bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary mucosal melanoma of the head and neck
Authors: Prasad Manju L. , Patel Snehal G. , Huvos Andrew G. , Shah Jatin P. , Busam Klaus J.
Published: March 2004

BACKGROUND

The current study was conducted to identify histologic predictors of survival in patients with localized, lymph node‐negative (Stage I, N0M0) primary mucosal melanomas of the head and neck (HNMM).

METHODS

The histology of 39 sinonasal, 20 oral, 1 pharyngeal, and 1 laryngeal Stage I HNMM was reviewed by 2 pathologists without knowledge of patient outcome. The invasion was evaluated as Level I: melanoma in situ (without invasion or with microinvasion only); Level II: invasion into the lamina propria only; and Level III: invasion into deep tissue (e.g., skeletal muscle, bone, or cartilage). The tumor architecture was defined as pseudopapillary when tumor cells clustered around blood vessels resembling papillae and sarcomatoid when they resembled high‐grade pleomorphic sarcoma. Survival analysis was performed with Kaplan–Meier survival curves using disease‐specific survival (DSS) as the endpoint.

RESULTS

The 5‐year DSS rate was 43% (median, 41.5 months). The median survival was found to decrease significantly with increasing level of invasion: Level I (n = 4): 138 months; Level II (n = 29): 69 months; and Level III (n = 28): 17 months (P = 0.003). The presence of pseudopapillary and sarcomatoid architecture (n = 20) and undifferentiated cells (n = 16) were found to be associated with a significantly poor DSS (P < 0.05). However, on multivariate analysis, only the level of invasion remained an independent predictor of survival (P = 0.03). Tumor thickness, vascular invasion, and necrosis were found to have no significant influence on survival.

CONCLUSIONS

Microstaging according to invasion into three tissue compartments was found to be a significant and independent predictor of poor survival in patients with localized, lymph node‐negative, Stage I HNMM. The presence of sarcomatoid and pseudopapillary architecture and undifferentiated cells also appear to be associated with significantly poor DSS. Cancer 2004. © 2004 American Cancer Society.
The aftermath of therapist–client sex: exploited women struggle with the consequences
Authors: Ben‐Ari Adital , Somer Eli
Published: March 2004

This study explores the ongoing experience of women who were sexually involved with their psychotherapists (therapist–client sex, TCS). Fourteen women who had been engaged in TCS were interviewed to examine the constructed meanings associated with their experiences. Respondents described themselves as having been problem‐saturated, lonely, and victimized by pre‐TCS sexual abuse. Many respondents resolved their TCS betrayal in subsequent therapy. For most interviewees, a significant step towards confronting their painful TCS experience was their initiated agreement to partake in this study. Our data suggest that participants went through a significant personal transformation process that encompassed four main themes: self‐perception; interpersonal relationships; the dilemma of filing a lawsuit; and their motivation to participate in this study. Copyright © 2004 John Wiley & Sons, Ltd.
Intrusive thoughts in non‐clinical subjects: the role of frequency and unpleasantness on appraisal ratings and control strategies
Authors: Belloch Amparo , Morillo Carmen , Lucero Mariela , Cabedo Elena , Carrió Carmen
Published: March 2004

This study explores the frequency of the appearance of intrusive thoughts in normal people, as well their association with cognitive appraisals and control strategies. A total of 336 subjects completed the Spanish adaptation of the Obsessional Intrusions Inventory‐Revised (ROII), designed by Purdon and Clark (1993, 1994a, 1994b). Most of the subjects (99.4%) reported experiencing intrusive thoughts occasionally, but only 13% reported having them with some frequency. The intrusions were included in two factors: aggression, sexually and socially inappropriate behaviours, and doubts, checking, and cleanliness. The frequency of appearance of the most upsetting intrusive thought was associated with: the likelihood/probability bias, the need to control the thoughts, and neutralizing strategies. Nevertheless, the unpleasantness was associated with the morality bias and a broad range of control strategies. These results are discussed in relation to the different roles that the appraisal and the thought control responses play, both regarding the persistence as well as the unpleasantness associated with the most upsetting intrusions. Copyright © 2004 John Wiley & Sons, Ltd.
Characteristics of 80 adolescents referred for secure inpatient care
Authors: Wheatley Malcolm , Waine Jo , Spence Kiran , Hollin Clive R.
Published: March 2004

Despite the recognition of the need for secure adolescent mental health provision, the extent and precise nature of the services required in the United Kingdom remains unquantified. The present study describes some of the key characteristics of 80 young people referred from around the United Kingdom for medium secure health care. The pattern of referrals indicates a substantial need for secure health care in the 14‐ to 18‐year‐old age range. Young people requiring such care present most commonly with psychotic, personality or post traumatic stress disorder. Nearly half of the young people (45%) were requiring constant observation. Over 90% of those assessed presented a risk of aggression and over 60% presented a suicide risk. Over half (53%) had been charged with one or more offence and 29% had at least one conviction. The need for the further development of an adolescent forensic specialism is supported by these data. Copyright © 2004 John Wiley & Sons, Ltd.
Factors predicting the short‐listing and selection of trainee clinical psychologists: a prospective national cohort study
Authors: Phillips Anna , Hatton Chris , Gray Ian
Published: March 2004

