bluuebunny/crossref_metadata_2025 huggingface dataset:
Volumetric Neuroimaging of the Atlantic White‐Sided Dolphin (Lagenorhynchus acutus) Brain from in situ Magnetic Resonance Images
Authors: Montie Eric W. , Schneider Gerald , Ketten Darlene R. , Marino Lori , Touhey Katie E. , Hahn Mark E.
Published: February 2008

The structure and development of the brain are extremely difficult to study in free‐ranging marine mammals. Here, we report measurements of total white matter (WM), total gray matter (GM), cerebellum (WM and GM), hippocampus, and corpus callosum made from magnetic resonance (MR) images of fresh, postmortem brains of the Atlantic white‐sided dolphin (Lagenorhynchus acutus) imaged in situ (i.e., the brain intact within the skull, with the head still attached to the body). WM:GM volume ratios of the entire brain increased from fetus to adult, illustrating the increase in myelination during ontogeny. The cerebellum (WM and GM combined) of subadult and adult dolphins ranged from 13.8 to 15.0% of total brain size, much larger than that of primates. The corpus callosum mid‐sagittal area to brain mass ratios (CCA/BM) ranged from 0.088 to 0.137, smaller than in most mammals. Dolphin hippocampal volumes were smaller than those of carnivores, ungulates, and humans, consistent with previous qualitative results assessed from histological studies of the bottlenose dolphin brain. These quantitative measurements of white matter, gray matter, corpus callosum, and hippocampus are the first to be determined from MR images for any cetacean species. We establish here an approach for accurately determining the size of brain structures from in situ MR images of stranded, dead dolphins. This approach can be used not only for comparative and developmental studies of marine mammal brains but also for investigation of the potential impacts of natural and anthropogenic chemicals on neurodevelopment and neuroanatomy in exposed marine mammal populations. Anat Rec, 291:263–282, 2008. © 2008 Wiley‐Liss, Inc.
Digit Ratios in Green Anolis Lizards (Anolis carolinensis)
Authors: Lombardo Michael P. , Thorpe Patrick A.
Published: February 2008

The development of tetrapod digits is directed by the Homeobox (Hox) genes. The expression of Hox genes is influenced by exposure to endogenous sex steroids during development so that prenatal exposure to estrogens and androgens positively influences the lengths of digits 2 (2D) and 4 (4D), respectively. Because of this, Manning (2002) predicted that male tetrapods should have smaller 2D:4D than that of females because males are exposed to higher levels of androgens during development. We measured digits in green anolis lizards (Anolis carolinensis) to (a) test Manning's prediction; (b) compare our results with those of other studies of digit ratios in reptiles and birds to test the phylogenetic constraint hypothesis, which argues that the digit ratios of reptiles and birds should be more similar to each other than either taxa is to mammals because the patterns have been conserved in living diapsids; and (c) compare our results with those of another study of digit ratio in anoles (Chang et al., 2006). We did not detect evidence of sexual dimorphism in 2D:4D. Our results did not support either Manning's prediction or the phylogenetic constraint hypothesis. Furthermore, our results did not match those found in Chang et al. (2006), suggesting that digit ratios in anolis lizards may not be reliable indicators of prenatal exposure to hormones. Anat Rec, 291:433–440, 2008. © 2008 Wiley‐Liss, Inc.
Immunohistochemical and Morphometric Study of Pituitary Pars Distalis Thyrotrophs of Male Viscacha (Lagostomus maximus maximus): Seasonal Variations and Effect of Melatonin and Castration
Authors: Filippa Verónica , Mohamed Fabian
Published: February 2008

The physiology and behavior of viscacha vary along the year according to the modifications of environmental signals such as the photoperiod length, temperature, rainfall pattern, food composition, and social interactions. The pituitary pars distalis thyrotrophs (TSH cells) of male viscacha were immunohistochemically identified, and the morphometric parameters: percentage of immunopositive area (% IA), cell percentage in pars distalis (% PDC), number of cells per reference area (no. cells/RA), and major cellular and nuclear diameters were analyzed. Three different groups of adult male viscachas were used: (1) captured in their natural habitat during the year, (2) melatonin‐administered, and (3) castrated. The thyrotrophs were localized in the ventromedial sector, mainly in the pars distalis cephalic extreme. They were oval or pyramidal in shape, and their immunostaining intensity was heterogeneous. The % IA, % PDC, and no. cells/RA exhibited a significant decrease in June–July (winter, gonadal regression period) in relation to February–March (summer–early autumn, reproductive period), and they were recovered in August–September (later winter–early spring, gonadal recovery period). No morphometric variations of TSH cells were observed in melatonin‐treated animals, whereas a decrease of the % IA, % PDC, and no. cells/RA was observed in castrated animals in relation to the intact animals. Our results show TSH cell morphometric variations during the year in agreement with the animal's different physiological conditions during the reproductive cycle, and probably in response to the environmental signals changes. Melatonin does not have a direct effect on the TSH cells. However, castration modifies some thyrotroph morphometric parameters, reinforcing the hypothesis that androgens affect the cells activity. Anat Rec, 291:400–409, 2008. © 2008 Wiley‐Liss, Inc.
A Solid‐State Fluorescent Host System with a 21‐Helical Column Consisting of Chiral (1R,2S)‐2‐Amino‐1,2‐diphenylethanol and Fluorescent 1‐Pyrenecarboxylic Acid
Authors: Imai Yoshitane , Murata Katuzo , Kawaguchi Kakuhiro , Sato Tomohiro , Tajima Nobuo , Kuroda Reiko , Matsubara Yoshio
Published: February 2008

