bluuebunny/crossref_metadata_2025 huggingface dataset:
The Epidemiology of Violence Against the Elderly
Authors: Bachman Ronet , Meloy Michelle L.
Published: March 2008

Although the elderly are generally less likely to become the victims of violent crime compared to younger cohorts, they have unique and somewhat alarming patterns of victimization. This article examines the extant literature on elderly victimization and presents homicide data from the Supplementary Homicide Reports and robbery and assault data from the National Crime Victimization Survey to illuminate the idiosyncratic vulnerabilities elderly individuals have to violence compared to their younger counterparts. In addition, research examining violence that occurs in nursing homes as the result of staff-to-patient assaults and resident-to-resident assaults is also highlighted. Policies aimed at both primary and secondary prevention of violence against the elderly are discussed.
Interpersonal Violence Against Women
Authors: Schwartz Martin D. , DeKeseredy Walter S.
Published: March 2008

Attempting to solve the problem of interpersonal violence by dealing with the private problems of individuals is a strategy doomed to failure. With high-level social forces combining to facilitate rape, abuse, and stalking, programs to end these problems must be painted with broad strokes. Male peer support is an important aspect of society giving permission to men to assault women or to encourage or ignore others who do so. Programs such as bystander education that encourage male leaders to speak out are essential. Schools and governments must put more money into education programs to protect youth. American society was outraged when a professional football player was accused of mistreating and killing fighting dogs. Hollywood, meanwhile, virtually cannot portray the mistreatment of animals. We need to move toward a society where the same level of outrage accompanies acts of interpersonal violence against women.
Acting at Work
Authors: Stormer Flora , Devine Kay
Published: March 2008

Façades of conformity (FOC) is a theoretical concept coined to describe employees who act as if they embrace an organization's values when they really don't in order to survive and/or succeed within that organization. This exploratory study combines value theory and the sociology of the professions to explore manifestations of FOC among professionals (university faculty members). Respondents' experiences of “acting at work” reveal the presence, absence, and dynamic nature of FOC. Response patterns allow us to confirm, disconfirm, and extend Hewlin's (2003) theory by identifying two types of FOC, four issues respondents typically “façade” about, behaviors enacted during the use of FOC, and the perceived risks associated with not using FOC at work. These results have significant implications for the scholarly and managerial practice of assessing value congruence between individuals and organizations.
Attribution and Self-Evaluation of Continuous Performance Test Task Performance in Medicated and Unmedicated Adults With ADHD
Authors: Barrilleaux Katie , Advokat Claire
Published: March 2008

Objective: To determine if adults with ADHD differed from children with ADHD, in assessing their performance on the Conners Continuous Performance Test (CPT). Method: ADHD-diagnosed adults ( n = 13) and adults without ADHD ( n = 17) were tested twice on the CPT and then completed self-evaluation and attribution surveys. Results: Nonmedicated ADHD-diagnosed adults performed significantly more poorly than controls; when medicated, they performed as well as controls and significantly better than when they were unmedicated. AD/HD adults evaluated their performance accurately, whether medicated or not. They also attributed their performance to medication significantly more than to ability or task difficulty. Conclusion: Unlike children, ADHD-diagnosed adults attributed their performance to medication rather than ability or task. It remains to be seen whether this difference is associated with lower self-esteem than non-ADHD adults or if the same outcome would occur in children with ADHD if they were also tested under naturalistic conditions. (J. of Att. Dis. 2009; 12(4) 291-298)
Pooling Restaurant Reservations to Increase Service Efficiency
Authors: Thompson Gary M. , Kwortnik Robert J.
Published: March 2008

