bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarized Production of T-Helper Cell Type 1 Cells in Peyer’s Patches in Crohn’s Disease
Authors: Kudo Takahiro , Nagata Satoru , Aoyagi Yo , Suzuki Ryuyo , Matsuda Hironori , Ohtsuka Yoshikazu , Shimizu Toshiaki , Okumura Ko , Yamashiro Yuichiro
Published: December 2004

Background/Aims: Although Peyer’s patches (PPs) serve as important antigen-sampling sites for the immune system, surprisingly little attention has been paid to their associations with the onset of Crohn’s disease (CD) as antigen entry sites. To examine the immunological events in PPs, we performed functional and phenotypical studies on PP cells, the lamina propria cells in the colonic mucosa and peripheral blood mononuclear cells (PBMC) in inflammatory bowel disease. Patients: The subjects were 9 children and adolescents with active CD, 9 with inactive CD, 11 with active ulcerative colitis (UC), and 22 normal controls. Methods: The cytokine profile in PPs and lamina propria was performed through Elispot assay and RT-PCR. PP mononuclear cells and PBMC from the subjects were analyzed by flow cytometry using monoclonal antibodies to interferon-γ and interleukin-4, and CC chemokine receptors (CCR) 4 and 5. Results: Th1 together with Tc1 cells were dominant in PPs in the active phase of CD, but not in inactive CD, UC, or normal controls. They did not actually produce interferon-γ, however they have abundant mRNA of the cytokine. Substantial levels of CCR5 ligands, MIP-1α and RANTES mRNA were found in the inflamed intestinal mucosa in CD. Conclusions: It is conceivable that PPs in the terminal ileum in CD may initially sample luminal antigens where Th1-type memory cells are activated which migrate to the peripheral intestinal mucosa. Those immunological changes may not be related to the etiology of UC.
Endoscopic Prediction of Hepatocellular Carcinoma by Evaluation of Bleeding Esophageal Varices
Authors: Nakayama Hisashi , Masuda Hideki , Miyake Hiroshi , Takayama Tadatoshi , Yokoyama Eise
Published: December 2004

Background: Prognostic indicators for patients with liver cirrhosis accompanied by esophageal varices are hemorrhage of the varices and development of hepatocellular carcinoma (HCC). Although predictors for HCC have been reported, few studies have investigated the correlation between carcinoma development and endoscopic findings of bleeding varices. We examined whether endoscopic variceal findings such as form (F factor), color (C factor) and red color sign (RC factor) predict development of HCC. Methods: This study included 124 patients with liver cirrhosis who received treatment for bleeding esophageal varices. Patients were followed up with blood chemistries including α-fetoprotein and by abdominal ultrasonography and computed tomography. The primary outcome measure of this study was the cumulative incidence of HCC after the treatment for esophageal varices. The secondary measure was whether endoscopic factors predicted the HCC development, and if so, which factors. Results: During follow-up, 32 of the 124 patients developed HCC. The cumulative carcinogenic rate after 3, 5 and 10 years was 11.8, 25.8 and 37.8%, respectively. Among the 32 patients who developed HCC, 29 (90.6%) had large esophageal varices (large F factor) prior to treatment of the varices. As the F factor increased, the percentage of patients who developed HCC also increased. In particular, independent predictors for HCC were: history of blood transfusion (p = 0.037), presence of hepatitis C virus antibody (p = 0.005), platelet count <7.5 × 104/ml (p = 0.004), α-fetoprotein level >10 ng/ml (p = 0.030), and large F factor (F3) (p = 0.002). Variceal RC and C factors were not independent predictors for carcinogenesis. Conclusion: The endoscopic F factor rating of bleeding esophageal varices can be a significant predictive factor for HCC in patients with liver cirrhosis.
Female Preponderance in Congenital Adrenal Hyperplasia due to CYP21 Deficiency in England: Implications for Neonatal Screening
Authors: Nordenström A. , Ahmed S. , Jones J. , Coleman M. , Price D.A. , Clayton P.E. , Hall C.M.
Published: December 2004

