bluuebunny/crossref_metadata_2025 huggingface dataset:
Das Petrusbildnis van Haelst 741 – eine Replik
Authors: Lührmann Dieter
Published: June 2006

Zu den erstaunlichen Entdeckungen meiner Arbeit an den apokryph gewordenen Evangelien gehört ein Ostrakon mit dem Bildnis des Petrus, mangels einer eigenen Inventarnummer als „van Haelst 741“ bezeichnet. Es war bereits vor einhundert Jahren veröffentlicht worden, wurde danach aber selten erwähnt, geschweige denn in seiner Bedeutung erkannt. Ich habe es in meine im Jahre 2000 erschienene Textausgabe aufgenommen und ihm 2001 einen Aufsatz gewidmet, dessen einschlägige Teile 2004 in leicht überarbeiteter Form noch einmal in einem größeren Zusammenhang aufgegangen sind. Thomas J. Kraus hat in einem längeren Artikel in dieser Zeitschrift meine Präsentation des Ostrakons zwar durchaus gelobt, sie jedoch so weitgehend zum „Gegenstand klärender Anmerkungen und einiger Richtigstellungen“ (204) gemacht, daß ich fürchten muß, dieses bemerkenswerte Stück könnte erneut in Vergessenheit geraten, wenn denn meiner Interpretation tatsächlich derartig viel an Unklarheit und Fehlern nachzusagen wäre.
The Effect of Biomass Density, Salinity, and Substrate on Transport Survival of Juvenile Freshwater Prawns Macrobrachium rosenbergii in Continuously Oxygenated, Vented Containers
Authors: Coyle Shawn D , Tidwell James H , Danaher Jason , Yasharian David K , Bright Leigh Anne
Published: June 2006

During the stocking of grow-out ponds, juvenile prawns are usually transported from regional nurseries by truck in vented tanks. Hauling stress and associated delayed mortality have been implicated as potential causes of low pond survival. An experiment was conducted to evaluate the effects of biomass density, substrate, and salinity on water quality and transport survival of juvenile freshwater prawns Macrobrachium rosenbergii. The trial was designed as a 3 × 2 × 2 factorial and evaluated three biomass densities (10, 20, and 30 g/L), the presence or absence of added substrate (plastic mesh to provide a 200% increase in surface area), and the presence or absence of added salt (0‰ or 6‰). Model transport tanks were 15-L, open styrofoam containers aerated with pure oxygen and compressed air. Water quality analyses were performed prior to stocking. After 24 h, water quality analyses were again conducted and all prawns were removed, designated as alive or dead, weighed, and counted. After 24 h of simulated transport, three-way analysis of variance indicated no significant interactions (P > 0.05) between the main effects of density, substrate, or salinity for prawn survival or water quality. When the main effects were analyzed separately, survival was significantly influenced by density. Survival was significantly lower (P < 0.05) in the high-density treatment (30 g/L: 89% survival) than in the medium- (20-g/L) and low-density (10-g/L) treatments, which were not significantly different (P > 0.05) and averaged 95% survival overall. Total ammonia nitrogen and un-ionized ammonia nitrogen concentrations significantly increased (P < 0.05) as biomass density increased. The addition of salt to the transport water did not significantly affect survival (P > 0.05) but did result in a significant decrease (P < 0.05) in both pH and un-ionized ammonia nitrogen. Added substrate had no significant (P > 0.05) impact on any measured variable. These data indicate that good survival can be achieved at a biomass density of 20 g/L and that increased salinity appears to reduce the buildup of toxic metabolites. The addition of substrate to the transport tank appears to provide no benefit.
Histopathological Effects in Fish Exposed to the Toxins from Karlodinium micrum
Authors: Deeds Jonathan R. , Reimschuessel Renate , Place Allen R.
Published: June 2006

Karlodinium micrum (family Dinophyceae) produces toxic compounds (KmTx's) that are associated with fish kills. For zebrafish Danio rerio larvae (24 h old) exposed to either KmTx 1 or KmTx 2, mortality (100% in 24 h) was observed at toxin concentrations of 1 μg/mL or more, whereas no mortality occurred after 24 h at concentrations of 0.5 μg/mL or less. Zebrafish and sheepshead minnow Cyprinodon variegatus juveniles (60–90 d old) exposed to KmTx 2 were more sensitive to the toxin's effects than larvae were; mortalities in the juveniles began at 0.1–0.5 μg/mL. In whole, sectioned juvenile zebrafish, gills were the primary site showing injury by light microscopy. Histology of gills in both species treated with 0.5 μg KmTx 2/mL (100% mortality in 1 h) showed epithelial necrosis and shortening or loss of secondary lamellae. Histology of zebrafish gills treated with 0.05 and 0.1 μg/mL (0–44% mortality in 4 h) showed clubbing and bridging between secondary lamellae within 4 h of exposure. Sheepshead minnow exposed to 0.1 μg/mL showed similar gill pathology but no mortality after 6 h. Sheepshead minnow exposed to KmTx 2 at 0.5 μg/mL or more all died in less than 1 h. Transmission electron microscopy of gills of moribund zebrafish exposed to 0.1 μg/mL revealed extensive cellular hypertrophy and lysis of epithelial and chloride cells. Because concentrations of KmTx 1 and KmTx 2 range from 0.1 to 0.8 μg/mL in filtered water samples from K. micrum–associated fish kills, these results suggest that the concentrations of KmTx 1 and KmTx 2 found during fish kills are acutely toxic to fish and that gills are a primary target.
Solvents, Industrial
Authors: Wypych George
Published: June 2006

User of industrial solvents has many available choices of commercial products but also a large number of parameters which must be considered to make proper selection. Existing research data, theories, and numerical values characterizing various aspects of solvent application are available in monographic sources and databases of solvents properties. This article is an introduction to all complexities of solvent selection because the scope of necessary information is much broader than it is possible to discuss in one chapter.

