bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusion protein of Vitreoscilla hemoglobin with D‐amino acid oxidase enhances activity and stability of biocatalyst in the bioconversion process of cephalosporin C
Authors: Khang Yong‐Ho , Kim In‐Wook , Hah Young‐Rhan , Hwangbo Jong‐Hyun , Kang Ki‐Kueon
Published: March 2003

In this study we constructed an artificial flavohemoprotein by fusing Vitreoscilla hemoglobin (VHb) with D‐amino acid oxidase (DAO) of Rhodotorula gracilis to determine whether bacterial hemoglobin can be used as an oxygen donor to immobilized flavoenzyme. This chimeric enzyme significantly enhanced DAO activity and stability in the bioconversion process of cephalosporin C. In a 200‐mL bioreactor, the catalytic efficiency of immobilized VHb‐DAO against cephalosporin C was 12.5‐fold higher than that of immobilized DAO, and the operational stability of the immobilized VHb‐DAO was approximately threefold better than that of the immobilized DAO. In the scaled‐up bioprocess with a 5‐L bioreactor, immobilized VHb‐DAO (2500 U/L) resulted in 99% bioconversion of 120 mM cephalosporin C within 60 min at an oxygen flow rate of 0.2 (v/v) × min. Ninety percent of the initial activity of immobilized VHb‐DAO could be maintained at up to 50 cycles of the enzymatic reaction without exogenous addition of H2O2 and flavin adenine dinucleotide (FAD). The purity of the final product, glutaryl‐7‐aminocephalosporanic acid, was confirmed to be 99.77% by high‐performance liquid chromatography (HPLC) analysis. Relative specificity of immobilized VHb‐DAO on D‐α‐aminoadipic acid, a precursor in cephalosporin C biosynthesis, increased twofold, compared with that of immobilized DAO, suggesting that conformational modification of the VHb‐DAO fusion protein may be altered in favor of cephalosporin C. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 480–488, 2003.
Role of pericellular matrix in development of a mechanically functional neocartilage
Authors: Graff Ronald D. , Kelley Scott S. , Lee Greta M.
Published: March 2003

The role of the chondrocyte pericellular matrix (PCM) was examined in a three‐dimensional chondrocyte culture system to determine whether retention of the native pericellular matrix could stimulate collagen and proteoglycan accumulation and also promote the formation of a mechanically functional hyaline‐like neocartilage. Porcine chondrocytes and chondrons, consisting of the chondrocyte with its intact pericellular matrix, were maintained in pellet culture for up to 12 weeks. Sulfated glycosaminoclycans and type II collagen were measured biochemically. Immunocytochemistry was used to examine collagen localization as well as cell distribution within the pellets. In addition, the equilibrium compressive moduli of developing pellets were measured to determine whether matrix deposition contributed to the mechanical stiffness of the cartilage constructs. Pellets increased in size and weight over a 6‐week period without apparent cell proliferation. Although chondrocytes quickly rebuilt a PCM rich in type VI collagen, chondron pellets accumulated significantly more proteoglycan and type II collagen than did chondrocyte pellets, indicating a greater positive effect of the native PCM. After 5 weeks in chondron pellets, matrix remodeling was evident by microscopy. Cells that had been uniformly distributed throughout the pellets began to cluster between large areas of interterritorial matrix rich in type II collagen. After 12 weeks, clusters were stacked in columns. A rapid increase in compressive strength was observed between 1 and 3 weeks in culture for both chondron and chondrocyte pellets and, by 6 weeks, both had achieved 25% of the equilibrium compressive stiffness of cartilage explants. Retention of the in vivo PCM during chondrocyte isolation promotes the formation of a mechanically functional neocartilage construct, suitable for modeling the responses of articular cartilage to chemical stimuli or mechanical compres‐ sion. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 457–464, 2003.
Heat and water transfer in a rotating drum containing solid substrate particles
Authors: Schutyser M. A. I. , Weber F. J. , Briels W. J. , Rinzema A. , Boom R. M.
Published: March 2003

In previous work we reported on the simulation of mixing behavior of a slowly rotating drum for solid‐state fermentation (SSF) using a discrete particle model. In this investigation the discrete particle model is extended with heat and moisture transfer. Heat transfer is implemented in the model via interparticle contacts and the interparticle heat transfer coefficient is determined experimentally. The model is shown to accurately predict heat transfer and resulting temperature gradients in a mixed wheat grain bed. In addition to heat transfer, the addition and subsequent distribution of water in the substrate bed is also studied. The water is added to the bed via spray nozzles to overcome desiccation of the bed during evaporative cooling. The development of moisture profiles in the bed during spraying and mixing are studied experimentally with a water‐soluble fluorescent tracer. Two processes that affect the water distribution are considered in the model: the intraparticle absorption process, and the interparticle transfer of free water. It is found that optimum distribution can be achieved when the free water present at the surface of the grains is quickly distributed in the bed, for example, by fast mixing. Alternatively, a short spraying period, followed by a period of mixing without water addition, can be applied. The discrete particle model developed is used successfully to examine the influence of process operation on the moisture distribution (e.g., fill level and rotation rate). It is concluded that the extended discrete particle model can be used as a powerful predictive tool to derive operating strategies and criteria for design and scale‐up for mixed SSF and other processes with granular media. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 552–563, 2003.
Theoretical distribution of truncation lengths in incremental truncation libraries
Authors: Ostermeier Marc
Published: March 2003

