bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and protein binding of the selective neuronal nitric oxide synthase inhibitor 7‐nitroindazole
Authors: Bush Mark A. , Pollack Gary M.
Published: August 2002

Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of NO in various central nervous system processes requires use of an inhibitor selective for neuronal NOS, and is facilitated by knowledge of the pharmacokinetics of the inhibitor. The present project was undertaken to elucidate the disposition of the selective neuronal NOS inhibitor 7‐nitroindazole (7‐NI). A simple, specific HPLC assay was developed with requisite sensitivity to quantitate 7‐NI in serum after administration of pharmacologically relevant doses. Further experiments were performed to assess the effects of administered dose on 7‐NI disposition. 7‐NI displayed marked nonlinearity, consistent with saturable elimination, when administered by ip injection in peanut oil. The nonlinearity was related to total dose, but not to the concentration of 7‐NI in the vehicle. Binding of 7‐NI in rat serum was concentration‐independent and does not contribute to the nonlinearity. Various formulations for iv administration of this water‐insoluble compound were evaluated; the optimal vehicle, from the standpoint of 7‐NI solubility, appeared to inhibit the clearance of 7‐NI from the systemic circulation. Considering the nonlinear disposition of 7‐NI, knowledge of the pharmacokinetics of this inhibitor is requisite to designing administration protocols to achieve the desired magnitude and duration of NOS inhibition. Copyright © 2000 John Wiley & Sons, Ltd.
Folinic acid protects against suppression of growth by Methotrexate in mice
Authors: Perwaiz Iqbal M. , Sultana Fakhara , Mehboobali Naseema , Pervez Shahid
Published: August 2002

The objective of this study was to investigate whether folinic acid supplementation would protect young mice against suppression of growth by methotrexate (MTX). Four equal groups of Balb/c young male mice (5 animals in each group; mean±SD body weight 9.64±0.85 g, in their rapid growth phase) were subjected to the following drug treatment: One group was given MTX (3.5 mg/kg body weight) intraperitoneally on every 2nd day, another received folinic acid (7.0 mg/kg body weight) intraperitoneally every 2nd day. The third group was given both of these drugs (MTX on every 2nd day and folinic acid 8 h post‐MTX injection). The fourth group was injected with physiological saline every other day to serve as a control group. Total body weight, food and water consumption by animals in each group were monitored every second day for a period of 3 weeks. After this period mice were sacrificed and liver, spleen and kidneys were excised, weighed and analyzed for MTX and dihydrofolate reductase activity. A small segment of the proximal part of small intestine and small pieces of liver and kidney were also removed to study morphological changes.

Compared to the groups, which received folinic acid alone, folinic acid plus MTX or physiological saline, mean increase in body weight (6.8±0.8 g) of mice over a period of 3 weeks was minimal in the group receiving MTX alone (one‐way ANOVA p=0.0001). The mean weights of liver and kidney in this group receiving MTX alone were also found to be significantly less than the mean weights of these organs in the 3 groups (p<0.001). The negative effect on growth of animals appears not only due to malabsorption but inhibition of pathway of de novo DNA synthesis may also be involved. This is supported by loss of villous pattern in small intestine of mice treated with MTX alone and increased accumulation of free MTX and decreased dihydrofolate reductase in the liver of the group receiving MTX alone as compared with the group receiving MTX plus folinic acid. The data indicate that the administration of folinic acid protects mice against suppression of growth by MTX. On the basis of these observations it can be deduced that patients suffering from juvenile rheumatoid arthritis or acute lymphoblastic leukaemia receiving MTX over a long period of time might be at a risk of experiencing short‐term suppression of growth, however they could benefit from supplementation with folinic acid. Copyright © 2001 John Wiley & Sons, Ltd.
Predicted SAR in sprague‐dawley rat as a function of permittivity values*†
Authors: Gajšek P. , Ziriax J.M. , Hurt W.D. , Walters T.J. , Mason P.A.
Published: August 2002

Specific absorption rate (SAR) value is dependent on permittivity value. However, variability in the published permittivity values for human and animal tissue and the development of sophisticated 3‐dimensional digital anatomical models to predict SAR values has resulted in the need to understand how model parameters (permittivity value) affect the predicted whole body and localized SAR values. In this paper, we establish the partial derivative of whole body SARs and localized SAR values (defined as SAR for individual organs with respect to a change in the permittivity values of all tissue types, as well as for those tissues with the most variable permittivity values. Variations in the published permittivity values may substantially influence whole body and localized SAR values, but only under special conditions. Orientation of the exposed object to the incident electromagnetic wave is one of the most crucial factors. Bioelectromagnetics 22:384–400, 2001. Published 2001 Wiley‐Liss, Inc.
Project NEMESIS: Perception of a 50 Hz electric and magnetic field at low intensities (laboratory experiment)
Authors: Mueller Christopher H. , Krueger Helmut , Schierz Christoph
Published: August 2002