This article contains condensed information on solvent classification and their main groups used by industry. Many different physical properties are discussed to show their importance in solvent selection. These include solvent power, solubility parameters, activity coefficient, solvent‐solute interaction and the major forces of this interaction, electronic and electrical effects, swelling and plasticization, rheological properties of solutions, transport phenomena, chemical reactivity, and behavior of solvents in mixtures.

Solvents used must perform but they should not harm users of products and environment. For this reasons environmental impact of solvents, health and safety information, and regulations are very important considerations here.

Various groups of solvents are compared and ranked according to their performance in the above technical and safety categories. Tabular form of this comparison permits generalization of solvent properties.
Analytical sensitivity of arsenobetaine on atomic spectrometric analysis and the purity of synthetic arsenobetaine
Authors: Narukawa T. , Kuroiwa T. , Yarita T. , Chiba K.
Published: June 2006

Arsenobetaine is one of the main organoarsenic compounds that exist in living organisms. Determination errors in total arsenic analyses for organoarsenic compounds occur because analytical sensitivities depend upon the chemical forms of the compounds. However, information on the analytical sensitivity of arsenobetaine by ICP‐MS and ICP‐AES and the purity of commercially available arsenobetaine standards is lacking. BCR CRM 626 (arsenobetaine solution) is a certified reference material from IRMM with a certified concentration of arsenobetaine. The sensitivity and behavior of arsenobetaine on ICP‐MS and ICP‐AES were investigated using the BCR arsenobetaine. The analytical sensitivity and behavior of arsenobetaine using ICP‐MS and ICP‐AES were also investigated using a commercially available synthetic arsenobetaine, and were compared with results for BCR‐AB based on a Japan calibration service system (JCSS) arsenic standard solution. In the results, arsenic determined directly in arsenobetaine showed about 15% greater sensitivity in analysis by ICP‐MS and ICP‐AES than did inorganic (JCSS) arsenic. Copyright © 2006 John Wiley & Sons, Ltd.
Localization of candidate stem and progenitor cell markers within the human cornea, limbus, and bulbar conjunctiva in vivo and in cell culture
Authors: Vascotto Sandy Gian , Griffith May
Published: June 2006

Corneal diseases are some of the most prevalent causes of blindness worldwide. While the most common treatment for corneal blindness is the transplantation of cadaver corneas, expanded limbal stem cells are finding recent application. Unknown, however, is the identity of the actual repopulating stem cell fraction utilized in both treatments and the critical factors governing successful engraftment and repopulation. In order to localize potential stem cell populations in vivo, we have immunohistochemically mapped a battery of candidate stem and progenitor cell markers including c‐Kit and other growth factor receptors, nuclear markers including ΔNp63, as well as adhesion factors across the cornea and distal sclera. Cell populations that differentially and specifically stained for some of these markers include the basal and superficial limbal/conjunctival epithelium and scattered cells within the substantia propria of the bulbar conjunctiva. We have also determined that the culture of differentiated cornea epithelial cells as dissociated and explant cultures induces the expression of several markers previously characterized as candidate limbal stem cell markers. This study provides a foundation to explore candidate corneal stem cell populations. As well, we show that expression of traditional stem cell markers may not be reliable indicator of stem cell content during limbal stem cell expansion in vitro and could contribute to the variable success rates of corneal stem cell transplantation. Anat Rec, Part A, 288A:921–931, 2006. © 2006 Wiley‐Liss, Inc.
Combinational numeral fingerprint spectra of Glycyrrhiza and analysis of common peak ratio invariableness in HPLC
Authors: Zou Huabin , Yang Guosheng , Du Aiqin , Yuan Jiurong , Qin Zhengran , Xia Yingying , Aboul‐Enein Hassan Y.
Published: June 2006

To overcome the instability of traditional Chinese medicine (TCM) fingerprint spectra (FPS) and to build up absolute identification standard of TCM, the construction method of combinational numeral fingerprint spectra (CNFPS) was set up. The analysis of invariableness based on CNFPS was carried out. It can be used as absolute quantitative standard to identify the difference of TCM samples. According to this method, the HPLC FPS of components extracted from Glycyrrhiza root samples by ethanol was analyzed. Stable results and accurate quality evaluation were obtained perfectly. The common peak ratio invariableness is an absolute standard in identifying TCM samples, which is better than the similarity method of the FPS. Copyright © 2006 John Wiley & Sons, Ltd.
The efficacy of certain anti‐tuberculosis drugs is affected by binding to α‐1‐acid glycoprotein
Authors: Johnson Deborah‐Ann , Smith Kevin D.
Published: June 2006

