bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of the acute myeloid leukemia cell line Kasumi‐6 from a patient with a dominant‐negative mutation in the DNA‐binding region of the C/EBPα gene
Authors: Asou Hiroya , Gombart Adrian F. , Takeuchi Seisho , Tanaka Hideo , Tanioka Maki , Matsui Hirotaka , Kimura Akiro , Inaba Toshiya , Koeffler H. Phillip
Published: January 2003

A myeloid leukemia cell line designated Kasumi‐6 was established from the bone marrow cells of an individual with acute myeloid leukemia, subtype M2. Both the original leukemic cells and the Kasumi‐6 cell line harbor a hemizygous point mutation in the gene encoding the CCAAT/enhancer binding protein alpha (C/EBPα), a critical myeloid transcriptional factor. The C to G transition at nucleotide 1063 of the C/EBPα gene results in amino acid transition R305P in the fork or hinge region between the DNA‐binding basic region and the leucine zipper dimerization domain of the C/EBPα protein. The Kasumi‐6 cells expressed both the p42 and p30 isoforms of the C/EBPα protein endogenously, but electrophoretic mobility shift assays demonstrated an absence of C/EBPα binding to its respective site. Exogenous expression of the mutant form of C/EBPα demonstrated that it was unable to bind DNA and activate transcription from a G‐CSF receptor–luciferase reporter construct. Furthermore, coexpression of the wild‐type and mutant forms revealed that the mutant form repressed reporter gene activation by the wild type in a dose‐responsive manner. This was concomitant with a dose‐responsive decrease in wild‐type protein binding to the G‐CSF receptor C/EBP site. The data suggest that the R305P alteration confers a dominant‐negative property on the mutant C/EBPα protein whereby the mutant polypeptide heterodimerizes with the wild‐type polypeptide and prevents it from binding to DNA, thus blocking transcriptional activation. The Kasumi‐6 cell line can serve as a model to study the cellular and molecular biology of the non‐t(8;21) M2 type of myeloid leukemia and can elucidate the role of mutated C/EBPα in leukemogenesis. © 2003 Wiley‐Liss, Inc.
Robustness of inference on measured covariates to misspecification of genetic random effects in family studies
Authors: M.Pfeiffer Ruth , Hildesheim Allan , H. Gail Mitchell , Pee David , Chen Chien‐Jen , M. Goldstein Alisa , R. Diehl Scott
Published: January 2003

Family studies to identify disease‐related genes frequently collect only families with multiple cases. It is often desirable to determine if risk factors that are known to influence disease risk in the general population also play a role in the study families. If so, these factors should be incorporated into the genetic analysis to control for confounding. Pfeiffer et al. [2001 Biometrika 88: 933–948] proposed a variance components or random effects model to account for common familial effects and for different genetic correlations among family members. After adjusting for ascertainment, they found maximum likelihood estimates of the measured exposure effects. Although it is appealing that this model accounts for genetic correlations as well as for the ascertainment of families, in order to perform an analysis one needs to specify the distribution of random genetic effects. The current work investigates the robustness of the proposed model with respect to various misspecifications of genetic random effects in simulations. When the true underlying genetic mechanism is polygenic with a small dominant component, or Mendelian with low allele frequency and penetrance, the effects of misspecification on the estimation of fixed effects in the model are negligible. The model is applied to data from a family study on nasopharyngeal carcinoma in Taiwan. Genet Epidemiol 24:14–23, 2003. © 2003 Wiley‐Liss, Inc.
On the use of DNA pooling to estimate haplotype frequencies
Authors: Wang Shuang , Kidd Kenneth K. , Zhao Hongyu
Published: January 2003

Genome‐wide association studies may be necessary to identify genes underlying certain complex diseases. Because such studies can be extremely expensive, DNA pooling has been introduced, as it may greatly reduce the genotyping burden. Parallel to DNA pooling developments, the importance of haplotypes in genetic studies has been amply demonstrated in the literature. However, DNA pooling of a large number of samples may lose haplotype information among tightly linked genetic markers. Here, we examine the cost‐effectiveness of DNA pooling in the estimation of haplotype frequencies from population data. When the maximum likelihood estimates of haplotype frequencies are obtained from pooled samples, we compare the overall cost of the study, including both DNA collection and marker genotyping, between the individual genotyping strategy and the DNA pooling strategy. We find that the DNA pooling of two individuals can be more cost‐effective than individual genotypings, especially when a large number of haplotype systems are studied. Genet Epidemiol 24:74–82, 2003. © 2003 Wiley‐Liss, Inc.
On a semiparametric test to detect associations between quantitative traits and candidate genes using unrelated individuals
Authors: Zhang Shuanglin , Zhu Xiaofeng , Zhao Hongyu
Published: January 2003