The Electrical Hypersensitivity Syndrome (EHS) is a condition where people suffer from various nonspecific health symptoms attributed to an assumed adverse effect of electric and magnetic fields (EMF). Many EHS patients report the ability to consciously perceive EMF at very low intensities. The existence of a direct EMF perception could be the key to explain at least partially the aetiology of EHS through stress mechanisms and allow the comparison with well known environmental stressors such as noise or odor. The double blind laboratory experiment tested the hypothesis that there are subjects with the ability to perceive 50 Hz EMF at 100 V/m and 6 μT (EMF sensitive) and to investigate the prevalence of EMF sensitivity in a group consisting of subjects with or without self‐reported EHS. A total of 63 volunteers, 49 with EHS and 14 controls, took part in the EMF perception experiment, where 10 sham and 10 exposed 2 min blocks had to be judged in randomized sequence (field on/field off). Seven out of 63 subjects reached a statistically significant result which points to the existence of a small EMF sensitive subgroup within the study group. There was no relevant difference between the subjects with self reported EHS and those without in terms of the success rate in the field perception experiment, as well as the number and types of symptoms encountered during the test. The results of the EMF perception experiment suggest that EHS is not a prerequisite for the ability to consciously perceive weak EMF and vice versa. Bioelectromagnetics 23:26–36, 2002. © 2002 Wiley‐Liss, Inc.
Memory in bacteria and phage
Authors: Casadesús Josep , D'Ari Richard
Published: August 2002

Whenever the state of a biological system is not determined solely by present conditions but depends on its past history, we can say that the system has memory. Bacteria and bacteriophage use a variety of memory mechanisms, some of which seem to convey adaptive value. A genetic type of heritable memory is the programmed inversion of specific DNA sequences, which causes switching between alternative patterns of gene expression. Heritable memory can also be based on epigenetic circuits, in which a system with two possible steady states is locked in one or the other state by a positive feedback loop. Epigenetic states have been observed in a variety of cellular processes, and are maintained by diverse mechanisms. Some of these involve alternative DNA methylation patterns that are stably transmitted to daughter molecules and can affect DNA–protein interactions (e.g., gene transcription). Other mechanisms exploit autocatalytic loops whereby proteins establish the proper conditions for their continued synthesis. Template polymers other than nucleic acids (e.g., components of the cell wall) may also propagate epigenetic states. Non‐heritable memory is exemplified by parasitic organisms that bear a signature of their previous host, such as host‐controlled modification of phage DNA or porin hitchhiking in predatory bacteria. The heterogeneous nature of the examples known may be indicative of widespread occurrence of memory mechanisms in bacteria and phage. However, the actual extent, variety and potential selective value of prokaryotic memory devices remain open questions, still to be addressed experimentally. BioEssays 24:512–518, 2002. © 2002 Wiley Periodicals, Inc.
Steroid signaling in plants: from the cell surface to the nucleus
Authors: Friedrichsen Danielle , Chory Joanne
Published: August 2002

Steroid hormones are signaling molecules important for normal growth, development and differentiation of multicellular organisms. Brassinosteroids (BRs) are a class of polyhydroxylated steroids that are necessary for plant development. Molecular genetic studies in Arabidopsis thaliana have led to the cloning and characterization of the BR receptor, BRI1, which is a transmembrane receptor serine/threonine kinase. The extracellular domain of BRI1, which is composed mainly of leucine‐rich repeats, can confer BR responsivity to heterologous cells and is required for BR binding. Although downstream components of BR action are mostly unknown, multiple genes whose expression are regulated by BRs have been identified and suggest mechanisms by which BRs affect cell elongation and division. BioEssays 23:1028–1036, 2001. © 2001 John Wiley & Sons, Inc.
Stimulus fading in the treatment of adipsia
Authors: Babbitt Roberta L. , Shore Bridget A. , Smith Marnie , Williams Keith E. , Coe David A.
Published: August 2002

Stimulus fading procedures have repeatedly been demonstrated as effective in shaping a wide variety of new behaviors. Borrowing from this body of research, the behavioral treatment of feeding disorders presents a new area of application for stimulus fading. The purpose of this study is to demonstrate the efficacy of stimulus fading in the treatment of adipsia. Two children who ate solids, but refused all liquids, were participants in the study. Results showed that a five step fading procedure starting with a spoon and thickened liquids, and ending with a cut‐out‐cup, was successful in establishing cup drinking skills for both children. Results of the study suggest that stimulus fading can facilitate feeding skill acquisition. Copyright © 2001 John Wiley & Sons, Ltd.
Homologs of 1,2,5‐hexahydro‐3‐one‐1H‐1,4‐diazepine (DAP) as novel dipeptidomimetics and molecular scaffolds: Efficient preparation of synthons
Authors: Han Yinglin , Mierke Dale F. , Chorev Michael
Published: August 2002