One of the most ubiquitous plasma proteins, α‐1‐acid glycoprotein (AGP), has a high affinity, low capacity binding for basic drugs positively charged at physiological pH. Moreover, as an acute phase protein its level is increased in various disease states in a manner that is likely to influence the free plasma level of a drug, the ability to attain minimum effective concentration and overall in vivo effectiveness. AGP is a glycoprotein known to display disease specific changes in glycosylation and although this secondary modification is not directly involved in drug binding, it may influence the conformation of the binding site. Binding studies reveal that α‐1‐acid glycoprotein bind mainly to the tuberculosis drugs: rifampicin; isoniazid; pyrazinamide; p‐aminosalicylic acid; capreomycin; ethionamide; levofloxacin and ofloxacin out with the therapeutic plasma range tested. These results are however still considered significant as not only are α‐1‐acid glycoprotein levels increased during the acute phase response but specific α‐1‐acid glycoprotein from tuberculosis samples are subject to glycosylation changes which can increase the binding affinity and cause binding to occur at the therapeutic concentration. Copyright © 2006 John Wiley & Sons, Ltd.
Determination of didanosine in maternal plasma, amniotic fluid, fetal and placental tissues by high‐performance liquid chromatography–tandem mass spectrometry
Authors: Clark T. Nicole , White Catherine A. , Bartlett Michael G.
Published: June 2006

A rapid and efficient high‐performance liquid chromatography (HPLC)‐tandem mass spectrometry method for the determination of didanosine concentrations in maternal rat plasma, amniotic fluid, placental and fetal tissue samples has been developed and validated. Tissue samples were homogenized in optima water and centrifuged. The supernatant was subjected to solid‐phase extraction (SPE) prior to analysis. Plasma and amniotic fluid samples were extracted without pretreatment. An Agilent 1100 Series HPLC coupled with a Micromass Quattro II triple quadrupole mass spectrometer was used for all analyses. Chromatographic resolution was achieved on a Nova‐Pak phenyl analytical column (2.0 × 150 mm, 4 µm particle size) equipped with a Phenomenex Security‐guard phenyl guard cartridge (2.0 × 4.0 mm) using 60% methanol in 10 mm ammonium acetate buffer mobile phase for all matrices at a flow rate of 0.15 mL/min. The method yields retention times of 2.9 min for didanosine and 3.0 min for the internal standard, stavudine. Limits of detection were 1 ng/mL for all matrices. Recoveries were 70% or greater for both compounds in the different matrices. Within‐ and between‐run precision (%RSD) and accuracy (%error) was less than 15% for all matrices. Copyright © 2006 John Wiley & Sons, Ltd.
A review of analytical methods for the identification and quantification of hydrocarbons found in jet propellant 8 and related petroleum based fuels
Authors: Gregg Shonetta D. , Fisher Jeffrey W. , Bartlett Michael G.
Published: June 2006

Jet propellant 8 (JP‐8) is a complex mixture of compounds that varies from batch to batch. Quantification of various compound classes of JP‐8, including BTEX, PAHs and VOCs, has been accomplished. Very few papers have tackled total JP‐8 quantification because of its complexity. The components in JP‐8 tend to co‐elute and present at low concentrations, often nondetectable. JP‐8 is the major source of chemical exposure for Department of Defense personnel and a potential hazard for civilians and marine animals. Some components of JP‐8 have been identified as possible human carcinogens and have been studied extensively. Development of analytical methods to analyze the components of this fuel are essential to measure the extent of exposure, as well as the short‐term and long‐term exposure in rodents, humans and marine life. To date, JP‐8 has been examined in urine, blood, contaminated water and fish tissue. This paper reviews methods currently utilized in the literature for the analysis of JP‐8 and its components. This paper also discusses extraction methods and detectors commonly used in JP‐8 and hydrocarbon analysis in general. Finally, the effects of exposure and the future of JP‐8 and petroleum analysis with respect to human health are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
Evolution of an open‐access quantitative bioanalytical mass spectrometry service in a drug discovery environment
Authors: Wright Patricia , Chassaing Christophe , Cussans Nigel , Gibson Drew , Green Caroline , Gleave Michelle , Jones Russell , Macrae Paul , Saunders Kenneth
Published: June 2006

Increased demand for assays for compounds at the early stages of drug discovery within the pharmaceutical industry has led to the need for open‐access mass spectrometry systems for performing quantitative analysis in a variety of biological matrices. The open‐access mass spectrometers described here are LC/MS/MS systems operated in ‘multiple reaction monitoring’ (MRM) mode to obtain the sensitivity and specificity required to quantitate low levels of pharmaceutical compounds in an excess of biological matrix. Instigation of these open‐access systems has resulted in mass spectrometers becoming the detectors of choice for non‐expert users, drastically reducing analytical method development time and allowing drug discovery scientists to concentrate on their core expertise of pharmacokinetics and drug metabolism. Setting up an open‐access facility that effectively allows a user with minimal mass spectral knowledge to exploit the MS/MS capability of triple quadrupole mass spectrometers presents a significantly different challenge from setting up qualitative single stage mass spectrometry systems. Evolution of quantitative open access mass spectrometry within a pharmaceutical drug metabolism and pharmacokinetics group, from its beginnings as a single generic system to a series of specialist fully integrated walk‐up facilities, is described. Copyright © 2006 John Wiley & Sons, Ltd.
Micro‐extraction techniques in analytical toxicology: short review
Authors: Flanagan R. J. , Morgan P. E. , Spencer E. P. , Whelpton R.
Published: June 2006