This article examines whether restaurant reservations should be locked to specific tables at the time the reservation is made or whether the reservations should be pooled and assigned to tables in real time. In two motivating studies, the authors find that there is a lack of consensus in the restaurant industry on handling reservations. Contrary to what might be expected based on research that shows the benefits of resource pooling in other contexts, a survey of 425 restaurants indicated that more than 80% lock reservations to tables. In two simulation studies, the authors determine that pooling reservations enables a 15-minute reduction in table turn times more than 15% of the time, which consequently increases service efficiency and enables a restaurant to serve more customers during peak periods. Pooling had the most consistent advantage with higher customer service levels, larger restaurants, customers who arrive late, and larger variation in customer arrival time.
Multidimensional Customer-Based Brand Equity and Its Consequences in Midpriced Hotels
Authors: Woo Gon Kim  , Jin-Sun Bongran , Hyun Jeong Kim
Published: March 2008

This study examined the relationship between hotel brand equity and guests' perceived value and revisit intention. The path model (brand equity factors leading to outcome variables) was formed to test research hypotheses. Data from 264 travelers who have stayed in midscale hotels were used for the structural equation modeling (SEM) analysis. All dimensions of brand equity (brand loyalty, perceived quality, and brand awareness/association) positively affected perceived value. Two brand-equity dimensions (brand loyalty and brand awareness/association) were found to increase guests' revisit intention. Although perceived quality was not a direct determinant of revisit intent, the effect of perceived quality on revisit intent was mediated by perceived value. Overall, this study highlights the importance of perceived value in lodging customers' mind. Managerial implications are provided based on the results.
Addressing alcohol problems in primary care settings: A study of general medical practitioners in Cape Town, South Africa
Authors: Koopman Fred A. , Parry Charles D.H. , Myers Bronwyn , Reagon Gavin
Published: March 2008

Aims: To explore alcohol-related practices among general practitioners (GPs) in the Cape Town metropole and to examine barriers to addressing risky drinking among patients. Method: A cross-sectional survey of 50 GPs was conducted between November 2004 and April 2005. A questionnaire assessing GPs' alcohol-related practices and barriers to alcohol-related interventions was administered to participating GPs. Results: In the past 12 months, most GPs reported seeing only 11—30 patients for alcohol problems specifically. While only 12% thought that they could effectively help patients reduce their alcohol consumption, 78% of GPs indicated that, given adequate training and support, they could become more effective. Among the barriers that hindered their ability to intervene in patients' alcohol-related problems were difficulties in getting reimbursed for treating patients with alcohol problems, insufficient training, lack of materials with which to do screening and counselling, perceptions of ineffectiveness, and time constraints. Conclusions: GPs are willing to conduct interventions for risky drinking but require additional training in these interventions as well as appropriate support and intervention tools.
Predictors of changes in physical activity in a prospective cohort study of the Danish adult population
Authors: Zimmermann Esther , Ekholm Ola , Grønbæk Morten , Curtis Tine
Published: March 2008

Aim: To investigate predictors of changes in physical activity, in a prospective population-based study. Methods: Data were from the Danish Health Interview Surveys in 1994 and 2000, and included persons between 16 and 64 years of age who answered the questions on physical activity and various covariates in 1994, and who were re-interviewed in 2000. In total 2,957 subjects participated (62% of the original sample). Data were analysed using logistic regression. Results: Predictors of physical inactivity were, for men and women respectively, heavy smoking (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.24—3.48, and OR 2.23, 95% CI 1.34—3.71), poor self-rated health (OR 2.11, 95% CI 1.25—3.58, and OR 1.75, 95% CI 1.10—2.80), and believing that one's own effort has no effect on health (OR 1.86, 95% CI 1.20—2.88, and OR 1.63, 95% CI 1.00—2.65). For men, further predictors for physical inactivity were obesity as compared to normal weight (OR 2.10, 95% CI 1.11—3.98), and being unmarried as compared to being married (OR 2.22, 95% CI 1.40—3.51). The only predictor for becoming physically active among initially sedentary respondents was meeting often with family (p=0.011). Conclusions: Our results show a number of strong predictors for physical inactivity. Variables of an unhealthy lifestyle tend to cluster in some individuals, and physical inactivity interventions may therefore be more successful if they also address smoking, self-belief, and obesity. Interventions tailored to raise inactive people's level of activity should focus on social support from the family.
Endurance and Resistance Exercise Training Programs Elicit Specific Effects on Sciatic Nerve Regeneration After Experimental Traumatic Lesion in Rats
Authors: Ilha Jocemar , Araujo Rafaela T. , Malysz Tais , Hermel Erica E. S. , Rigon Paula , Xavier Léder L. , Achaval Matilde
Published: March 2008

