bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Devonian subduction and early‐orogenic exhumation of eclogite‐facies rocks from the Champtoceaux Complex (Variscan belt, France)
Authors: Bosse Valerie , Feraud Gilbert , Ruffet Gilles , Ballèvre Michel , Peucat Jean‐Jacques , De Jong Koen
Published: August 2002

In order to define the mechanisms involved during exhumation of the eclogite‐facies rocks from the Champtoceaux Complex (Armorican Massif, France), Sm‐Nd, Rb‐Sr and 40Ar/39Ar methods are combined with a petrological study to construct a pressure–temperature–time (P–T–t) path for the Cellier Unit.

The Champtoceaux Complex is a crustal‐scale thrust sheet located in the South Armorican Domain. The lower unit, the Cellier Unit, consists of leucocratic gneisses, mica‐schists and well‐preserved eclogites. Petrological data on selected samples from different lithologies show (1) preservation of growth zoning in garnet, (2) no amphibolite‐ or greenschist‐facies overprint in the eclogite and (3) variations in the Si content of phengite as a function of bulk‐rock chemistry, P–T conditions and partial re‐equilibration during decompression.

Sm‐Nd analyses on the eclogite sample give a Grt–Cpx–whole‐rock age of 362 ± 25 Ma, consistent with the U‐Pb age of 356 ± 8 Ma (recalculated) obtained from the same sample by J. L. Paquette in 1987. Preservation of growth zoning in the garnet and the absence of late overprint show that resetting of both Sm‐Nd and U‐Pb systems is unlikely. The age of c. 360 Ma is thus interpreted as the age of the high‐pressure event.

Eight 40Ar/39Ar plateau ages, ranging from 352.0 ± 1.6 to 340.5 ± 1.4 Ma, are obtained from phengite single grains from six samples. The existence of Ar inheritance is unlikely, because (1) 40Ar/39Ar ages are younger than the age of the high‐pressure event as deduced from U‐Pb and Sm‐Nd ages, (2) duplicates display a high reproducibility of plateau ages in all cases, and (3) a concordant Rb‐Sr age is obtained on one common sample. These plateau ages probably represent closure temperatures (possibly on the order of 450–500°C) for the best preserved and oldest samples, whereas the younger plateau ages may represent a later closure of the K/Ar system due to continuous deformation and chemical re‐equilibration during retrogression. Copyright © 2000 John Wiley & Sons, Ltd.
Astrocytes attenuate oligodendrocyte death in vitro through an α6 integrin‐laminin–dependent mechanism
Authors: Corley Shannon M. , Ladiwala Uma , Besson Arnaud , Yong V. Wee
Published: August 2002

Oligodendrocyte (OL) death occurs in many disorders of the CNS, including multiple sclerosis and brain trauma. Factors reported to induce OL death include deprivation of growth factors, elevation of cytokines, oxidative stress, and glutamate excitotoxicity. Because astrocytes produce a large amount of growth factors and antioxidants and are a major source of glutamate uptake, we tested the hypothesis that astrocytes may have a protective role for OL survival. We report that when OLs from the adult mouse brain were initiated into tissue culture, DNA fragmentation and chromatin condensation resulted, indicative of apoptosis. OL death was significantly reduced in coculture with astrocytes, but not with fibroblasts, which provided a similar monolayer of cells as astrocytes. The protection of OL demise by astrocytes was not reproduced by its conditioned medium and was not accounted for by several neurotrophic factors. In contrast, interference with the α6 integrin subunit, but not the α1, α2, α3, α4, α5, or αv integrin chains, negated astrocyte protection of OLs. Furthermore, a function‐blocking antibody to α6β1 integrin reduced the ability of astrocytes to promote OL survival. The extracellular matrix ligand for α6β1 is laminin, which is expressed by astrocytes. Significantly, neutralizing antibodies to laminin‐2 and laminin‐5 inhibited the astrocyte mediation of OL survival. These results implicate astrocytes in promoting OL survival through a mechanism involving the interaction of α6β1 integrin on OLs with laminin on astrocytes. Enhancing this interaction may provide for OL survival in neurological injury. GLIA 36:281–294, 2001. © 2001 Wiley‐Liss, Inc.
Olfactory identification is impaired in clinic‐based patients with vascular dementia and senile dementia of Alzheimer type
Authors: Gray Alison J. , Staples Vince , Murren Karen , Dhariwal Avtar , Bentham Peter
Published: August 2002

Aims

It is now well established that there are abnormalities in the sense of smell in patients suffering from Alzheimer's disease (AD). They have both raised olfactory thresholds and impaired odour identification. The situation in vascular dementia is unclear. We used the University of Pennsylvania Smell Identification Test (UPSIT), a 40‐item, forced choice, cued, ‘scratch‐and‐ sniff’ test, to examine olfactory identification in vascular dementia and to determine whether it would differentiate the disorder from AD and normal elderly.

Methods

We investigated three matched subject groups: 13 people having a Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) diagnosis of definite senile dementia of Alzheimer type, 13 having a CAMDEX diagnosis of definite vascular dementia and 13 non‐cognitively impaired controls. The subjects were then tested with the UPSIT in their own home by an independent blind researcher to see if the test could distinguish the different diagnostic groups in this setting.