Concerns have frequently been raised about equal opportunities in the short‐listing and selection procedures used by clinical psychology training courses, although little evidence exists. The aim of the study is to identify factors predicting short‐listing and selection to clinical psychology training courses. A prospective study of one national cohort of applicants to UK clinical psychology training (the 2000 entry cohort of 1538 applicants) was carried out. Application forms (n = 1538), references (n = 1538) and postal questionnaires (n = 396) were used to collect demographic, biographical, academic and work experience information. Relationships between these variables and short‐listing or selection to training were examined using univariate odds ratios and effect sizes, and multivariate logistic regressions. Factors most strongly predictive of short‐listing and selection were proxies for academic ability (post‐16 education at school, degree class, involvement in postgraduate education, authoring publications), relevant educational qualifications (a degree eligible for registration into the BPS), relevant vocational experience (a greater number and range of psychology assistant posts), and positive ratings from academic and clinical psychologist experience‐related referees. Short‐listing and selection to clinical psychology training relies on proxy factors related to academic ability, education, vocational experience and ratings from referees. There is little evidence of direct discrimination, although certain subgroups of applicants may be disadvantaged in their opportunities to gain relevant academic qualifications and vocational experience. Copyright © 2004 John Wiley & Sons, Ltd.
Easy Synthesis of New Chiral Tridentate Schiff Bases and Their Use as [N,N,O] Ligands for Ni and Pd Complexes − Catalytic Behaviour versus Hydrogenation Reactions
Authors: González‐Arellano Camino , Gutiérrez‐Puebla Enrique , Iglesias Marta , Sánchez Félix
Published: March 2004

The chiral [N,N,O] tridentate unsymmetrical Schiff bases 3−5 (aryl = phenyl, 1‐naphthyl, 2‐naphthyl) were synthesised easily in high purity and good yields. All the organic compounds were characterised by elemental analysis, mass spectrometry, IR, 1H and 13C NMR spectroscopy. Palladium(II) and nickel(II) Schiff‐base complexes were prepared as air‐stable solids. Because the [N,N,O] ligand is tridentate after deprotonation of the −OH group, the coordination of the metal ion is completely stereospecific and gives rise to only one diastereoisomer. The X‐ray crystal structures of the complexes [Ni(3)(OAc)] and [Pd(4)(OAc)] were determined. These complexes were shown to be very active catalysts (TOF up to 106 h−1) for the hydrogenation of olefins and imines under mild conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Crystal Structure and Magnetic Properties of Bi(Bi9)[NbCl6]3, a New Member of the Structure Family Bi(Bi9)[MX6]3, and the Crystal Structure of Bi8[Ta2O2Br7]2
Authors: Beck Johannes , Hilbert Tobias
Published: March 2004

Bi and BiIII halides comproportionate to form subvalent cationic Bi clusters of various size and shape that can be stabilized in the solid state in the presence of suitable complex ions. Transition metal chlorides and bromides of group 4 elements lead to compounds of the Bi(Bi9)[MX6]3 family, of which all members with M = Zr, Hf; X = Cl, Br are known. At 550 K Bi, BiCl3 and NbCl5, surprisingly, yield the isotypic Bi+(Bi95+)([NbCl6]2−)3 containing NbIV formed by reduction of NbV. The crystal structure [hexagonal; P63/m; a = 1377.1(2), c = 1065.5(2) pm; Z = 2] contains Bi95+ clusters, octahedral [NbCl6]2− and disordered Bi+ ions. The low, temperature‐dependent paramagnetic moment (76 K: 0.99 B.M.; 295 K: 1.22 B.M.) confirms the reduction of Nb to the +IV state. Bi8[Ta2O2Br7]2, formed by a trace of H2O in a reaction of Bi, BiBr3 and TaBr5 at 570 K, adopts a new structure type [tetragonal; P4/mnc; a = 1448.0(1), c = 1830.6(2) pm; Z = 4] and consists of square‐antiprismatic Bi82+ clusters and onedimensional polymeric bromooxotantalate(V) anions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
New Nitrosylrhenium Hydrides as Precursors of “Diazo” Complexes: Preparation of Hydrazine and Diazene Derivatives
Authors: Albertin Gabriele , Antoniutti Stefano , Bacchi Alessia , Fregolent Barbara , Pelizzi Giancarlo
Published: March 2004