Objective. To evaluate the effects of endurance, resistance, and a combination of both types of exercise training on hindlimb motor function recovery and nerve regeneration after experimental sciatic nerve lesion in rats. Methods. Sciatic nerve crush was performed on adult male rats, and after 2 weeks of the nerve lesion, the animals were submitted to endurance, resistance, and a combination of endurance-resistance training programs for 5 weeks. Over the training period, functional recovery was monitored weekly using the Sciatic Functional Index (SFI) and histological and morphometric nerve analyses were used to assess the nerve regeneration at the end of the trainings. Results. The SFI values of the endurance-trained group reached the control values from the first posttraining week and were significantly better than both the resistance-trained group at the first, second, and third posttraining weeks and the concurrent training group at the first posttraining week. At the distal portion of the regenerating sciatic nerve, the endurance-trained group showed a greater degree of the myelinated fiber maturation than the sedentary, resistance-trained, and concurrent training groups. Furthermore, the endurance-trained group showed a smaller percentage area of endoneurial connective tissue and a greater percentage area of myelinated fibers than the sedentary group. Conclusion . These data provide evidence that endurance training improves sciatic nerve regeneration after an experimental traumatic injury and that resistance training or the combination of 2 strategies may delay functional recovery and do not alter sciatic nerve fiber regeneration.
Motor Cortical Disinhibition During Early and Late Recovery After Stroke
Authors: Manganotti P. , Acler M. , Zanette G. P. , Smania N. , Fiaschi A.
Published: March 2008

Background. Functional neuroimaging studies show adaptive changes in areas adjacent and distant from the stroke. This longitudinal study assessed whether changes in cortical excitability in affected and unaffected motor areas after acute stroke correlates with functional and motor recovery. Methods. We studied 13 patients with moderate to severe hemiparesis 5 to 7 days (T1), 30 days (T2), and 90 days (T3) after acute unilateral stroke, as well as 10 healthy controls. We used paired-pulse transcranial magnetic stimulation to study intracortical inhibition and facilitation, recording from the bilateral thenar eminences. F waves were also recorded. Results. At T1, all patients showed significantly reduced intracortical inhibition in the unaffected hemisphere. At T2, in patients whose motor function recovered, intracortical inhibition in the unaffected hemisphere returned to normal. In patients with poor clinical motor recovery, abnormal disinhibition persisted in both hemispheres. At T3, in patients whose motor function progressively recovered, the abnormal disinhibition in the unaffected hemisphere decreased further, whereas in patients whose motor function remained poor, abnormal inhibition in the unaffected hemisphere persisted. No modification of F-wave latency and amplitude were found in patients and controls. Conclusions. During early days after stroke, motor cortical disinhibition involves both cerebral hemispheres. Longitudinal changes in motor disinhibition of the unaffected hemisphere may reflect the degree of clinical motor recovery.
Determining the Optimal Challenge Point for Motor Skill Learning in Adults With Moderately Severe Parkinson's Disease
Authors: Onla-or Somporn , Winstein Carolee J.
Published: March 2008