Results

The median UPSIT score was 30 (out of a maximum of 40) for controls, 12 for the vascular group and 15 for the AD group. The difference was significant (p = 0.05) between both demented groups and the normal controls. Similarly there was a significant difference in the UPSIT score between the AD group and controls (p = 0.001) and between the vascular dementia group and controls (p = 0.001), but there was no significant difference between the AD group and the vascular dementia group. The UPSIT score correlated strongly with the degree of cognitive impairment as measured by the CAMCOG (rs = 0.683, p = 0.01)

Conclusions

Patients with vascular dementia had a similar degree of olfactory impairment to those with AD. The UPSIT successfully differentiated between dementia patients and normal elderly British subjects tested in their own homes. The UPSIT did not differentiate between those with AD and vascular dementia. Copyright © 2001 John Wiley & Sons, Ltd
Nonlinear phase desynchronization in human electroencephalographic data
Authors: Breakspear Michael
Published: August 2002

Ensembles of coupled nonlinear systems represent natural candidates for the modeling of brain dynamics. The objective of this study is to examine the complex signal produced by coupled chaotic attractors, to discuss their potential relevance to distributed processes in the brain, and to illustrate a method of detecting their contribution to human EEG morphology. Two measures of quantifying the behavior of coupled nonlinear systems are presented: a measure of phase synchrony and a novel measure of intermittent phase desynchronization. These are used to quantify the behavior of numerical examples of coupled chaotic attractors. Experimental evidence of their contribution to the morphology of the human alpha rhythm is then illustrated in a study of EEG recordings from 40 healthy human subjects. Amplitude‐adjusted phase‐randomized surrogate data is used to test the null hypothesis that the observed patterns of phase coherence can be described by purely linear methods. Statistical analysis reveals that this null hypothesis can be robustly rejected in a small number (∼4%) of EEG epochs. These findings are discussed with reference to the adaptive function and complex dynamics of the brain. Hum. Brain Mapping 15:175–198, 2002. © 2002 Wiley‐Liss, Inc.
Nonlinear temporal dynamics of the cerebral blood flow response
Authors: Miller Karla L. , Luh Wen‐Ming , Liu Thomas T. , Martinez Antigona , Obata Takayuki , Wong Eric C. , Frank Lawrence R. , Buxton Richard B.
Published: August 2002

The linearity of the cerebral perfusion response relative to stimulus duration is an important consideration in the characterization of the relationship between regional cerebral blood flow (CBF), cerebral metabolism, and the blood oxygenation level dependent (BOLD) signal. It is also a critical component in the design and analysis of functional neuroimaging studies. To study the linearity of the CBF response to different duration stimuli, the perfusion response in primary motor and visual cortices was measured during stimulation using an arterial spin labeling technique with magnetic resonance imaging (MRI) that allows simultaneous measurement of CBF and BOLD changes. In each study, the perfusion response was measured for stimuli lasting 2, 6, and 18 sec. The CBF response was found in general to be nonlinearly related to stimulus duration, although the strength of nonlinearity varied between the motor and visual cortices. In contrast, the BOLD response was found to be strongly nonlinear in both regions studied, in agreement with previous findings. The observed nonlinearities are consistent with a model with a nonlinear step from stimulus to neural activity, a linear step from neural activity to CBF change, and a nonlinear step from CBF change to BOLD signal change. Hum. Brain Mapping 13:1–12, 2001. © 2001 Wiley‐Liss, Inc.
Localization of MDMA‐induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA)
Authors: Frei Edi , Gamma Alex , Pascual‐Marqui Roberto , Lehmann Dietrich , Hell Daniel , Vollenweider Franz X.
Published: August 2002

3,4‐Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5‐HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA‐naïve volunteers. Thirty‐one‐channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA‐specific EEG pattern with that of various 5‐HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior. Hum. Brain Mapping 14:152–165, 2001. © 2001 Wiley‐Liss, Inc.
Vocal process granuloma
Authors: Hoffman Henry T. , Overholt Edwin , Karnell Michael , McCulloch Tim M.
Published: August 2002

Background

This review article reports the evolution of knowledge regarding the benign proliferations of the posterior glottis commonly termed “vocal process granuloma”.

Methods

A comprehensive review of publications addressing lesions of the posterior glottis is affected to analyze the contemporary management of vocal process granuloma.

Results

Contemporary management emphasizes interventions to decrease irritation to the posterior glottis. Multiple causes of this irritation preclude use of a single management plan that will successfully address all cases.

Conclusions

Management to diminish laryngopharyngeal reflux, as well as to correct vocally abusive behavior, will appropriately address the majority of vocal process granuloma. Surgical removal is best reserved for cases when conservative management fails, when airway obstruction is a concern, or when a biopsy is needed to establish the diagnosis. Ancillary measures that may be beneficial in specific cases include the use of steroids, antibiotics, membranous vocal fold augmentation, and laryngeal botulinum neurotoxin injection. © 2001 John Wiley & Sons, Inc. Head Neck 23: 1061–1074, 2001.
Cutaneous botryomycosis of the cervicofacial region
Authors: Yencha Myron W. , Walker Clark W. , Karakla Daniel W. , Simko Eric J.
Published: August 2002

Background

Botryomycosis is a rare, chronic, bacterial infection of insidious onset involving the integument or viscera that often mimics actinomycosis or a deep fungal infection. The pathogenesis is thought to be a symbiotic relationship between the host and the infecting organism.