Incremental truncation is a method for constructing libraries of every one base pair truncation of a segment of DNA. Incremental truncation libraries can be created using a time‐dependent nuclease method or through the incorporation of α‐phosphothioate dNTPs by PCR or by primer extension (THIO(pcr) truncation and THIO(extension) truncation, respectively). Libraries created by the fusion of two truncation libraries, known as ITCHY libraries, can be created using the above methods or by the incremental truncation‐like method SHIPREC. Knowing and being able to tailor the distribution of truncations in incremental truncation, ITCHY and SHIPREC libraries would be beneficial for their use in protein engineering and other applications. However, the experimental determination of the distributions would require extensive, cost‐prohibitive, DNA sequencing to obtain statistically relevant data. Instead, a theoretical prediction of the distributions was developed. Time‐dependent incremental truncation libraries had the most uniform distribution of truncation lengths, but were biased against longer truncations. Essentially uniform distribution over the desired truncation range (from zero to Nmax base pairs) required that truncations be prepared up to at least 1.2–1.5 Nmax. THIO(pcr) and THIO(extension) truncation libraries had a very nonuniform distribution of truncation lengths with a bias against longer truncations. Such nonuniformity could be significantly diminished by decreasing the incorporation rate of αS‐dNTPs but at the expense of having a large fraction of the DNA truncated beyond the desired range or completely degraded. ITCHY libraries created using time‐dependent truncation had the most uniform distribution of possible fusions and had the highest fraction of the library being parental‐length fusions. However, the distribution of parental‐length fusions was biased against fusions near the beginning/ends of genes unless the truncation libraries are prepared with a uniform distribution up to Nmax. In contrast, SHIPREC libraries and THIO(pcr) ITCHY libraries, by the very nature of the nonuniform distributions of the truncated DNA, are ensured of having a uniform distribution of fusion points in parental‐length fusions. This comes at the expense of having a smaller fraction of the library being parental‐length fusions; however, this limitation can be overcome by performing size selection on the library. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 564–577, 2003.
Profiles of the parents of adolescent CSA perpetrators attending a voluntary outpatient treatment programme in Ireland
Authors: Duane Yvonne , Carr Alan , Cherry Joan , McGrath Kieran , O'Shea Deirdre
Published: March 2003

A group of 22 parents of adolescent sexual offenders (PASO) was compared with a group of 19 normal controls (NC) and 10 clinical controls (CC) on demographic, developmental, personal adjustment and family environment variables. The assessment protocol included the General Health Questionnaire‐12, the Culture‐Free Self‐Esteem Inventory, the Child Behaviour Checklist, the Family Assessment Device, the Parent Satisfaction Scale and the Multidimensional Scale of Perceived Social Support. Compared with clinical and normal controls, more parents in the PASO group reported that they had been arrested or charged for a criminal offence; had personally experienced child abuse; and more of their adolescents had experienced child abuse, with emotional abuse being the most common form of abuse for both parents and adolescents. Compared with clinical and normal controls, more adolescents of parents in the PASO group had witnessed parental drug or alcohol abuse and had been placed in care outside their home. While parents in the PASO group did not differ from clinical or normal controls in terms of personal adjustment, their adolescents had significantly more internalizing behaviour problems than normal controls, whereas adolescents of parents in the clinical control group had significantly more externalizing behaviour problems than normal controls. Compared with normal controls, parents in both the PASO and clinical control groups reported more difficulties with general family functioning, roles, affective responsiveness, affective involvement and behaviour control and lower levels of parental satisfaction. However, the groups did not differ significantly in their levels of perceived social support. Copyright © 2003 John Wiley & Sons, Ltd.
Photocrosslinking in Ruthenium‐Labelled Duplex Oligonucleotides
Authors: Lentzen O. , Constant J.‐F. , Defrancq E. , Prévost M. , Schumm S. , Moucheron C. , Dumy P. , Kirsch‐De Mesmaeker A.
Published: March 2003

The formation of a photoadduct between a [Ru(1,4,5,8‐tetraazaphenanthrene)24,7‐diphenylphenanthroline]2+ complex chemically attached to a synthetic oligonucleotide, and a guanine moiety in a complementary targeted single‐stranded DNA molecule was studied for ten 17‐mer duplexes by denaturing gel electrophoresis. This photoadduct formation leads to photocrosslinking of the two strands. The percentage quenching of luminescence of the complex by electron transfer was compared to the resulting yield of photocrosslinked product. This yield does not only depend on the ionisation potential of the guanine bases, which are electron donors, but also on other factors, such as the position of the guanine bases as compared to the site of attachment of the complex. The photocrosslinking yield is higher when the guanine moieties are towards the 3′ end on the complementary strand as compared to the tethering site. Computer modelling results are in agreement with this preference for the 3′ side for the photoreaction. Interestingly, the photocrosslink is not alkali labile. Moreover, a type III exonuclease enzyme is blocked at the position of photocrosslinking.
Substrate Specificity of Mutants of the Hydroxynitrile Lyase from Manihot esculenta
Authors: Bühler Holger , Effenberger Franz , Förster Siegfried , Roos Jürgen , Wajant Harald
Published: March 2003