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (CYP21) deficiency causes symptoms ranging from life-threatening neonatal adrenal crises to minimal virilization in adulthood. The relationship between CYP21 genotype and phenotypic markers in a non-screened population of 73 CAH children (44 female, 29 male; 54 white, 19 Asian) treated at the Royal Manchester Children’s Hospital was investigated and ethnic and sex differences assessed. The patients were categorized according to the mutation on the mildest allele. The age at the time of diagnosis differed significantly between the groups (p = 0.02): all 25 Null and 25 of 26 of the I2 splice patients were diagnosed during the neonatal period, whereas 7 of 11 I172N patients were diagnosed late. Degree of female genital virilization, 17-hydroxyprogesterone level at diagnosis, and fludrocortisone requirement during the 1st year of treatment correlated with the genotype, although Asian Null patients required more fludrocortisone than their white counterparts (p = 0.055). There was an equal sex ratio in both the I2 splice (12 female/14 male) and I172N (5 female/6 male) groups. However, in the Null group, the ratio was 4.0 (20 female/5 male; p = 0.003), suggesting that some Null male infants perish before being clinically detected to have CYP21 deficiency. Our findings strongly support the need for implementation of a neonatal screening programme for CAH in the UK which may reduce the male infant mortality.
A Cell-Based Multifactorial Approach to Angiogenesis
Authors: Hasson Eilat , Arbel Dan , Verstandig Anthony , Shimoni Yael , Mitrani Eduardo
Published: December 2004

We here propose an alternative cell therapy approach to induce angiogenesis. We prepared small organ fragments whose geometry allows preservation of the natural epithelial/mesenchymal interactions and ensures appropriate diffusion of nutrients and gases to all cells. Fragments derived from lung are shown to behave as fairly independent units, to undergo a marked upregulation of angiogenic factors and to continue to function for several weeks in vitro in serum-free media. When implanted into hosts, they transcribe a similar array of angiogenic factors that specifically induce the formation of a potent vascular network. The angiogenic induction capacity of these fragments was also tested in a mouse and rat model of limb ischemia. We report that such fragments, when implanted in the vicinity of the ischaemic area, induce an angiogenic response which can rescue the ischaemia-induced damage. The approach presented differs from single factor application, gene therapy and other cell therapy methods in that it exploits the complex behaviour of autologous cells in their near to normal environment in order to achieve secretion of a whole range of angiogenic stimuli continuously and in an apparently coordinated fashion.
A Single Chinese Center Investigation of Renal Artery Stenosis in 141 Consecutive Cases with Coronary Angiography
Authors: Liu Bi-Cheng , Tang Ri-Ning , Feng Yi , Wang Yan-Li , Yin Lian-Fang , Ma Gen-Shan
Published: December 2004

Background: There is an increasing prevalence of ischemic nephropathy in the aging population of the world. However, the exact incidence of ischemic nephropathy in the Chinese population is still uncertain. The present study investigated the incidence of renal artery stenosis (RAS) in patients with suspected coronary artery disease (CAD) using renal angiography. Methods: Renal angiography was performed immediately after coronary artery angiography in 141 patients with suspected CAD, including 59 males and 82 females whose mean ages were 59 ± 10 years. Comorbidities included hypertension (n = 69), diabetes mellitus (n = 21), hyperlipidemia (n = 19), hypokalemia (n = 7) and preoperative renal insufficiency (Cr >132 µmol/l; n = 14). The patients were divided into CAD (luminal narrowing of ≧50%) and non-CAD (luminal narrowing of <50%) subgroups, and RAS (luminal narrowing of ≧50%) and non-RAS subgroups. In the RAS group, there were 11 patients (5 males, 6 females) in whom percutaneous transluminal renal angioplasty was performed in conjunction with stent implantation due to refractory hypertension. Results: The incidence of RAS was 18.4% (26/141) in all cases and 30.8% (16/52) in patients with CAD identified by coronary artery angiography. Ten cases with RAS were found among the 89 cases with normal coronary arteries (11.2%). The incidence of RAS in patients with CAD was higher than that in patients without CAD (30.8 vs. 11.2%, p< 0.05). In 52 cases with CAD, the incidence of RAS with three vessel lesions was significantly higher than that with one or two vessel lesions. Hypertension, CAD, renal insufficiency, hyperlipidemia and hypokalemia were associated with a higher risk of RAS. Conclusions: This study suggests that RAS is very common in the elderly Chinese population, specifically for those with three vessel lesions in CAD. For early detection of potential ischemic nephropathy, renal angiography is necessary in patients who receive coronary artery angiography.
Possible New Role of Monocyte Chemoattractant Protein-1 in Hemodialysis Patients with Cardiovascular Disease
Authors: Pawlak Krystyna , Pawlak Dariusz , Mysliwiec Michal
Published: December 2004