Methods

Case report of a patient with a chronic infection involving the cervicofacial region diagnosed as cutaneous botryomycosis arising from a chronic osteomyelitis of the mandible. The diagnosis was based on the chronicity of the infection along with the identification of botryomycotic (bacteria‐containing) granules on histopathologic examination. Special stains excluded fungi and mycobacterium. Cultures identified the offending bacteria, and antibiotic therapy was initiated on the basis of the sensitivities, resulting in resolution of this chronic infectious process. A review of the English language literature revealed that this is the first case of cutaneous botryomycosis arising from a chronic osteomyelitis of the mandible.

Results

Medical therapy proved curative at 14 months follow‐up. Surgery was performed for diagnostic purposes only.

Conclusions

Botryomycosis is exceedingly rare in the head and neck, and consideration of this entity in the differential diagnosis is critical to the diagnosis. The mainstay of therapy is medical with surgery reserved for biopsy and/or excision of persistent disease. Published 2001 John Wiley & Sons, Inc. Head Neck 23: 594–598, 2001.
Cholinergic system regulation of spatial representation by the hippocampus
Authors: Ikonen Sami , McMahan Robert , Gallagher Michela , Eichenbaum Howard , Tanila Heikki
Published: August 2002

The role of the basal forebrain cholinergic system in hippocampal spatial representation was explored by examining the effects of immunotoxic lesions of the septo‐hippocampal cholinergic neurons on the firing patterns of hippocampal place cells as rats explored familiar and novel environments. In a highly familiar environment, the basic qualities and stability of place fields were unaffected by the lesion. When first exposed to a set of novel environmental cues without otherwise disorienting the animals, place cells in both normal and lesioned animals responded with similar alterations in their firing patterns. Upon subsequent repetitive exposures to the new environment, place cells of normal rats developed a spatial representation distinct from that of the familiar environment. By contrast, place cells of lesioned animals reconverged in the direction of the representation associated with the familiar environment. These results suggest that cholinergic input may determine whether new visual information or a stored representation of the current environment will be actively processed in the hippocampal network. Hippocampus 2002;12:386–397. © 2002 Wiley‐Liss, Inc.
Mass balance and streamflow variability at Place Glacier, Canada, in relation to recent climate fluctuations
Authors: Moore R. D. , Demuth M. N.
Published: August 2002

Although a great deal of research has focused on the hydrologic effects of climate variability and change, relatively little research has examined the effects on streamflow of interactions between climate variability and change and resulting glacier response. Place Glacier, in the southern Coast Mountains of British Columbia, Canada, has been monitored for mass balance since 1965, and a stream gauge was operated just below the glacier terminus from 1969 to 1989. This paper presents analyses of the mass balance history and streamflow variations in relation to recorded climatic variability.

Place Glacier's winter and net balances are correlated with the Pacific Decadal Oscillation (PDO). Summer balance is positively correlated with summer temperature and negatively with the preceding winter balance, which enhances the effects of changes in winter balance on net balance. The well‐documented post‐1976 shift from the PDO cold phase to the present warm phase initiated a significant and persistent period of more negative net balance and terminal retreat. A reconstruction of net balance extending back to the 1890s, based on a regression with winter precipitation and summer temperature, displays decadal‐scale fluctuations consistent with the PDO. Summer streamflow responded to interannual variations in winter snow accumulation and summer temperatures, which control the rate of rise of the glacier snowline and melt rates. After accounting for these influences via regression analysis, August streamflow displayed a negative trend in total runoff. Examination of air photographs and the reconstructed mass balance history suggest that significant firn depletion had occurred prior to 1965, such that the dominant effect of glacier changes was a reduction in ice area, resulting in decreased meltwater production. Copyright © 2001 John Wiley & Sons, Ltd.
Post‐fire runoff and erosion from rainfall simulation: contrasting forests with shrublands and grasslands
Authors: Johansen Mathew P. , Hakonson Thomas E. , Breshears David D.
Published: August 2002

Rainfall simulations allow for controlled comparisons of runoff and erosion among ecosystems and land cover conditions. Runoff and erosion can increase greatly following fire, yet there are few rainfall simulation studies for post‐fire plots, particularly after severe fire in semiarid forest. We conducted rainfall simulations shortly after a severe fire (Cerro Grande) in ponderosa pine forest near Los Alamos, New Mexico, USA, which completely burned organic ground cover and exposed unprotected soil. Measurements on burned plots showed 74% of mineral soil was exposed compared with an estimated 3% exposed prior to the fire. Most of the remaining 26% surface area was covered by easily moveable ash. Rainfall was applied at 60 mm h−1 in three repeated tests over 2 days. Runoff from burned plots was about 45% of the total 120 mm of applied precipitation, but only 23% on the unburned plots. The most striking difference between the response of burned and unburned plots was the amount of sediment production; burned plots generated 25 times more sediment than unburned plots (76 kg ha−1 and 3 kg ha−1 respectively per millimetre of rain). Sediment yields were well correlated with percentage bare soil (r = 0·84). These sediment yields were more than an order of magnitude greater than nearly all comparable rainfall simulation studies conducted on burned plots in the USA, most of which have been in grasslands or shrublands. A synthesis of comparable studies suggests that an erosion threshold is reached as the amount of soil exposed by fire increases to 60–70%. Our results provide sediment yield and runoff data from severely burned surfaces, a condition for which little rainfall simulation data exist. Further, our results contrast post‐fire hydrologic responses in forests with those in grasslands and shrublands. These results can be applied to problems concerning post‐fire erosion, flooding, contaminant transport, and development of associated remediation strategies. Copyright © 2001 John Wiley & Sons, Ltd.
Prevalence of Kaposi's sarcoma‐associated herpesvirus infection in sex workers and women from the general population in Spain
Authors: de Sanjosé Sílvia , Marshall Vickie , Solà Judit , Palacio Virgilio , Almirall Rosa , Goedert James J. , Bosch F. Xavier , Whitby Denise
Published: August 2002