Although genetic association studies using unrelated individuals may be subject to bias caused by population stratification, alternative methods that are robust to population stratification such as family‐based association designs may be less powerful. Recently, various statistical methods robust to population stratification were proposed for association studies, using unrelated individuals to identify associations between candidate markers and traits of interest (both qualitative and quantitative). Here, we propose a semiparametric test for association (SPTA). SPTA controls for population stratification through a set of genomic markers by first deriving a genetic background variable for each sampled individual through his/her genotypes at a series of independent markers, and then modeling the relationship between trait values, genotypic scores at the candidate marker, and genetic background variables through a semiparametric model. We assume that the exact form of relationship between the trait value and the genetic background variable is unknown and estimated through smoothing techniques. We evaluate the performance of SPTA through simulations both with discrete subpopulation models and with continuous admixture population models. The simulation results suggest that our procedure has a correct type I error rate in the presence of population stratification and is more powerful than statistical association tests for family‐based association designs in all the cases considered. Moreover, SPTA is more powerful than the Quantitative Similarity‐Based Association Test (QSAT) developed by us under continuous admixture populations, and the number of independent markers needed by SPTA to control for population stratification is substantially fewer than that required by QSAT. Genet Epidemiol 24:44–56, 2003. © 2003 Wiley‐Liss, Inc.
Correcting for nonrandom ascertainment in generalized linear mixed models (GLMMs), fitted using Gibbs sampling
Authors: Burton Paul R.
Published: January 2003

Gibbs sampling‐based generalized linear mixed models (GLMMs) provide a convenient and flexible way to extend variance components models for multivariate normally distributed continuous traits to other classes of phenotype. This includes binary traits and right‐censored failure times such as age‐at‐onset data. The approach has applications in many areas of genetic epidemiology. However, the required GLMMs are sensitive to nonrandom ascertainment. In the absence of an appropriate correction for ascertainment, they can exhibit marked positive bias in the estimated grand mean and serious shrinkage in the estimated magnitude of variance components. To compound practical difficulties, it is currently difficult to implement a conventional adjustment for ascertainment because of the need to undertake repeated integration across the distribution of random effects. This is prohibitively slow when it must be repeated at every iteration of the Markov chain Monte Carlo (MCMC) procedure. This paper motivates a correction for ascertainment that is based on sampling random effects rather than integrating across them and can therefore be implemented in a general‐purpose Gibbs sampling environment such as WinBUGS. The approach has the characteristic that it returns ascertainment‐adjusted parameter estimates that pertain to the true distribution of determinants in the ascertained sample rather than in the general population. The implications of this characteristic are investigated and discussed. This paper extends the utility of Gibbs sampling‐based GLMMs to a variety of settings in which family data are ascertained nonrandomly. Genet Epidemiol 24:24–35, 2003. © 2003 Wiley‐Liss, Inc.
Haplotype sharing analysis with SNPs in candidate genes: the genetic analysis workshop 12 example
Authors: Fischer Christine , Beckmann Lars , Majoram Paul , te Meerman Gerard , Chang‐Claude Jenny
Published: January 2003

Haplotype sharing analysis was used to investigate the association of affection status with single nucleotide polymorphism (SNP) haplotypes within candidate gene 1 in one sample each from the isolated and the general population of Genetic Analysis Workshop (GAW) 12 simulated data. Gene 1 has direct influence on affection and harbors more than 70 SNPs. Haplotype sharing analysis depends heavily on previous haplotype estimation. Using GENEHUNTER haplotypes, strong evidence was found for most SNPs in the isolated population sample, thus providing evidence for an involvement of this gene, but the maximum −log10(p) values for the haplotype sharing statistics (HSS) test statistic did not correspond to the location of the true variant in either population. In comparison, transmission disequilibrium test (TDT) analysis showed the strongest results at the disease‐causing variant in both populations, and these were outstanding in the general population. In this example, TDT analysis appears to perform better than HSS in identifying the disease‐causing variant, using SNPs within a candidate gene in an outbred population. Simulations showed that the performance of HSS is hampered by closely spaced SNPs in strong linkage disequilibrium with the functional variant and by ambiguous haplotypes. Genet Epidemiol 24:68–73, 2003. © 2003 Wiley‐Liss, Inc.
Detecting genotype combinations that increase risk for disease: Maternal‐Fetal genotype incompatibility test
Authors: Sinsheimer Janet S. , Palmer Christina G.S. , Woodward J. Arthur
Published: January 2003

Biological mechanisms that involve gene‐by‐environment interactions have been hypothesized to explain susceptibility to complex familial disorders. Current research provides compelling evidence that one environmental factor, which acts prenatally to increase susceptibility, arises from a maternal‐fetal genotype incompatibility. Because it is genetic in origin, a maternal‐fetal incompatibility is one possible source of an adverse environment that can be detected in genetic analyses and precisely studied, even years after the adverse environment was present. Existing statistical models and tests for gene detection are not optimal or even appropriate for identifying maternal‐fetal genotype incompatibility loci that may increase the risk for complex disorders. We describe a new test, the maternal‐fetal genotype incompatibility (MFG) test, that can be used with case‐parent triad data (affected individuals and their parents) to identify loci for which a maternal‐fetal genotype incompatibility increases the risk for disease. The MFG test adapts a log‐linear approach for case‐parent triads in order to detect maternal‐fetal genotype incompatibility at a candidate locus, and allows the incompatibility effects to be estimated separately from direct effects of either the maternal or the child's genotype. Through simulations of two biologically plausible maternal‐fetal genotype incompatibility scenarios, we show that the type‐I error rate of the MFG test is appropriate, that the estimated parameters are accurate, and that the test is powerful enough to detect a maternal‐fetal genotype incompatibility of moderate effect size. Genet Epidemiol 24:1–13, 2003. © 2003 Wiley‐Liss, Inc.
Association mapping of complex diseases in linked regions: estimation of genetic effects and feasibility of testing rare variants
Authors: Wang William Y.S. , Cordell Heather J. , Todd John A.
Published: January 2003