The reaction of [ReCl2(OCH3)(NO)(PPh3)2] with phosphane in the presence of NaBH4 gives different dihydride [ReH2(NO){PPh2(OEt)}3] (1) and alkoxy‐hydride [ReH(OR1)(NO)P3] (2, 3) [R1 = CH3, C2H5; P = PPh(OEt)2, P(OEt)3] derivatives depending on the nature of the phosphane and the solvent used. The protonation reactions of the new hydrides with Brønsted acid were performed and led to thermally unstable [Re(OR1)(η2‐H2)(NO)P3]+ (2*, 3*) dihydrogen cations. Hydrazine complexes [ReH(RNHNH2)(NO){PPh2(OEt)}3]BPh4 (4) (R = H, CH3,C6H5) and [Re(OR1)(RNHNH2)(NO)P3]BPh4 (5, 6) [R1 = CH3, C2H5; R = H, CH3,C6H5; P = PPh(OEt)2] were prepared by allowing the hydrides [ReH2(NO)P3] and [ReH(OR1)(NO)P3] to react first with triflic acid and then with hydrazine. The complexes were characterized spectroscopically and by the X‐ray crystal structure determination of [Re(OC2H5)(NH2NH2)(NO){PPh(OEt)2}3]BPh4 (5a). Oxidation of the hydrazine complexes 4−6 was studied with Pb(OAc)4 at −30 °C and, depending on the nature of the hydrazine and the stoichiometry of the complexes, led to aryldiazene [ReH(C6H5N=NH)(NO){PPh2(OEt)}3]BPh4 (7c), [Re(OC2H5)(C6H5N=NH)(NO){PPh(OEt)2}3]BPh4 (8c), methyldiazene [ReH(CH3N=NH)(NO){PPh2(OEt)}3]BPh4 (7b) and a mixture of methyldiazene [Re(OCH3)(CH3N=NH)(NO){PPh2(OEt)}3]BPh4 (9b) and methyleneimine [Re(OCH3)(η1‐NH=CH2)(NO){PPh2(OEt)}3]BPh4 (9*b) derivatives. Mono‐ and binuclear aryldiazene complexes [ReH(ArN=NH)(NO){PPh2(OEt)}3]BPh4 (10), [{ReH(NO)[PPh2(OEt)]3}2(µ‐HN=NAr−ArN=NH)](BPh4)2 (11), [Re(OR1)(ArN=NH)(NO)P3]BPh4 (12, 14, 16) and [{Re(OR1)(NO)P3}2(µ‐HN=NAr−ArN=NH)](BPh4)2 (13, 15) [R1 = CH3, C2H5; P = PPh(OEt)2, P(OEt)3; Ar = C6H5, 4‐CH3C6H4; Ar‐Ar = 4,4′‐C6H4‐C6H4] were also prepared by allowing hydrides [ReH2(NO)[PPh2(OEt)}3] and [ReH(OR1)(NO)P3] to react with mono‐ and bis‐aryldiazonium cations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Structural Studies of Two New Base Adducts of Bis(2,4‐pentanedionato)cobalt(II)
Authors: Tanase Stefania , Bouwman Elisabeth , Reedijk Jan , Driessen Willem L. , Ferbinteanu Marilena , Huber Martina , Mills Allison M. , Spek Anthony L.
Published: March 2004

The syntheses, spectroscopic properties and crystal structures of two new base adducts of bis(2,4‐pentanedionato)cobalt(II) with 3,5‐dimethylpyrazole (Hdmpz) (1) and dimethylethanolamine (Hdmea) (2) are described. The crystal structures of both compounds contain monomeric CoIIcomplexes withcis‐distorted octahedral environments, even for the monodentate Hdmpz ligand which is quite unique. These mononuclear complexes are linked by hydrogen bonds between the anionic 2,4‐pentanedionato groups and the neutral Hdmpz or Hdmea ligands. The low‐temperature polycrystalline‐powder EPR spectra display unresolved metal hyperfine coupling. Thegvalues are anisotropic in both cases; the anisotropy is larger for the Hdmea adduct. Interesting insights into the coordination effects were gained with the help of electron‐density descriptors (Laplacian of density and Natural Bond Orbitals). This revealed a slight deviation of the coordinating lone pairs of the pentanedionato ligands from the Co−O axis, as well as a nonstandard hybrid composition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Fluidity in the self‐concept: the shift from personal to social identity
Authors: Onorato Rina S. , Turner John C.
Published: March 2004

Dominant personality models of the self‐concept (e.g. self‐schema theory) conceive of the self as a relatively stable cognitive representation or schema. The self‐schema controls how we process self‐relevant information across a myriad of situations. Conversely, self‐categorization theory argues that self‐perception is highly variable and context‐dependent. It was hypothesized in two studies (N=114 and 200) that the effect of personal self‐schemas on information‐processing would be eliminated when the context makes a conflicting higher‐order identity salient. Results largely supported self‐categorization theory. Across various dependent measures (trait endorsements, response latencies, and confidence in self‐descriptions), participants generally responded in line with the salient identity, even if this pattern of responding directly contradicted their personal self‐schema. Implications for dominant personality models of the self‐concept are examined. Copyright © 2004 John Wiley & Sons, Ltd.
Inclusiveness of identification among farmers in The Netherlands and Galicia (Spain)
Authors: Klandermans Bert , Sabucedo Jose Manuel , Rodriguez Mauro
Published: March 2004

In this paper we discuss inclusiveness of identification among farmers in Galicia (Spain) and The Netherlands. Identification with three nested categories—farmers in the local community, farmers in the country, and farmers in Europe was assessed among 167 Dutch and 248 Galician farmers at three points in time: winter of 1993/94, winter 1995 and fall 1995. Our findings suggest that inclusiveness reduces the level of identification. However, the observed patterns of identification were more complex than inclusiveness per se can account for. Borrowing from the common ingroup‐identity model, functional and socialization models of identity formation, and a model of politicized collective identity we formulated hypotheses about patterns of identification that were to be expected. On the whole our findings supported our theoretical reasoning. Galician farmers appear to identify much less with farmers in their country and Europe than Dutch farmers do. Inclusiveness of identification appears to be linked to experience with national and supranational political institutions. More political knowledge and involvement appear to generate more inclusive patterns of identification. Among Galician farmers evaluation of the agricultural policy of the European Union is negatively related to identification with farmers in Europe, among Dutch farmers the two are positively related. Finally, more inclusive identities seem to be more politicized. Copyright © 2004 John Wiley & Sons, Ltd.
Group membership and everyday social comparison experiences
Authors: Smith Heather J. , Leach Colin W.
Published: March 2004