Transmission routes of Kaposi's sarcoma‐associated herpesvirus (KSHV) in the general population are poorly understood. Whereas sexual transmission appears to be common in homosexual men, the evidence for heterosexual transmission is less convincing. In our study, prevalence of KSHV infection was examined among women in the Spanish general population and among sex workers. Subjects consisted of 100 prostitutes and 100 women randomly sampled from the general population and age‐matched to the prostitutes. Women had a personal interview and gynecologic examinations in which a blood sample, cervical cells and oral cells were obtained. Peripheral blood mononuclear cells (PBMC), oral and cervical samples were tested for KSHV DNA by quantitative real‐time PCR. Sera were tested for antibodies against human immunodeficiency virus (HIV) by ELISA and against KSHV by latent IFA and K8.1 ELISA. Women who were positive in either serologic assay or PCR were considered infected by KSHV. Human papillomavirus (HPV) DNA in cervical scrapes were evaluated using the Hybrid Capture System™. The study population had an average age of 30 years and were HIV‐negative. Women from the general population were largely of Spanish nationality, and 61% reported lifetime monogamy. The majority of the prostitutes (76%) were immigrants, primarily from South America. Sex workers were twice as likely to be infected with KSHV than women in the general population (16% vs. 8%, prevalence odds ratio [OR] = 2.2). KSHV was more prevalent among HPV DNA‐positive women (OR = 2.5) and among women with an early age at first sexual intercourse (OR = 2.7, p < 0.05). KSHV DNA was detected by PCR in 3% of the oral cavity samples, in 2% of the cervical samples of the prostitutes and in 1% of the cervical samples of women in the general population. All PBMC samples were negative. These results suggest that in low‐risk countries for KSHV, oral shedding and heterosexual contacts are potential pathways for KSHV transmission. © 2001 Wiley‐Liss, Inc.
Constructing an adenocarcinoma vaccine: Immunization of mice with synthetic KH‐1 nonasaccharide stimulates anti‐KH‐1 and anti‐Ley antibodies
Authors: Ragupathi Govindaswami , Deshpande Prashant P. , Coltart Don M. , Kim Hyunjin M. , Williams Lawrence J. , Danishefsky Samuel J. , Livingston Philip O.
Published: August 2002

There is mounting evidence to suggest that immunization‐based strategies can be used to mobilize the human immune system against specific carbohydrate antigens displayed on the surface of cancer cells. Following isolation and identification, such antigens can be administered as conjugate vaccines. The tumor‐associated carbohydrate antigen KH‐1 is 1 such antigen and may serve as a potential target for immunization against adenocarcinoma. However, a serious impediment to the application of a vaccine‐based approach involving this antigen is that its availability from natural sources is severely limited. In order to overcome this limitation, we have developed an efficient total synthesis of this complex glycolipid. We have extended our synthesis to reach a structurally related analog in which the ceramide portion of KH‐1 is replaced with an allyl substituent. These synthetic advances have led to the preparation of 2 potential vaccine constructs, each based on the conjugation of the KH‐1 nonasaccharide and the carrier protein keyhole limpet hemocyanin (KLH). In 1 construct (KH‐1‐Et‐KLH), the nonasaccharide is conjugated to KLH via a simple ethyl linkage, while in the other (KH‐1‐MMCCH‐KLH), conjugation is mediated by a 4‐(4‐N‐maleimidomethyl)cyclohexane‐1‐carboxyl hydrazide (MMCCH) cross‐linker. We report here the immunological properties of these 2 constructs. Mice were immunized with either of the 2 KH‐1‐KLH vaccine candidates or the KH‐1 ceramide, along with the immunological adjuvant QS‐21. Immunization with the ceramide served as a negative control and, as expected, failed to stimulate the production of antibodies against the KH‐1 glycolipid. The construct in which the KH‐1 nonasaccharide is linked to KLH via a simple alkyl chain stimulated significant quantities of IgM antibodies, whereas the construct linked to KLH by MMCCH induced high titers of both IgM and IgG antibodies. Inhibition data demonstrated that antibodies generated in response to immunization with the KH‐1‐KLH constructs recognize not only the KH‐1 antigen but also the Lewisy (Ley) antigen, which, from a structural perspective, is similar to the 4 residues located at the non‐reducing end of the KH‐1 nonasaccharide. Thus, the KH‐1‐KLH constructs elicit an immune response that successfully targets 2 adenocarcinoma markers. As assessed by FACS analysis, the antibodies raised were strongly reactive with the KH‐1/Ley positive cell line MCF‐7 but not with KH‐1 and Ley negative melanoma cell lines. Based on the results of our study, a KH‐1‐KLH plus QS‐21 vaccine is being prepared for clinical evaluation. © 2002 Wiley‐Liss, Inc.
TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression cloning
Authors: Aarnoudse Corlien A. , Krüse Margreet , Konopitzky Renate , Brouwenstijn Nathalie , Schrier Peter I.
Published: August 2002