Association mapping in linked regions is a current major approach for the identification of genes for complex diseases. Loci contributing to linkage, even with small values of sibling recurrence risk (λs), may be equivalent to substantial underlying genetic effects for association studies. For disease alleles with a frequency as low as 1%, highly reliable association studies (80% power for significance level α=10−6) require only 277, 781, and 1,289 families or cases and controls for loci detected with λs of 1.5, 1.1, and 1.05, respectively, under a multiplicative genetic model. Under alternative models, provided epistatic effects are minor, larger achievable sample sizes will provide sufficient power to map almost any disease gene that may have initially contributed to linkage. Genet Epidemiol 24:36–43, 2003. © 2003 Wiley‐Liss, Inc.
On selecting markers for association studies: Patterns of linkage disequilibrium between two and three diallelic loci
Authors: Garner Chad , Slatkin Montgomery
Published: January 2003

Association studies depend on linkage disequilibrium (LD) between a causative mutation and linked marker loci. Selecting markers that give the best chance of showing useful levels of LD with the causative mutation will increase the chances of successfully detecting an association. This report examines the variation in the extent of LD between a disease locus and one or two diallelic marker loci (termed single nucleotide polymorphisms or SNPs). We use a simulation method based on the neutral coalescent in a population of variable size to find the distribution of LD as a function of allele frequencies, the recombination rate, and the population history. Given that LD exists, the allele frequencies determine if a site will be useful for detecting an association with the disease mutation. We show that there is extensive variation in LD even for closely linked loci, implying that several markers may be needed to detect a disease locus. The distribution of LD between common variants is strongly influenced by ancestral population size. We show that in general, best results will be obtained if the frequencies of marker alleles are at least as large as the frequency of the causative mutation. Haplotypes of two or more SNPs generally have a higher probability than individual SNPs of showing useful LD with a disease mutation, although exceptions are described. Genet Epidemiol 24:57–67, 2003. © 2003 Wiley‐Liss, Inc.
Astrocytes selectively enhance N‐type calcium current in hippocampal neurons
Authors: Mazzanti Mary , Haydon Philip G.
Published: January 2003

Astrocytes influence neuronal development, synapse formation, and synaptic transmission, partly through affecting neuronal calcium signals. In order to elucidate the extent to which astrocytes modulate neuronal voltage‐gated calcium currents, we performed a whole‐cell patch clamp analysis of neurons in astrocyte‐deplete and astrocyte‐enriched conditions. We demonstrate that hippocampal neurons in an astrocyte‐enriched environment show augmentation of voltage‐gated calcium current at 1–3 days in vitro. Further study in pairs of adjacent neurons showed that the augmentation in calcium current was dependent on direct contact with the astrocyte. Pharmacological analysis demonstrated the augmentation is selective for the N‐type calcium current, although immunochemical labeling of the α1B subunit of the N‐type calcium channel was unchanged. These findings show that astrocytes regulate neuronal voltage‐gated calcium currents in a contact‐dependent manner. The specificity of the effect for the N‐type calcium current at early days in culture has special significance regarding the role of astrocytes in hippocampal synaptogenesis. GLIA 41:128–136, 2003. © 2003 Wiley‐Liss, Inc.
Peroxynitrite‐induced oligodendrocyte toxicity is not dependent on poly(ADP‐ribose) polymerase activation
Authors: Scott Gwen S. , Virág Laszlo , Szabó Csaba , Hooper D. Craig
Published: January 2003

Oligodendrocyte loss is a characteristic feature of several CNS disorders, including multiple sclerosis (MS) and spinal cord injury. However, the mechanisms responsible for oligodendrocyte destruction remain undefined. As recent studies have implicated peroxynitrite in the pathogenesis of both spinal cord injury and MS, we have examined whether peroxynitrite may mediate at least some of the oligodendrocyte damage and demyelination observed in these conditions. Primary rat oligodendrocytes were exposed to authentic peroxynitrite in vitro and assessed for cytotoxicity. Mitochondrial function, measured by the reduction of MTT to formazan, and mitochondrial membrane potential were used as indicators of cell viability. Cell death was quantitated by measuring either the release of lactate dehydrogenase from, or the uptake of propidium iodide into, damaged and dying cells. Peroxynitrite dose‐dependently reduced the viability of primary oligodendrocytes and induced cell death. Furthermore, peroxynitrite significantly increased DNA strand breakage and the activity of poly(ADP‐ribose) polymerase (PARP) in oligodendrocyte cultures. To identify whether PARP activation plays a role in peroxynitrite‐induced oligodendrocyte toxicity, we examined the effects of the PARP inhibitors 3‐aminobenzamide (3AB) and 5‐iodo‐6‐amino‐1,2‐benzopyrone (INH2BP) on mitochondrial function and cell death in oligodendrocytes. The presence of 3AB and INH2BP did not protect oligodendrocytes from peroxynitrite‐induced cytotoxicity. However, both compounds significantly reduced PARP activity in these cells. Primary oligodendrocytes generated from PARP‐deficient mice were also highly susceptible to peroxynitrite‐induced cell death. Therefore, our results show that peroxynitrite exerts cytotoxic effects on oligodendrocytes in vitro independently of PARP activation. GLIA 41:105–116, 2003. © 2003 Wiley‐Liss, Inc.
Gabaergic signaling mediates the morphological organization of astrocytes in the adult rat forebrain
Authors: Runquist Martin , Alonso Gérard
Published: January 2003