Structurally constraint dipeptidomimetics represent an important class of conformationally rigid dipeptide surrogates and molecular scaffolds, which are frequently employed in peptide‐based structure–activity relationships (SAR) and construction of combinatorial libraries. We report on the design of an improved and general synthetic procedure to prepare synthons related to the trisubstituted 1,2,5‐hexahydro‐3‐one‐1H‐1,4‐diazepines [DAP(Xxx)α7] (DAP: 1,2,5‐hexahydro‐3‐one‐1H‐1,4‐diazepine; DAP(Xxx)α7: the homologous series of DAP in which α refers to the location of the chiral carbon in the ith amino acid, Xxx represents the three letter notation for the i−1 amino acids, and 7 denotes the number of atoms in the ring) and their higher homologs [DAP(Xxx)αN] [Xxx = Phe, Asp(β‐OcHex) (cHex: cyclohexyl), and Arg(NG‐Tos] (Tos: p‐toluenesulfonyl); N = 8–10]. These dipetidomimetic structures are generated by reductive alkylation‐mediated Cαi‐to‐Ni−1 bridging between a Cα i‐(CH2)‐COSEt (n = 1–4) and H2N‐Ci−1HR‐CO2Fm (Fm: 9‐fluorenylmethyl) followed by H2Ni‐to‐Ci−1‐CO2H lactam formation. We also describe the preparation of blocked N‐Ac‐[DAP(Phe)αN]‐CONMe2 (N = 8–10), which serve as model systems for detailed conformational analysis reported in the accompanying article. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 1–15, 2002
Study of interaction between aspartic acid and silver by surface‐enhanced Raman scattering on H2O and D2O sols
Authors: Arenas J. F. , Castro J. L. , Otero J. C. , Marcos J. I.
Published: August 2002

Three different surface‐enhanced Raman scattering (SERS) spectra are recorded for aspartic acid on H2O silver sols under different concentrations and pH values. The analysis of the results shows that it interacts with the metal surface in its dianionic form in two different ways, depending on the pH and concentration. Moreover, in some cases the fumarate anion is detected, which results from the chemical surface transformation of the aspartate. The N‐deuterated aspartic acid adsorbed on the D2O silver sols gives rise to only one SERS spectrum as a consequence of the interaction of amino and carboxylate functional groups of the dianion with the metal, independent of the concentration and pD. © 2001 John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 62: 241–248, 2001
Overexpression of alcohol dehydrogenase or pyruvate decarboxylase improves growth of hairy roots at reduced oxygen concentrations
Authors: Shiao Tien‐li , Ellis Marc H. , Dolferus Rudy , Dennis Elizabeth S , Doran Pauline M
Published: August 2002

Overexpression of Arabidopsis thaliana genes for the fermentation enzymes, alcohol dehydrogenase and pyruvate decarboxylase, improved the tolerance of A. thaliana hairy roots to low oxygen conditions. Whereas the specific growth rate of untransformed hairy roots in shake flasks and in a multiple‐tube recirculation bioreactor declined significantly with decreasing oxygen tension down to 25% air saturation, growth of the transformant root lines was maintained at rates similar to those achieved with full aeration. This work demonstrates that altering the expression of selected genes involved in anaerobic metabolism can alleviate the problems of oxygen deficiency in hairy root cultures caused by poor mixing and mass transfer conditions. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 455–461, 2002; DOI 10.1002/bit.10147
Rapamycin reduces hybridoma cell death and enhances monoclonal antibody production
Authors: Balcarcel R. Robert , Stephanopoulos Gregory
Published: August 2002

Rapamycin was used as a medium additive to slow the progression of CRL 1606 hybridomas through the cell cycle, under the hypothesis that such a modulation might reduce cell death. Cell cycle distributions for CRL hybridomas in the G1 phase of the cell cycle ranged from 20% to 35% during batch, fed‐batch, and continuous culture experiments, independent of culture time, dilution rate, growth rates, or death rates. Rapamycin, an mTOR signaling inhibitor, immunosuppressant, and G1‐phase arresting agent, was identified and tested for efficacy in restraining cell cycle progression in CRL 1606 hybridoma cultures. However, in the presence of 100 nM rapamycin, the percentage of cells in the G1 phase of the cell cycle during fed‐batch cultures was only increased from 28% to 31% in control cultures to 37% to 48% for those with rapamycin. Accordingly, rapamycin only slightly reduced culture growth rate. Instead, the use of rapamycin more notably kept viability higher than that of control cultures by delaying cell death for 48 h, thereby enabling viable proliferation to higher maximum viable cell densities. Furthermore, rapamycin enhanced specific monoclonal antibody production by up to 100% during high‐viability growth. Thus, over the course of 6‐day fed‐batch cultivations, the beneficial effects of rapamycin on viable cell density and specific productivity resulted in an increase in final monoclonal antibody titer from 0.25 to 0.56 g/L (124%). As rapamycin is reported to influence a much broader range of cellular functions than cell cycle alone, these findings are more illustrative of the influence that signal transduction pathways related to mTOR can have on overall cell physiology and culture productivity. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 1–10, 2001.
Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins
Authors: Pollard D. J. , Kirschner T. F. , Hernandez D. , Hunt G. , Olewinski R. , Salmon P. M.
Published: August 2002