In two everyday experience studies, we examined the degree to which everyday social comparisons are framed by group membership. In the first study, 30 undergraduates attending a public university in the United States completed short questionnaires about their social comparison experiences whenever they were signalled. In the second study, 34 ethnic minority undergraduates from the same university completed similar questionnaires about their social comparison experiences. Across both studies, comparisons in which participants viewed themselves as an ingroup member in comparison to an outgroup comprised less than 10% of the comparison experiences reported by participants. However, minorities in the second study who reported closer identification with their ethnic group reported more comparison experiences in which they mentioned their own or the comparison target's ethnicity. Copyright © 2004 John Wiley & Sons, Ltd.
Getting ready for the bad times: self‐esteem and anticipatory coping
Authors: Newby‐Clark Ian R.
Published: March 2004

When we cannot alter the characteristics of an aversive event, we are still able to prepare ourselves for what is to come. In other words, we can engage in ‘anticipatory coping.’ Known self‐esteem differences in self‐regulation led to the prediction that low self‐esteem (LSE) individuals would evidence different anticipatory coping patterns than high self‐esteem (HSE) people. HSE and LSE participants were faced with either a low or high probability of engaging in a painful task. They were told about, and given the opportunity to engage in, a preparatory strategy aimed at minimizing discomfort during the painful task. Those participants in the low probability condition prepared for the painful task less than did those participants in the high probability condition. As hypothesized, the effect of probability condition was more pronounced for HSE, compared to LSE, participants. Also, in the low probability condition, there was a trend towards LSE participants preparing more than HSE participants. Copyright © 2004 John Wiley & Sons, Ltd.
What is smart in a social dilemma? differential effects of priming competence on cooperation
Authors: Utz Sonja , Ouwerkerk Jaap W. , Van Lange Paul A. M.
Published: March 2004

Prior theorizing of rationality in social dilemmas suggests that individuals pursuing different interaction goals may ‘perceive’ different associations between competence and behaviour in a social dilemma, arguing that competitive individuals associate competence with noncooperation (i.e. noncooperation=smart), whereas prosocial individuals associate competence with cooperation (i.e. cooperation=smart; goal‐prescribes‐rationality principle, Van Lange & Kuhlman, 1994). The present research examines whether cooperative interaction can be affected by subtle activation (or priming) of competence, and whether the effects may differ for competitive versus prosocial participants. Consistent with hypotheses, two experiments revealed that priming competence yielded reduced levels of cooperation (and greater exploitation) among competitors, and yielded no effects (Experiment 1) or a tendency towards enhanced cooperation (Experiment 2) among prosocials. The discussion considers theoretical implications of relatively subtle influences on cooperative interaction in social dilemmas. Copyright © 2004 John Wiley & Sons, Ltd.
When procedural fairness does not influence how positive I feel: the effects of voice and leader selection as a function of belongingness need
Authors: De Cremer David , Alberts Hugo J. E. M.
Published: March 2004

The present research examined the effect of receiving voice or not on positive affect as a function of how the enacting authority was selected and the extent to which people experienced strong belongingness needs. Participants were asked to generate ideas with respect to an electronic portfolio. Their opinions were then evaluated by a group leader who was either appointed by the experimenter, elected by the group and who reflected the participant's own choice, or elected by the group but who did not reflect the participant's own choice. This group leader then gave participants the opportunity to voice their ideas or not. Participants reported positive affect did not vary as a function of receiving voice or not when the enacting leader was elected and did not reflect the participant's own choice. The voice effect on positive affect did, however, appear in the other two leadership selection conditions. Further, this pattern was found only among those with a strong need to belong. Copyright © 2004 John Wiley & Sons, Ltd.
Controlling the healthy worker effect in the presence of an intermediate variable
Authors: Kim Jinheum , Nam Chung Mo , Kang Dae Ryong
Published: April 2004

The healthy worker effect is an important issue in occupational epidemiology. We propose a new statistical method to test the relationship between exposure and time to death in the presence of the healthy worker effect. The basic idea of the proposed method reflects length bias sampling caused by job changes. According to simulation studies, both the proposed test and a test based on the Cox model including job changes as a time‐dependent covariate seem to be satisfactory at the upper 5% significance level. However, the Cox models involving job changes as a time‐independent covariate are unsatisfactory. The proposed test is superior in power to the test based on the Cox model with time‐dependent employment status. Copyright © 2004 John Wiley & Sons, Ltd.
VOC emission fluxes as a function of lateral distance from the source
Authors: Lowell Philip S. , Eklund Bart
Published: March 2004