A solid‐state fluorescent host system was created by self‐assembly of a 21‐helical columnar organic fluorophore composed of (1R,2S)‐2‐amino‐1,2‐diphenylethanol and fluorescent 1‐pyrenecarboxylic acid. This host system has a characteristic 21‐helical columnar hydrogen‐ and ionic‐bonded network. Channel‐like cavities are formed by self‐assembly of this column, and various guest molecules can be included by tuning the packing of this column. Moreover, the solid‐state fluorescence of this host system can change according to the included guest molecules. This occurs because of the change in the relative arrangement of the pyrene rings as they adjust to the tuning of the packing of the shared 21‐helical column, according to the size of the included guest molecules. Therefore, this host system can recognize slight differences in molecular size and shape.
Synthesis of syn‐2,4‐Dimercapto‐1,3,2,4‐dithiadigermetane and Its Application to Ge2PdS4 Cluster Synthesis
Authors: Matsumoto Tsuyoshi , Matsui Yosuke , Ito Mikinao , Tatsumi Kazuyuki
Published: February 2008

The sulfurization of DmpGeH3 (Dmp=2,6‐dimesitylphenyl) afforded the trinuclear germanium sulfide [DmpGe(μ‐S)]2(μ‐S)2Ge(SH)‐Dmp and a series of polythiadigermabicyclo[x.1.1]alkanes (x=3, 4, 5). The reduction of the SS bonds of these germabicycloalkanes by NaBH4 at 0 °C afforded the dinuclear mercaptogermane syn‐[DmpGe(SH)(μ‐S)2Ge(SH)‐Dmp] (5) in good yield. The reaction of [Pd(dppe)Cl2] (dppe=1,2‐bis(diphenylphosphanyl)ethane) and the dilithium salt of 5 prepared in situ by the addition of nBuLi (2 equiv) gave the Ge2PdS4 cluster [DmpGe(μ‐S)]2[(μ‐S)2Pd(dppe)], in which the dithiadigermetanedithiolate is bound to the Pd atom at the two thiolato sulfur atoms. The same reaction with [Pd(PPh3)2Cl2] gave another Ge2PdS4 cluster, [DmpGe(μ‐S)]2[(μ‐S)2Pd(PPh3)], but with the dithiadigermetanedithiolate and the Pd center conjoined through a μ‐S atom between the two germanium atoms in addition to the two thiolato sulfur atoms to form a highly distorted cluster core. The formation of two different types of Ge2PdS4 clusters represents the usefulness of 5 in the synthesis of various polynuclear complexes composed of germanium and transition metals.
Pulsed electromagnetic fields induced femoral metaphyseal bone thickness changes in the rat
Authors: Márquez‐Gamiño S. , Sotelo F. , Sosa M. , Caudillo C. , Holguín G. , Ramos M. , Mesa F. , Bernal J. , Córdova T.
Published: February 2008

The effect of 1 Hz, 30 mT pulsed magnetic fields on young adult rat femoral metaphyseal bone thickness was assessed. Ten same litter, female Wistar rats were studied; five of them underwent 30 min magnetic stimulation sessions for 20 consecutive days. The anterior and posterior cortical, as well as trabecular bone transverse thicknesses were measured. The results obtained under clear field microscopy in stimulated and control histological cuts were (in µm) 398 ± 32 versus 260 ± 22 (P = 0.002), 380 ± 68 versus 252 ± 21 (P = 0.03), and 168 ± 11 versus 112 ± 11 (P = 0.002), respectively. The transcranial magnetic stimulation system, approved for human therapy, generates pulsed electromagnetic fields, which induce a significant thickness increase in cortical and trabecular in vivo stimulated bone tissues. This is the first time this effect in healthy animals is shown. Bioelectromagnetics 29:406–409, 2008. © 2008 Wiley‐Liss, Inc.
Self‐assembled polyhydroxy fatty acids vesicles: a mechanism for plant cutin synthesis
Authors: Heredia‐Guerrero José A. , Benítez José J. , Heredia Antonio
Published: February 2008

Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self‐assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation. BioEssays 30:273–277, 2008. © 2008 Wiley Periodicals, Inc.
Parasitism genes and host range disparities in biotrophic nematodes: the conundrum of polyphagy versus specialisation
Authors: Blok Vivian C. , Jones John T. , Phillips Mark S. , Trudgill David L.
Published: February 2008

This essay considers biotrophic cyst and root‐knot nematodes in relation to their biology, host–parasite interactions and molecular genetics. These nematodes have to face the biological consequences of the physical constraints imposed by the soil environment in which they live while their hosts inhabit both above and below ground environments. The two groups of nematodes appear to have adopted radically different solutions to these problems with the result that one group is a host specialist and reproduces sexually while the other has an enormous host range and reproduces by mitotic parthenogenesis. We consider what is known about the modes of parasitism used by these nematodes and how it relates to their host range, including the surprising finding that parasitism genes in both nematode groups have been recruited from bacteria. The nuclear and mitochondrial genomes of these two nematode groups are very different and we consider how these findings relate to the biology of the organisms. BioEssays 30:249–259, 2008. © 2008 Wiley Periodicals, Inc.
The blood–CSF barrier explained: when development is not immaturity
Authors: Johansson Pia A. , Dziegielewska Katarzyna M. , Liddelow Shane A. , Saunders Norman R.
Published: February 2008