The identification of novel tumor antigens is of extreme importance for effective immunotherapy against cancer. A major obstacle in this field is the limited life span of tumor‐specific cytotoxic T lymphocytes (CTLs) in vitro. Therefore we searched for a method to isolate the tumor specificity of these CTLs, i.e., their T‐cell receptors (TCRs) and transfer it to an immortalized T‐cell line. For this purpose, a TCR‐negative Jurkat T‐cell line was equipped with a nuclear factor of activated T cells (NFAT)‐luciferase reporter construct to allow measurement of TCR‐mediated activation. To establish the feasibility of this tumor‐specific TCR transduction, we cloned the TCR genes of a known T‐cell clone specific for the tumor antigen CAMEL (CTL‐recognized antigen on melanoma) into a retroviral construct. Jurkat reporter cells transduced with this construct, Jrt‐TCRα3β5, were tested for their reactivity against CAMEL‐expressing melanoma cells, peptide‐loaded T2 cells and CAMEL‐transfected COS‐1 cells. The melanoma cell lines were poorly recognized, but peptide‐pulsed and ‐transfected cells effectively stimulated NFAT signaling. The activation of TCR+ Jurkat reporter cells was shown to be dependent on the antigen density on the target cells and the expression level of the coreceptor CD8 on the Jurkat cells. To verify the benefit of this TCR reconstitution method for identification of novel antigens, pools of the cDNA library from which CAMEL was originally cloned were transfected in COS‐1 cells and screened with Jrt‐TCRα3β5. Identical cDNA pools were found that were positive with these cells and with the CAMEL‐specific CTL clone. Our results illustrate that TCR‐reconstituted Jurkat reporter cells are a useful tool in the identification of novel tumor antigens by cDNA expression cloning. © 2002 Wiley‐Liss, Inc.
Molecular staging of colorectal cancer in African‐American and Caucasian patients using phenotypic expression of p53, Bcl‐2, MUC‐1 AND p27kip‐1
Authors: Grizzle William E. , Manne Upender , Weiss Heide L. , Jhala Nirag , Talley Lynya
Published: August 2002

The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that “molecular staging” be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53nac) and phenotypic expression of Bcl‐2, MUC‐1 and p27kip‐1 may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers. © 2001 Wiley‐Liss, Inc.
Acute toxicity studies of α‐Ketoglutarate: a promising antidote for cyanide poisoning
Authors: Bhattacharya R. , Kumar Deo , Sugendran K. , Pant S. C. , Tulsawani R. K. , Vijayaraghavan R.
Published: August 2002

Recently we have shown that cyanide poisoning by the oral (p.o.) route could be antagonized significantly by pretreatment or simultaneous treatment of α‐ketoglutarate (α‐KG), administered p.o. in rodents. The protective effect of α‐KG was dose dependent (0.125–2.0 g kg−1) and the effect was significant at a dose above 1.0 g kg−1. In order to establish the safety of α‐KG, various haematological, biochemical and histological parameters were studied following p.o. administration of 2.0 g kg−1α‐KG in female rats, and various physiological parameters were studied following p.o. administration of 2.0 or 4.0 g kg−1α‐KG in anaesthetized male rats. The p.o. LD50 of α‐KG in male and female rats was >5.0 g kg−1 and no toxic signs were observed in the surviving animals. Except for an increase in plasma alkaline phosphatase and urea levels after 1 h and a decrease in inorganic phosphorus levels after 7 days of treatment, no significant change in haematology, biochemistry or histology of the vital organs were observed. Mean arterial pressure and neuromuscular transmission were decreased at 4.0 g kg−1α‐KG but other physiological variables such as heart rate, respiratory rate, rectal temperature, left ventricular pressure (systolic), arterial pressure (systolic) and arterial pressure (diastolic) were not altered. The changes observed at 4.0 g kg−1α‐KG are unlikely to be of toxicological concern. The results indicate that α‐KG at 2.0 g kg−1 (p.o.)—a dose offering maximum antidotal efficacy—is non‐toxic and therefore can be considered suitable for cyanide poisoning. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of chemical composition on the corrosion behavior of Ni‐Cr‐Mo dental casting alloys
Authors: Huang Her‐Hsiung
Published: August 2002