Aims: Reactive oxygen species have been implicated in increased vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) levels in vascular cells, which may promote atherosclerosis progression. Methods: We studied the association between pre-dialysis plasma levels of VEGF and MCP-1 in 45 hemodialysis (HD) patients with and without cardiovascular disease (CVD) in conditions of increased oxidative stress (SOX). Results: Compared to the controls, HD patients, especially those with CVD, showed a significant increase in plasma concentrations of Cu/Zn superoxide dismutase (Cu/Zn SOD), C-reactive protein (CRP), MCP-1 and VEGF. The levels of CRP, MCP-1 and VEGF were more increased in patients with CVD than in patients without CVD (all p < 0.01). VEGF strongly and positively correlated with MCP-1 only in HD patients with CVD. Additionally, both VEGF and MCP-1 were associated with Cu/Zn SOD in the whole HD group. Conclusion: For the first time our data indicate a correlation between VEGF and MCP-1 levels in HD patients with CVD in conditions of increased SOX. This interaction may reflect the new role of MCP-1 as an arteriogenic factor in HD patients with CVD.
The responses of black-casqued hornbills to predator vocalisations and primate alarm calls
Authors: Slater Peter , Rainey Hugo , Zuberbühler Klaus
Published: December 2004

Black-casqued hornbills (Ceratogymna atrata) forage in small flocks in the tropical forests of West Africa, often in the vicinity of primate groups, including Diana and Campbell's monkeys (Cercopithecus diana, C. campbelli). Previous work has shown that these monkey species produce acoustically distinct alarm calls to crowned eagles (Stephanoaetus coronatus) and leopards (Panthera pardus), two of their main predators. Black-casqued hornbills are highly vulnerable to crowned eagles, but not leopards, suggesting that individuals may respond differently to these two predators. We analysed the vocal response of these birds to field playbacks conducted on different monkey species in Taï National Park, Ivory Coast. We tested six stimuli, three of which related to the presence of a crowned eagle (eagle shrieks, Diana and Campbell's eagle alarm calls) and three to the presence of a leopard (leopard growls, Diana and Campbell's leopard alarm calls). Results showed that hornbills consistently distinguished between eagle- and leopard-related stimuli, suggesting that birds attended to the predator class associated with the various stimuli. Second, within eagle-related stimuli, hornbills responded more strongly to the actual predator vocalizations than the associated alarm calls. One interpretation of these data is that birds were sensitive to the precision of information concerning the location of the eagle. We discuss these results in light of previous data on hornbill behaviour and cognitive capacities.
Flexibility and context-sensitivity during the vocal exchange of coo calls in wild Japanese macaques (Macaca fuscata yakui)
Authors: Koda Hiroki
Published: December 2004

This study investigated the extent to which vocal production in wild Japanese macaques, Macaca fuscata yakui, is flexible. Japanese macaques frequently exchange coo calls with other group members to maintain auditory contact. When a coo call is emitted but no other members respond within a short interval, the same monkey often emits another call repeatedly. This study focused on these two successive coo call sequences. First, the sequences of eleven females in a free-ranging group were recorded and analyzed. Comparisons of the acoustic properties between the initial and repeated coo calls revealed that the repeated call was higher in fundamental frequency and longer in duration than the initial call. Next, playback experiments were conducted to examine the efficiency of the exaggerated acoustic features of these repeated coo calls. Eight pairs of initial and repeated coo calls were prepared from eight female monkeys as the playback stimuli, and played back to the eight subject females. Comparisons of subject responses to the initial and repeated coo call stimuli revealed that the repeated call stimuli elicited more frequent vocal responses. These field observation and playback results suggest that monkeys might be able to modify the acoustic properties of vocalizations according to the preceding context so as to elicit a more effective vocal response from other group members. The pattern of vocal interactions among wild Japanese macaques is therefore likely to be flexible and to some extent context-sensitive.
Variation in the stability of cockatiel (Nymphicus hollandicus) pair relationships: the roles of males, females, and mate compatibility
Authors: Millam James , Spoon Tracey , Owings Donald
Published: December 2004

Pair relationships and their emergent properties represent potentially significant sources of proximate and ultimate influence on mating systems, but the study of such relational factors has been rare compared to the volume of literature dedicated to individual-level measures of mate quality. This study assessed variation in the stability of pair relationships in cockatiels (Nymphicus hollandicus) and sought sources for that variation in both the behavior of mated individuals and their compatibility. Pair relationships represent an especially salient aspect of the social system of cockatiels, a socially monogamous species with long-term pairing.In a semi-natural, captive setting, this study compared (1) the social interactions between cockatiel mates to those individuals' interactions with opposite-sex non-mates, (2) the roles of males and females in pair relationships, and (3) the various pairs in their displays of intrapair and extrapair interactions. We also assessed the behavioral features underlying pair relationships by examining the interrelationships among social behaviors within pairs and the degree to which emergent properties structure pair relationships. Interactions between mates, as compared to opposite-sex non-mates, were characterized by closer proximity, greater behavioral synchrony, less aggression, more allopreening, and greater sexual behavior. Males and females displayed little dimorphism in many intrapair and extrapair behaviors; however, males approached and courted their mates more than females did, and males but not females exhibited more intersexual aggression to non-mates than to their mates. Social interactions between mates varied significantly among pairs in ways that reflected variation in the degree of behavioral compatibility between mates. In other words, suites of highly correlated behaviors characterized the interactions between mates such that pairs exhibiting greater affiliative or accordant behaviors exhibited less aggressive or discordant behaviors and vice versa. Emergent properties appeared to play an especially important role in compatibility. By examining significant within-species variation in pair relationships, this study complements the increasing knowledge of mating relationships gained from comparative studies and illustrates the importance of emergent, pair-level behavior in the maintenance of long-term monogamous pair-bonds.
Reconsidering Geometries of Development
Authors: Shah Hemant , Wilkins Karin Gwinn
Published: December 2004