The filamentous fungus Glarea lozoyensis produces a novel, pharmaceutically important pneumocandin (B0) that is used to synthesize a lipopeptide which demonstrates cidal activity against clinically relevant pathogens. A range of unwanted pneumocandin analogs are also produced by the organism. To maintain the unwanted impurities to acceptable levels upon scaleup, a good understanding of the impact of chemical and physical environment on the cell physiology is required, which benefits downstream processing. Pilot‐scale studies were performed to determine the impact of dissolved oxygen, temperature, pH, and carbon dioxide on the process. Experiments included multiple fermenters (up to seven) at 0.07 and 0.8 m3 scale using single source medium sterilization and inoculum. Gas blending was used to separate effects of dissolved oxygen from agitation. The process was significantly influenced by dissolved oxygen level. The critical dissolved oxygen tension (Ccrit) for growth was below 2% air saturation. The Ccrit for production of pneumocandin B0 was 20% air saturation, with a significant reduction of the specific production rate below this value. In contrast, low dissolved oxygen levels produced a substantial increase of pneumocandins B1, B5, and E0, while high dissolved oxygen levels produced a disproportionate increase of D5. This sensivity to dissolved oxygen was independent of agitation within a power range of 2–15 kW/m3. Broth viscosity was impacted below 10% dissolved oxygen, suggesting an effect on morphology. The process was shown to be sensitive to temperature but relatively insensitive to pH and carbon dioxide (in the exhaust gas) within the ranges studied. This scaledown analysis explained phenomena seen at pilot scale and helped define operating boundary conditions for successful scale up to 19 m3. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 270–279, 2002.
Equilibrium modeling of extractive enzymatic hydrolysis of penicillin G with concomitant 6‐aminopenicillanic acid crystallization
Authors: Diender M. B. , Straathof A. J. J. , van der Does T. , Ras C. , Heijnen J. J.
Published: August 2002

In the present downstream processing of penicillin G, penicillin G is extracted from the fermentation broth with an organic solvent and purified as a potassium salt via a number of back‐extraction and crystallization steps. After purification, penicillin G is hydrolyzed to 6‐aminopenicillanic acid, a precursor for many semisynthetic β‐lactam antibiotics. We are studying a reduction in the number of pH shifts involved and hence a large reduction in the waste salt production. To this end, the organic penicillin G extract is directly to be added to an aqueous immobilized enzyme suspension reactor and hydrolyzed by extractive catalysis.

We found that this conversion can exceed 90% because crystallization of 6‐aminopenicillanic acid shifts the equilibrium to the product side. A model was developed for predicting the equilibrium conversion in batch systems containing both a water and a butyl acetate phase, with either potassium or D‐p‐hydroxyphenylglycine methyl ester as counter‐ion of penicillin G. The model incorporates the partitioning equilibrium of the reactants, the enzymatic reaction equilibrium, and the crystallization equilibrium of 6‐aminopenicillanic acid. The model predicted the equilibrium conversion of Pen G quite reasonably for different values of pH, initial penicillin G concentration and phase volume ratio. The model can be used as a tool for optimizing the enzymatic hydrolysis. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 395–402, 2002.
Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of glyceric acid in urine of patients with D‐glyceric and L‐glyceric acidurias
Authors: Rashed Mohamed S. , Aboul‐Enein Hassan Y. , AlAmoudi Mohamed , Jakob Minnie , Al‐Ahaideb Lujaine Y. , Abbad Abbas , Shabib Suhail , Al‐Jishi Emtethal
Published: August 2002

Glyceric acid is a highly polar chiral carboxylic acid that is usually not detected during routine organic acid analysis. Increased excretion is observed in two phenotypically distinct and rare inherited metabolic diseases, D‐glyceric aciduria, and L‐glyceric aciduria (also known as primary hyperoxaluria type 2). The determination of the exact configuration of the excreted glyceric acid is necessary for the accurate diagnosis of D‐glyceric aciduria and for the differentiation between type 1 and type 2 primary hyperoxaluria. The separation of the two stereoisomers was achieved using a narrow‐bore ristocetin A glycopeptide antibiotic silica gel bonded column. Triethylamine acetate at pH 4.1 with 10% methanol was used as mobile phase. The column was directly interfaced to a triple quadrupole tandem mass spectrometer and the electrospray ion source was operated in the negative ion mode. Three parent‐to‐daughter transitions were employed to specifically detect eluting glyceric enantiomers from essentially untreated urine samples. The two forms of glyceric acid were satisfactorily separated at 3.6 and 4.5 min. Application of the method led to the confirmation of three cases of D‐glyceric aciduria from three different families. Two other cases are suspected to be L‐glyceric aciduria but further confirmation is needed. The method allowed the detection of the glyceric acid stereoisomers in control urine where it was found without exception that L‐glyceric was the predominate metabolite. Copyright © 2002 John Wiley & Sons, Ltd.
Constraints to organizational change processes regarding the introduction of organic products: case findings from the Swiss food industry
Authors: Maier Simone , Finger Matthias
Published: August 2002