Several tryptophan128‐substituted mutants of the hydroxynitrile lyase from Manihot esculenta (MeHNL) are constructed and applied in the MeHNL‐catalyzed addition of HCN to various aromatic and aliphatic aldehydes as well as to methyl and ethyl ketones to yield the corresponding cyanohydrins. The mutants (especially MeHNL‐W128A) are in most cases superior to the wild‐type (wt) enzyme when diisopropyl ether is used as the solvent. Substitution of tryptophan128 by an alanine residue enlarges the entrance channel to the active site of MeHNL and thus facilitates access of sterically demanding substrates to the active site, as clearly demonstrated for aromatic aldehydes, especially 3‐phenoxybenzaldehyde. These experimental results are in accordance with the X‐ray crystal structure of MeHNL‐W128A. Aliphatic aldehydes, surprisingly, do not demonstrate this reactivity dependence of mutants on substrate bulkiness. Comparative reactions of 3‐phenoxybenzaldehyde with wtMeHNL and MeHNL‐W128A in both aqueous citrate buffer and a two‐phase system of water/methyl tert‐butyl ether again reveal the superiority of the mutant enzyme: 3‐phenoxybenzaldehyde was converted quantitatively into a cyanohydrin nearly independently of the amount of enzyme present, with a space‐time yield of 57 g L−1 h−1.
Tools for Design and Control of Industrial Crystallizers – State of Art and Future Needs
Authors: Kramer H.J.M. , Jansens P.J.
Published: March 2003

The design and control of industrial crystallizers continues to be a tremendous challenge. The tendency to move away from base‐chemicals towards fine‐chemicals will give a new impulse to the utilisation of crystallization technology for the separation and the formulation of particulate products. This paper reviews the most recent developments in the design industrial crystallizers and the development of novel crystallization processes. Furthermore it discusses emerging modeling tools needed for a flexible design and operation of crystallizers and crystallization processes that meet rapid changing product yield and specifications. Finally a new approach towards model‐based predictive control of crystallization processes is presented.
In‐Line Monitoring of Crystallization Processes Using a Laser Reflection Sensor and a Neural Network Model
Authors: Giulietti M. , Guardani R. , Nascimento C.A.O. , Arntz B.
Published: March 2003

Laboratory‐scale experiments were carried out for measuring the chord length distribution of different particle systems using a laser reflection sensor. Samples consisted of monodisperse, polydisperse and bimodal FCC catalyst and PVC particles of different sizes, ranging from about 20 to 500 μm. The particles were dispersed in water, forming suspensions with solid‐phase mass fractions ranging from ca. 0.2 % until ca. 30 %. The experimental results, consisting of the particle number counting per chord length class, were used in fitting a neural network model for estimating the mass concentration of particles in the suspension and the volume‐based size distribution, eliminating the effects of suspension concentration and particle shape. The results indicate the feasibility of using such a model as a software sensor in crystallization processes monitoring.
In‐line Control and Automatic Management of Industrial Crystallizations using NIR Technique
Authors: Vaccari G. , Tamburini E. , Tosi S. , Sgualdino G. , Bernardi T.
Published: March 2003

The correct and automatic management of a crystallization process would require the knowledge, in real‐time, of the amount of the crystals present in the magma, the supersaturation of the mother liquor, the growth kinetics etc. To solve this problem, we tried to utilize the NIR (Near Infra‐Red Spectroscopy) technique using a probe submerged in the growing magma. The first results obtained following the cooling crystallization of sucrose are presented and discussed.
A Micro‐Mechanical Model for the Rate of Aggregation during Precipitation from Solution
Authors: Liew T.L. , Barrick J.P. , Hounslow M.J.
Published: March 2003

Our group has proposed [1,2] that the rate of aggregation between crystals in a supersaturated solution depends on the rate of collision and on the probability of that collision surviving. It has been suggested that the probability, or efficiency, depends on the strength of the newly formed neck between the crystals and the hydrodynamic force acting to pull them apart. That strength has been quantified by assuming that the crystals first touch at a point and thus the area of the neck increases with the square of time. In this paper, over 400 data points were considered for calcium oxalate monohydrate (COM), and more than 250 for calcite, relating the rate of aggregation in a stirred tank to the stirrer speed, the supersaturation and the particle size and show that the existing model cannot account for the relationship seen. It is proposed instead that the first contact between crystals lies along a line and thus the area of the neck grows linearly with time. A dimensionless strength formulated in this way is able to account for the dependence seen.
Modeling Growth Rate Dispersion in Industrial Crystallizers
Authors: Westhoff G.M. , van de Rijt J. , Kramer H.J.M. , Jansens P.J.
Published: March 2003