There has been a great deal of recent interest in evaluating the potential for vapor transport from subsurface contamination into nearby buildings. There does not exist, however, any method for calculating whether buildings that are not directly over the source of contamination may be impacted. For simplicity, typical modeling approaches for estimating vapor migration through soil into buildings assume that the contaminated plume or soil lies directly underneath the building. The models do not take into account the lateral distance, if any, between the source of VOC emissions and the indoor space. This paper presents an approach to calculate diffusion‐limited emission fluxes as a function of lateral distance and evaluates the significance of these emissions over relatively short lateral distances from the source. A theoretical, mathematical approach was used. The results show that soil‐gas concentration and emission flux are both a decreasing exponential function of the lateral distance from the edge of the contaminant plume. Based on our calculations, the emission flux and the soil‐gas concentration are insignificant within a relatively short lateral distance from the source (e.g., 30 m). © 2004 American Institute of Chemical Engineers Environ Prog, 23: 52–58, 2004
Essential oil of Marrubium cuneatum Russell and its secretory elements
Authors: Baher Nik Z. , Mirza M. , Shahmir F.
Published: April 2004

The structure of the glandular trichomes and essential oil of the aerial parts of Marrubium cuneatum Russell were studied. Most secretory tissues are located in glandular trichomes. The essential oil isolated by steam distillation were analysed by GC–MS. Among 25 compounds identiﬁed, representing about 89% of the oil, the major components were bicyclogermacrene (37.9%) and germacrene D (24.1%). Copyright © 2004 John Wiley & Sons, Ltd.
Von Wahrheit, Würde und Versöhnung
Authors: Wüstenberg Ralf K.
Published: March 2004

An welche Bedingungen ist politische Versöhnung geknüpft? Eine theologische Studie zeigt, dass das Aufarbeiten der Vergangenheit zwischen Opfern und Tätern immer das bewusste Überwinden von Schuld voraussetzt
Das Fagott und die Strömungsmechanik
Authors: Grundmann Roger
Published: March 2004

Weil der Reibungswiderstand beträchtlich reduziert wird, muss der Fagottspieler weniger kräftig blasen: eine Optimierung des „S‐Bogens”︁ am Mundstück des Instruments macht es möglich
Die Mundwerkzeuge der Sporenfresser
Authors: Betz Oliver
Published: March 2004

Das Erforschen der Mundwerkzeuge von Insekten ist für den Biologen aufschlussreich. Das komplexe Wechselspiel zwischen Nahrungsvorlieben und körperlichen Strukturen gibt Aufschluss über den Prozess der Evolution
Wenn sich die Feldlerche vom Acker macht
Authors: Mückschel Claus , Frede Hans Georg , Köhler Wolfgang , Kuhlmann Friedrich , Otte Annette , Wolters Volkmar
Published: March 2004

Die moderne Landwirtschaft schadet der Tier‐ und Pflanzenwelt, indem sie deren Artenvielfalt in Gefahr bringt. Neue computergestützte Modelle helfen, eine Landnutzung zu entwerfen, die sowohl den Bedürfnissen des Menschen als auch dem Bewahren des natürlichen Ökosystems dient
Die Welt der Lebenden und die Welt der Toten
Authors: Pfälzner Peter
Published: March 2004

Das erste ungeplünderte Königsgrab Syriens entdeckten Archäologen bei Ausgrabungen der Palastanlage von Qatna. Die Grabkammern erlauben neuartige Einblicke in Ahnenkult und Bestattungspraktiken des alten Orient
Familial platelet disorder with propensity to acute myelogenous leukemia: Genetic heterogeneity and progression to leukemia via acquisition of clonal chromosome anomalies
Authors: Minelli Antonella , Maserati Emanuela , Rossi Gabriele , Bernardo Maria Ester , De Stefano Piero , Cecchini Maria Paola , Valli Roberto , Albano Veronica , Pierani Paolo , Leszl Anna , Sainati Laura , Lo Curto Francesco , Danesino Cesare , Locatelli Franco , Pasquali Francesco
Published: March 2004

Familial platelet disorder with propensity to acute myelogenous leukemia, or FPD/AML (OMIM #601399), is a rare autosomal dominant condition, with only 12 families reported. It is characterized by qualitative and quantitative platelet defects and predisposition to the development of myeloid malignancies. Causal mutations have been identified in the RUNX1 gene (also known as AML1, CBFA2) in the 11 families so far analyzed. RUNX1 is a gene frequently involved in the pathogenesis of sporadic leukemia and myelodysplastic syndromes, through acquired chromosome rearrangements and point mutations. We report an Italian family with three members affected with FPD/AML, two sibs and their father, who developed myelodysplastic syndromes (which in one subsequently evolved into AML). Direct sequencing and polymorphisms haplotype analysis of the region of chromosome 21 where RUNX1 is mapped demonstrated that FPD/AML in this family was not caused by any mutation of the RUNX1 gene, thus providing evidence for the genetic heterogeneity of this disorder. Cytogenetic studies showed monosomy 7 in the marrow of all the three affected subjects, as well as an independent clone with trisomy 8 in the father. The importance of mutator effects in the pathogenesis of familial myeloid malignancies characterized by relevant chromosome changes, in the presence or absence of an underlying Mendelian disorder, has already been suggested. Our results and a review of the cytogenetic literature led us to postulate that mutations also causing FPD/AML may have a mutator effect that could give origin to myelodysplastic syndromes and acute myeloid leukemias through acquired chromosome changes. © 2004 Wiley‐Liss, Inc.
A model for karyotypic evolution in testicular germ cell tumors
Authors: Frigyesi Attila , Gisselsson David , Hansen Gunnar B. , Soller Maria , Mitelman Felix , Höglund Mattias
Published: March 2004