The objective of this investigation was to study the compositional influence on the corrosion behavior of Ni‐Cr‐Mo dental casting alloys in acidic artificial saliva. Cyclic potentiodynamic and potentiostatic tests were used to evaluate the corrosion behavior of different Ni‐Cr‐Mo dental casting alloys in deaerated artificial saliva with pH 5 at 37°C. Optical microscope observations were made following the cyclic potentiodynamic tests. Surface chemical analyses were characterized by X‐ray photoelectron spectroscopy and auger electron spectroscopy following the potentiostatic tests. The results show that the corrosion resistance of the Ni‐Cr‐Mo casting alloys investigated is associated with the formation of passive film containing Ni(OH)2, NiO, Cr2O3, and MoO3, on the surface. The pitting potential and passive range, respectively, were statistically different among the different Ni‐Cr‐Mo alloys. The Ni‐Cr‐Mo alloys with higher Cr (≈21%) and Mo (≈8%) contents had a much larger passive range in the polarization curve and were immune to pitting corrosion due to the presence of high Cr (maximum ≈31–35%) and Mo (maximum ≈12%) contents in the surface passive film. The presence of Ti lower than 4% in the Ni‐Cr‐Mo casting alloy had no effect on corrosion resistance. A pitting resistance equivalent (PRE) of about 49 could provide the Ni‐Cr‐Mo alloy with a good pitting corrosion resistance. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 458–465, 2002; DOI 10.1002/jbm.10080
Adsorption of proteins from infant and adult plasma to biomaterial surfaces
Authors: Cornelius Rena M. , Archambault Jacques G. , Berry Leslie , Chan Anthony K. C. , Brash John L.
Published: August 2002

The hemostatic mechanism of the newborn is immature. In general, the clotting times in screening tests are prolonged, the coagulation factors are low, and the coagulation inhibitors (with the exception of alpha‐2‐macroglobulin) are low. Recognizing that many of the proteins present in infant plasma are at low levels, it is of interest to determine if, following exposure to artificial surfaces, the profile of adsorbed proteins is different for infant versus adult plasma. The question of whether differences in protein profiles could lead to differences in thromboembolic episodes associated with the use of central venous catheters (or other blood‐contacting devices) in infant versus adult subjects also is relevant. To address these issues, the adsorption of proteins from pooled infant plasma and pooled normal adult plasma to three different polymer surfaces (polyvinyl chloride, PVC; polymethyl methacrylate, PMMA; and polyethylene oxide‐modified polyurethane, PEO‐PU) was studied using SDS‐PAGE and immunoblotting techniques. The total amount of protein adsorbed to each surface also was determined. It was found that the PMMA and PVC surfaces adsorbed considerably more protein than the PEO‐PU surface. Furthermore, the amount of protein adsorbed to the PMMA and PVC surfaces from infant plasma was significantly less than that adsorbed from adult plasma. No such difference was seen for the protein‐repellent PEO‐PU surface. The immunoblot responses of proteins bound to the PMMA and PVC surfaces from infant plasma were, in general, weaker than those bound from adult plasma. It is likely that these differences were due to decreased protein levels in infant plasma. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 622–632, 2002
Effect of initiation chemistry on the fracture toughness, fatigue strength, and residual monomer content of a novel high‐viscosity, two‐solution acrylic bone cement
Authors: Hasenwinkel Julie M. , Lautenschlager Eugene P. , Wixson Richard L. , Gilbert Jeremy L.
Published: August 2002

Porous‐free, two‐solution bone cements have been developed in our laboratory as an alternative to commercial powder/liquid formulations. Each pair of solutions consist of poly(methyl methacrylate) (PMMA) powder dissolved in methyl methacrylate (MMA) monomer, with benzoyl peroxide (BPO) added to one solution as the initiator and N,N‐dimethyl‐p‐toluidine (DMPT) added to the other as the activator. When mixed, the solutions polymerize via a free radical reaction, which is governed by the concentrations of initiator and activator and their molar stoichiometry. Previous work by the authors has demonstrated that these two‐solution cement compositions are comparable to Simplex P bone cement in polymerization exotherm, setting time, and flexural mechanical properties. This study was designed to evaluate the effect of BPO and DMPT concentrations, along with their molar ratio, on the fracture toughness, fatigue strength, and residual monomer content of the experimental compositions. The results showed that fracture toughness and fatigue strength for the solution cements were comparable to Simplex P and were not significantly affected by the BPO concentration or the BPO:DMPT molar ratio; however, the highest DMPT concentration yielded significantly lower values for both variables. Residual monomer content was significantly affected by both the individual concentrations of BPO and DMPT and their molar ratios. The two‐solution cements had significantly higher residual monomer contents versus Simplex P; however, this can be attributed to their higher initial monomer concentration rather than a lower degree of conversion. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 411–421, 2002
Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr‐1, a zinc finger transcriptional regulator
Authors: Kaufmann Katrin , Thiel Gerald
Published: August 2002