The combination of the power dimension with the cognitive dimension on the basis of Giddens' theory of structuration provides a powerful concept for analysing constraints to organizational change. In the case of the introduction of organic products to Swiss food processing companies, four interacting and mutually re‐enforcing factors could be identified to constrain organizational change for a successful introduction of organic products: the organic products' low share of overall turnover (resources), missing top management support (power), missing adjustment of the collaborators' performance assessment criteria (norms) and missing collaborators' acceptance for the organic ideology (interpretative schemes). The strategies to overcome these constraints must be designed carefully according to the specific situation of the organization. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
The role of accounting and the accountant in the environmental management system
Authors: Wilmshurst Trevor D. , Frost Geoffrey R.
Published: August 2002

This paper explores the role of accounting and the accountant in the Environmental Management System (EMS). This study was founded on a postal survey of chief executive officers (CEOs) and chief financial officers (CFOs) from the top 500 listed Australian companies. From responses to the surveys, this paper firstly documents the adoption of environmental accounting processes by respondent companies and secondly management attitudes as to the role of environmental accounting in these companies. The senior executives responding to the survey suggest that they believe the environment is an important issue, and recognize the need for a business response. However, there appeared to be limited participation of the accountant in the EMS, which suggests there is a gap between the aggregate observations of this sample and literature support with respect to the role of environmental accounting. It is suggested that this might reflect a lack of understanding of the potential role accounting and the accountant could (and arguably should) play as a member of the EMS team. It is the intention of this paper to provide some input to enhance an understanding of the potential and important role accounting and the accountant could play in the EMS. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
Predicting the home location of serial offenders: a preliminary comparison of the accuracy of human judges with a geographic profiling system
Authors: Snook Brent , Canter David , Bennell Craig
Published: August 2002

The accuracy with which human judges, before and after ‘training’, could predict the likely home location of serial offenders was compared with predictions produced by a geographic profiling system known as Dragnet. All predictions were derived from ten spatial displays, one for each of ten different U.S. serial murderers, indicating five crime locations. In all conditions participants were asked to place an ‘X’ on each spatial display corresponding to where they thought the offender lived. In the control condition, a comparison was made between the accuracy of these predictions for 21 participants on two separate occasions a few minutes apart. In the experimental condition, between their first and second predictions the 21 participants were given two heuristics to follow—distance‐decay and circle hypothesis. Results showed that participants with no previous knowledge of geographic profiling were able to use the two heuristics to improve the accuracy of their predictions. The overall accuracy of the second set of predictions for the experimental group was also not significantly different from the accuracy of predictions generated by Dragnet. Copyright © 2002 John Wiley & Sons, Ltd.
Dissection: A positive experience
Authors: Mc Garvey M.A. , Farrell T. , Conroy R.M. , Kandiah S. , Monkhouse W.S.
Published: August 2002

First‐year medical students were surveyed by questionnaire to assess levels of stress and physical symptoms resulting from their experience of the anatomy room. There was a 100% response rate from the 188 students. Most students (95%) found the prospect of their first visit to the anatomy room exciting. A small number initially experienced physical symptoms, but these had improved significantly 10 weeks later. Most students suffered very little or no stress (80%) on their first visit with only 2% of respondents rating their stress levels as high. Ten weeks later, 87% experienced little or no stress with only 1% stating that they had high stress levels. The anatomy room was rated to be less stressful than workload and assessments. Students reported that the anatomy room provoked thoughts of mortality, and 27% suggested that there should be more preparation before the first visit to the anatomy room. Our findings support previous studies suggesting that American/Canadian students in particular find anatomy stressful. However, the wisdom of interpreting adverse reactions as symptomatic of post‐traumatic stress disorder is questioned. This study shows the anatomy room to be a positive learning experience for the students of the Royal College of Surgeons in Ireland. Clin. Anat. 14:227–230, 2001. © 2001 Wiley‐Liss, Inc.
Representations of ethnicity in people's accounts of local community participation in a multi‐ethnic community in England
Authors: Campbell Catherine , McLean Carl
Published: August 2002

In this paper we examine the impact of the social construction of ethnic identities on the likelihood of local community participation. We do so in the context of an applied interest in the current policy emphasis on partnerships between government and local communities in initiatives to reduce health inequalities, and a conceptual interest in the role of social representations in perpetuating unequal power hierarchies. Semi‐structured interviews were conducted with 75 residents of a deprived multi‐ethnic area in south England. Informants described themselves as African‐Caribbean, Pakistani and White English; half men and half women, aged 15–75. We draw attention to the way in which ethnic identities may be constructed in ways that undermine the likelihood of local community participation. Stereotypical representations of ethnically defined ingroups and outgroups (the ethnic ‘other’) constituted key symbolic resources used by our informants in accounting for their low levels of engagement with local community networks. We examine the content of these stereotypes, and highlight how their construction is shaped by historical, economic and social forces, within the context of the ‘institutional racism’ that exists in England. Copyright © 2001 John Wiley & Sons, Ltd.
Concurrent Enrollment in Arizona: Encouraging Success in High School
Authors: Puyear Donald , Thor Linda , Mills Karen
Published: August 2002