Previous studies have provided evidence that the morphological organization of immature astrocytes is influenced by the inhibitory neuronal transmitter gamma amino‐butyric acid (GABA). The present study was designed to determine whether the occurrence of differential organization of mature astrocytes throughout various regions of the adult brain is related to differential GABAergic signaling. For this we first used Western blotting and high‐performance liquid chromatography to quantify the levels of the astrocytic protein glial fibrillary acidic protein (GFAP) and GABA, respectively, within the same tissue punches taken from different forebrain regions of the adult rat, as well as immunocytochemistry for GFAP, GABA, or glutamate decarboxylase to visualize the morphological organization of astrocytes and of GABAergic axons in these regions. These data indicate that GFAP and GABA contents are correlated throughout the different forebrain regions analyzed, and that the regions containing the highest densities in GABAergic terminals are those that contain astrocytes exhibiting the highest degree of stellation. Secondly, we chronically increased GABAergic signaling in vivo by the systemic administration of an inhibitor of GABA transaminase or by the intracerebroventricular infusion of muscimol, a potent agonist of GABAA receptors. Our data show that in both cases, the GFAP content of the different forebrain regions is significantly augmented, in close association with a marked increase in the number of astrocytic processes and with their degree of branching. Taken together, these data strongly suggest that GABAergic signaling mediates the morphological organization of astrocytes and their expression of GFAP in the adult brain. GLIA 41:137–151, 2003. © 2003 Wiley‐Liss, Inc.
Cytokine‐stimulated inducible nitric oxide synthase expression in astroglia: Role of Erk mitogen‐activated protein kinase and NF‐κB
Authors: Marcus Joshua S. , Karackattu Sharon L. , Fleegal Melissa A. , Sumners Colin
Published: January 2003

Expression of inducible nitric oxide synthase (iNOS), which leads to the production of nitric oxide (NO), is stimulated by proinflammatory cytokines such as interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). Here we report on the roles of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein (MAP) kinases in IL‐1β/TNF‐α–induced iNOS expression in adult rat astroglia. Cytokine‐induced increases in nitrite accumulation (an index of NO production) and iNOS expression were attenuated by inhibition of NF‐κB with pyrrolidine dithiocarbamate (PDTC). Similar attenuation of these cytokine‐induced responses was produced by inhibition of MAP kinase (MEK), the immediate upstream activator of Erk, using PD098,059. Combined treatment of astroglia with PDTC and PD098,059 completely abolished the cytokine‐induced increases in iNOS expression and nitrite accumulation. By contrast, the selective p38 kinase inhibitor SB203,580 amplified the effects of IL‐1β/TNF‐α on nitrite accumulation. In accordance with these findings, IL‐1β– and TNF‐α–induced a time‐dependent increase in Erk1/Erk2 activation. This cytokine action was completely abolished by PD098,059 but was not altered by PDTC. Finally, IL‐1β and TNF‐α induced degradation of NF‐κB's bound inhibitory protein, IκB‐α, leading to translocation of NF‐κB into the nucleus. IκB‐α expression was not restored to control levels by inhibition of MEK. Furthermore, inhibition of MEK with PD098,059 did not alter IL‐1β– and TNF‐α–induced expression of active NF‐κB. The results demonstrate that autonomous Erk and NF‐κB pathways mediate cytokine‐induced increases in iNOS expression in astroglia. GLIA 41:152–160, 2003. © 2003 Wiley‐Liss, Inc.
Suppression of activated microglia promotes survival and function of transplanted oligodendroglial progenitors
Authors: Zhang Su‐Chun , Goetz Brian D. , Duncan Ian D.
Published: January 2003

To evaluate the functional consequence of microglial activation in vivo, oligodendroglial progenitors were transplanted into the spinal cord of Long Evans shaker, a myelin mutant rat in which myelin defects are associated with progressive microglial activation. Cells grafted into neonatal rats at the initiation of gliosis successfully myelinated axons. However, cells transplanted during peak microglial activation did not lead to myelination due to death of the grafted cells within 3 days after transplantation. Pretreatment of these animals with minocycline, a tetracycline derivative, resulted in cell survival and myelination by the grafted cells. In culture, minocycline did not affect the survival, proliferation, or differentiation of oligodendroglial progenitors. Hence, minocycline likely modulates the function of reactive glia in vivo to promote the survival and myelination of transplanted oligodendroglial progenitors. GLIA 41:191–198, 2003. © 2003 Wiley‐Liss, Inc.
Sphingosine 1‐phosphate induces the production of glial cell line‐derived neurotrophic factor and cellular proliferation in astrocytes
Authors: Yamagata Kazuo , Tagami Motoki , Torii Yasuyoshi , Takenaga Fumio , Tsumagari Shigehisa , Itoh Shingo , Yamori Yukio , Nara Yasuo
Published: January 2003