Testicular germ cell tumor karyotypes are characterized by near‐triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole‐chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner. © 2004 Wiley‐Liss, Inc.
EEG‐fMRI of focal epileptic spikes: Analysis with multiple haemodynamic functions and comparison with gadolinium‐enhanced MR angiograms
Authors: Bagshaw Andrew P. , Aghakhani Yahya , Bénar Christian‐G. , Kobayashi Eliane , Hawco Colin , Dubeau François , Pike G. Bruce , Gotman Jean
Published: March 2004

Combined EEG‐fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG‐fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium‐enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co‐registration of statistical maps with gadolinium‐enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs. Hum. Brain Mapp. 22:179–192, 2004. © 2004 Wiley‐Liss, Inc.
Postsynaptic injection of calcium‐independent phospholipase A2 inhibitors selectively increases AMPA receptor‐mediated synaptic transmission
Authors: St‐Gelais Fannie , Ménard Caroline , Congar Patrice , Trudeau Louis‐Eric , Massicotte Guy
Published: April 2004

The calcium‐independent form of phospholipase A2 (iPLA2), an enzyme known to generate arachidonic acid (AA), was recently identified as the predominant constitutive phospholipase in the hippocampus. The present study shows that the iPLA2 inhibitor bromoenol lactone, when introduced into hippocampal CA1 pyramidal cells through a patch pipette, generated a dose‐dependent increase in the amplitude of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor‐mediated excitatory postsynaptic currents (EPSCs). The iPLA2 inhibitor by itself interfered with neither paired pulse facilitation nor N‐methyl‐D‐aspartate (NMDA) receptor‐mediated EPSCs, suggesting that its influence on synaptic transmission is postsynaptic in origin and specific to the AMPA subtype of glutamate receptors. Comparable results were obtained with palmitoyl trifluoromethyl ketone, a second structurally distinct iPLA2 inhibitor. The ability of iPLA2 inhibitors to increase AMPA receptor‐mediated currents was also reproduced by MK‐866, an inhibitor recognized to interfere with the generation of 5‐lipoxygenase by‐products of AA. At the biochemical level, we found that AMPA, but not NMDA glutamate receptor subunits, were upregulated in rat brain sections pre‐incubated with the iPLA2 inhibitors. Collectively, these results provide the first experimental evidence that constitutive iPLA2 and/or its metabolites play an important role in the postsynaptic modulation of neurotransmission in CA1 pyramidal cells of the hippocampus. © 2004 Wiley‐Liss, Inc.
Role of hepatitis C virus infection in malignant lymphoma in Spain
Authors: de Sanjose Silvia , Nieters Alexandra , Goedert James J. , Domingo‐Domenech Eva , Fernandez de Sevilla Alberto , Bosch Ramon , Herrera Pilar , Domingo Alicia , Petit Jose , Bosch Xavier , Kallinowski Birgit
Published: March 2004

Hepatitis C virus (HCV) has been implicated in the etiology of malignant lymphomas. We estimated the risk of lymphoma associated with detection of HCV infection. Cases (n = 529) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in 4 centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (n = 600) were hospitalized patients matched to the cases by 5‐year age group, gender and study center. Several medical conditions associated with severe immunosuppression precluded the eligibility of controls. Patients underwent a personal interview and blood sampling. HCV positive subjects were considered those with antibody response to third generation ELISA or detection of HCV RNA with Amplicor 2.0. Cases were systematically tested for HIV antibodies. We used the χ2 test and unconditional logistic regression to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for lymphoma associated with HCV. HCV infection was detected in 40 cases (7.5%) and 23 (3.8%) control subjects. Six of 16 patients with HIV‐related lymphomas and 4 of 8 organ‐recipient‐related lymphomas were HCV positive. The analysis, excluding HIV‐infected subjects and organ recipients, led to a prevalence of HCV of 5.9% among cases and 3.8% among controls. The age‐, gender‐ and center‐adjusted OR for all lymphomas was 1.58 (95% CI = 0.89–2.79). Among all lymphoma categories, HCV was associated with an increased risk of low grade B‐cell lymphomas not otherwise specified (NOS) (OR = 35.98, 95% CI = 4.70–275.4). A 2‐fold excess risk associated to HCV was observed for marginal B‐cell lymphomas, diffuse large B‐cell lymphoma and lymphoma B NOS but the associations were not statistically significant. HCV infection is associated with an increased risk of a broad spectrum of lymphoid neoplasms among non severely immunocompromised subjects in Spain. © 2004 Wiley‐Liss, Inc.
Hepatitis C virus infection and non‐hodgkin lymphoma: Results of the NCI‐seer multi‐center case‐control study
Authors: Engels Eric A. , Chatterjee Nilanjan , Cerhan James R. , Davis Scott , Cozen Wendy , Severson Richard K. , Whitby Denise , Colt Joanne S. , Hartge Patricia
Published: March 2004