This chapter presents a brief history of concurrent enrollment initiatives and then gives an overview of activity in Arizona, including research on student achievement, as well as tracking studies. In spite of growth in the number of programs and successes in student achievement, not everyone in the state understands and appreciates the benefits of the program; the final section of this chapter describes some of the realities of politics and necessary compromises.
Radial approach to right heart catheterization: Early experience with a promising technique
Authors: Gilchrist Ian C. , Kharabsheh Suleiman , Nickolaus Michelle J. , Reddy Rallapalli
Published: August 2002

Transradial cardiac catheterization has been historically limited to arterial catheterization. Using small‐diameter introducers and catheters, a technique of combined right and left heart catheterization is described using both the radial artery and its neighboring vein. Evaluation of 55 sequential right and left heart procedures showed that it could be accomplished in > 50% using venous access in the forearm. This approach has many potential advantages, although the ability to access routinely both venous and arterial vessels at the level of the wrist is unclear. Cathet Cardiovasc Intervent 2002;55:20–22. © 2002 Wiley‐Liss, Inc.
Common femoral artery anatomy is influenced by demographics and comorbidity: Implications for cardiac and peripheral invasive studies
Authors: Schnyder Guido , Sawhney Neil , Whisenant Brian , Tsimikas Sotirios , Turi Zoltan G.
Published: August 2002

We assessed the angiographic size of the common femoral artery (CFA) and the influence of demographics and comorbidites. In addition, the location of the CFA bifurcation and the site of femoral puncture were also assessed. Consecutive CFA angiograms (n = 200) were prospectively analyzed. CFA diameter was 6.9 ± 1.4 mm and length 43.3 ± 16.2 mm. By multivariate analysis, only diabetes (P < 0.001), female gender (P < 0.0005), and small body surface area (P < 0.01) predicted small vessel size. Vessel length correlated with patient height (P < 0.0005). CFA bifurcation occurred at or below the femoral head center in 98.5%. The femoral puncture was into a vessel other than the CFA in 13%, and 54% of punctures were in a less than ideal anatomical location. In conclusion, the CFA is a relatively small diameter vessel, particularly in diabetics and women. Puncture above the femoral head center and below the superior margin of the acetabulum accurately predicts an ideal puncture site. Thus, routine fluoroscopic guidance should be considered. Cathet Cardiovasc Intervent 2001;53:289–295. © Wiley‐Liss, Inc.
Bilateral selective internal mammary artery angiography via right radial approach: Clinical experience with newly designed Yumiko catheter
Authors: Kim Moo Hyun , Cha Kwang Soo , Kim Hye Jin , Kim Jong Seong
Published: August 2002

The radial artery has been increasingly used as a primary access site for coronary angiography and intervention. But the technique for internal mammary artery (IMA) visualization via the right radial artery has not been well described. Therefore, the study was conducted to investigate the feasibility, safety, and adequacy of selective bilateral IMA angiography via the right radial artery using the recently developed Yumiko catheter. From November 1999 to October 2000, both IMA angiographies were undertaken immediately following the diagnostic coronary angiogram taken from right transradial approach in 114 patients. IMA angiography was successfully obtained in 99% (113/114) patients. For left IMA angiography, 73 (64%), 28 (25%), and 12 (11%) imagings were obtained in a selective, a semiselective, and a nonselective way, respectively. After initial periods of 33 left‐IMA‐only imaging, right IMA angiography was obtained in 81 patients (phase 2). Selective right IMA imaging was done in 73 (90%), semiselective in 6, and nonselective in 2 patients. The reasons for failure of selective or semiselective visualization were severe vascular tortuosity, far distal anatomical origin of left IMA and ulcerative plaque, or acutely angled left subclavian artery. The feasibility and safety of selective and semiselective bilateral IMA angiography were demonstrated using a 5 Fr Yumiko catheter from the right radial approach. Cathet Cardiovasc Intervent 2001;54:19–24. © 2001 Wiley‐Liss, Inc.
Glutamate receptor ligands: Synthesis, stereochemistry, and enantiopharmacology of methylated 2‐aminoadipic acid analogs
Authors: Guldbrandt Mette , Johansen Tommy N. , Frydenvang Karla , Bräuner‐Osborne Hans , Stensbøl Tine B. , Nielsen Birgitte , Karla Rolf , Santi Flavio , Krogsgaard‐Larsen Povl , Madsen Ulf
Published: August 2002