Sphingosine 1‐phosphate (S1P) is a platelet‐derived bioactive sphingolipid that evokes a variety of biological responses. To understand the role of S1P in the central nervous system, we have examined the effect of S1P on the production of glial cell line‐derived neurotrophic factor (GDNF) and growth regulation of cortical astrocytes from rat embryo. Moreover, we examined the possibility that the expression of GDNF is regulated differently in cultured astrocytes from the stroke‐prone spontaneously hypertensive rat (SHRSP) than in those from Wistar kyoto rats (WKY). The mRNA expression was quantitated by RT‐PCR based on the fluorescent TaqMan methodology. A new instrument capable of measuring fluorescence in real time was used to quantify gene amplification in astrocytes. GDNF protein was investigated by enzyme‐linked immunosorbent assay. S1P induced the expression of GDNF mRNA and the production of GDNF protein in a dose‐dependent manner in WKY astrocytes. Moreover, S1P increased cell numbers and induced the proliferation of astrocytes. In addition, the level of mRNA expression and protein production of GDNF was significantly lower in SHRSP than WKY astrocytes following exposure to S1P. These findings revealed that S1P augments GDNF protein production and cellular growth in astrocytes. Also, our results indicate that production in SHRSP astrocytes was attenuated in response to S1P compared with that observed in WKY. We conclude that S1P specifically triggers a cascade of events that regulate the production of GDNF and cell growth in astrocytes. Our results also suggest that the reduced expression of GDNF caused by S1P is a factor in the stroke proneness of SHRSP. GLIA 41:199–206, 2003. © 2003 Wiley‐Liss, Inc.
Annamaria Cimini, Antonietta Bernardo, Maria Grazia Cifone, Luisa Di Marzio, Silvia Di Loreto. TNF downregulates PPAR expression in oligodendrocyte progenitor cells: Implications for demyelinating diseases. GLIA 2003;41(1):3–14.
Authors: Cimini Annamaria , Bernardo Antonietta , Grazia Cifone Maria , Di Marzio Luisa , Di Loreto Silvia
Published: January 2003

The original article to which this Erratum refers was published in GLIA (2003)41:3–14
Psychosocial adjustment in head and neck cancer: The impact of disfigurement, gender and social support
Authors: Katz Mark R. , Irish Jonathan C. , Devins Gerald M. , Rodin Gary M. , Gullane Patrick J.
Published: January 2003

Background.

The purpose of this study was to examine the psychosocial impact of disfigurement, gender, and social support after surgical treatment of head and neck cancer.

Method.

Eighty‐two ambulatory head and neck cancer patients, 6 months or more after treatment and free of active disease were assessed. Ratings of disfigurement were obtained using a valid and reliable 9‐point scale developed for the study. Standardized measures of social support, depressive symptoms, well‐being, and life happiness were used.

Results.

The sample as a whole displayed high levels of life happiness, low levels of depression, and positive feelings of well‐being. Women demonstrated higher levels of depression and lower life happiness; subjects with greater disfigurement were more depressed. Social support seemed to buffer the impact of greater levels of disfigurement on well‐being for women but not for men.

Conclusion.

These results suggest that women with head and neck cancer who experience low social support and face disfiguring treatment are at greatest risk for psychosocial dysfunction. © 2003 Wiley Periodicals, Inc. Head Neck 25: 103–112, 2003
Different prognostic indices in 310 patients with tonsillar carcinomas
Authors: Hannisdal Kirsten , Boysen Morten , Evensen Jan F.
Published: January 2003

Background.

Several modifications of the TNM system have been reported as better prognostic tools than the original classification in head and neck cancer, but none of these modifications has been tested in a large series of tonsillar carcinomas. These studies did not examine host and treatment factors as predictors in addition to TNM.

Methods.

Three hundred and ten consecutively untreated patients with squamous cell carcinoma of the tonsillar region admitted to the Norwegian Radium Hospital and/or the National Hospital between 1960 and 1996 were included.

Results.

The five reported TN‐based stage modifications were all highly significant predictors of survival. Four clinical variables indicating shorter disease‐specific survival were identified: age > 60, male gender, total radiation dose < 70 Gy, and duration of radiotherapy > 50 days.

Conclusions.

Earlier reported TNM‐based stage modifications are all very useful predictors of survival in tonsillar carcinomas. In addition, age, gender, total radiation dose, and duration of radiotherapy were important prognostic factors. We propose that both host and treatment factors should be tested carefully when building new prognostic indices in tonsillar carcinomas. © 2003 Wiley Periodicals, Inc. Head Neck 25: 123–131, 2003
Phase 1 trial of combined chemotherapy and reirradiation for recurrent unresectable head and neck cancer
Authors: Spencer Sharon , Wheeler Richard , Peters Glenn , Meredith Ruby , Beenken Sam , Nabel Lisle , Wooten Ann , Soong Seng‐jaw , Salter Merle
Published: January 2003

Background.

The management of recurrent unresectable head and neck cancer remains a challenging problem. Based on the circadian rhythm concept, we sought to determine the maximum tolerated dose (MTD) of infusional 5‐flourouracil (5‐FU), hydroxyurea (HU), and reirradiation (RT).

Method.

Bolus 5‐FU was escalated from 300mg/m2/d to a 10‐hour infusion beginning at midnight, increased at 150 mg/m2/d increments. HU, 1.5 g, remained constant. Chemotherapy was given on weeks 1 and 4. RT was given daily, 2.0 Gy per fraction on weeks 1 and 2 followed by a 1‐week break, then hyperfractionated weeks 4 and 5, total dose 50 Gy. The goal was to deliver a continuous course of RT to 60 Gy after the MTD was determined with an additional week of chemotherapy.