The phenomenon of healing appears to be a plausible explanation for the growth rate dispersion observed in many industrial crystallizers. In this paper a growth model is postulated, which describes the healing of plastically deformed attrition fragments. The rate of healing is assumed to be inversely proportional to the initial strain and to the rate of change of either the length, the area, or the volume of the crystal. The validity of the proposed model is verified by the simulation of growth of the smallest crystals (L0) in time in a growth experiment for specific combinations of the model parameters. In addition, the applicability of the proposed model is evaluated through simulations of steady state experimental data obtained in a 75‐liter Draft Tube (DT) crystallizer. It is concluded that the proposed model is able to fit reasonably well the experimental crystal size distribution. The model predicts the existence of a ‘dead time’ during which attrition fragments with large initial strain do not grow and which may last several residence times.
Derivation of Supersaturation and Nucleation Flux in a Stirred Tank from Tracer Concentration Measurements
Authors: Fall A. , Lecoq O. , David R.
Published: March 2003

The PLIF (Planar Laser Induced Fluorescence Technique) method is applied to determine experimentally the field of supersaturation in a separate double jet reactive precipitator from the local instantaneous field of concentrations of an inert tracer. The nucleation flux in the mixing region is derived.
Kinetic Characteristics of Amino Acid Salt Crystallization in Methanol‐Water System
Authors: Hasznos‐Nezdei M. , Liszi I. , Lakatos B.G.
Published: March 2003

Nucleation and growth mechanisms and kinetics of crystals of an amino acid salt were investigated in a methanol‐water system by measuring and evaluating the induction time as a function of the supersaturation ratio and temperature in batch salting out crystallization experiments. Discrimination between the possible crystallization mechanisms, and estimation of the kinetic parameters were carried out using nonlinear parameter identification. The results concerning the growth mechanism obtained were checked additionally by measuring the induction time as a function of number density of seed crystals.
Studies into the Internal Structure of Gibbsite Agglomerates
Authors: Ilievski D. , Austin P. , Whittington B.
Published: March 2003

This paper outlines techniques that have been developed or adapted to characterise the internal structure of gibbsite agglomerates and their application to selected laboratory gibbsite sample. The specific structural properties investigated include the quantification of gibbsite voidage (Floc Density Analyser), determination of relative changes in gibbsite crystal orientation (Raman spectroscopy and electron backscattered diffraction) and location of the cement binding agglomerated gibbsite particles (Raman spectroscopy, charge contrast and orientation contrast imaging). This paper also describes the use of Kikuchi patterns for investigating crystal orientation at a point and as a tool to assess if a particle is a single crystal or an agglomerate or a multi‐fold twin.
Herausforderungen für die Lehre am Beispiel der mechanischen Verfahrenstechnik
Authors: Peukert W. , Schmid H.‐J.
Published: March 2003

Rasche technologische Entwicklungen haben für Chemieingenieure bzw. Verfahrenstechniker neue Beschäftigungsmöglichkeiten eröffnet, wodurch sich zusätzliche Anforderungen an die Ausbildung ergeben. Der vorliegende Beitrag beschreibt die Lösungsansätze im Fachgebiet der Partikeltechnik: Es findet eine noch stärkere Betonung der Grundlagen statt, wobei Beispiele aus klassischen und neuen Anwendungen exemplarisch vertieft werden. Kernpunkt des Curriculums sind die Produkteigenschaften. Besonderes Gewicht wird außerdem auf die Betrachtung ganzer Prozesse gelegt. Die Vorlesungen sind in drei Ebenen strukturiert: Grundlagen, Grundoperationen und Prozesse/Anwendungen. Methodisch wird ein zweifacher Ansatz verfolgt: Die Lehre der grundlegenden Fakten wird ergänzt durch eine aktive Teilnahme der Studenten, insbesondere bei der Erarbeitung von Beispielen und in Labor‐ bzw. Rechnerpraktika. Durch eine ganzheitliche Sicht der Universitätsausbildung sollen auch „soft skills“ gefördert werden.
Numerische Simulationen transienter und turbulenter Strömungen – Abscheideverhalten in Tellerseparatoren
Authors: Breitling M. , Janoske U. , Piesche M.
Published: March 2003

No abstracts.
Anfahren dreiphasiger Rektifikationskolonnen: Simulation und Experiment
Authors: Tran T.K. , Repke J.‐U. , Wozny G.
Published: March 2003

No abstracts.
Herstellung rekombinanter Proteine mit Pichia pastoris in integrierter Prozessführung
Authors: Cornelissen G. , Bertelsen H.‐P. , Hahn B. , Schultz M. , Scheffler U. , Werner E. , Leptien H. , Krüß S. , Jansen A.‐K. , Gliem T. , Hielscher M. , Wilhelm B.‐U. , Sowa E. , Radeke H.H. , Luttmann R.
Published: March 2003

No abstracts.
Kontinuierliche Isolierung von Pharmawirkstoffen mittels annularer Chromatographie
Authors: Schmidt S. , Wu P. , Konstantinov K. , Kaiser K. , Kauling J. , Henzler H.‐J. , Vogel J.H.
Published: March 2003

No abstracts.
A Phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma
Authors: Jatoi Aminah , Ellison Neil , Burch Patrick A. , Sloan Jeff A. , Dakhil Shaker R. , Novotny Paul , Tan Winston , Fitch Tom R. , Rowland Kendrith M. , Young Charles Y. F. , Flynn Patrick J.
Published: March 2003

BACKGROUND

Recent laboratory and epidemiologic studies have suggested that green tea has antitumor effects in patients with prostate carcinoma. This Phase II trial explored green tea's antineoplastic effects in patients with androgen independent prostate carcinoma.