We argue that the dominant geometry of development should be discarded, given the many limitations this model imposes on development policies and programs. Following a description of the dominant geometry of development, we critique this conceptualization based on grounds of morality and validity. Referencing illustrations of Japan as a development donor and the Chipko movement as an engaged community, we argue that new alternative geometries of development consider other structural and social arrangements. Finally, we consider more holistic, alternative perspectives that integrate material welfare with other humanitarian issues that transcend national boundaries.
Reproductive ecology of the slow worm (Anguis fragilis) in the northwest Iberian Peninsula
Authors: Ferreiro Ricardo , Galán Pedro
Published: December 2004

The reproductive characteristics of the slow worm (Anguis fragilis) were studied in A Coruña (Galicia, NW Spain) in 1999, 2000, 2001 and 2002. Data were mainly obtained through pregnant females captured in natural populations which subsequently gave birth under controlled conditions in the laboratory and the resulting neonates were examined. Marked individuals in a field population were also monitored. This field study allowed us to gain knowledge of the activity and reproductive cycle of the monitored population. A total of 68 births and 468 neonates were obtained, allowing us to determine the basic reproductive characteristics of the populations studied such as the litter size, offspring weight, offspring size and minimum maturity size for females: 135-150 mm snout vent length (SVL). The relationship between several variables related to offspring and their mothers showed a positive relation between size and mass of the litter and offspring with maternal size. A relationship between maternal tail length and litter mass was not observed. Unlike other studied populations of this species, most of the females of the A Coruña population (88.8%) reproduce annually. We found a probable relationship between female annual reproductive output and latitude, likely related to differences in environmental temperature. The activity cycle for the monitored population (from February to mid-December) is the longest known for the species.
Immunocompetence and testosterone-induced condition traits in male ruffs (Philomachus pugnax)
Authors: Lozano  , Lank
Published: December 2004

The immune system is costly to operate, so we expect allocation to this function to relate to other indices of overall phenotypic condition. In captive male ruffs (Philomachus pugnax), we examine covariation between three seasonal male characteristics induced by testosterone (neck 'ruff', facial wattles, and increases in mass/size) and cell-mediated and humoral immunity. The ruff has two genetically distinct morphs of males, 'independents' and 'satellites', which differ in mating behaviour, somewhat in body size, and possibly life history strategy. Ruff length and wattle number were significantly correlated with each other and with body size, but unrelated to mass/size. Humoral immunity was weakly correlated with size, but not with secondary male traits, or with cell-mediated immunity. We did not detect differences in humoral immunity between morphs. Cell-mediated immunity was weakly correlated with ruff length, but not with wattle number, size, or mass/size. Cell-mediated immunity decreased significantly with age. Controlling for age, independents had higher cell-mediated immunity responses than satellites. The expected relationships between two measures of immune function and other measures of condition were not always present, which suggests we need more data and/or more specific predictions about how the different aspects of immune function relate to each other and to ecological variables.
Experimental Weekly to Seasonal U.S. Forecasts with the Regional Spectral Model
Authors: Roads J.
Published: December 2004

Since 27 September 1997, the Scripps Experimental Climate Prediction Center (ECPC) has been making near real-time experimental global and regional dynamical forecasts with the National Centers for Environmental Prediction (NCEP) global spectral model (GSM) and the corresponding regional spectral model (RSM), which is based on the GSM, but which provides higher-resolution simulations and forecasts for limited regions. The global and regional forecast skill of the GSM was previously described in several papers. The purpose of this paper is to describe the RSM-based U.S. regional forecast system, various biases and errors in these regional U.S. forecasts, as well as the significant skill of the of temperature, precipitation, soil moisture, relative humidity, wind speed, and planetary boundary layer height forecasts at weekly to seasonal time scales. The skill of these RSM forecasts is comparable to the skill of the GSM forecasts.
Evaluating Parameterizations in General Circulation Models: Climate Simulation Meets Weather Prediction
Authors: Phillips Thomas J. , Potter Gerald L. , Williamson David L. , Cederwall Richard T. , Boyle James S. , Fiorino Michael , Hnilo Justin J. , Olson Jerry G. , Xie Shaocheng , Yio J. John
Published: December 2004