It is often suggested that during development the brain barriers are immature. This argument stems from teleological interpretations and experimental observations of the high protein concentrations in fetal cerebrospinal fluid (CSF) and decreases in apparent permeability of passive markers during development. We argue that the developmental blood–CSF barrier restricts the passage of lipid‐insoluble molecules by the same mechanism as in the adult (tight junctions) rendering the paracellular pathway an unlikely route of entry. Instead, we suggest that both protein and passive markers are transferred across the epithelium through a transcellular route. We propose that changes in volume of distribution can largely explain the decrease in apparent permeability for passive markers and that developmentally regulated cellular transfer explains changes in CSF protein concentrations. The blood–CSF tight junctions are functionally mature from very early in development, and it appears that transfer from blood into embryonic brain occurs predominately via CSF rather than the vasculature. BioEssays 30:237–248, 2008. © 2008 Wiley Periodicals, Inc.
Whole genome amplification using single‐primer PCR
Authors: Lao Kaiqin , Xu Nan Lan , Straus Neil A.
Published: February 2008

Comprehensive genomic molecular analyses require relatively large DNA amounts that are often not available from forensic, clinical and other crucial biological samples. Numerous methods to amplify the whole genome have been proposed for cancer, forensic and taxonomic research. Unfortunately, when using truly random primers for the initial priming step, all of these procedures suffer from high background problems for sub‐nanogram quantities of input DNA. Here we report an approach to eliminate this problem for PCR‐based methods even at levels of DNA approaching that of a single cell.
Development of bioadhesives from marine mussels
Authors: Cha Hyung Joon , Hwang Dong Soo , Lim Seonghye
Published: February 2008

Mussel adhesive proteins have received increased attention as potential biomedical and environmentally friendly underwater adhesives thanks to their fascinating properties, including strong and flexible adhesion, adhesion to various material substrates, water displacement, that they are harmless to human body, and controlled biodegradability. Several mussel adhesive proteins have been identified and characterized from mussels, and profound biochemical knowledge for mussel adhesions has been accumulated. In addition, a lot of effort has been put into realizing the promise of these bioadhesive materials from marine mussels. Here, progress in the diverse developmental approaches, with particular emphasis on functional production of mussel adhesive proteins, are reviewed.
Infrared spectroscopic study of the binding of divalent cations to Akazara scallop troponin C: The effect of the methylene side chain of glutamate residue
Authors: Nara Masayuki , Yumoto Fumiaki , Kagi Hiroyuki , Tanokura Masaru
Published: February 2008

Akazara scallop striated adductor muscle troponin C (TnC) binds only one Ca2+ because the three EF‐hand motifs are short of critical residues for the coordination of Ca2+. Fourier‐transform infrared spectroscopy was applied to study coordination structures of M2+ (= Mg2+, Ca2+, Sr2+, and Ba2+) bound in an Akazara scallop TnC mutant (E142D) and the wild‐type TnC C‐lobe in D2O solution. The region of the COO− antisymmetric stretch provides information regarding the coordination modes of a COO− group to a metal ion. The side chain COO− group of Asp142 did not bind to Ca2+ in the bidentate coordination mode, suggesting that the absence of a methylene group is critical for the Ca2+ coordination structure of Akazara scallop TnC (Nara et al., Vib Spect 2006, 42, 188–191). The present study has shown that the absence of a methylene group is not compensated for by a larger metal ion such as Sr2+ or Ba2+. CD spectra showed that the secondary structures are conserved between M2+‐free (apo), Mg2+‐loaded, Ca2+‐loaded, Sr2+‐loaded, and Ba2+‐loaded states, which was consistent with the results estimated from their amide I band patterns. The metal‐ligand interaction at position 12 of site IV is discussed in comparison with the coordination mode of the side chain COO− group of the wild‐type TnC C‐lobe. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 595–599, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Effects of reduction on the denaturation kinetics of human hair
Authors: Wortmann F.‐J. , Popescu C. , Sendelbach G.
Published: February 2008

Although human hair as an α‐keratinous fiber exhibits a complex morphology, it can be considered as a nano‐structured filament/matrix composite for the context of thermal analysis. Using differential scanning calorimetry (DSC) in water, the denaturation performance of the α‐helical protein fraction and the effects of reductive treatments were studied. The results are viewed in the context of a previous study for oxidative treatments. It was found that the course of the denaturation process remains generally unperturbed by the treatment, following an irreversible, one‐step, first‐order process. Arrhenius activation energies and pre‐exponential factors were determined from the DSC‐curves by applying the principles of the Friedman‐method. Comparing activation energy values between reductive and oxidative processes shows the differences of the effects on the components of the composite. In contrast, the values of the rate constant at the denaturation temperature, though showing differences in their trends with cumulative treatments, are very similar. This further emphasizes the theory that the viscosity of the matrix affects strict kinetic control over the denaturation of the α‐helical segments. Once the viscosity of the matrix has decreased enough for the denaturation process to occur, this follows a path that is largely independent of the temperature range and of the chemical pre‐history. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 600–605, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
In vitro interaction between calf thymus DNA and Escherichia coli LPS in the presence of divalent cation Ca2+
Authors: Panja Subrata , Jana Bimal , Aich Pulakesh , Basu Tarakdas
Published: February 2008

