhesion/propagation of the osteoblast is substantially improved by the topography of the TiO2 nanotubes with the filopodia of growing cells actually going into the nanotube pores, producing an interlocked cell structure. The presence of the nanotube structure induced a significant acceleration in the growth rate of osteoblast cells by as much as ∼300–400%. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Cytokine release of mononuclear leukocytes (PBMC) after contact to a carbonated calcium phosphate bone cement
Authors: Schildhauer T.A. , Chapman J.R. , Muhr G. , Köller M.
Published: April 2006

Human leukocytes (peripheral blood mononuclear cells, PBMC) were overlaid on calcium phosphate bone cement (CBC, Norian SRS®) and allowed to settle for 1 h under cell culture conditions. Subsequently, the cells were either left unstimulated (i.e. sham stimulation using cell culture medium), or stimulated with toxic shock syndrome toxin‐1 (TSST‐1, 10 ng/mL), staphylococcal enterotoxin B (SEB, 10 ng/mL), or concanavalin A (ConA, 2 μg/mL) for further 24 h using cell culture conditions. Supernatants were then analyzed for cytokine content (interleukin‐1 receptor antagonist, IL‐1ra; IL‐2; IL‐6; IL‐10; IL‐12) by enzyme‐linked immunosorbent assay. While the spontaneous generation of cytokines was not influenced, the IL‐2 release from stimulated PBMC was significantly decreased in contrast to other analyzed cytokines after contact to the curing CBC compared to control incubations without CBC. This decrease in IL‐2 release was not due to known inhibitors of IL‐2 synthesis platelet factor‐4 (PF‐4), IL‐10, TGF‐β, or elevated calcium ion concentrations. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Modulation of amino acid uptake by TGF‐β in lung myofibroblasts
Authors: Subramanian Mangalalaxmy , Kuang Ping‐Ping , Wei Lin , Rishikof David C. , Liu Hanqiao , Goldstein Ronald H.
Published: April 2006

Hormones such as insulin, growth factors, and cell stress stimulate system A amino acid transporter. Transforming growth factor‐β (TGF‐β) stimulates amino acid uptake thereby inducing cell proliferation, cellular hypertrophy, and matrix synthesis. Insulin appears to activate amino acid in smooth muscle cells via a phosphatidylinositol 3‐kinase (PI3‐kinase)‐dependent pathway. We examine the effect and interaction of TGF‐β, insulin, and PI3‐kinase activity on amino acid uptake in human lung myofibroblasts. TGF‐β treatment induced large increases in system A activity and a small delayed increase in the phosphorylation of protein kinase B, also termed phospho‐Akt. In contrast, insulin induced small increases in system A activity and large increases in phospho‐Akt levels. LY294002, a PI3‐kinase inhibitor, blocked the TGF‐β‐induced amino acid uptake only partially, but completely blocked TGF‐β‐induced Akt phosphorylation. Moreover, the level of phospho‐Smad3 was found to be high even when LY294002 blocked TGF‐β‐induced phospho‐Akt levels. Inhibition of PI3‐kinase activity resulted in increase in Km, consistent with a major change in transporter activity without change in transporter number. The PI3‐kinase inhibitor also did not change the amino acid transporter 2 (ATA2) mRNA levels. Taken together, these results suggest that TGF‐β induced Smad‐3 and amino acid uptake through a PI3‐kinase independent pathway. © 2006 Wiley‐Liss, Inc.
Elevated serum kininogen in patients with paget's disease of bone: A role in marrow stromal/preosteoblast cell proliferation
Authors: Tsuruga Eichi , Rao D. Sudhaker , Baatz John E. , Reddy Sakamuri V.
Published: April 2006

Paget's disease (PD) of bone is a chronic focal skeletal disorder characterized by excessive bone resorption followed by abundant new bone formation. Enhanced levels of IL‐6, RANKL, M‐CSF, and endothelin‐1 have been associated with PD. In the present study, we identified increased serum levels (2 to 5‐fold) of inflammatory cytokine, kininogen (KNG) in patients with PD compared to normal subjects. Treatment of pagetic bone marrow derived stromal/preosteoblast cells with recombinant KNG (25 ng/ml) for 24 h period resulted in a 5‐fold increase in the levels of phospho‐HSP27 and a 3‐fold increase in ERK1/2 phosphorylation in these cells. However, pagetic stromal cells stimulated with KNG in the presence of ERK activation inhibitor peptide did not significantly affect the levels of phospho‐HSP27. KNG increased normal and pagetic marrow stromal cell proliferation at 1.4‐fold and 2.5‐fold, respectively. KNG in the presence of an ERK inhibitor peptide did not stimulate pagetic marrow stromal cell proliferation. Furthermore, siRNA suppression of HSP27 expression significantly decreased KNG inhibition of etoposide‐induced caspase‐3 activation and apoptosis in these cells. In summary, KNG modulate bone marrow derived stromal/preosteoblast cell proliferation and suppress etoposide‐induced apoptosis through ERK and HSP27 activation, respectively. These results implicate a pathophysiologic role for KNG in patients with PD. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Nuclear addressing provides a clue for the transforming activity of amino‐truncated CCN3 proteins
Authors: Planque Nathalie , Long Li Chang , Saule Simon , Bleau Anne‐Marie , Perbal Bernard
Published: April 2006

CCN3 is a founding member of the CCN (Cyr61, Ctgf, Nov) family of cell growth and differentiation regulators. These secreted proteins are key regulators in embryonic development, and are associated with severe pathologies including fibrotic diseases and cancers. CCN3 was discovered as a MAV integration site in an avian nephroblastoma. Previous work established that the amino‐truncated protein expressed in this tumor was inducing morphological transformation of chicken embryo fibroblasts, whereas the full‐length secreted CCN3 protein was inhibiting cell growth. Amino‐truncated variants were identified in cancer cell lines. Since the lack of signal peptide was expected to alter the fate of the truncated proteins, we hypothesized that modifications of CCN3 subcellular addressing could be responsible for the oncogenic activities of CCN3. The CCN proteins are composed of four structural modules (IGFBP, TSP1, VWC, and CT). We report that amino‐truncated variants of CCN3 are addressed to the nucleus and that the carboxyterminal (CT) module of CCN3 is responsible for the nuclear addressing. Furthermore, our data identify nuclear CCN3 variants as potential transcriptional regulators. In this context, the CT module confers on nuclear CCN3 proteins a negative regulatory effect on transcription. We propose that the nuclear localization of amino‐truncated CCN3 proteins be correlated to oncogenicity. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways
Authors: Shinoda Yusuke , Yamaguchi Masayuki , Ogata Naoshi , Akune Toru , Kubota Naoto , Yamauchi Toshimasa , Terauchi Yasuo , Kadowaki Takashi , Takeuchi Yasuhiro , Fukumoto Seiji , Ikeda Toshiyuki , Hoshi Kazuto , Chung Ung‐il , Nakamura Kozo , Kawaguchi Hiroshi
Published: April 2006

Since interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. We initially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin‐deficient (Ad−/−) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad−/− mice, osteogenesis was decreased compared to the wild‐type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin‐induced phosphorylations of the main downstream molecule insulin receptor substrate‐1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.