Homologation and substitution on the carbon backbone of (S)‐glutamic acid [(S)‐Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)‐Glu receptor ligands. We describe a series of methyl‐substituted 2‐aminoadipic acid (AA) analogs, and the synthesis, stereochemistry, and enantiopharmacology of 3‐methyl‐AA (4a–d), 4‐methyl‐AA (5a–d), 5‐methyl‐AA (6a–d), and (E)‐Δ4‐5‐methyl‐AA (7a and 7b) are reported. The compounds were resolved using chiral HPLC and the configurational assignments of the enantiomers were based on X‐ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)‐Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S‐configuration at the α‐carbon generally showed mGluR2 agonist activity of similar or slightly lower potencies than (S)‐AA [e.g., EC50 = 76 μM for (2S,4S)‐4‐methyl‐AA (5a) as compared to EC50 = 35 μM for (S)‐AA]. The position of the methyl substituent had a profound effect on the observed pharmacology, whereas the absolute stereochemistry at the methylated carbon atom had a very limited effect on pharmacology. Structure–activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC50 =110 μM for (2S,5RS)‐5‐methyl‐AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e.g., IC50 = 300 μM for (2R,4S)‐4‐methyl‐AA (5d)]. The two unsaturated analogs (S)‐ (7a) and (R)‐(E)‐Δ4‐5‐methyl‐AA (7b) turned out to be a weak AMPA receptor agonist and a weak mixed NMDA/AMPA receptor antagonist, respectively. Chirality 14:351–363, 2002. © 2002 Wiley‐Liss, Inc.
Angiogenesis in patients with craniopharyngiomas
Authors: Vidal Sergio , Kovacs Kalman , Lloyd Ricardo V. , Meyer Frederic B. , Scheithauer Bernd W.
Published: August 2002

BACKGROUND

Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that often exhibit aggressive and invasive growth. The authors hypothesized that tumor proliferation, spread, and recurrence are angiogenesis dependent and investigated the significance of vascularization relative to biologic behavior. To the authors' knowledge, angiogenesis for patients with craniopharyngiomas has not been examined to date.

METHODS

The authors measured microvessel densities in resected, histologically proven craniopharyngiomas using immunostains for CD‐34, a monoclonal antibody that selectively recognizes endothelial cells. Both histologic types of craniopharyngiomas, adamantinomatous and papillary, were included in the study. In addition, the cellular distribution of vascular endothelial growth factor (VEGF), a strong stimulator of new vessel formation, was assessed by both immunohistochemistry and in situ hybridization for VEGF receptor 2 (VEGFR‐2) mRNA expression.

RESULTS

Histologically, small numbers of capillaries were identified in temporal stroma but not in their epithelial components. Immunohistochemistry revealed strong, conclusive cytoplasmic immunoreactivity for VEGF in the epithelial cells of both adamantinomatous craniopharyngiomas and papillary craniopharyngiomas. In situ hybridization showed that VEGFR‐2 mRNA was expressed widely, not only in neoplastic epithelium but also in capillary endothelium.

CONCLUSIONS

Tumors with greater microvessel density regrow more frequently compared with tumors that have lower microvessel density, suggesting that the extent of angiogenesis is of prognostic value in patients with craniopharyngioma. VEGFR‐2 may act as a key modulator of VEGF activity in endothelial cells and nonendothelial cells, indicating that VEGF plays an important role in the behavior of craniopharyngiomas. Cancer 2002;94:738–45. © 2002 American Cancer Society.

DOI 10.1002/cncr.10281
Primary central nervous system lymphomas
Authors: van der Sanden Gitty A. C. , Schouten Leo J. , van Dijck Jos A. A. M. , van Andel Joke P. , van der Maazen Richard W. M. , Coebergh Jan‐Willem W. ,   Working Group of Specialists in Neuro‐Oncology in the Southern and Eastern Netherlands
Published: August 2002

BACKGROUND

An excessive increase in the incidence of primary central nervous system lymphoma (PCNSL) has been reported since the mid‐1980s in the U.S. and U.K. Clinical studies have shown that radiotherapy and chemotherapy may prolong survival. In the current study, the authors describe the incidence, treatment, and survival of an unselected group of patients with PCNSL in the southern and eastern Netherlands.

METHODS

Data regarding patients diagnosed between 1989–1994 were obtained from 4 population‐based regional cancer registries in the southern and eastern Netherlands (n = 86) and the Eindhoven Cancer Registry for 1980–1988 (n = 6). Lymphomas were registered as PCNSL when a tissue diagnosis of CNS lymphoma was established for a patient with neurologic symptoms (i.e., lymphomas were not necessarily restricted to the CNS at the time of diagnosis). Only patients diagnosed during their lifetime with Stage I disease, Stage “IV” disease (i.e., diffuse CNS lymphoma), or disease of unknown stage were included (63 patients, 8 patients, and 15 patients, respectively, between 1989–1994). For 80 patients (93%) follow‐up was complete until January 1, 1997.

RESULTS

Between 1989–1994, an average World Standardized Rate of 2.3 cases and 1.7 cases per 1 million person‐years, respectively, was reported for males and females. The median age of the patients at the time of diagnosis was 62 years, and was 66 years for patients with an unknown disease stage. In the area of the Eindhoven Cancer Registry the occurrence of PCNSL more than doubled from < 2% of all histologically confirmed primary CNS malignancies diagnosed between 1980–1985 to approximately 4% of cases diagnosed between 1986–1994. The median survival of all the patients was 4.1 months; the median survival was 5.8 months for patients with limited (Stage I and Stage IV) disease and was 0.6 months for patients with an unknown stage of disease. Approximately 65% of the patients with limited disease received radiotherapy and approximately 35% of such patients received chemotherapy. Furthermore, chemotherapy was given more often to patients age < 60 years who tended to have a slightly better survival than patients age ≥ 60 years.