With increasing addition of Escherichia coli LPS to calf thymus DNA, both dissolved in CaCl2, absorption maxima of DNA at 260 nm decreased gradually with the appearance of isosbastic points at both ends of spectra, which implied some binding between DNA and LPS. Hill plot of absorbance data showed that the binding interaction was positive cooperative in nature. For any fixed concentration of DNA and LPS, extent of interaction increased as concentration of CaCl2 was raised from 1.0 to 100 mM, signifying the electrostatic nature of the interaction, mediated through Ca2+ ion. Stepwise addition of EDTA, a chelating agent for divalent cations, to DNA–LPS bound complex gradually reversed the spectral shift with increase in absorbance at 260 nm, which implied opening up of the complex, that is, reversible nature of the interaction. Circular dichroism spectral changes of DNA by the addition of LPS indicated partial transition of DNA from B to A form. Isothermal titration calorimetric (ITC) study showed that the DNA–LPS binding was an exothermic and enthalpy‐driven phenomenon. Moreover, in the presence of 100 mM CaCl2, binding constant of the interaction was found to be 2.6 × 104 M−1 and 3.1 × 104 M−1 from the analysis of Hill plot and ITC result, respectively. DNA‐melting study showed that the LPS binding had increased the melting temperature of DNA, indicating more stabilization of DNA double helix. The binding of LPS to DNA made the complex resistant to digestion with endonucleases EcoRI and DNase I. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 606–613, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Analysis of Organo–Silica Interactions during Valve Formation in Synchronously Growing Cells of the Diatom Navicula pelliculosa
Authors: Heredia Alejandro , van der Strate Han J. , Delgadillo Ivonne , Basiuk Vladimir A. , Vrieling Engel G.
Published: February 2008

Biologically formed silica is produced at ambient conditions under the control of molecular and physicochemical processes that are apparently integrated in biosilica morphogenesis, but the mechanisms are not yet fully understood. With the recent identification of small polypeptides and proteins that are encapsulated inside the biosilica and functional in silica polymerization in vitro, it is of importance to determine whether interactions between inorganic silica species and these organic compounds occur in vivo. A time‐resolved analysis of valve formation in synchronously growing cells of the diatom species Navicula pelliculosa enabled us to characterize the relevant chemical bonds by attenuated total reflectance Fourier‐transformed infrared (ATR‐FTIR) spectroscopy. Typically, inorganic bonds of SiOSi (bands at 1058, 843 cm−1), SiOH (3689 cm−1), and PO (1239 cm−1) and organic bonds of proteinaceous matter (with the amide I and II bands at 1642 and 1543 cm−1, respectively) were positively identified during one cycle of valve formation. The observed variations in FTIR band intensity and location represented specific interactions between organic and inorganic molecules during the major silicification event, during which stretching of the SiO bonds was predominantly noticed. The experimentally obtained frequencies (ν) of the major bonds corresponded to those that were obtained by MM+ and PM3 FTIR simulations for organo–silica interactions based on biomolecules that are proposed to be involved in biosilica formation. The results indicated that hydrogen bonds originated from interactions, albeit weak, between organic phosphate or amine groups to the inorganic hydroxyl groups or oxygen atoms from the silicic acid and/or silica. The existence of covalent POSi bonds and electrostatic interactions could not be excluded. These interactions clearly suggest that biomolecules actively contribute to the silica polymerization process during valve formation in N. pelliculosa, and also might act comparably in other diatoms species in which similar biomolecules have been identified.
Patent foramen ovale closure with the Intrasept occluder: Complete 6–56 months follow‐up of 247 patients after presumed paradoxical embolism
Authors: Spies Christian , Timmermanns Ines , Reissmann Ulrich , van Essen Jörg , Schräder Rainer
Published: February 2008

Objective:

We report our experience of transcatheter patent foramen ovale (PFO) closure with the new Intrasept occluder.

Background:

The Intrasept device is the fourth generation of the Cardia occluder family. Developed for transcatheter closure of PFO, the main difference between the Intrasept and prior generations of the Cardia occluder is its articulating center post. This modification allows better alignment of the umbrellas on both sides of the atrial septum. We report our experience with this new PFO occluder.

Methods:

From July 2002 until October 2006, PFO closure with the Intrasept occluder was attempted in 247 patients with presumed paradoxical embolism. Prior to PFO closure, a total of 269 cerebrovascular thromboembolic events (TEs) had occurred. Implantation of the device was guided by fluoroscopy and transesophageal echocardiography with conscious sedation.

Results:

Median age was 53 years (range, 21–77). One hundred twenty‐seven (51%) patients had an atrial septal aneurysm. The device was implanted successfully in all cases. Acute complications occurred in 4 (1.6%) patients (air embolism = 2, pericardial effusion = 1, supraventricular tachycardia = 1). Follow‐up information is available for all 247 (100%) patients. Median follow‐up time was 14 months (range 6–56). Residual shunt at 6 months follow‐up was 13%. After 1 year, the presence of residual shunt rate decreased to 10%. Following PFO closure, seven recurrent TEs (TIA = 4, CVA = 3) were observed in 6 patients. No wire fractures or device‐associated thrombi were seen.