To significantly improve the simulation of climate by general circulation models (GCMs), systematic errors in representations of relevant processes must first be identified, and then reduced. This endeavor demands that the GCM parameterizations of unresolved processes, in particular, should be tested over a wide range of time scales, not just in climate simulations. Thus, a numerical weather prediction (NWP) methodology for evaluating model parameterizations and gaining insights into their behavior may prove useful, provided that suitable adaptations are made for implementation in climate GCMs. This method entails the generation of short-range weather forecasts by a realistically initialized climate GCM, and the application of six hourly NWP analyses and observations of parameterized variables to evaluate these forecasts. The behavior of the parameterizations in such a weather-forecasting framework can provide insights on how these schemes might be improved, and modified parameterizations then can be tested in the same framework.

To further this method for evaluating and analyzing parameterizations in climate GCMs, the U.S. Department of Energy is funding a joint venture of its Climate Change Prediction Program (CCPP) and Atmospheric Radiation Measurement (ARM) Program: the CCPP-ARM Parameterization Testbed (CAPT). This article elaborates the scientific rationale for CAPT, discusses technical aspects of its methodology, and presents examples of its implementation in a representative climate GCM.
Type I Error Rates for Parscale’s Fit Index
Authors: Demars Christine E.
Published: December 2004

Type I error rates for PARSCALE’s fit statistic were examined. Data were generated to fit the partial credit or graded response model, with test lengths of 10 or 20 items. The ability distribution was simulated to be either normal or uniform. Type I error rates were inflated for the shorter test length and, for the graded-response model, also for the longer test length when the ability distribution was uniform. In conditions in which α was inflated, it was particularly high when one or more response categories were used infrequently. Overall, PARSCALE’s fit index is not recommended for short tests.
Validation of Scores on the Marlowe-Crowne Social Desirability Scale and the Balanced Inventory of Desirable Responding
Authors: Leite Walter L. , Beretvas S. Natasha
Published: December 2004

The Marlowe-Crowne Social Desirability Scale (MCSDS), the most commonly used social desirability bias (SDB) assessment, conceptualizes SDB as an individual’s need for approval. The Balanced Inventory of Desirable Responding (BIDR) measures SDB as two separate constructs: impression management and self-deception. Scores on SDB scales are commonly used to validate other measures although insufficiently validated themselves. This study used college students’ responses to the MCSDS and the BIDR to investigate their factorial validity. Using confirmatory factor analysis, neither a one-nor a two-factor model was found to be strongly supported. It is recommended that researchers be cautious when using scores on these SDB scales until their dimensionality is better understood.
Items in Context: Assessing the Dimensionality of Raven’s Advanced Progressive Matrices
Authors: Vigneau François , Bors Douglas A.
Published: December 2004

The problem of dimensionality with respect to Raven’s Advanced Progressive Matrices (APM) specifically and, more generally, g or fluid intelligence, has been a long-standing issue. The present article reports two studies examining the dimensionality of both the original Set II of the APM ( n = 506) and a short form ( n = 644), using principal component analysis and Rasch analysis. Although the results from the principal component analysis were equivocal, results from the Rasch analyses more strongly suggested that both forms of the test are best described as being multidimensional. Furthermore, comparison of items common to both forms indicated a context effect, thus making adaptive testing versions of this test difficult.
Situational Judgment Tests and their Predictiveness of College Students’ Success: The Influence of Faking
Authors: Peeters Helga , Lievens Filip
Published: December 2004

There is increasing interest in using situational judgment tests (SJTs) to supplement traditional student admission procedures. An important unexplored issue is whether students can intentionally distort or fake their responses on SJTs. This study examined the fakability of an SJT of college students’ performance. Two hundred ninety-three psychology students completed a cognitive test, a personality measure, and an SJT. Only for the SJT, the students were assigned to either an honest or a fake condition. The scores of students in the fake condition were significantly higher than those of students in the honest condition ( d = .89). Furthermore, faking had a negative effect on the criterion-related validity (there was a significant drop from r = .33 to r = .09) and the incremental validity of the SJT over cognitive ability and personality. These results are discussed in terms of the use of SJTs in high-stakes testing programs.
The Mind of the Terrorist
Authors: Victoroff Jeff
Published: December 2004