The epidermal growth factor (EGF) receptor is highly expressed in HaCaT keratinocytes as shown by Western blotting. Stimulation of HaCaT cells with EGF, and also with the serine protease thrombin, induced DNA synthesis, measured by incorporation of 5‐bromo‐2′‐deoxyuridine into the DNA of proliferating cells. Using antibodies directed against the active form of the EGF receptor, we show that in HaCaT cells EGF and thrombin triggered a rapid activation of the EGF receptor, followed by the phosphorylation and activation of the extracellular signal‐regulated protein kinase (ERK). Moreover, EGF and thrombin induced a transient synthesis of the zinc finger transcriptional regulator Egr‐1. Proliferation, activation of ERK, and biosynthesis of Egr‐1 was completely inhibited in EGF or thrombin‐treated HaCaT cells by the MAP kinase kinase inhibitor PD98059 and by AG1487, an EGF receptor‐specific tyrosine kinase inhibitor. These data indicate that phosphorylation and activation of both the EGF receptor and ERK are essential for mitogenic signaling via EGF and thrombin. The synthesis of Egr‐1 in HaCaT cells as a result of EGF or thrombin stimulation suggests that Egr‐1 may be an important “late” part of the EGF and thrombin‐initiated signaling cascades. We postulate that Egr‐1 may function as a “third messenger” in keratinocytes connecting mitogenic stimulation with changes in gene transcription. J. Cell. Biochem. 85: 381–391, 2002. © 2002 Wiley‐Liss, Inc.
Mapping of Sp1 regulation sites in the promoter of the human α1‐proteinase inhibitor gene
Authors: Maruyama Yasuhiro , Li Yuhong , Zhang Yan , Wang Xinping , Sugar Joel , Y.J.T. Yue Beatrice
Published: August 2002

Keratoconus is a potentially blinding disease that thins the central cornea. In afflicted corneas, the level of an inhibitor, α1‐proteinase inhibitor (α1‐PI), is found reduced. An increased expression of transcription factor Sp1 is also demonstrated. To examine the role of Sp1 in regulation of the human α1‐PI gene, a 1.4‐kb (−1397/+9) 5′‐flanking promoter sequence that contains 10 Sp1 sites was cloned. Previous transient transfection experiments showed that Sp1 expression indeed repressed the α1‐PI promoter activity. In this study, 12 DNA segments, a series of 5′, 3′, and internal deletions of the 1.4‐kb α1‐PI promoter sequence, were ligated into the SEAP (secreted alkaline phosphatase) reporter gene vector and transfected into human corneal stromal cells. Co‐transfection with a Sp1 expression vector pPacSp1 was also performed in parallel. The SEAP enzyme activity was assayed. A fragment with 489 bp (−480/+9) of the 3′ sequence, and three fragments with internal deletions, were found to confer a majority of the full promoter activity. Other deletions significantly abolished the promoter activity. Site‐directed mutagenesis experiments further revealed that the most proximal Sp1 site (−100/−87) may be an essential element involved in the negative regulation of α1‐PI promoter activity by Sp1. Interaction between the proximal and distal Sp1 sites also seemed to be important. These results provide the first in‐depth characterization of the transcription mechanisms regulating the expression of α1‐PI. Mapping of the Sp1 sites may help elucidate the molecular pathway leading to the alterations observed in keratoconus. J. Cell. Biochem. 85: 482–489, 2002. © 2002 Wiley‐Liss, Inc.
Zinc suppresses IL‐6 synthesis by prostaglandin F2α in osteoblasts: Inhibition of phospholipase C and phospholipase D
Authors: Hatakeyama Daijiro , Kozawa Osamu , Otsuka Takanobu , Shibata Toshiyuki , Uematsu Toshihiko
Published: August 2002

We previously reported that prostaglandin F2α (PGF2α) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP‐binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast‐like MC3T3‐E1 cells and that PGF2α stimulates the synthesis of interleukin‐6 (IL‐6) via PKC‐dependent p44/p42 mitogen‐activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF2α‐induced IL‐6 synthesis in these cells. Zinc complex of l‐carnosine (l‐CAZ) dose‐dependently suppressed the PGF2α‐stimulated IL‐6 synthesis. In addition, zinc alone reduced the IL‐6 synthesis. L‐CAZ suppressed the PGF2α‐induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP‐binding protein, was not affected by l‐CAZ. l‐CAZ reduced the PGF2α‐stimulated formation of inositol phosphates and choline. However, l‐CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF2α‐induced IL‐6 synthesis via suppression of phosphoinositide‐hydrolyzing phospholipase C and phosphatidylcholine‐hydrolyzing phospholipase D in osteoblasts. J. Cell. Biochem. 85: 621–628, 2002. © 2002 Wiley‐Liss, Inc.
Human BMP‐7/OP‐1 induces the growth and differentiation of adipocytes and osteoblasts in bone marrow stromal cell cultures*
Authors: Chen Theresa L. , Shen Wen‐Jun , Kraemer Fredric B.
Published: August 2002

We studied the effects of BMP‐7/OP‐1 on growth and differentiation of bone marrow stromal cells. BMS2, a mouse bone marrow stromal cell line capable of differentiating into adipocytes and osteoblasts, were treated in a serum‐free medium containing differentiation agents that favor the expression of both lineages. BMP‐7/ OP‐1 stimulated cell proliferation and differentiation concomitantly. These effects were dose‐ and growth phase‐dependent. Cells were more sensitive to the treatment early in the culture (30–40% confluence) with a significant increase in cell proliferation and markers of differentiation at low concentrations. When treated later in the growth phase (90–100% confluence), no significant increase in cell proliferation was seen. The concentration requirement for cells later in the culture to reach an equivalent degree of differentiation was 3–10‐ fold higher than for cells treated early. In both cases, the effects on adipocyte differentiation were biphasic; low concentrations stimulated adipocyte differentiation which was inhibited at higher concentrations where stimulation of osteoblast markers were observed. We conclude that cell proliferation and cell differentiation into adipocyte/osteoblast can occur simultaneously under BMP‐7/OP‐1 treatment. J. Cell. Biochem. 82: 187–199, 2001. Published 2001 Wiley‐Liss, Inc.
Subcellular distribution of native estrogen receptor α and β isoforms in rabbit uterus and ovary
Authors: Monje Paula , Boland Ricardo
Published: August 2002