Conclusions:

PFO closure with the Intrasept occluder is safe and efficient. Rates of residual shunt and recurrent TE compare favorably with other contemporary devices. © 2008 Wiley‐Liss, Inc.
Pseudoasymmetry: A final twist?
Authors: Chandrasekhar Sosale
Published: February 2008

The original definition of “pseudoasymmetry” conveyed the apparent paradox that a tetrahedral center with four different groups did not result in overall chirality. However, there are problems in applying the concept to cyclic systems that do not contain chirotopic centers. Pseudoasymmetry appears most appropriate to acyclic systems with chirotopic carbon centers, e.g. the meso trihydroxyglutaric acids. Analogous cyclic cases, e.g. the isomeric 1,4‐dimethylcyclobutanes, are best treated as diastereomers, and may indeed be described by an interesting extension of the like–unlike notation. Remarkably, in several tri‐ and tetramethylcyclohexanes, CIP descriptors cannot be applied even to chirotopic centers, which can only be described by the modified l–u notation. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Microscale HPLC enables a new paradigm for commercialization of complex chiral stationary phases
Authors: Welch Christopher J. , Hyun Myung Ho , Kubota Takateru , Schafer Wes , Bernardoni Frank , Choi Hee Jung , Wu Naijun , Gong Xiaoyi , Lipshutz Bruce
Published: February 2008

The small column size (0.3 mm i.d. × 15 cm) used in microscale HPLC contains only a small fraction (<1%) of the chromatographic packing material of a typical analytical HPLC column. Consequently, chromatographic stationary phases that are prohibitively expensive in conventional HPLC, owing either to synthetic complexity or costly starting materials, may become commercially viable in the microscale format. To illustrate this point, a previously described, synthetically complex, crown ether chiral stationary phase was prepared and evaluated in the microscale format, showing excellent separation of the enantiomers of underivatized amine analytes. Chirality 2008. © 2008 Wiley‐Liss, Inc.
Is there an optimal comorbidity index for prostate cancer?
Authors: Alibhai Shabbir M. H. , Leach Marc , Tomlinson George A. , Krahn Murray D. , Fleshner Neil E. , Naglie Gary
Published: February 2008

BACKGROUND.

Comorbidity is an important consideration in oncology practice, particularly among older patients. Although a variety of comorbidity indices have been employed in research studies, it is unclear whether any one index is preferred.

METHODS.

An age‐stratified random sample of 345 men (mean age of 69 years) who were newly diagnosed with prostate cancer were identified from a cancer registry in Ontario, Canada. Comorbidity and treatment information were obtained from chart review. Four comorbidity indices were utilized: Charlson Index, Diagnosis Count, Index of Coexistent Disease (ICED), and number of medications. Logistic regression analysis was used to compare the performance of comorbidity measures with respect to predicting receipt of curative treatment (radical prostatectomy or radiotherapy) and overall 6‐year survival. Multivariable model performance including each of the comorbidity measures was compared by calculating the area under the receiver operating characteristic curve (AUROC).

RESULTS.

Among men with localized disease (n = 231), in models adjusted for age, Gleason score, and prostate‐specific antigen level, only the Charlson Index was found to be a statistically significant predictor of receipt of curative treatment (P < .05), although all comorbidity indices had similar AUROC in adjusted models. After a median follow‐up of 6.5 years, 116 of 345 men (33.6%) had died. In adjusted models, all 4 comorbidity indices performed similarly in predicting overall survival.

CONCLUSIONS.

Although comorbidity is an important predictor of both curative treatment and overall survival in prostate cancer, the optimal comorbidity index for use in research remains unclear. Selecting the optimal comorbidity index may depend on both the specific patient population and the outcome being considered. Cancer 2008. © 2008 American Cancer Society.
A nomogram predicting long‐term biochemical recurrence after radical prostatectomy
Authors: Suardi Nazareno , Porter Christopher R. , Reuther Alwyn M. , Walz Jochen , Kodama Koichi , Gibbons Robert P. , Correa Roy , Montorsi Francesco , Graefen Markus , Huland Hartwig , Klein Eric A. , Karakiewicz Pierre I.
Published: February 2008

BACKGROUND

Men who undergo radical prostatectomy (RP) are at long‐term risk of biochemical recurrence (BCR). In this report, the authors have described a model capable of predicting BCR up to at least 15 years after RP that can adjust predictions according to the disease‐free interval.

METHODS

Cox regression was used to model the probability of BCR (a prostate‐specific antigen level >0.1 ng/mL and rising) in 601 men who underwent RP with a median follow‐up of 11.4 years. The statistical significance of nomogram predictors was confirmed with a competing‐risks regression model. The model was validated internally with 200 bootstraps and externally at 5 years, 10 years, and 15 years in 2 independent cohorts of 2963 and 3178 contemporary RP patients from 2 institutions.