Results.

Six cohorts were treated to establish the 5‐FU MTD of 900 mg/m2/d. The seventh cohort received continuous RT and 5‐FU, 750 mg/m2/d, one dose level below the MTD. Two hematologic, three skin, and six mucosal ≥ grade 3 toxicities were noted in 7 of 16 patients. The median survival was 10.2 months and the 1‐year survival was 41%. The median survival for the entire group was 9.4 months, with a 1‐ and 2‐year survival of 39% and 15%, respectively.

Conclusion.

RT can be given in a continuous fashion with concurrent 5‐FU and HU. Because radiation sensitization should be achievable at nontoxic doses of 5‐FU, we recommend 600 mg/m2/d in phase a II setting. © 2003 Wiley Periodicals, Inc. Head Neck 25: 118–122, 2003
The usefulness of fluorine 18–labelled deoxyglucose positron emission tomography in the investigation of patients with cervical lymphadenopathy from an unknown primary tumor
Authors: Fogarty Gerald B. , Peters Lester J. , Stewart Josephine , Scott Clare , Rischin Danny , Hicks Rodney J.
Published: January 2003

Background.

The usefulness of fluorine 18‐labelled deoxyglucose positron emission tomography (PET) in the detection of unknown primary tumor in patients seen with malignant cervical lymphadenopathy thought to arise from a head and neck primary differs in the published reports to date. To assess the role of PET in this scenario in our institution, an audit was performed.

Methods.

The records of 21 patients who met the clinical indication were reviewed. End points were the ability of PET to detect an unknown primary tumor and/or distant metastatic disease.

Results.

In 8 of the 21 patients, PET detected a potential primary site, although none was unequivocally PET positive. One case was pathologically confirmed. In five patients the potential primary site identified on PET could not be confirmed: two had negative biopsies, and three had no clinical evolution in the PET‐suspect area for at least 24 months after the initial study. In the remaining two patients, the potential primary site detected by PET was treated without biopsy. PET detected additional regional and/or distant disease that had not been previously documented in nine cases.

Conclusions.

PET did not add significantly to the detection of an occult primary tumor in patients who had already been comprehensively evaluated by clinical and radiologic investigations. It was of substantial benefit, however, in detecting unsuspected distant disease in patients with undifferentiated nodal histologic findings and helped in delineating regional disease in patients with N2 disease. © 2003 Wiley Periodicals, Inc. Head Neck 25: 138–145, 2003
Decreased salivary gland function in patients with autoimmune thyroiditis
Authors: Chang Cheng‐Pei , Shiau Yu‐Chien , Wang Jhi‐Joung , Ho Shung‐Tai , Kao Chia‐Hung
Published: January 2003

Background/Aims.

It has been speculated that impaired salivary flow contributes to autoimmune thyroiditis (chronic thyroiditis, Hashimoto's thyroiditis). To test this hypothesis, salivary function was measured by quantitative salivary scintigraphy in autoimmune thyroiditis patients, as well as in age‐ and gender‐matched controls for comparison.

Methodology.

One hundred and twenty patients with an autoimmune thyroiditis history of more than 10 years each and 36 healthy controls were enrolled in the study. All the 120 autoimmune thyroiditis patients had good blood sugar control. None had autonomic neuropathy. These 120 autoimmune thyroiditis patients were separated into two subgroups: group 1, 60 patients with xerostomia; and group 2, 60 patients without xerostomia. After intravenous injection of 5 mCi Tc‐99m pertechnetate, sequential images at 1 min/frame were acquired for 30 min. The first‐ and 15th‐minute uptake ratios (UR) were calculated from the tracer uptakes in the four major salivary glands over the background regions of interest (ROIs). Saliva excretion was stimulated by 1 tablet of 200 mg ascorbic acid given orally 15 min after injection of the tracer. Then, the maximal excretion ratios (ER) of the four major salivary glands after sialagogue stimulation were calculated.

Results.

Impaired salivary function, represented by significantly decreased UR and ER values, in autoimmune thyroiditis patients with xerostomia was demonstrated in this study. In addition, there was a significantly higher prevalence of salivary gland dysfunction in group 1 patients than in group 2 patients.

Conclusions.

Significantly poorer salivary function was found in autoimmune thyroiditis patients with xerostomia compared with autoimmune thyroiditis patients without xerostomia and healthy controls by means of objective and quantitative salivary scintigraphy. © 2003 Wiley Periodicals, Inc. Head Neck 25: 132–137, 2003
A novel mutation in the SDHD gene in a family with inherited paragangliomas—implications of genetic diagnosis for follow up and treatment
Authors: Renard Laurette , Godfraind Catherine , Boon Laurence M. , Vikkula Miikka
Published: January 2003

Background.

Early detection of paragangliomas (PGs) has been linked to low morbidity after surgical resection. Recent identification of causative genes (SDHB, SDHC, and SDHD) has made it possible to detect individuals at high risk for tumors.

Methods.

We identified a three‐generation family, with four individuals affected with PGs. Because pedigree analysis suggested maternal imprinting (the phenotype is present only if inherited through the paternal line), the SDHD gene (PGL1) was screened.

Results.