This paper discusses new developments in plasma micro‐extraction techniques in the context of established micro‐extraction and protein precipitation methodology. Simple liquid–liquid solvent extraction (LLE) of plasma with direct GC or HPLC analysis of the resulting extract has been used for many years. Butyl acetate and methyl t‐butyl ether (MTBE) give efficient extraction of many drugs and metabolites from small volumes of plasma or whole blood at an appropriate pH, and form the upper layer, thus simplifying extract removal. Butyl acetate does not interfere with NPD, ECD or MS in GC, whilst MTBE has a relatively low UV cutoff (220 nm). Thus, HPLC eluents that use a high proportion of an organic component allow MTBE extracts to be analysed directly. ‘Salting‐out’ and extractive derivatization using acetic anhydride or phenylboronic acid can be used with appropriate analytes. As regards protein precipitation, an important consideration is lowering the pH, although this is not feasible with acid‐labile analytes. More recent developments include sold‐phase micro‐extraction (SPME) and liquid‐phase micro‐extraction (LPME). This latter technique especially may prove invaluable as analytes that cannot easily be extracted with LLE can be isolated simply at low cost with a minimum of apparatus. Copyright © 2006 John Wiley & Sons, Ltd.
Fingerprint analysis of Flos Lonicerae japonicae using binary HPLC profiling
Authors: Li Famei , Yuan Bo , Xiong Zhili , Lu Xiumei , Qin Feng , Chen Huashan , Liu Zhigang
Published: June 2006

Binary chromatographic profiling was employed in fingerprint analysis of Flos Lonicerae japonicae, the flower bud of Lonicera japonica Thunb. Standardized procedures were used to develop the profiling for both aqueous and ethanolic extracts. Other species in the previous Chinese Pharmacopoeia and some in folk remedy were successfully differentiated from L. japonica Thunb. by hierarchiral cluster analysis of the chromatographic profiles. Correlation analysis showed that six chromatographic peaks in ethanolic extract were positively correlated with in vitro bacteriostasis activity. Two standard fingerprints were developed with 10 genuine samples of L. japonica Thunb. Similarity analysis with a limited number of samples showed a fair consistence in the chromatographic profiling of L. japonica Thunb. from various sources and two harvests, and significant differences from other species. Combination use of the two fingerprints demonstrated confirmative identification and quality assessment of Flos Lonicerae japonicae. Copyright © 2006 John Wiley & Sons, Ltd.
Drug disposition of chiral and achiral drug substrates metabolized by cytochrome P450 2D6 isozyme: case studies, analytical perspectives and developmental implications
Authors: Srinivas Nuggehally R.
Published: June 2006

The concepts of drug development have evolved over the last few decades. Although number of novel chemical entitities belonging to varied classes have made it to the market, the process of drug development is challenging, intertwined as it is with complexities and uncertainities. The intention of this article is to provide a comprehensive review of novel chemical entities (NCEs) that are substrates to cytochrome P450 (CYP) 2D6 isozyme. Topics covered in this review aim: (1) to provide a framework of the importance of CYP2D6 isozyme in the biotransformation of NCEs as stand‐alones and/or in conjunction with other CYP isozymes; (2) to provide several case studies of drug disposition of important drug substrates, (3) to cover key analytical perspectives and key assay considerations to assess the role and involvement of CYP2D6, and (4) to elaborate some important considerations from the development point of view. Additionally, wherever applicable, special emphasis is provided on chiral drug substrates in the various subsections of the review. Copyright © 2006 John Wiley & Sons, Ltd.
A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone‐refractory prostate cancer
Authors: Flaig Thomas W. , Barqawi Albaha , Miller Gary , Kane Madeleine , Zeng Chan , Crawford E. David , Glodé L. Michael
Published: June 2006

BACKGROUND.

A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25‐dihydroxyvitamin D3), and carboplatin in patients with hormone‐refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies.

METHODS.

All patients had pathologically confirmed prostate cancer with at least 2 consecutive increases in prostate‐specific antigen (PSA). Treatment started with 1 mg of oral dexamethasone given daily with 0.5 mcg of daily calcitriol added at the start of Week 5. Carboplatin (area under the concentration time curve = 2) was started at the beginning of Week 7. Initially, carboplatin was given weekly; however, the protocol was changed later to give carboplatin for the first 4 weeks of a 6‐week cycle. Of 40 patients who consented to participate, 6 patients were ineligible or declined to start therapy, leaving 34 treated patients. The median follow‐up was 80.7 weeks (range, 11.5–260 weeks).

RESULTS.

A formal PSA response was seen in 13 of 34 treated patients (38.2%; 95% confidence interval [95% CI], 22.2–56.4%). The median overall survival was 97.7 weeks (95% CI, 61–114 weeks). Significant adverse events that were observed during the trial period included 2 deaths (myocardial infarction and cardiogenic shock), 4 patients with Grade 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria, version 2.0), 2 patients with thrombosis, 2 patients with inflammatory bowel symptoms, and 2 patients with new‐onset diabetes mellitus.

CONCLUSIONS.

The novel combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side‐effect profile. Cancer 2006. © 2006 American Cancer Society.
A phase II evaluation of a 3‐hour infusion of paclitaxel, cisplatin, and 5‐fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck
Authors: Worden Francis P. , Moon James , Samlowski Wolfram , Clark Joseph I. , Dakhil Shaker R. , Williamson Stephen , Urba Susan G. , Ensley John , Hussain Maha H. ,   and Southwest Oncology Group, the Head and Neck Working Group
Published: June 2006

BACKGROUND.

Previous data from an institutional pilot study in patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) who received treated a combined chemotherapy regimen of paclitaxel, cisplatin, and 5‐fluorouracil indicated an overall response rate of 60% and a median survival of 6 months. To validate these results and to determine the feasibility of this combination, a Phase II study was conducted by the Southwest Oncology Group (SWOG S0007).

METHODS.