RESULTS

The 5‐year, 10‐year, 15‐year, and 20‐year actuarial rates of BCR‐free survival were 84.8%, 71.2%, 61.1%, and 58.6%, respectively. Pathologic stage, surgical margin status, pathologic Gleason sum, type of RP, and adjuvant radiotherapy represented independent predictors of BCR in both Cox and competing‐risks regression models and constituted the nomogram predictor variables. In internal validation, the nomogram accuracy was 79.3%, 77.2%, 79.7%, and 80.6% at 5 years, 10 years, 15 years, and 20 years, respectively, after RP. In external validation, the nomogram was 77.4% accurate at 5 years in the first cohort and 77.9%, 79.4%, and 86.3% accurate at 5 years, 10 years, and 15 years, respectively, in the second cohort.

CONCLUSIONS

Patients who undergo RP remain at risk of BCR beyond 10 years after RP. The nomogram described in this report distinguishes itself from other tools by its ability to accurately predict the conditional probability of BCR up to at least 15 years after surgery. Cancer 2008. © 2008 American Cancer Society.
Multiple gene methylation of nonsmall cell lung cancers evaluated with 3‐dimensional microarray
Authors: Wang Yan , Zhang Dingdong , Zheng Wenli , Luo Junfeng , Bai Yunfei , Lu Zuhong
Published: February 2008

BACKGROUND

Aberrant DNA methylation of the CpG islands for cancer‐related genes is among the earliest and most frequent alterations in cancer and may be useful for diagnosing cancer or evaluating recurrent disease.

METHODS

In this study, a 3‐dimensional (3‐D), polyacrylamide gel‐based DNA microarray coupled with linker‐polymerase chain reaction (PCR) was developed to detect hypermethylation of CpG islands in multiple genes from a large group of different samples. The authors determined the frequency of aberrant promoter methylation of 15 genes in 28 resected primary nonsmall cell lung cancers (NSCLCs) and in 12 corresponding nonmalignant lung tissues.

RESULTS

Methylation frequencies in the tumor samples were detected in 18% of samples for the breast cancer 1 gene BRCA1, in 43% of samples for the tissue inhibitor of metalloproteinase 3 gene TIMP‐3, in 38% of samples for the cyclin‐dependent kinase inhibitor 4A gene p16INK4a, in 54% of samples for the cadherin 13 gene CDH13, in 50% of samples for the death‐associated protein kinase gene DAPK, in 11% of samples for the E‐cadherin gene ECAD, in 25% of samples for the insulin‐like growth factor binding protein 7 gene IGFBP7, in 18% of samples for the Ras association domain family 1 gene RASSF1, in 68% of samples for the adenomatous polyposis coli gene APC, in 7% of samples for the cyclin‐dependent kinase inhibitor gene p15, in 18% of samples for the CD44 cell adhesion molecule gene, in 29% of samples for the human Mut‐L homolog gene hMLH, in 32% of samples for the human telomerase reverse transcriptase gene hTERT, in 64% of samples for the calcitonin gene‐related polypeptide α gene CALCA, and in 54% of samples for the estrogen receptor gene ER; however, methylation was not observed in the majority of corresponding nonmalignant tissues. Six samples in from 28 tumors had >6 genes methylated, and 1 sample had 13 genes methylated. Methylation of these genes was correlated with some clinicopathologic patient characteristics.

CONCLUSIONS

This study demonstrated that a 3‐D microarray could be used to detect DNA hypermethylation and provided a high‐throughput platform for DNA hypermethylation analysis. Cancer 2008. © 2008 American Cancer Society.
Dying with cancer
Authors: Kendal Wayne S.
Published: February 2008

BACKGROUND

Cancer survival is influenced by age, comorbidity, and type of cancer. A population‐based study was conducted to compare the interplay between age and mortality for different cancers.

METHODS

This study analyzed 784,378 cases, comprising 22 of the commonest SEER cancers diagnosed between 1984 and 1993. Competing hazards and proportional hazard analyses for cancer‐specific and comorbid death were performed.

RESULTS

Median follow‐up was up to 159 months, and the median age of diagnosis was 67 years. Cancer‐specific and comorbid deaths accumulated most within the first years of diagnosis. With the more biologically aggressive cancers, cancer deaths invariably exceeded comorbid deaths. For the remaining 70% of cancers, comorbidity remained the dominant mode of death. Deaths attributable to both cancer and comorbidity accumulated mostly after the seventh decade of life. Cancer site had a 3‐fold greater effect on overall survival than age at diagnosis and a 30‐fold effect with cancer‐specific survival; age at diagnosis had a 5‐fold greater effect on comorbid deaths than site.

CONCLUSIONS

Both the age of the affected individual and the biology of the particular cancer have major influences on cancer survival and mode of death. Cancer is largely a disease of the elderly. Within affected individuals, fatalities attributable to cancer and comorbidity appeared inter‐related, with cancer‐specific deaths dominating for more lethal cancers and comorbid deaths dominating for the remaining majority. For these reasons, further improvements in overall survival may be best anticipated from better geriatric and general medical management as much as from better cancer management. Cancer 2008. © 2008 American Cancer Society.
Risk of early recurrence among postmenopausal women with estrogen receptor‐positive early breast cancer treated with adjuvant tamoxifen
Authors: Kennecke Hagen , McArthur Heather , Olivotto Ivo A. , Speers Caroline , Bajdik Chris , Chia Stephen K. , Ellard Susan , Norris Brian , Hayes Malcolm , Barnett Jeff , Gelmon Karen A.
Published: February 2008

BACKGROUND

Adjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)‐positive breast cancer. An understanding of which patients are at risk of early recurrence while they are receiving tamoxifen may improve clinical decision making.