A novel mutation that causes skipping of exon 3 was identified. Ten of the seventeen tested individuals carried the mutation. All six clinically unaffected individuals inherited the mutation from their mother. Five of them are men, with a 50% risk for affected progeny.

Conclusions.

To allow early treatment with low morbidity, genetic counseling is needed when familial paraganglioma is suspected. Asymptomatic carriers should be followed by cervical MRI. In addition, because pheochromocytomas may occur, catecholamine excretion can be performed. This screening should probably be proposed at 5 to 10 years of age. © 2003 Wiley Periodicals, Inc. Head Neck 25: 146–151, 2003
Posttraumatic stress symptoms in Croatian children exposed to war: A prospective study
Authors: Kuterovac‐Jagodić Gordana
Published: January 2003

This study examined symptoms of posttraumatic stress in 252 school‐aged children from Osijek, Croatia, which was subjected to massive military attacks from Yugoslavian forces. The children's symptoms were assessed in 1994 while the war was still going on and 30 months later when the war was over. In addition to changes in posttraumatic stress disorder symptoms over time, the study examined the predictive power of (a) different types and number of war traumata, (b) loss of social community, (c) the children's demographic characteristics (age and gender), (d) types of coping strategies and locus of control, and (e) the perceived availability of different kinds of social support. Although symptoms of posttraumatic stress declined over time, 10% of the children reported a severe level of symptomatology 30 months after the war. The results supported the hypothesized predictive power of all investigated factors for predicting short‐ and long‐term posttraumatic stress reactions. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 9–25, 2003.
Determinants of posttraumatic adjustment in adolescents from Sarajevo who experienced war
Authors: Duraković‐Belko Elvira , Kulenović Alija , Dapić Renko
Published: January 2003

The purpose of this study was to examine risk and protective factors of postwar adjustment among adolescents from Sarajevo who have been exposed to war traumas during the war in Bosnia and Herzegovina. More specifically, we wanted to examine differential linkages between Posttraumatic Stress Disorder (PTSD) symptoms and depression (as outcomes) and (a) war traumas, (b) individual and socioenvironmental factors, and (c) cognitive appraisals and coping mechanisms. Results of hierarchical multiple regression analyses indicate that dimensions of war traumas, individual characteristics, and cognitive appraisals and coping mechanisms play a significant role in determining who will have more serious PTSD symptoms. Although individual and socioenvironmental factors are the strongest predictors of depression, dimensions of war traumas also are significantly correlated with depressive symptoms. Common risk factors for more serious depression and PTSD symptoms in postwar adjustment were female gender and low optimism. While the strongest predictor of posttraumatic stress reactions (PTSR) was trauma experience in the category of loss, the strongest predictor of depressive symptoms was female gender. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 27–40, 2003.
Posttraumatic Stress Disorder three years after the siege of Sarajevo
Authors: Rosner Rita , Powell Steve , Butollo Willi
Published: January 2003

The goals of this study were to estimate the lifetime prevalence of traumatic events, the current prevalence of Posttraumatic Stress Disorder (PTSD), and the connection between the kinds of traumatic events experienced and the probability of developing PTSD in three study samples in Sarajevo, Bosnia‐Herzegovina, three years after the end of the war. A total of 311 people surviving the siege of Sarajevo were assessed with the Checklist for War Related Experiences (CWE) and an adapted version of the Posttraumatic Diagnostic Scale (PDS). The study groups consisted of a randomly selected residents sample (n = 98), a group of individuals in psychological treatment (n = 114), and a group in medical treatment (n = 99). Each individual survived an average of 24 traumatic events. According to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM‐IV; American Psychiatric Association, 1994) criteria, 18.6% of individuals in the residents sample, 32.7% of those in medical treatment, and 38.6% of those in psychological treatment developed PTSD. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 41–55, 2003.
Posttraumatic growth after war: A study with former refugees and displaced people in Sarajevo
Authors: Powell Steve , Rosner Rita , Butollo Willi , Tedeschi Richard G. , Calhoun Lawrence G.
Published: January 2003

Research carried out with survivors of a variety of different traumata indicates that a large proportion of them perceive positive changes in themselves after the trauma. This study investigated whether posttraumatic growth also could be found among people who had been exposed to particularly severe traumata over a period of several years (1991 to 1995) during the war in the area of the former Yugoslavia. Included in the study were two representative samples of adult former refugees and displaced people who lived anywhere in former Yugoslavia before the war and were currently living in Sarajevo, Bosnia and Herzegovina, three and a half years after the war. The main instrument was a new Bosnian translation of the Posttraumatic Growth Inventory. Results indicated some differences in the factor structure as compared with the original instrument. The overall means for the scale were considerably lower than reported in most studies
on other kinds of trauma. Younger people reported considerably more growth than older people. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 71–83, 2003.
Empirical support for interrater reliability of Rorschach Comprehensive System coding
Authors: Viglione Donald J. , Taylor Nicole
Published: January 2003

Although a great deal of data has been published in the past 20 years supporting the interrater reliability of the Rorschach, recently commentators have raised anew concerns over the interrater reliability of this well‐known and frequently used measure. An analysis of the literature reveals that these concerns are based on a selective review of the literature. The current study reports interrater reliability statistics for 70 interpretive Rorschach variables (n = 84), breaking down intraclass correlations statistics by base rate. Results confirm the strong empirical evidence of the interrater reliability of this measure when scored by a well‐trained and diverse group of researchers and clinicians. Reliability is especially strong and consistent for the high base‐rate variables from which clinicians often base their interpretations. These data further suggest that large samples are needed for stable reliability estimates of low base‐rate variables and that estimates of the reliability of low base‐rate variables are subject to error. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 111–121, 2003.
Detection of intentional sub‐optimal performance on a computerized finger‐tapping task
Authors: Tanner Barry A. , Bowles Richard L. , Tanner Evan L.
Published: January 2003