Several studies have noted elevated hepatitis C virus (HCV) prevalence among patients with non‐Hodgkin lymphoma (NHL), suggesting that HCV infection increases NHL risk through chronic immune stimulation. Population‐based data from the U.S. are lacking. In a population‐based case‐control study of NHL in the United States, we identified HCV infection using an enzyme immunoassay, confirmed by recombinant immunoblot assay or HCV RNA detection. The association between HCV and NHL was assessed using logistic regression, adjusting for demographic factors, illicit drug use or medical history. Thirty‐two of 813 (3.9%) NHL cases and 14 of 684 (2.1%) controls were HCV‐infected [odds ratio (OR) 1.96, 95%CI 1.07–4.03]. For separate NHL subtypes, numbers were limited. Nonetheless, positive associations were noted for follicular (OR 2.46, 95%CI 1.01–5.81), marginal zone (3.99, 0–13.6) and mucosa‐associated lymphoid tissue (2.04, 0–7.20) NHLs. For all NHLs combined, the HCV‐NHL association changed little after adjustment for sex, age, race and study center (OR 1.89, 95%CI 1.00–4.00). HCV was common in controls who had injected drugs (40%) or used other illicit drugs (6.5%), but adjustment for drug use did not affect the HCV‐NHL association (OR 1.87, 95%CI 0.95–4.10). Transfusion history was unrelated to HCV status, and adjustment for this exposure did not attenuate the HCV‐NHL association (OR 2.15, 95%CI 1.12–4.76). Excluding 4 subjects with a history of hemodialysis or 3 subjects with organ transplants also did not affect the results. Our study demonstrates an association between HCV infection and NHL in the United States. HCV infection may be a cause of NHL. © 2004 Wiley‐Liss, Inc.
Correlation of hMLH1 and HPP1 hypermethylation in gastric, but not in esophageal and cardiac adenocarcinoma
Authors: Geddert Helene , Kiel Sibylle , Iskender Erol , Florl Andrea R. , Krieg Thomas , Vossen Sandra , Gabbert Helmut E. , Sarbia Mario
Published: March 2004

Using methylation‐specific real‐time PCR, we determined the prevalence of aberrant methylation in the mismatch repair gene hMLH1 and in the recently described HPP1 gene among 50 esophageal, 50 cardiac and 50 gastric ADCs. Additionally, expression of hMLH1 protein was detected immunohistochemically and correlated with DNA MSI. Hypermethylation of hMLH1 was found in 14% of esophageal, 28% of cardiac and 32% of gastric ADCs, whereas HPP1 hypermethylation was found more frequently in the 3 tumor types (64% vs. 38% vs. 54%). In gastric ADC, HPP1 hypermethylation was found more frequently in tumors with concomitant hMLH1 hypermethylation (81%) than in those without hMLH1 hypermethylation (41%, p = 0.008). Complete loss of hMLH1 protein expression, which was present in 10 carcinomas (5 cardiac and 5 gastric), was invariably correlated with hMLH1 hypermethylation and MSI. In conclusion, our data indicate that MSI and loss of the mismatch repair protein hMLH1, which is mainly caused by hMLH1 gene hypermethylation, are more prevalent in stomach and cardia carcinogenesis than in that of the esophagus. Moreover, in gastric cancer, hMLH1 hypermethylation is correlated with hypermethylation of the HPP1 gene. © 2004 Wiley‐Liss, Inc.
Attenuation by cyclic phosphatidic acid of peritoneal metastasis of azoxymethane‐induced intestinal cancers in Wistar rats
Authors: Ishihara Ryu , Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Uedo Noriya , Higashino Koji , Mukai Mutsuko , Ishiguro Shingo , Kobayashi Susumu , Murakami‐Murofushi Kimiko
Published: March 2004

The effect of cyclic phosphatidic acid, a unique analogue of lysophosphatidic acid, on the induction of bombesin‐enhanced peritoneal metastases from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. Rats were given 10 weekly injections of azoxymethane (7.4 mg/kg body weight, s.c.) and of bombesin (40 μg/kg body weight, s.c.) every other day from the start of the experiment, and from week 16, they received injections of cyclic phosphatidic acid (3 or 6 mg/kg body weight, s.c.) every other day until the end of the experiment in week 45. Cyclic phosphatidic acid at both dosages significantly decreased the incidence of bombesin‐enhanced cancer metastases to the peritoneum but had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Cyclic phosphatidic acid at either dose decreased significantly the incidence of lymphatic vessel invasion of adenocarcinomas and the activity of RhoA protein in the tumors, both of which were enhanced by bombesin. Our findings indicate that cyclic phosphatidic acid inhibits cancer metastasis through inhibition of RhoA protein activation. © 2004 Wiley‐Liss, Inc.
Glutathione S‐transferase T1 null‐genotype is associated with an increased risk of lung cancer
Authors: Sørensen Mette , Autrup Herman , Tjønneland Anne , Overvad Kim , Raaschou‐Nielsen Ole
Published: March 2004