METHODS

This study, which was conducted by the North Central Cancer Treatment Group, evaluated 42 patients who were asymptomatic and had manifested, progressive prostate specific antigen (PSA) elevation with hormone therapy. Continued use of luteinizing hormone‐releasing hormone agonist was permitted; however, patients were ineligible if they had received other treatments for their disease in the preceding 4 weeks or if they had received a long‐acting antiandrogen therapy in the preceding 6 weeks. Patients were instructed to take 6 grams of green tea per day orally in 6 divided doses. Each dose contained 100 calories and 46 mg of caffeine. Patients were monitored monthly for response and toxicity.

RESULTS

Tumor response, defined as a decline ≥ 50% in the baseline PSA value, occurred in a single patient, or 2% of the cohort (95% confidence interval, 1–14%). This one response was not sustained beyond 2 months. At the end of the first month, the median change in the PSA value from baseline for the cohort increased by 43%. Green tea toxicity, usually Grade 1 or 2, occurred in 69% of patients and included nausea, emesis, insomnia, fatigue, diarrhea, abdominal pain, and confusion. However, six episodes of Grade 3 toxicity and one episode of Grade 4 toxicity also occurred, with the latter manifesting as severe confusion.

CONCLUSIONS

Green tea carries limited antineoplastic activity, as defined by a decline in PSA levels, among patients with androgen independent prostate carcinoma. Cancer 2003;97:1442–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11200
Extent of extracapsular spread
Authors: Greenberg Jayson S. , Fowler Robert , Gomez Jose , Mo Vivian , Roberts Dianna , El Naggar Adel K. , Myers Jeffrey N.
Published: March 2003

BACKGROUND

Extracapsular spread (ECS) of metastatic squamous cell carcinoma of the head and neck to regional lymph nodes is the most reliable predictor of poor treatment outcomes. Recently, the authors have shown that ECS is significantly associated with higher rates of locoregional recurrence, distant metastasis, and decreased survival in patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this review was to determine if the degree of ECS impacts distant metastasis rates and survival.

METHODS

Two hundred sixty‐six patients treated for SCCOT with surgery +/− adjuvant radiotherapy from 1980–1995 were reviewed. The setting was a tertiary referral center. The extent of ECS on histopathologic review of involved lymph nodes was measured from the capsular margin to the farthest perinodal extension in mm. Extent of ECS and the number of pathologic lymph nodes with or without ECS were analyzed for disease‐free interval, survival rates, and distant metastases.

RESULTS

No differences in the survival of patients with ECS of ≤ 2 mm or > 2 mm was found (P = 0.92). Patients with both ECS and multiple positive lymph nodes had decreased overall survival (P = 0.0003), disease‐specific survival (P = 0.0005), and a shorter disease‐free interval (P = 0.019) when compared with those with a single positive lymph node with ECS. Those with multiple ECS+ lymph nodes had the worst prognosis (P = 0.001).

CONCLUSIONS

Based on these findings, the authors recommended that all patients with SCCOT with ECS or multiple positive lymph nodes with or without ECS on pathologic review be considered for clinical trials that intensify regional and systemic adjuvant therapy. Cancer 2003;97:1464–70. © 2003 American Cancer Society.

DOI 10.1002/cncr.11202
Trends in prostate cancer mortality among black men and white men in the United States
Authors: Chu Kenneth C. , Tarone Robert E. , Freeman Harold P.
Published: March 2003

BACKGROUND

Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States.

METHODS

The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969–1999 U.S. prostate cancer mortality rates and the 1975–1999 prostate cancer incidence, survival, and incidence‐based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population.

RESULTS

Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age‐adjusted prostate cancer mortality rates for men age 50–84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50–79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence‐based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease.

CONCLUSIONS

Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men. Cancer 2003;97:1507–16. Published 2003 by the American Cancer Society.

DOI 10.1002/cncr.11212
Barriers to the participation of African‐American patients with cancer in clinical trials
Authors: Advani Anjali S. , Atkeson Benjamin , Brown Carrie L. , Peterson Bercedis L. , Fish Laura , Johnson Jeffrey L. , Gockerman Jon P. , Gautier Marc
Published: March 2003

BACKGROUND

African‐American patients have been under‐represented in oncology clinical trials. Better understanding barriers to African‐American participation may help increase the accrual of African‐American patients onto clinical trials.