Twenty‐four undergraduates were assigned to two groups to determine if the T3 computerized finger‐tapping task could discriminate between persons motivated to perform optimally and those motivated to perform sub‐optimally. Group HI was instructed to simulate a head‐injured person undergoing an insurance evaluation, whereas group J was instructed to simulate an applicant undergoing a job interview. Group HI tapped slower, demonstrated less fatigue, less similarity between their right‐ and left‐hand performance, and showed less of a speed advantage for the preferred hand. While group HI displayed less variability for the non‐preferred hand, the groups did not differ on variability for the preferred hand. Therefore, the T3 successfully discriminates on multiple measures between persons simulating optimal and sub‐optimal performance. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 123–131, 2003.
Client and therapist reasons for termination: A conceptualization and preliminary validation
Authors: Todd David M. , Deane Frank P. , Bragdon Rodney A.
Published: January 2003

While the comparison of client and therapist reasons for termination might shed light on their respective views of outcome and process, only one published study has examined directly the reasons given by therapist–client pairs. One barrier to such research is the absence of a systematic conceptualization of reasons for termination that incorporates both therapist and client perspectives. This article describes a comprehensive conceptualization, drawn from the existing literature, and applies a coding system based on that conceptualization to naturalistic clinical data from 123 therapist–client pairs in a psychology training clinic. Coders were able to categorize reliably open‐ended client data into reasons for termination. For therapist and client data, the relationships between coding categories and participants' outcome ratings, generally were consistent with expectations, providing limited validation. Some support was found for concordance between therapist and client reasons, especially for those related to therapist or client departures, which were prominent in this setting. As expected, however, therapists were more likely than clients to endorse success as a reason for termination. Negative client feelings about therapy, including dissatisfaction, were reported infrequently as reasonsfor termination, and with little agreement between clients and therapists, but this may be due to methodological limitations. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 133–147, 2003.
A confirmatory factor analysis of a self‐report version of the Liebowitz Social Anxiety Scale
Authors: Oakman Jonathan , Van Ameringen Michael , Mancini Catherine , Farvolden Peter
Published: January 2003

One of the most popular measures of social phobia is the Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987). The LSAS is a 24‐item semi‐structured interview measure of fear and avoidance experienced in a range of social and performance situations. Recently, the LSAS has been modified to a self‐report version (LSAS‐SR) by several independent groups (Cox, Ross, Swinson, & Direnfeld, 1998; Fresco et al., 2001; Mancini, Van Ameringen, & Oakman, 1999). A self‐report version offers ease of administration, but it may differ from the structured interview version in its psychometric properties. We conducted confirmatory factor analyses of the self‐report version of the LSAS using data from a sample of 188 outpatients with anxiety disorders. The structure and psychometric properties of the LSAS‐SR are highly similar to that of the LSAS and robust across groups of patients with a variety of primary anxiety disorders. We argue in favor of adopting the 4‐factor model for the LSAS proposed by Safren et al. (1999) instead of the models implied by the scoring instructions for the LSAS. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 149–161, 2003.
Predicting psychological mindedness from personality style and attachment security
Authors: Beitel Mark , Cecero John J.
Published: January 2003

The aim of this study was to increase the construct validity of the Psychological Mindedness Scale (PM Scale) by investigating its relationship to well‐established measures of personality style (NEO Five‐Factor Inventory) and attachment security (Inventory of Parent and Peer Attachment). Personality and attachment variables functioned as differential predictors of psychological mindedness (PM). Openness to Experience emerged as the best predictor of PM, followed by Extraversion, Neuroticism (inversely related to PM), and Attachment to Peers. Neither Attachment to Mother nor Attachment to Father predicted PM. The results of this study indicate that PM is related positively to healthy, rather than pathological, personal and interpersonal constructs. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 163–172, 2003.
Reduction of eddy‐current‐induced distortion in diffusion MRI using a twice‐refocused spin echo
Authors: Reese T.G. , Heid O. , Weisskoff R.M. , Wedeen V.J.
Published: January 2003

Image distortion due to field gradient eddy currents can create image artifacts in diffusion‐weighted MR images. These images, acquired by measuring the attenuation of NMR signal due to directionally dependent diffusion, have recently been shown to be useful in the diagnosis and assessment of acute stroke and in mapping of tissue structure. This work presents an improvement on the spin‐echo (SE) diffusion sequence that displays less distortion and consequently improves image quality. Adding a second refocusing pulse provides better image quality with less distortion at no cost in scanning efficiency or effectiveness, and allows more flexible diffusion gradient timing. By adjusting the timing of the diffusion gradients, eddy currents with a single exponential decay constant can be nulled, and eddy currents with similar decay constants can be greatly reduced. This new sequence is demonstrated in phantom measurements and in diffusion anisotropy images of normal human brain. Magn Reson Med 49:177–182, 2003. © 2003 Wiley‐Liss, Inc.