Patients with advanced or recurrent SCCHN were eligible if they had received 1 previous regimen of induction/adjuvant chemotherapy or no prior systemic therapy. Patients received treatment with paclitaxel (135 mg/m2 on Day 1), followed by cisplatin (75 mg/m2 on Day 1), and 5‐fluorouracil (1000 mg/m2per day as a 96‐hour continuous infusion on Days 1–4) every 21 days.

RESULTS.

Seventy‐six patients received a combined total of 286 cycles of chemotherapy. Sixty‐nine patients were evaluable for response. There were 5 complete responses (7%) and 23 partial responses (33%) partial responses, for an overall response rate of 41%. The median progression‐free survival was 4 months, and the median overall survival was 10 months. Six treatment‐related deaths were documented, including deaths in 2 patients who had a Zubrod PS of 2. Grade 3 or 4 neutropenia (according to National Cancer Institute Common Toxicity Criteria [version 2.0]) was observed in 47% of patients. Other Grade 3 or 4 adverse events included mucositis (34% of patients), nausea (20% of patients), anemia (9% of patients), and neuropathy (8% of patients).

CONCLUSIONS.

The combination of paclitaxel, cisplatin, and 5‐fluorouracil had efficacy similar to that of standard treatment regimens in patients with advanced or recurrent SCCHN but with increased toxicity. Cancer 2006. © 2006 American Cancer Society.
Late gastrointestinal toxicity after radiation for prostate cancer
Authors: Giordano Sharon H. , Lee Andrew , Kuo Yong‐Fang , Freeman Jean , Goodwin James S.
Published: June 2006

BACKGROUND.

The current study was designed to determine rates and predictors of late, lower gastrointestinal toxicity after radiation therapy in a population‐based cohort of older men with prostate cancer.

METHODS.

The study population consisted of men with localized or regional stage prostate cancer who were age ≥66 years and were diagnosed between 1992 and 1999 who were identified in the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database. Gastrointestinal diagnoses were ascertained through claims from 6 to 60 months after diagnosis. The relative rates of diagnoses in the radiation group versus the nonradiation group were used as a means of estimating toxicity from radiotherapy. Cox modeling was used to determine factors associated with gastrointestinal diagnoses.

RESULTS.

A total of 57,955 men were included, 24,130 of whom were treated with radiation therapy. Among patients with 5 years of follow‐up, the rates of gastrointestinal diagnoses were 19.4% higher in irradiated patients than among patients who did not have local therapy. Hemorrhage was the most common diagnosis, and was increased by 18.9% among patients treated with radiation (39.6% of irradiated patients vs. comparison rates of 18.2% in patients treated with radical prostatectomy and 20.7% in patients with no local therapy). Diagnostic lower endoscopies were performed in an additional 20.9% of men (32.4% of men treated with radiation vs. 12.7% of men who underwent prostatectomy). In all, 4.4% of irradiated men were hospitalized with a gastrointestinal diagnosis versus comparison rates of 3.2% among men with no local therapy. In multivariate models, increasing patient age, hormonal therapy, comorbidity, diabetes, peripheral vascular disease, and hemorrhoids were all associated with gastrointestinal diagnoses consistent with toxicity, whereas tumor stage and grade were not predictors.

CONCLUSIONS.

Lower gastrointestinal toxicity after radiation therapy for prostate cancer continues for at least 5 years and may be more common than previously reported. Cancer 2006. © 2006 American Cancer Society.
14th century example of the four unique hues
Authors: Pridmore Ralph W.
Published: June 2006

It is generally thought that Ewald Hering (19th century), or possibly Leonardo da Vinci (16th century), first recognized the concept of four unique hues (blue, green, yellow, red). However, in the Alhambra palaces, Granada, Spain, in a room roped off from tourist traffic, is a stained glass window featuring the four unique hues, built about 1370. © 2006 Wiley Periodicals, Inc. Col Res Appl, 31, 364–365, 2006
Identifying the origin of groundwater and ﬂow processes in complex landslides affecting black marls: insights from a hydrochemical survey
Authors: Montety V. de , Marc V. , Emblanch C. , Malet J.‐P. , Bertrand C. , Maquaire O. , Bogaard T.A.
Published: June 2006

The Super‐Sauze mudslide is a persistently active slow‐moving landslide occurring in the black marl outcrops of the French South Alps. It has been intensively studied since the early 1990s. Geotechnical, geomorphological, geophysical and hydrological investigations have led to a better understanding of the processes governing the landslide motion. Water ﬂows inside the system have been proven to have a major impact. To look closer at the processes involved and especially to gain a better idea of the origin and pathways of the waters, a hydrochemical study was carried out from May 2003 to May 2004. The groundwater was sampled during ﬁve ﬁeld campaigns spread uniformly over the year. Groundwater from a network of boreholes was collected as well as spring waters from the fractured bedrock (in situ black marl) and from the moraine aquifer above the landslide. Results showed that the groundwater chemistry could not be fully explained by rainfall recharge or simple water–matrix equilibrium. A contribution of saline waters coming from the bottom of a thrust sheet overhanging the landslide was required to get the observed high mineralization. On a ﬂow line, the hydrochemical evolution was related to both soil–matrix equilibrium and deep water sources coming up to the surface by means of major faults, the bedding planes and the schistosity. Hydrochemical anomalies made it possible to point out such contributions locally. It was shown that water chemistry and landslide activity were closely related. This hydrochemical investigation also enabled us to better deﬁne the hydrosystem limits.Copyright © 2006 John Wiley & Sons, Ltd.
The Hyper‐CVAD chemotherapy regimen has an adverse long‐term impact on the ability to mobilize peripheral blood stem cells, which can be readily circumvented by using the early cycles for mobilization
Authors: Keane Colm , Gibbs Simon , Seymour John F , Mills Anthony K , Grimmett Karen , Kuilenberg Rosita Van , Saal Russell , Gill Devinder , Prince H Miles , Marlton Paula , Mollee Peter
Published: June 2006