CONCLUSIONS

The increase in the incidence of PCNSL in the 1980s may be explained in large part by changes in diagnostics and registration. The relatively high incidence and low survival rate of PCNSL in the southern and eastern Netherlands reported in the 1990s may be due in part to the inclusion of patients with systemic lymphoma and immunodeficiency disorders. However, a significant improvement in the prognosis of patients with PCNSL in the southern and eastern Netherlands diagnosed in the 1990s is unlikely. Cancer 2002;94:1548–56. © 2002 American Cancer Society.

DOI 10.1002/cncr.10357
Prognostic significance of Tie‐1 protein expression in patients with early chronic phase chronic myeloid leukemia
Authors: Verstovsek Srdan , Kantarjian Hagop , Manshouri Taghi , O'Brien Susan , Faderl Stefan , Talpaz Moshe , Cortes Jorge , Albitar Maher
Published: August 2002

BACKGROUND

The Tie‐1 tyrosine kinase receptor and its thus far unidentified ligand appear to play a distinct role in the regulatory pathways of early hematopoiesis and angiogenesis. Because vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML), the authors evaluated the clinical significance of Tie‐1 expression in such patients.

METHODS

Using Western blot analysis and solid‐phase radioimmunoassay (RIA), the authors quantified Tie‐1 protein in bone marrow samples from 128 patients with CML and 31 normal controls.

RESULTS

The median Tie‐1 RIA value of CML samples was significantly higher than in normal controls (P = 0.01). The authors found no significant differences in Tie‐1 levels in patients with early chronic, late chronic, accelerated, and blastic phases (P = 0.2). High Tie‐1 levels correlated with short survival in patients with early chronic phase (P = 0.003; Cox proportional hazard model) but not in patients with late chronic (P = 0.2) or accelerated/blastic (P = 0.2) phase CML. Tie‐1 protein level was also prognostic when patients were separated into two groups by the median value. High Tie‐1 level in early chronic phase was associated with significantly shorter survival than low Tie‐1 level (median survival, 116 vs. 61 months; P = 0.03). In patients with early chronic phase CML, Tie‐1 levels correlated directly with patient age (P = 0.004) and platelet count (P = 0.003), and inversely with leukocyte count (P = 0.007). Tie‐1 as a predictor of survival in early chronic phase CML was independent of risk group, spleen size, age, hemoglobin, and basophil count (P = 0.03; multivariate Cox proportional hazard model).

CONCLUSIONS

The authors' findings support the hypothesis that angiogenesis may play a major role in the pathophysiology of chronic phase CML. Cancer 2002;94:1517–21. © 2002 American Cancer Society.

DOI 10.1002/cncr.10363
Monoclonal antibodies to target epidermal growth factor receptor–positive tumors
Authors: Herbst Roy S. , Shin Dong M.
Published: August 2002

BACKGROUND

Traditional cytotoxic approaches to tumor management are associated with efficacy and toxicity limitations. Blockade of the epidermal growth factor receptor (EGFR) and its ligands is a novel approach to the treatment of human tumors that offers a noncytotoxic alternative to cancer treatment.

METHODS

An English‐language literature search was conducted to identify studies assessing the in vitro and in vivo effects of EGFR blockade with an emphasis on approaches that use monoclonal antibody therapy.

RESULTS

The EGF pathway regulates normal cellular processes and appears to be correlated with the development of malignancy. Approximately 30% of human tumors express EGFR, which has been reported to be correlated with poor prognosis and diminished disease‐free and overall survival in selected tumor types. A number of anti‐EGFR monoclonal antibodies have been developed, which currently are undergoing clinical trials in humans. Effective anti‐EGFR monoclonal antibodies compete with endogenous ligands, primarily EGF and transforming growth factor–α, for receptor ligand‐binding sites. Binding to EGFR blocks critical signaling pathways and interferes with the growth of tumors expressing EGFR. Anti‐EGFR monoclonal antibodies that currently are under study include IMC‐C225, EMD 55900, ICR 62, and ABX‐EGF.

CONCLUSIONS

These antibodies have demonstrated promising results and appear to have been well tolerated. EGFR‐targeted therapy addresses important, unmet needs in the treatment of human tumors, particularly EGFR‐positive epithelial tumors including common malignancies of the head and neck, lung, and colon. Cancer 2002;94:1593–611. © 2002 American Cancer Society.

DOI 10.1002/cncr.10372
Somatostatin analogs and prednisone in advanced refractory thymic tumors
Authors: Palmieri Giovannella , Montella Liliana , Martignetti Angelo , Muto Pietro , Di Vizio Dolores , De Chiara Annarosaria , Lastoria Secondo
Published: August 2002

BACKGROUND

Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium‐labeled octreotide (111In‐DTPA‐D‐Phe1‐octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study.

METHODS

Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow‐up). In 8 cases, octreotide was replaced by the long‐acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated.

RESULTS

The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow‐up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients).

CONCLUSIONS

Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long‐acting analog lanreotide, which requires fewer injections, improves patients' compliance. Cancer 2002;94:1414–20. © 2002 American Cancer Society.

DOI 10.1002/cncr.10374