The association of estrogen receptors with non‐nuclear/cytoplasmic compartments in target tissues has been documented. However, limited information is available on the distribution of estrogen receptor isoforms, specially with regard to the newly described β isotype. The subcellular localization of estrogen receptor α and β isoforms was investigated in rabbit uterus and ovary. Native α and β subtypes were immunodetected using specific antibodies after subjecting the tissue to fractionation by differential centrifugation. The ovary expressed α and β estrogen receptors in predominant association to cytosolic components. However, in the uterus, a substantial proportion of the total estrogen binding capacity and coexpression of the two isoforms was detected in mitochondria and microsomes. The mitochondrial‐enriched subfraction represented an important source of 17β‐estradiol binding, where the steroid was recognized in a stereospecific and high affinity manner. The existence of mitochondrial and membrane estrogen binding sites correlated with the presence of estrogen receptor α but mainly with estrogen receptor β proteins. Using macromolecular 17β‐estradiol derivatives in Ligand Blot studies, we could confirm that both α and β isoforms were expressed as the major estrogen binding proteins in the uterus, while estrogen receptor α was clearly the dominant isoform in the ovary. Other low molecular weight estrogen receptor α‐like proteins were found to represent an independent subpopulation of uterine binding sites, expressed to a lesser extent. This differential cellular partitioning of estrogen receptor α and β forms may contribute to the known diversity of 17β‐estradiol effects in target organs. Both estrogen receptor α and β expression levels and cellular localization patterns among tissues, add complexity to the whole estrogen signaling system, in which membrane and mitochondrial events could also be implicated. J. Cell. Biochem. 82:467–479, 2001. © 2001 Wiley‐Liss, Inc.
Accompanying coordinate expansion formulas derived with the solid harmonic gradient
Authors: Ishida Kazuhiro
Published: August 2002

A series of accompanying coordinate expansion (ACE) formulas for calculating the electron repulsion integral (ERI) over both generally and segmentally contracted solid harmonic (SH) Gaussian‐type orbitals (GTOs) can be rederived by the use of the modified operator (called solid harmonic gradient here) of the spherical tensor gradient of Bayman and the reducing solid harmonic gradient defined in this article. The final general formulas contain the reducing mixed solid harmonics defined in a previous article [Ishida, K. J Chem Phys 1999, 111, 4913] and the reducing triply mixed solid harmonics defined previously [Ishida, K. J Chem Phys 2000, 113, 7818]. Each general formula in the series is named ACEb1k1, ACEb2k3, or ACEb3k3. New general algorithm can be obtained inductively from the general formula named ACEb2k3, in addition to the previously developed ACEb1k1 and ACEb3k3. For calculating ERI practically, we select one of these ACE algorithms, as it gives the minimum floating‐point operation (FLOP) count. Theoretical assessment by the use of the FLOP count is performed for the (LL|LL) class of ERIs over both generally and segmentally contracted SH‐GTOs (L=1–3). It is found that the present ACE is theoretically the fastest among all rigorous methods in the literature. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 378–393, 2002
Modeling aspects of mechanisms for reactions catalyzed by metalloenzymes
Authors: Siegbahn P. E. M.
Published: August 2002

Different models to treat metal‐catalyzed enzyme reactions are investigated. The test case chosen is the recently suggested full catalytic cycle of manganese catalase including eight different steps. This cycle contains OO and OH activations, as well as electron transfer steps and redox active reactions, and is therefore believed to be representative of many similar systems. Questions concerning modeling of ligands and the accuracy of the computational model are studied. Imidazole modeling of histidines are compared to ammonia modeling, and formate modeling compared to acetate modeling of glutamates. The basis set size required for the geometry optimization and for the final energy evaluation is also investigated. The adequacy of the model is judged in relation to the inherent accuracy achievable with the hybrid DFT method B3LYP. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1634–1645, 2001
Treating the bisexual client
Authors: Dworkin Sari H.
Published: August 2002

Therapists, having recently come to terms with treating gay and lesbian clients, now must consider the issues that bisexual clients face. This article reviews the literature on what it means to identify as bisexual in a world where sexual identity is viewed as dichotomous, heterosexual at one end and gay or lesbian at the other end. The article explores sexual identity and its biological versus social origins, internalized biphobia, coming out, relationship patterns, and therapist issues. Two cases illustrate issues that might arise when a therapist is treating a bisexual client. The first case is a 17‐year‐old young woman who is accepting of her bisexual identity, and the second case is a 56‐year‐old woman, heterosexually identified and married, who suddenly fell in love with a woman. Concluding remarks focus on some future directions for research and work with bisexual clients. © 2001 John Wiley & Sons, Inc. J Clin Psychol/In Session 57: 671–680, 2001.