METHODS

Two hundred eighteen patients with malignant disease (72 African‐American patients and 146 white patients) were recruited from the Duke Cancer Clinic and from Duke Oncology Outreach Clinics (DOORS). Patients were interviewed using a standardized survey. Questions included patients' knowledge of cancer, religious/spiritual beliefs, satisfaction with medical care, knowledge of clinical trials, reasons for participating or refusing to participate in a clinical trial, financial/transportation issues, and demographic factors, such as age and education. Data on attitudes and belief were analyzed for group differences between African‐American patients and white patients as well as between patients who were treated at the Duke Cancer Clinic and patients who were treated at DOORS clinics.

RESULTS

Willingness to participate in a clinical trial depended on both race and clinic site. Forty‐five percent of white patients, compared with 31% of African‐American patients, were willing to participate in a clinical trial (P = 0.05). white and African‐American patients who were treated at the Duke Cancer Clinic were more willing to participate in a trial compared with their counterparts who were treated at DOORS clinics (47% vs. 37%, respectively; P = 0.09). The greatest differences between groups (African‐American patients vs. white patients and Duke Cancer Clinic patients vs. DOORS patients) were education and income: Much greater percentages of African‐American patients and DOORS patients did not complete high school and had annual incomes < $15,000. In addition, more African‐American patients than white patients believed that God would determine whether they would be cured or would die from their disease. In a multivariate analysis, education, income, and belief that God would determine the patient's outcome also were correlated with a decreased willingness to participate in clinical trials.

CONCLUSIONS

Factors associated with religion, education, and income, rather than race, may be major barriers to clinical trial participation. Interventions that target education and income may increase the recruitment of African‐American oncology patients onto clinical trials. Cancer 2003;97:1499–506. © 2003 American Cancer Society.

DOI 10.1002/cncr.11213
Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma
Authors: Zablotska Lydia B. , Neugut Alfred I.
Published: March 2003

BACKGROUND

Prior studies have demonstrated that women who receive adjuvant radiation therapy (RT) after mastectomy for breast carcinoma have an increased risk of a second primary lung carcinoma after 10 years, but, to the authors' knowledge, the risk associated with adjuvant RT after breast‐conserving surgery (lumpectomy) has yet to be determined. The purpose of the current study was to confirm and extend earlier findings of the effects of postmastectomy RT on second primary lung carcinoma and to investigate the impact of postlumpectomy RT on second primary lung carcinoma in the same population and to compare the results.

METHODS

The authors used data from the population‐based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute, encompassing approximately 10% of the U.S. population, from 1973 to 1998. Of the women with nonmetastatic invasive breast carcinoma, 194,981 had been treated with mastectomy and 65,560 were treated with lumpectomy. Cox regression analysis was used to estimate the relative risk (RR) of a second primary lung carcinoma among women treated with RT compared with those who received surgery alone as a function of time interval since treatment and laterality for both types of surgery.

RESULTS

Although no statistically significant elevation in risk for second primary lung carcinoma prior to 10 years was observed, the authors estimated a RR of 2.06 (95% confidence interval [95% CI], 1.53–2.78) and 2.09 (95% CI, 1.50–2.90) for ipsilateral lung carcinoma at 10–14 years and 15+ years after postmastectomy RT, respectively, whereas no increased risk was observed for the contralateral lung. The excess risk of ipsilateral lung carcinoma after postmastectomy RT was found for all three major histologic subtypes of lung carcinoma (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). No increased risk of lung carcinoma was observed at 10–14 years after postlumpectomy RT for either lung.

CONCLUSIONS

Postmastectomy RT was found to provide a moderate increase in risk for ipsilateral lung carcinoma starting 10 years after exposure; this increased risk is reported to persist to at least 20 years. Postlumpectomy RT does not appear to incur an increased risk. These findings should be reassuring to women treated with either type of RT, but the excess risk in the postmastectomy group should be considered in the choice between treatment options. Cancer 2003;97:1404–11. © 2003 American Cancer Society.

DOI 10.1002/cncr.11214
Use of quality indicators to evaluate the care of patients with localized prostate carcinoma
Authors: Miller David C. , Litwin Mark S. , Sanda Martin G. , Montie James E. , Dunn Rodney L. , Resh Jennifer , Sandler Howard , Wei John T.
Published: March 2003

BACKGROUND

The goal of quality assurance in health care is to preserve and improve patient care. Recently, RAND developed a set of evidence‐based candidate indicators for evaluating the quality of care for patients with localized prostate carcinoma; however, the feasibility and sensitivity of these indicators have not been tested in a clinical setting. The objectives of this study were to evaluate the feasibility of measuring these quality indicators and to determine their sensitivity to change in practice patterns over time.

METHODS

One hundred sixty‐eight men who presented in either 1995 or in 2000 and were treated for localized prostate carcinoma were selected randomly from the University of Michigan tumor registry. A combination of electronic data base review and explicit chart review was used to assess the feasibility of measuring compliance for each indicator. For each indicator in which assessment was feasible, compliance with the RAND indicators was determined for patients in both years. Multivariate regression analysis was used to adjust for potential confounding effects of disease stage, tumor grade, prostate specific antigen (PSA) level, patient age, and therapy.