The Hyper‐CVAD chemotherapy regimen is being increasingly applied to a number of haematological malignancies. We assessed the impact of Hyper‐CVAD on peripheral blood stem cell (PBSC) yields and examined the optimal timing of PBSC collection when using this regimen. Seventy‐four consecutive patients were identified in whom an attempt was made to collect PBSC, usually on recovery from cycle A or B. Where PBSC collection was attempted after cycle 3B, only 18% (3/17) of patients successfully mobilized. Fifty‐seven patients were mobilized on recovery from cycle 1B (n = 13), 2A (n = 22), 2B (n = 14) or 3A (n = 8). Compared with cycle 2A, 1B was not superior in achieving the minimum of ≥2 × 106/kg CD34+ cells (100% vs. 77%, p = 0.13), but was superior in terms of total CD34+ yield (21.4 vs. 3.2 × 106/kg, p < 0.001), achieving the target CD34+ cell count of ≥5 × 106/kg (92% vs 36%, p = 0.002), and obtaining both a minimum (92% vs. 18%, p < 0.001) and target (77% vs. 0%, p < 0.001) graft with a single apheresis. There were no significant differences in PBSC yields following cycles 2A, 2B and 3A. Hyper‐CVAD has substantial stem cell toxicity which can be readily circumvented by using the early chemotherapy cycles for mobilization. Copyright © 2006 John Wiley & Sons, Ltd.
Biodegradable porous polyurethane scaffolds for tissue repair and regeneration
Authors: Gorna Katarzyna , Gogolewski Sylwester
Published: June 2006

Critical‐size bone defects usually require the insertion of autogenous bone graft to heal. Harvesting of bone is traumatic and results in high morbidity at the donor site. A potential alternative to bone graft may be a bone substitute with adequate biocompatibility and biological properties produced from ceramics or bioresorbable/biodegradable polymers. In the present study, new elastomeric biodegradable polyurethanes with an enhanced affinity toward cells and tissues were synthesized using aliphatic diisocyanate, poly(ϵ‐caprolactone) diol, and biologically active 1,4:3,6‐dianhydro‐D‐sorbitol (isosorbide diol) as chain extender. The polymers were processed into 3D porous scaffolds by applying a combined salt leaching‐phase inverse process. The critical parameters controlling pore size and geometry were the solvents and nonsolvents used for scaffold preparation and the sizes of the solid porogen crystals. Scaffolds prepared from the polymer solution in solvents such as dimethylsulfoxide or methyl‐2‐pyrrolidone did not have a homogenous pore structure. Many pores were interconnected, but numerous pores were closed. Irrespective of the high pore‐to‐volume ratio (75%), the scaffolds showed poor water permeability. The best solvent for the preparation of scaffolds from the polyurethane used in the study was dimethylformamide (DMF). The type of nonsolvent admixed to the polymer solution in DMF strongly affected the scaffolds' pore structure. The elastomeric polyurethane scaffold prepared from the optimal solvent–nonsolvent mixture had regular interconnected pores, high water permeability, and a pore‐to‐volume ratio of 90%. The osteoconductive properties of the 3D porous polyurethane scaffolds can be additionally promoted by loading them with calcium phosphate salts such as hydroxyapatite or tricalcium phosphate, thus making them promising candidates for bone graft substitutes. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
SP100B, a repressor of gene expression preferentially binds to DNA with unmethylated CpGs
Authors: Isaac Anne , Wilcox Kent W. , Taylor Jerry L.
Published: June 2006

SP100A and SP100B are mammalian nuclear proteins encoded by alternatively‐spliced transcripts from the SP100 gene. The N‐terminal portion of SP100B (aa 1–476) is identical to SP100A and contains an HP1 interaction domain. The C‐terminal portion of SP100B (aa 477–688) contains an HMG2 interaction domain and a SAND domain. The SAND domain is a DNA‐binding domain identified in several nuclear proteins involved in transcriptional regulation. We have previously reported that SP100B represses expression of genes present on transfected DNA in a SAND domain‐dependent manner. The goal of the present study was to characterize the DNA binding properties of full‐length SP100B expressed in mammalian cells. SP100B associated with DNA whereas SP100A did not. The SP100B SAND domain was essential for DNA binding. Deletion of the HP1‐ or HMG2‐binding domain had no effect on DNA binding. SP100B preferentially associated with sequences containing CpG dinucleotides. Our results did not reveal any preference of SP100B for bases flanking CpG dinucleotides. The number of CpGs in a DNA sequence and spacing between CpGs influenced SP100B binding, suggesting that multimers of SP100B bind DNA in a cooperative manner. Binding of SP100B was abrogated by methylation of the cytosine residue within the context of the CpG dinucleotide. We propose that the preference of SP100B for non‐methylated CpGs provides a mechanism to target SP100B to foreign DNA, including plasmid DNA or viral DNA genomes, most of which are hypomethylated. J. Cell. Biochem. 98: 1106–1122, 2006. © 2006 Wiley‐Liss, Inc.
Chromium (VI) inhibits heme oxygenase‐1 expression in vivo and in arsenic‐exposed human airway epithelial cells
Authors: O'Hara Kimberley A. , Nemec Antonia A. , Alam Jawed , Klei Linda R. , Mossman Brooke T. , Barchowsky Aaron
Published: June 2006