METHODS

The patients who were included in this study were women aged ≥50 years with early‐stage, ER‐positive breast cancer diagnosed between 1986 and 1999 and had been treated with tamoxifen. Characteristics of the patients with early recurrences (within 2.5 years of diagnosis), late recurrences (between 2.5 years and 5 years) and no recurrence within 5 years were compared. Logistic regression analyses were conducted to identify which groups were at risk of early recurrence.

RESULTS

Among 3844 women, 304 women (7.9%) developed disease recurrence within 2.5 years. Higher than average rates of recurrence within 2.5 years were observed in cohorts with lymph node (N)‐positive tumors (11.5%), grade 3 histology (14.3%), or low‐positive ER levels, ie, 10–49 fmol/mg or 10%–20% staining (14.9%). In multivariate analyses, only pathologically N‐positive tumors (1–3 vs 0 positive lymph nodes: odds ratio [OR], 1.6; 4–9 vs 0 positive lymph nodes: OR, 2.23 [P = .03]) and low‐positive ER status (OR, 2.04; P = .01) were associated with recurrence within 2.5 years compared with recurrence between 2.5 years and 5 years. Other clinical and pathologic variables were not predictive of early recurrence.

CONCLUSIONS

Subgroups of women with early ER‐positive breast cancer may be identified who are at increased risk of recurrence within 2.5 years of diagnosis despite tamoxifen. It remains to be proven whether upfront AI therapy results in an advantage to these women. Cancer 2008. © 2008 American Cancer Society.
Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down‐regulated in human ovarian cancers by loss of heterozygosity and promoter methylation
Authors: Feng Weiwei , Marquez Rebecca T. , Lu Zhen , Liu Jinsong , Lu Karen H. , Issa Jean‐Pierre J. , Fishman David M. , Yu Yinhua , Bast Robert C.
Published: February 2008

BACKGROUND

Imprinted tumor suppressor genes may be particularly important in the pathogenesis of ovarian cancer. Two imprinted genes, paternally expressed 3 (PEG3) and aplasia Ras homologue member I (ARHI), are the most frequently down‐regulated in ovarian cancers on gene expression arrays.

METHODS

PEG3 and ARHI expression levels were evaluated with real‐time reverse‐transcriptase polymerase chain reaction (PCR) analysis. Promoter methylation was measured by pyrosequencing, and loss of heterozygosity (LOH) was detected by PCR‐LOH assays.

RESULTS

PEG3 was down‐regulated in 75% and ARHI was down‐regulated in 88% of 40 ovarian cancers. ARHI CpG islands I and II were hypermethylated in 13 of 42 ovarian cancers (31%) and in 5 of 42 ovarian cancers (12%), respectively, and hypermethylation was associated with reduced ARHI expression in all 18 samples of ovarian cancer with CpG island hypermethylation. PEG3 was hypermethylated in 11 of 42 ovarian cancers (26%), and PEG3 expression was down‐regulated in 10 of those 11 cancers. LOH was detected in 8 of 35 informative cases for ARHI (23%) and in 5 of 25 informative cases for PEG3 (20%). PEG3 and ARHI expression was highly correlated in human ovarian cancers (correlation coefficient [R] = 0.69; P < .0001). PEG3 and ARHI also were methylated concordantly in ovarian cancers (R = 0.36; P = .019). Re‐expression of PEG3, similar to that of ARHI, markedly inhibited ovarian cancer growth. ARHI and PEG3 expression could be restored by treatment with 5‐aza‐2′‐deoxycytidine and trichostatin A, consistent with the importance of promoter methylation and histone acetylation in regulating expression of both genes.

CONCLUSIONS

Loss of expression of the growth‐inhibitory imprinted genes ARHI and PEG3 through promoter methylation, LOH, and other mechanisms may stimulate clonogenic growth and contribute to the pathogenesis of a majority of ovarian cancers. Cancer 2008. © 2008 American Cancer Society.
Gemcitabine and vinorelbine in pemetrexed‐pretreated patients with malignant pleural mesothelioma
Authors: Zucali Paolo A. , Ceresoli Giovanni L. , Garassino Isabella , De Vincenzo Fabio , Cavina Raffaele , Campagnoli Elisabetta , Cappuzzo Federico , Salamina Silvia , Soto Parra Hector J. , Santoro Armando
Published: February 2008

BACKGROUND

Pemetrexed‐cisplatin chemotherapy is the standard of care in the first‐line treatment of unresectable malignant pleural mesothelioma (MPM). Second‐line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first‐line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine‐vinorelbine combination in pemetrexed‐pretreated patients with MPM.

METHODS

From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum‐derivative were enrolled. Gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity.

RESULTS

A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1–26.5%), and 10 patients (33.3%; 95% CI, 17.3–52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5–62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6–12.1 months), and the median survival was 10.9 months (range, 0.8–25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild.