RESULTS

Based on review of available clinical data, measurement of compliance was feasible for 19 of 22 RAND candidate quality indicators (86%). For five indicators, significant differences in documentation (compliance) were detected between 1995 and 2000 (P < 0.05). Treatment received and higher PSA levels were associated independently with documentation of compliance for several indicators (P < 0.05).

CONCLUSIONS

Measurement of the majority of the RAND quality indicators for the treatment of patients with localized prostate carcinoma was feasible, and improvements in several indicators were observed between 1995 and 2000. Demonstration of such variation, even within a single institution, suggests that the indicators are sufficiently sensitive to detect differences in practice patterns. Cancer 2003;97:1428–35. © 2003 American Cancer Society.

DOI 10.1002/cncr.11216
Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinoma
Authors: Bos Reinhard , van der Groep Petra , Greijer Astrid E. , Shvarts Avi , Meijer Sybren , Pinedo Herbert M. , Semenza Gregg L. , van Diest Paul J. , van der Wall Elsken
Published: March 2003

BACKGROUND

Hypoxia‐inducible factor‐1 (HIF‐1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis to survive cellular hypoxia. Increased levels of HIF‐1α, the O2‐regulated subunit of HIF‐1, were noted during breast carcinogenesis. In this study, the prognostic value of HIF‐1α expression and its correlation with various clinicopathologic variables in patients with invasive breast carcinoma were investigated.

METHODS

Expression levels of HIF‐1α, HER‐2/neu, estrogen receptor, and progesterone receptor were analyzed in 150 patients with early‐stage breast carcinoma by immunohistochemistry. HER‐2/neu gene amplification was investigated with automated fluorescent in situ hybridization. The mitotic activity index, histologic grade, and tumor type were assessed in hematoxylin and eosinstained specimens. Clinical data included disease‐free survival, overall survival, lymph node status, and tumor size. The data were analyzed with two‐sided univariate and multivariate tests, with P values < 0.05 considered significant.

RESULTS

High levels of HIF‐1α had an association of borderline significance with decreased overall survival (P = 0.059) and disease‐free survival (P = 0.110) that was ascribed completely to the subgroup of women with lymph node negative tumors (n = 81 patients; P = 0.008 and P = 0.004, respectively). HER‐2/neu immunoreactivity (P < 0.001) and gene amplification (P < 0.001), vascular endothelial growth factor expression (P = 0.016), and Ki‐67 expression (P < 0.001) were correlated strongly with HIF‐1α positivity, although none of those factors had an independent effect on survival.

CONCLUSIONS

Increased levels of HIF‐1α were associated independently with shortened survival in patients with lymph node negative breast carcinoma. Therefore, the use of immunohistochemical assessment of HIF‐1α as a new predictor of poor outcome may improve clinical decision‐making regarding adjuvant treatment of patients with lymph node negative breast carcinoma. Cancer 2003;97:1573–81. © 2003 American Cancer Society.

DOI 10.1002/cncr.11246
Fatigue in ovarian carcinoma patients
Authors: Holzner Bernhard , Kemmler Georg , Meraner Verena , Maislinger Andrea , Kopp Martin , Bodner Thomas , Nguyen‐Van‐Tam Dominic , Zeimet Alain G. , Fleischhacker W. Wolfgang , Sperner‐Unterweger Barbara
Published: March 2003

BACKGROUND

Although fatigue is a commonly reported symptom in cancer patients it is rarely investigated, especially in patients with ovarian carcinoma. The main focus of the current study was to assess fatigue in these patients and to investigate the impact of fatigue and other clinical and psychosocial variables on their quality of life (QOL).

METHODS

Ninety‐eight ovarian carcinoma survivors (average age of 57.4 ± 12.5 years) were included in the study. All women had received cancer therapy but had not been treated for at least 6 months. The average time elapsed since first diagnosis was 5.7 ± 5.5 years. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI‐20) and QOL was measured with the Functional Assessment of Cancer Therapy (FACT)‐ovarian carcinoma part and the European Organization for Research and Treatment of Cancer Care Questionnaire, including the ovarian carcinoma module.

RESULTS

Thirty‐two of 98 ovarian carcinoma patients (32.7%, 95% confidence interval, 23.5–42.9%) reported MFI‐20 General Fatigue scores ≥ 12.0 and therefore could be characterized as suffering from fatigue. This group of patients had a significantly lower QOL, had higher scores of anxiety and depression, and perceived that they had less social support. In a multiple regression model, mental adjustment, social support, anxiety, and depression as well as fatigue were significant predictors of QOL (FACT‐generic part total score) whereas clinical and sociodemographic variables were not.

CONCLUSION

A remarkably high proportion of ovarian carcinoma survivors suffered from fatigue. Because this symptom is a key predictor of QOL, it should be given more attention in aftercare programs. Cancer 2003;97:1564–72. © 2003 American Cancer Society.