Inhaled hexavalent chromium (Cr(VI)) promotes lung injury and pulmonary diseases through poorly defined mechanisms. One hypothesis for this lung pathogenesis is that Cr(VI) silences induction of cytoprotective genes, such as heme oxygenase‐1 (HO‐1), whose total lung mRNA levels were reduced 21 days after nasal instillation of potassium dichromate in C57BL/6 mice. To investigate the mechanisms for this inhibition, Cr(VI) effects on basal and arsenic (As(III))‐induced HO‐1 expression were examined in cultured human bronchial epithelial (BEAS‐2B) cells. An effect of Cr(VI) on the low basal HO‐1 mRNA and protein levels in BEAS‐2B cells was not detectible. In contrast, Cr(VI) added to the cells before As(III), but not simultaneously with As(III), attenuated As(III)‐induced HO‐1 expression. Transient transfection with luciferase reporter gene constructs controlled by the full length ho‐1 promoter or deletion mutants demonstrated that this inhibition occurred in the E1 enhancer region containing critical antioxidant response elements (ARE). Cr(VI) pretreatment inhibited As(III)‐induced activity of a transiently expressed reporter construct regulated by three ARE tandem repeats. The mechanism for this Cr(VI)‐attenuated transactivation appeared to be Cr(VI) reduction of the nuclear levels of the transcription factor Nrf2 and As(III)‐stimulated Nrf2 transcriptional complex binding to the ARE cis element. Finally, exposing cells to Cr(VI) prior to co‐exposure with As(III) synergized for apoptosis and loss of membrane integrity. These data suggest that Cr(VI) silences induction of ARE‐driven genes required for protection from secondary insults. The data also have important implications for understanding the toxic mechanisms of low level, mixed metal exposures in the lung. J. Cell. Physiol. 209: 113–121, 2006. © 2006 Wiley‐Liss, Inc.
Signaling through the small G‐protein Cdc42 is involved in insulin‐like growth factor‐I resistance in aging articular chondrocytes
Authors: Fortier Lisa A. , Miller Brian J.
Published: June 2006

During aging, chondrocytes become unresponsive to insulin‐like growth factor‐I (IGF‐I). This study examined the role of Cdc42 (cell‐division‐cycle 42) in IGF‐I signaling during aging. Experiments were performed using cartilage and chondrocytes isolated from horses ages 1 day–25 years. Northern analysis was used to examine expression of the small GTPases Cdc42, Rac, and RhoA. Western analysis was utilized to assess total Cdc42 (GTP + GDP‐bound); active, GTP‐Cdc42 was assessed using a pulldown assay with Western analysis. GTP‐Cdc42 was also measured following IGF‐I treatment. Gene expression for Cdc42 and Rac were decreased in mature samples, but there was no difference in total Cdc42 (GTP + GDP‐bound) protein expression due to age. GTP‐Cdc42 was significantly greater in prepubescent samples compared to other age groups. IGF‐I diminished the GTP‐bound state of Cdc42 in prepubescent chondrocytes; however, this effect was lost during aging. No differences in results were observed due to sample type; that is, cartilage tissues versus isolated chondrocytes. These studies suggest that loss of IGF‐I‐mediated regulation of Cdc42 activation may be a mechanism for the chondrocyte unresponsive state during aging. Further, the activation state of Cdc42, measured in native and IGF‐I‐treated cartilage tissue for the first time, is similar to that of isolated chondrocytes, indicating that the activation state of small G‐proteins is not affected by isolation of chondrocytes from the extracellular matrix. Continued studies will identify the upstream regulators of Cdc42, which will further elucidate the molecular mechanism of IGF‐I resistance during aging thereby providing insight into targeted strategies for age‐related osteoarthritis. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1765–1772, 2006
Variation in external rotation moment arms among subregions of supraspinatus, infraspinatus, and teres minor muscles
Authors: Langenderfer Joseph E. , Patthanacharoenphon Cameron , Carpenter James E. , Hughes Richard E.
Published: June 2006

A rotator cuff tear causes morphologic changes in rotator cuff muscles and tendons and reduced shoulder strength. The mechanisms by which these changes affect joint strength are not understood. This study's purpose was to empirically determine rotation moment arms for subregions of supraspinatus, infraspinatus, and for teres minor, and to test the hypothesis that subregions of the cuff tendons increase their effective moment arms through connections to other subregions. Tendon excursions were measured for full ranges of rotation on 10 independent glenohumeral specimens with the humerus abducted in the scapular plane at 10 and 60°. Supraspinatus and infraspinatus tendons were divided into equal width subregions. Two conditions were tested: tendon divided to the musculotendinous junction, and tendon divided to the insertion on the humerus. Moment arms were determined from tendon excursion via the principle of virtual work. Moment arms for the infraspinatus (p < 0.001) and supraspinatus (p < 0.001) were significantly greater when the tendon was only divided to the musculotendinous junction versus division to the humeral head. Moment arms across subregions of infraspinatus (p < 0.001) and supraspinatus (p < 0.001) were significantly different. A difference in teres minor moment arm was not found for the two cuff tendon conditions. Moment arm differences between muscle subregions and for tendon division conditions have clinical implications. Interaction between cuff regions could explain why some subjects retain strength after a small cuff tear. This finding helps explain why a partial cuff repair may be beneficial when a complete repair is not possible. Data presented here can help differentiate between cuff tear cases that would benefit from cuff repair and cases for which cuff repair might not be as favorable. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1737–1744, 2006
Comparing ectopic bone growth induced by rhBMP‐2 on an absorbable collagen sponge in rat and rabbit models
Authors: Hsu H.‐P. , Zanella J.M. , Peckham S.M. , Spector M.
Published: June 2006