This article reviews the state of the art of available theories and data regarding the psychology of terrorism. Data and theoretical material were gathered from the world’s unclassified literature. Multiple theories and some demographic data have been published, but very few controlled empirical studies have been conducted investigating the psychological bases of terrorism. The field is largely characterized by theoretical speculation based on subjective interpretation of anecdotal observations. Moreover, most studies and theories fail to take into account the great heterogeneity of terrorists. Many practical, conceptual, and psychological barriers have slowed progress in this important field. Nonetheless, even at this early stage of terrorism studies, preliminary reports suggest that modifiable social and psychological factors contribute to the genesis of the terrorist mind-set. Psychological scholarship could possibly mitigate the risk of catastrophic attack by initiating the long overdue scientific study of terrorist mentalities.
Saving Positive Freedom
Authors: Christman John
Published: December 2004

In this article, I respond to Eric Nelson’s claim (in “Liberty: One Concept Too Many?”) that the most prominent versions of a positive concept of freedom all reduce to negative notions. I argue that in his otherwise scholarly and well-argued article, Nelson confuses a conceptual dispute with a normative one based on moral or political principle. Further, I point out that the traditional critique of positive conceptions of liberty, which rests on skepticism about perfectionist conceptions of political value, is lost if we see the debate in the way Nelson lays it out. When these issues are disentangled, I suggest that there is indeed conceptual space for uniquely “positive” conceptions of freedom, and I suggest that the idea of “autonomy” can be taken for such a notion and indeed represents a value worth taking seriously in current discussions of justice.
Differences in Self-Report Measures by Adolescent Sex Offender Risk Group
Authors: Smith Susan , Wampler Richard , Jones Janelle , Reifman Alan
Published: December 2004

Differences in self-reports among three groups of juvenile sex offenders (N = 162) were examined. Risk was defined as the sum of the following static variables based on interviews with juveniles and others and from written records: type of offense (violent or predatory =1, not = 0), prior sex offense (any =1, none = 0), history of sexual abuse (self or family= 1, none = 0), history of substance abuse (self or family =1, none = 0), history of behavior problems (yes =1, no = 0), and unstable home life (yes =1, stable = 0). Low-risk (0 to 2 risk factors), medium-risk (3 factors), and high-risk (4 to 6 factors) groups of offenders were formed. Univariate ANCOVAs indicated that the high-risk group reported less family cohesion, more aggression, lower self-esteem, more social discomfort, and more frequent and extreme sexual fantasies. The implications of these findings for differential identification of and interventions with adolescent sex offenders are discussed.
Is Teen Court Effective for Repeat Offenders? A Test of the Restorative Justice Approach
Authors: Forgays Deborah Kirby , DeMilio Lisa
Published: December 2004

Teen Courts are an effective judicial alternative for many youth offenders. The majority of youth courts deal solely with first-time offenders. However, repeat offenders are at a greater risk for future crime. Is Teen Court effective with more experienced offenders? In this study, the authors examine the outcomes of 26 Whatcom County Teen Court offenders with at least one prior conviction. The sentence completion rate was higher and the recidivism was lower for the Teen Court offenders when compared with a sample of first-time Court Diversion offenders. This objective evidence of program success is augmented by an offender’s perspective on his or her court experience. These perspectives as well as the continued voluntary involvement with Teen Court are discussed in relation to empowerment theory.
Autoimmunity in a Phase I Trial of a Fully Human Anti-Cytotoxic T-Lymphocyte Antigen-4 Monoclonal Antibody With Multiple Melanoma Peptides and Montanide ISA 51 for Patients With Resected Stages III and IV Melanoma
Authors: Sanderson Kristin , Scotland Ronald , Lee Peter , Liu Dongxin , Groshen Susan , Snively Jolie , Sian Shirley , Nichol Geoffrey , Davis Thomas , Keler Tibor , Yellin Michael , Weber Jeffrey
Published: December 2004

Purpose

Nineteen patients with high-risk resected stage III and IV melanoma were immunized with three tumor antigen epitope peptides from gp100, MART-1, and tyrosinase emulsified with adjuvant Montanide ISA 51 and received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) monoclonal antibody MDX-010. Each of three cohorts received escalating doses of antibody with vaccine primarily to evaluate the toxicities and maximum-tolerated dose (MTD) of MDX-010 with vaccine. MDX-010 pharmacokinetics and immune responses were secondary end points.

Patients and Methods

Peptide immunizations with MDX-010 were administered every 4 weeks for 6 months and then every 12 weeks for 6 months. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was performed before treatment and after the sixth vaccination. Patients were observed until relapse.

Results

Grade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) was observed in three patients in the highest dose cohort and one in the middle dose cohort who seemed to be autoimmune. That defined the MTD with vaccine on this schedule at 1 mg/kg. Of eight patients with evidence of autoimmunity, three have experienced disease relapse. Of 11 patients without autoimmune symptoms, nine have experienced disease relapse. Significant immune responses were measured by tetramer and enzyme-linked immunospot assays against gp100 and MART-1.