DOI 10.1002/cncr.11253
Reductions in N‐acetylaspartylglutamate and the 67 kDa form of glutamic acid decarboxylase immunoreactivities in the visual system of albino and pigmented rats after optic nerve transections
Authors: Moffett John R.
Published: March 2003

This study compares the immunohistochemical distributions of N‐acetylaspartylglutamate (NAAG) and the large isoform of the γ‐aminobutyric acid (GABA)‐synthesizing enzyme glutamic acid decarboxylase (GAD67) in the visual system of albino and pigmented rats. Most retinal ganglion cells and their axons were strongly immunoreactive for NAAG, whereas GAD67 immunoreactivity was very sparse in these cells and projections. In retinorecipient zones, NAAG and GAD67 immunoreactivities occurred in distinct populations of neurons and in dense networks of strongly immunoreactive fibers and synapses. Dual‐labeling immunohistochemistry indicated that principal neurons were stained for NAAG, whereas local interneurons were stained for GAD67. In contrast to the distribution observed in retinorecipient zones, most or all neurons were doubly stained for NAAG and GAD67 in the thalamic reticular nucleus. Ten days after unilateral optic nerve transection, NAAG‐immunoreactive fibers and synapses were substantially reduced in all contralateral retinal terminal zones. The posttransection pattern of NAAG‐immunoreactive synaptic loss demarcated the contralateral and ipsilateral divisions of the retinal projections. In addition, an apparent transynaptic reduction in GAD67 immunoreactivity was observed in some deafferented areas, such as the lateral geniculate. These findings suggest a complicated picture in which NAAG and GABA are segregated in distinct neuronal populations in primary visual targets, yet they are colocalized in neurons of the thalamic reticular nucleus. This is consistent with NAAG acting as a neurotransmitter release modulator that is coreleased with a variety of classical transmitters in specific neural pathways. J. Comp. Neurol. 458:221–239, 2003. © 2003 Wiley‐Liss, Inc.
Inverse expression of olfactory cell adhesion molecule in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat main olfactory bulb
Authors: Treloar Helen B. , Gabeau Darlene , Yoshihara Yoshihiro , Mori Kensaku , Greer Charles A.
Published: March 2003

The projection of olfactory sensory neuron (OSN) axons from the olfactory epithelium (OE) to the olfactory bulb (OB) is highly organized but topographically complex. Evidence suggests that odorant receptor expression zones in the OE map to the OB about orthogonal axes. One candidate molecule for the formation of zone‐specific targeting of OSN axon synapses onto the OB is the olfactory cell adhesion molecule (OCAM). OCAM+ OSNs are restricted to three of the four zones in the OE and project their axons to the ventral OB where they form synapses with mitral/tufted (M/T) cells. To determine when this zonal connection is established, we have examined OCAM expression in rat olfactory system, during seminal periods of glomerular formation. OCAM+ axons sort out in the ventral olfactory nerve layer of the OB before glomerular formation. Surprisingly, OCAM was also expressed transiently by subsets of M/T cell dendrites located in the dorsal OB. The expression of OCAM by OSN axons and M/T dendrites was asymmetrical; in the dorsal OB, OCAM− OSN axons synapsed on OCAM+ M/T dendrites, whereas in the ventral OB, OCAM+ OSN axons synapsed on OCAM− M/T dendrites. The restricted spatial map of OCAM+ M/T cells appeared earlier in development than the zonal segregation of OCAM+ OSN axons. Thus, OCAM on M/T cell dendrites may act in a spatiotemporal window to specify regions of the developing rat OB, thereby establishing a foundation for mapping of the OE zonal organization onto the OB. J. Comp. Neurol. 458:389–403, 2003. © 2003 Wiley‐Liss, Inc.
Spatial organization of the pigeon tectorotundal pathway: An interdigitating topographic arrangement
Authors: Marín Gonzalo , Letelier Juan Carlos , Henny Pablo , Sentis Elisa , Farfán Gonzalo , Fredes Felipe , Pohl Nélida , Karten Harvey , Mpodozis Jorge
Published: March 2003

The retinotectofugal system is the main visual pathway projecting upon the telencephalon in birds and many other nonmammalian vertebrates. The ascending tectal projection arises exclusively from cells located in layer 13 of the optic tectum and is directed bilaterally toward the thalamic nucleus rotundus. Although previous studies provided evidence that different types of tectal layer 13 cells project to different subdivisions in Rt, apparently without maintaining a retinotopic organization, the detailed spatial organization of this projection remains obscure. We reexamined the pigeon tectorotundal projection using conventional tracing techniques plus a new method devised to perform small deep‐brain microinjections of crystalline tracers. We found that discrete injections involving restricted zones within one subdivision retrogradely label a small fraction of layer 13 cells that are distributed throughout the layer, covering most of the tectal representation of the contralateral visual field. Double‐tracer injections in one subdivision label distinct but intermingled sets of layer 13 neurons. These results, together with the tracing of tectal axonal terminal fields in the rotundus, lead us to propose a novel “interdigitating” topographic arrangement for the tectorotundal projection, in which intermingled sets of layer 13 cells, presumably of the same particular class and distributed in an organized fashion throughout the surface of the tectum, terminate in separate regions within one subdivision. This spatial organization has significant consequences for the understanding of the physiological and functional properties of the tectofugal pathway in birds. J. Comp. Neurol. 458:361–380, 2003. © 2003 Wiley‐Liss, Inc.