Recombinant human Bone Morphogenetic Protein‐2 (rhBMP‐2) is currently employed as an autograft replacement for spinal fusion. The morphogen is incorporated onto its carrier, an absorbable collagen sponge (ACS), in the operating room. Although the effectiveness of the rhBMP‐2/ACS implant in stimulating bone formation in human subjects has now been well established, further investigations of its use are necessary to deepen our understanding of its performance. The objective of the present study was to determine whether fluid released from the rhBMP‐2/ACS implant could induce bone growth in tissue sites away from the implant site. We first measured the amount of protein in the fluid released from the rhBMP‐2‐soaked ACS during intraoperative handling. Variables included soak time and degree of compression. In the compression group that most closely approximated intraoperative conditions, more than 95% of the rhBMP‐2 protein was retained by the ACS following a 15‐min. soak time. This in vitro study was followed by an in vivo ectopic implant experiment using rat and rabbit models. The animal investigation compared the amount of bone induced by rhBMP‐2 solution alone versus the de novo bone formation induced by rhBMP‐2/ACS implants with varying concentrations of rhBMP‐2. No ossicles were found at the sites where rhBMP‐2 solution was injected in either animal species. Twenty‐two of the 24 subcutaneous sites in the rats implanted with the rhBMP‐2/ACS constructs displayed the presence of the typical 4‐ and 12‐week ossicle. There were no noticeable differences in the size and shape of the ossicles after 4 and 12 weeks. There was a greater percentage of implant sites without ossicles in the rabbits, compared to the rats. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1660–1669, 2006
Stiff man–like syndrome and generalized myokymia in spinocerebellar ataxia type 3
Authors: Berciano José , Infante Jon , García Antonio , De Pablos Carmen , Amer Guillermo , Miguel Polo José , Volpini Victor , Combarros Onofre
Published: June 2006

We describe the novel association of spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) phenotype combining classical clinical presentation and semeiology mimicking stiff man syndrome (SMS). The studied pedigree comprises seven affected members in three generations. Their clinical picture consisted of cerebellar ataxia, pyramidal signs, facial myokymia, and ophthalmoplegia. The proband was a 39‐year‐old man in whom such a clinical picture, 5 years after onset at age 29, evolved to severe SMS and widespread myokymia. Electrophysiological study revealed continuous muscle activity in proximal limb muscles. Molecular study demonstrated the MJD gene mutation in all four examined patients with 73 to 76 CAG repeats in the expanded allele. We conclude that an excess of motor unit activity including stiff man–like syndrome and widespread myokymia may be an integral part of the SCA3 clinical spectrum. © 2006 Movement Disorder Society
The barrier for proton transport in aquaporins as a challenge for electrostatic models: The role of protein relaxation in mutational calculations
Authors: Kato Mitsunori , Pisliakov Andrei V. , Warshel Arieh
Published: June 2006

The origin of the barrier for proton transport through the aquaporin channel is a problem of general interest. It is becoming increasingly clear that this barrier is not attributable to the orientation of the water molecules across the channel but rather to the electrostatic penalty for moving the proton charge to the center of the channel. However, the reason for the high electrostatic barrier is still rather controversial. It has been argued by some workers that the barrier is due to the so‐called NPA motif and/or to the helix macrodipole or to other specific elements. However, our works indicated that the main reason for the high barrier is the loss of the generalized solvation upon moving the proton charge from the bulk to the center of the channel and that this does not reflect a specific repulsive electrostatic interaction but the absence of sufficient electrostatic stabilization. At this stage it seems that the elucidation and clarification of the origin of the electrostatic barrier can serve as an instructive test case for electrostatic models. Thus, we reexamine the free‐energy surface for proton transport in aquaporins using the microscopic free‐energy perturbation/umbrella sampling (FEP/US) and the empirical valence bond/umbrella sampling (EVB/US) methods as well as the semimacroscopic protein dipole Langevin dipole model in its linear response approximation version (the PDLD/S‐LRA). These extensive studies help to clarify the nature of the barrier and to establish the “reduced solvation effect” as the primary source of this barrier. That is, it is found that the barrier is associated with the loss of the generalized solvation energy (which includes of course all electrostatic effects) upon moving the proton charge from the bulk solvent to the center of the channel. It is also demonstrated that the residues in the NPA region and the helix dipole cannot be considered as the main reasons for the electrostatic barrier. Furthermore, our microscopic and semimacroscopic studies clarify the problems with incomplete alternative calculations, illustrating that the effects of various electrostatic elements are drastically overestimated by macroscopic calculations that use a low dielectric constant and do not consider the protein reorganization. Similarly, it is pointed out that microscopic potential of mean force calculations that do not evaluate the electrostatic barrier relative to the bulk water cannot be used to establish the origin of the electrostatic barrier. The relationship between the present study and calculations of pKas in protein interiors is clarified, pointing out that approaches that are applied to study the aquaporin barrier should be validated by pKas calculations. Such calculations also help to clarify the crucial role of solvation energies in establishing the barrier in aquaporins. Proteins 2006. © 2006 Wiley‐Liss, Inc.