Glutathione S‐transferases (GSTs) are involved in detoxification of carcinogens, e.g., from tobacco smoke. Therefore, polymorphisms in the GST genes have been considered as potential modifiers of individual cancer risk. In a population‐based case‐cohort study where cases and the subcohort sample were matched on duration of smoking, we investigated the occurrence of lung cancer and histological subtypes of lung cancer in relation to deletion polymorphism in both GSTM1 and GSTT1, single nucleotide polymorphisms (SNPs) in GSTP1 (Ile105Val and Ala114Val) and a 3 base pair deletion polymorphism in GSTM3. We further investigated the effects of the GST polymorphisms on lung cancer risk within subgroups of subjects defined by gender and age. The results showed a 2.4‐fold (CI = 1.31–4.41) increased risk of lung cancer in GSTT1 null‐genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1‐105 or GSTP1‐114. The association was strongest in lower age groups, with a 9.6‐fold increase in risk for subjects with the GSTT1 null‐genotype in the 50–55 years age interval (CI = 3.03–30.59). Positive associations were found for GSTT1 within all major histological subtypes. Squamous cell carcinoma was the histological type most strongly associated with the GSTT1 genotype, with a 5.0‐fold (CI = 2.26–11.18) increase in risk for subjects carrying the GSTT1 null‐genotype. The effects of the GSTT1 null‐genotype seemed stronger in the presence of the GSTM1 null‐genotype or the GSTP1‐105 variant allele. These results suggest that the GSTT1 null‐genotype is associated with an increased risk of lung cancer, especially in younger individuals. © 2004 Wiley‐Liss, Inc.
Comparison of K‐ras point mutation distributions in intraductal papillary‐mucinous tumors and ductal adenocarcinoma of the pancreas
Authors: Kitago Minoru , Ueda Masakazu , Aiura Koichi , Suzuki Keiichi , Hoshimoto Sojun , Takahashi Shin , Mukai Makio , Kitajima Masaki
Published: March 2004

Intraductal papillary‐mucinous tumors (IPMT) consist of cells with varying histologic degrees of severity and exhibit multiple tumor loci; however, whether or not these lesions exhibit the same genetic changes has not been clarified. To investigate this point, we analyzed K‐ras mutations in multiple IPMT lesions from each patient enrolled in our study and compared our findings to those for patients with ductal adenocarcinoma of the pancreas (DC). Twenty IPMT specimens and 7 DC specimens were resected, microdissected and analyzed for the presence of K‐ras mutations. The mutated genes were then sequenced using a genetic analyzer. K‐ras mutations were observed in 80% of IPMT and 100% of DC patients. More than 2 types of K‐ras mutation were observed in the main tumors of 43.8% of IPMT and 0% of DC patients. K‐ras mutations in peritumoral and separated lesions were observed in 66.7% and 62.5% of IPMT patients, respectively. At least one identical mutation between the main tumor and the peritumoral or separated lesions was recognized in all of the IPMT patients with those lesions. Different mutations from those in the main tumor were observed in 40% of IPMT patients with separated lesions. The survival curve of IPMT‐carcinoma patients with more than 2 types of K‐ras mutation in the main tumor was better than that with one type of K‐ras mutation. IPMT patients exhibit a remarkably genetic heterogeneity in main tumor and have good prognosis. © 2004 Wiley‐Liss, Inc.
A prospective study of dietary lactose and ovarian cancer
Authors: Fairfield Kathleen M. , Hunter David J. , Colditz Graham A. , Fuchs Charles S. , Cramer Daniel W. , Speizer Frank E. , Willett Walter C. , Hankinson Susan E.
Published: March 2004

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow‐up (1980–1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m2), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98–2.01). We observed a 2‐fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27–3.40). For each 11‐gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04–1.39). Skim and low‐fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low‐fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97–1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12–2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study. © 2004 Wiley‐Liss, Inc.
Thalidomide reduces serum C‐reactive protein and interleukin‐6 and induces response to IL‐2 in a fraction of metastatic renal cell cancer patients who failed IL‐2‐based therapy
Authors: Kedar Igal , Mermershtain Wilmosh , Ivgi Hefziba
Published: March 2004

Interleukin‐2 (IL‐2) has some antitumor activity in patients with renal cell carcinoma. It has been noted that response to IL‐2 and prognosis may be adversely affected by elevated serum levels of C‐reactive protein (CRP) or interleukin‐6 (IL‐6). We used thalidomide to treat patients with cancer‐induced cachexia and noted that the drug significantly reduced serum levels of CRP and IL‐6 to normal or near normal levels in a substantial fraction of patients. We tested whether thalidomide might potentiate the response of patients with renal cell carcinoma to IL‐2. Four patients with metastatic renal cell carcinoma and high serum levels of CRP and IL‐6 who had experienced disease progression on IL‐2 were retreated with the same IL‐2 regimen combined with thalidomide 300 mg p.o. daily. Two patients achieved good partial responses and 2 patients had prolonged disease stabilization with the combination of IL‐2 plus thalidomide. The regimen was well tolerated without increased IL‐2‐associated toxicity. Reduction of serum CRP or IL‐6 levels with thalidomide may enhance the responsiveness of renal cell carcinoma to IL‐2. A Phase II study of the combination is in order. It is possible that the thalidomide‐induced normalization of serum acute phase proteins might improve the response of other types of malignancy to IL‐2 or other immune‐based therapies. © 2004 Wiley‐Liss, Inc.