CONCLUSIONS

The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed‐pretreated patients with MPM. The role of second‐line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors. Cancer 2008. © 2008 American Cancer Society.
Alkali Metal Complexes of the Dipeptides PheAla and AlaPhe: IRMPD Spectroscopy
Authors: Polfer Nick C. , Oomens Jos , Dunbar Robert C.
Published: February 2008

Complexes of PheAla and AlaPhe with alkali metal ions Na+ and K+ are generated by electrospray ionization, isolated in the Fourier‐transform ion cyclotron resonance (FT–ICR) ion trapping mass spectrometer, and investigated by infrared multiple‐photon dissociation (IRMPD) using light from the FELIX free electron laser over the mid‐infrared range from 500 to 1900 cm−1. Insight into structural features of the complexes is gained by comparing the obtained spectra with predicted spectra and relative free energies obtained from DFT calculations for candidate conformers. Combining spectroscopic and energetic results establishes that the metal ion is always chelated by the amide carbonyl oxygen, whilst the C‐terminal hydroxyl does not complex the metal ion and is in the endo conformation. It is also likely that the aromatic ring of Phe always chelates the metal ion in a cation‐π binding configuration. Along with the amide CO and ring chelation sites, a third Lewis‐basic group almost certainly chelates the metal ion, giving a threefold chelation geometry. This third site may be either the C‐terminal carbonyl oxygen, or the N‐terminal amino nitrogen. From the spectroscopic and computational evidence, a slight preference is given to the carbonyl group, in an ROaOt chelation pattern, but coordination by the amino group is almost equally likely (particularly for K+PheAla) in an ROaNt chelation pattern, and either of these conformations, or a mixture of them, would be consistent with the present evidence. (R represents the π ring site, Oa the amide oxygen, Ot the terminal carbonyl oxygen, and Nt the terminal nitrogen.) The spectroscopic findings are in better agreement with the MPW1PW91 DFT functional calculations of the thermochemistry compared with the B3LYP functional, which seems to underestimate the importance of the cation–π interaction.
Photodissociation of Hydrated Hydrogen Iodide Clusters
Authors: Lee Han Myoung , Kolaski Maciej , Kim Kwang S.
Published: February 2008

Using high‐level ab initio calculations and excited state ab initio molecular dynamics simulations, we show that hydrated iodic acids release hydrogen radicals and/or hydrogen molecules as well as iodine radicals upon excitation. Its photoreaction process involving charge transfer to the solvent takes place in four steps: 1) hydration of the acid, 2) charge transfer to water upon excitation of hydrated acid, 3) detachment of the neutral iodine atom, and 4) detachment of the hydrogen radical. The iodine detachment process from excited hydrated hydro–iodic acids is exothermic and the detachment of hydrogen radicals from hydrated hydronium radicals is spontaneous if the initial kinetic energy of the cluster is high enough to get over the activation barrier of the detachment. The complete release of the radicals can be understood in terms of kinetics. This study shows how the hydrogen and halogen radicals are dissociated and released from their hydrated acids. Simple experiments corroborate our predicted mechanism for the release of hydrogen molecules from iodic acid in water by ultraviolet light.
Light Harvesting and Energy Transfer in Multiporphyrin‐Modified CdSe Nanoparticles
Authors: Kang Soonchul , Yasuda Masakazu , Miyasaka Hiroshi , Hayashi Hironobu , Kawasaki Mitsuo , Umeyama Tomokazu , Matano Yoshihiro , Yoshida Kaname , Isoda Seiji , Imahori Hiroshi
Published: February 2008

Multiporphyrin‐modified CdSe nanoparticles (CdSe‐H2P) were prepared to elucidate the interaction between chromophores and luminescent semiconducting nanoparticles in the excited and ground states. The CdSe‐H2P nanoparticles were obtained by place‐exchange reactions of hexadecylamine‐thiophenol‐modified CdSe nanoparticles with porphyrin alkanethiols in toluene. The number of porphyrin molecules on the surface of a single CdSe nanoparticle increased with increasing reaction time to reach a saturated maximum of 21. The porphyrins as well as the core in CdSe‐H2P can absorb UV/Vis radiation. Steady‐state emission and emission‐lifetime measurements reveal efficient energy transfer from the CdSe excited state to the porphyrins in the CdSe‐H2P nanoparticles. The resulting porphyrin excited singlet state is not quenched by the CdSe core. These unique properties are in sharp contrast with those of multiporphyrin‐modified metal and silica nanoparticles. Thus, semiconducting nanoparticle–multiporphyrin composites are highly promising as novel artificial photosynthetic materials.
Early adolescents show enhanced acute cocaine‐induced locomotor activity in comparison to late adolescent and adult rats
Authors: Badanich Kimberly A. , Maldonado Antoniette M. , Kirstein Cheryl L.
Published: February 2008

Initiation of drug use during adolescence is associated with an increased probability to develop a drug addiction. The present study examined dose–response effects of cocaine (0, 5, 10, or 20 mg/kg, i.p.) on locomotor activity in early adolescent (postnatal day (PND) 35), late adolescent (PND 45), and young adults (PND 60) by measuring total distance moved (TDM) and frequency of start–stops. In response to 20 mg/kg cocaine, early adolescents showed the greatest cocaine‐induced increase in TDM in comparison to late adolescent and adult rats. At this same dose, early adolescents showed the greatest cocaine‐induced attenuation of start–stops relative to older rats. Results suggest that early adolescents engage in more cocaine‐induced locomotor activity and less stationary behavior indicating that early adolescents are more sensitive to locomotor activating effects of high dose cocaine than older rats. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 127–133, 2008.