Conclusion

Dose-related autoimmune adverse events, predominantly skin and GI toxicities, were reversible. Patients mounted an antigen-specific immune response to a peptide vaccine when combined with a human anti–CTLA-4 antibody.
Phase II Study of Proteasome Inhibitor Bortezomib in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Authors: Goy Andre , Younes Anas , McLaughlin Peter , Pro Barbara , Romaguera Jorge E. , Hagemeister Frederick , Fayad Luis , Dang Nam H. , Samaniego Felipe , Wang Michael , Broglio Kristine , Samuels Barry , Gilles Frederic , Sarris Andreas H. , Hart Susan , Trehu Elizabeth , Schenkein David , Cabanillas Fernando , Rodriguez Alma M.
Published: December 2004

Purpose

Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Patients and Methods

Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles.

Results

Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenström's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study.

Conclusion

Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.
Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab
Authors: Horning Sandra J. , Younes Anas , Jain Vinay , Kroll Stewart , Lucas Jennifer , Podoloff Donald , Goris Michael
Published: December 2004

Purpose

To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab (131I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.

Patients and Methods

From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response ≥ 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of131I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.

Results

Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors ≤ 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.

Conclusion

131I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors ≤ 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.
Activity and subcellular compartmentalization of peroxisome proliferator-activated receptor α are altered by the centrosome-associated protein CAP350
Authors: Patel Hansa , Truant Ray , Rachubinski Richard A. , Capone John P.
Published: December 2004

Peroxisome proliferator-activated nuclear hormone receptors (PPAR) are ligand-activated transcription factors that play pivotal roles in governing metabolic homeostasis and cell growth. PPARs are primarily in the nucleus but, under certain circumstances, can be found in the cytoplasm. We show here that PPARα interacts with the centrosome-associated protein CAP350. CAP350 also interacts with PPARδ, PPARγ and liver-X-receptor α, but not with the 9-cis retinoic acid receptor, RXRα. Immunofluorescence analysis indicated that PPARα is diffusely distributed in the nucleus and excluded from the cytoplasm. However, in the presence of coexpressed CAP350, PPARα colocalizes with CAP350 to discrete nuclear foci and to the centrosome, perinuclear region and intermediate filaments. In contrast, the subcellular distribution of RXRα or of thyroid hormone receptor α was not altered by coexpression of CAP350. An amino-terminal fragment of CAP350 was localized exclusively to nuclear foci and was sufficient to recruit PPARα to these sites. Mutation of the single putative nuclear hormone receptor interacting signature motif LXXLL present in this fragment had no effect on its subnuclear localization but abrogated recruitment of PPARα to nuclear foci. Surprisingly, mutation of the LXXLL motif in this CAP350 subfragment did not prevent its binding to PPARα in vitro, suggesting that this motif serves some function other than PPARα binding in recruiting PPARα to nuclear spots. CAP350 inhibited PPARα-mediated transactivation in an LXXLL-dependent manner, suggesting that CAP350 represses PPARα function. Our findings implicate CAP350 in a dynamic process that recruits PPARα to discrete nuclear and cytoplasmic compartments and suggest that altered intracellular compartmentalization represents a regulatory process that modulates PPAR function.
Nuclear receptor NHR-25 is required for cell-shape dynamics during epidermal differentiation inCaenorhabditis elegans
Authors: Šilhánková Marie , Jindra Marek , Asahina Masako
Published: December 2004

Epithelial cell shape changes underlie important events in animal development. During the postembryonic life of the nematode Caenorhabditis elegans, stem epidermal seam cells lose and actively renew mutual adherens junction contacts after each asymmetric division that separates them. The seam cell contacts are important for epidermal differentiation, but what regulates the cell-shape changes that restore them is unknown. Here, we show that NHR-25, a transcription factor of the nuclear receptor family, is expressed in the seam cells and is necessary for these cells to elongate and reach their neighbors after the asymmetric divisions. A failure to do so, caused by nhr-25 RNA interference, compromises the subsequent fate of seam-cell anterior daughters. Unexpectedly, the lack of cell-cell contacts does not prevent a unique seam cell to produce a neuroblast, even though a homeotic gene (mab-5) that normally prevents the neuroblast commitment is ectopically expressed in the absence of nhr-25 function. Seam cells lacking mutual contacts display reduced expression of a Fat-like cadherin marker cdh-3::gfp. Although some seam cells retain the ability to fuse at the final larval stage, the resulting syncytium shows gaps and bifurcations, translating into anomalies in cuticular ridges (alae) produced by the syncytium. nhr-25 RNAi markedly enhances branching of the alae caused by a mutant cuticular collagen gene rol-6. Silencing of nhr-25 also disturbs epidermal ultrastructure, which is probably the cause of compromised cuticle secretion and molting. Cell shape dynamics and molting thus represent distinct roles for NHR-25 in epidermal development.
RNA association and nucleocytoplasmic shuttling by ataxin-1
Authors: Irwin Stuart , Vandelft Mark , Pinchev Deborah , Howell Jenny L. , Graczyk Joanna , Orr Harry T. , Truant Ray
Published: December 2004

Spinocerebellar ataxia type 1 (SCA1) is a dominant neurodegenerative disease caused by the expression of mutant ataxin-1 containing an expanded polyglutamine tract. Ataxin-1 is a nuclear protein that localizes to punctate inclusions similar to neuronal nuclear inclusions seen in many polyglutamine expansion disease proteins. We demonstrate that ataxin-1 localization to inclusions and inclusion dynamics within the nucleus are RNA and transcription dependent, but not dependent on the polyglutamine tract. Ataxin-1 nuclear inclusions are distinct from other described nuclear bodies but recruit the mRNA export factor, TAP/NXF1, in a manner that is enhanced by cell heat shock. By FRAP protein dynamic studies in live cells, we found that wild-type, but not mutant, ataxin-1 was capable of nuclear export. These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease.
Overexpression of Exportin 5 enhances RNA interference mediated by short hairpin RNAs and microRNAs
Authors: YI RUI , DOEHLE BRIAN P. , QIN YI , MACARA IAN G. , CULLEN BRYAN R.
Published: December 2004

Plasmids or viral vectors that express short hairpin RNAs (shRNAs) have emerged as important tools for the stable inhibition of specific genes by RNA interference. shRNAs are structural and functional homologs of pre-microRNAs, intermediates in the production of endogenously encoded microRNAs (miRNAs). Therefore, overexpressed shRNAs could inhibit miRNA function by competing for a limiting level of one or more factors involved in miRNA biogenesis or function. Here, we demonstrate that overexpressed shRNAs can saturate the activity of endogenous Exportin 5, a factor required for nuclear export of both shRNAs and pre-miRNAs. While shRNA overexpression can therefore inhibit miRNA function, simultaneous overexpression of Exportin 5 reverses this effect. Moreover, Exportin 5 overexpression can significantly enhance RNA interference mediated by shRNAs. These data have implications for the future clinical utilization of shRNAs and also provide a simple method to enhance RNA interference by shRNAs in culture.
Undertreatment of Urinary Incontinence in General Practice
Authors: Beest Fernie JA Penning-van , Sturkenboom Miriam CJM , Bemelmans Bart LH , Herings Ron MC
Published: December 2004

BACKGROUND:

In the urinary incontinence guidelines that are issued by the Dutch College of General Practitioners, treatment guidelines are related to the type of incontinence. It is unknown whether treatment of urinary incontinence in general practice complies with these guidelines.

OBJECTIVE:

To describe treatment patterns and costs of urinary incontinence.

METHODS:

The source population for this retrospective cohort study included all women aged ≥40 years in the Integrated Primary Care Information general practice research database. Women were included in the final study cohort if they were newly identified as being urinary incontinent during the study period (1998–2000) and had at least one year of follow-up after the first diagnosis/treatment. The type of incontinence, treatment course, and costs of incontinence were assessed during the first year after the subjects' identification.

RESULTS:

The final study cohort comprised 1663 women (mean age 68.5 y). Overall, 71% of newly identified women with urinary incontinence did not receive active treatment within one year after identification. In 13%, the first treatment was bladder training or pelvic floor exercises, and 11% started treatment with a bladder relaxant drug. First treatment was related to the type of incontinence; however, in <50% of the women, the type of incontinence was reported or could be assessed. Absorbent products were used by 66% of the women; 87% of them received no active treatment. The mean direct costs of urinary incontinence over the first year amounted to ¢392 per woman, of which ¢200 (51%) for absorbent products.

CONCLUSIONS:

Less than one-third of the women with newly identified urinary incontinence were actively treated for their incontinence. Although treatment patterns were in line with guidelines, the high rate of undertreatment points to the need for better patient and physician education.
Effect of Lepirudin on the International Normalized Ratio
Authors: Stephens Jennifer L , Koerber John M , Mattson Joan C , Smythe Maureen A
Published: December 2004

BACKGROUND:

Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited.

OBJECTIVE:

To evaluate the effect of lepirudin on the INR.

METHODS:

Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy.

RESULTS:

Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean ± SD lepirudin dose was 0.05 ± 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45–75 seconds (1.5–2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45–75 seconds with lepirudin correlated to an INR of 1.6–3.2.

CONCLUSIONS:

Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.