Objective. To test the predictions of the Challenge Point Framework (CPF) for motor learning in individuals with Parkinson's disease (PD) by manipulating nominal task difficulty and conditions of practice. Methods. Twenty adults with PD and 20 nondisabled controls practiced 3 variations of a laboratory-based goal-directed arm movement over 2 days. A between-group (PD, nondisabled) 2-factor design compared 2 levels of nominal task difficulty (low, high) and 2 levels of practice condition (low, high demand). Learning was assessed with a no-feedback recall test 1 day after practice. Performance was quantified using a root mean square error difference between the goal and participant-generated movement. Results. All participants improved with practice. Under the low-demand practice condition, adults with PD demonstrated comparable learning to that of controls when nominal task difficulty was low but not high. In contrast, under the high-demand practice condition, adults with PD demonstrated preserved motor learning for both levels of task difficulty, but only if recall was tested under the same context as that used during practice. Conclusions. In general, the predictions of CPF were supported. Together, the level of nominal task difficulty and the inherent demand of the practice condition played a critical role in determining the optimal challenge point for motor learning in individuals with PD. More important, and in contrast to the predictions of CPF, a high-demand practice condition appeared to have a facilitative effect on motor learning. However, this benefit revealed the context specificity of motor learning in adults with PD.
Augmenting Clinical Evaluation of Hemiparetic Arm Movement With a Laboratory-Based Quantitative Measurement of Kinematics as a Function of Limb Loading
Authors: Ellis Michael D. , Sukal Theresa , DeMott Tobey , Dewald Julius P. A.
Published: March 2008

Background. Kinematic and kinetic measurements used in laboratory settings can quantify upper extremity movement impairment following stroke, but their relationship to clinical methods of evaluating movement impairment is unclear. Objective. To test whether the Arm Coordination Training 3D device (ACT3D) could provide a repeatable quantitative measurement of range of motion during upper extremity reaching along a range of functional levels of loads on the arm and correlate with clinical assessments of arm impairment. Methods . Work area during reaching along clockwise and counterclockwise hand paths was measured under 9 limb-loading conditions ranging from no load to twice the weight of the upper extremity in 11 individuals with chronic hemiparetic stroke on 2 separate occasions. Participants were given a battery of clinical assessments that included the Fugl-Meyer Motor Assessment, Chedoke McMaster Stroke Assessment, Reaching Performance Scale, Modified Ashworth Scale, and the Stroke Impact Scale, by a physical therapist who did not know the results of the kinematic studies. Results. A reproducible testretest reduction in work area was found when participants were required to support up to and beyond the weight of their limb. Work area was correlated with most upper extremity clinical assessments, suggesting criterion validity. Conclusions . Reaching work area during various loading conditions is a robust measurement that quantifies the effect of abnormal joint torque coupling and provides useful data that can be applied in the clinical setting.
Utilizing Neuropsychological Testing to Inform ADHD Diagnosis and Treatment
Authors: Sugalski Thomas D. , Scott Albert J. , Cleary Michael J.
Published: March 2008

This article describes a case study in which a 7-year-old first grade boy (Phil) underwent neuropsychological assessment to determine the possible existence of attention deficit hyperactivity disorder. Subsequent performances on tests of attention and executive functioning were quite variable. Specifically, there were indicators of inattention, erratic response style, and executive dysfunction evidenced by a large number of commission errors. In addition, there were difficulties maintaining attentional focus in the presence of distracters, weaknesses in working memory, information processing speed, and difficulties with planning and inhibition. Treatment implications are subsequently described, particularly the growing use of computer-assisted cognitive training to address working memory and executive functioning. Finally, the article concludes with a discussion about how to employ neuropsychological results in an effort to meaningfully engage the family of an attention deficit hyperactivity disorder child in long-term therapy.
Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPα
Authors: Pinto Jorge P. , Ribeiro Sara , Pontes Helena , Thowfeequ Shifaan , Tosh David , Carvalho Félix , Porto Graça
Published: March 2008

Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. Recent in vivo studies have shown that hepcidin is down-regulated by erythropoiesis, anemia, and hypoxia, which meets the need of iron input for erythrocyte production. Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin regulation can be hypothesized. We report here the regulation of hepcidin expression by EPO, in a dose-dependent manner, in freshly isolated mouse hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated through EPOR signaling, since hepcidin mRNA levels are restored by pretreatment with an EPOR-blocking antibody. The transcription factor C/EBPα showed a pattern of expression similar to hepcidin, at the mRNA and protein levels, following EPO and anti-EPOR treatments. Chromatin immunoprecipitation experiments showed a significant decrease of C/EBPα binding to the hepcidin promoter after EPO supplementation, suggesting the involvement of this transcription factor in the transcriptional response of hepcidin to EPO.
CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment
Authors: Patten Piers E. M. , Buggins Andrea G. S. , Richards Julie , Wotherspoon Andrew , Salisbury Jon , Mufti Ghulam J. , Hamblin Terry J. , Devereux Stephen
Published: March 2008

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with a highly variable outcome. The prognosis of patients with CLL may be predicted using a number of biomarkers, including the level of CD38 expression at the leukemic cell surface. This study investigates the hypothesis that CD38 expression by CLL cells reflects interactions with nonmalignant cells within pseudofollicles in secondary lymphoid tissue where tumor cell proliferation is thought to occur. CD38 expression is higher in tissues that contain pseudofollicles compared with those that do not. In addition, we show that CD38 expression in CLL is dynamic, changes in response to contact with activated CD4+ T cells, and identifies cells that are primed to proliferate. Finally, we demonstrate close contact between activated CD4+ T cells and proliferating tumor in primary patient tissue. Proliferating tumor cells in lymph nodes express CD38, which is in turn associated with an increased number of CD31+ vascular endothelial cells. Although the factors resulting in colocalization of tumor, T cells, and endothelium remain unclear, the existence of these cellular clusters may provide an explanation for the association between CD38 expression and adverse outcome in CLL and suggests novel therapeutic targets.
α4β1 integrin and 190-kDa CD44v constitute a cell surface docking complex for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells
Authors: Redondo-Muñoz Javier , Ugarte-Berzal Estefanía , García-Marco José A. , del Cerro Mercedes Hernández , Van den Steen Philippe E. , Opdenakker Ghislain , Terol María José , García-Pardo Angeles
Published: March 2008

As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells extravasate and infiltrate lymphoid tissues. Several molecules, including gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted protease, some MMP-9 is present at the B-CLL cell surface and the function, mode of anchoring, and interactions of this MMP-9 are unknown. Here we show that anti–MMP-9 antibodies immunoprecipitated a 190-kDa CD44v isoform and α4β1 integrin from B-CLL cells, but not from normal B cells. Function-blocking antibodies to α4β1 or CD44, or transfection with specific siRNAs, decreased cell-associated proMMP-9 and increased the secreted form. B-CLL cells attached to and bound proMMP-9 and active MMP-9, and this was inhibited by blocking the expression or function of α4β1 or CD44. The MMP-9 hemopexin domain was critical in these interactions. α4β1 and 190-kDa CD44v (but not CD44H) formed a complex at the cell surface, since they both coimmunoprecipitated with anti-α4, anti-β1, or anti-CD44 antibodies. Immunofluorescence analyses confirmed that α4β1 and CD44v colocalized with MMP-9. Binding of proMMP-9 inhibited B-CLL cell migration, and this required MMP-9 proteolytic activity. Thus, we have identified α4β1 and CD44v as a novel proMMP-9 cell surface docking complex and show that cell-associated MMP-9 may regulate B-CLL cell migration and arrest.
Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin
Authors: Xia Yin , Babitt Jodie L. , Sidis Yisrael , Chung Raymond T. , Lin Herbert Y.
Published: March 2008

Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling that regulates hepcidin expression and iron metabolism. However, the precise combinations of BMP ligands and receptors used by HJV remain unknown. HJV has also been demonstrated to bind to neogenin, but it is not known whether this interaction has a role in regulating hepcidin expression. In the present study, we show that BMP-2, BMP-4, and BMP-6 are endogenous ligands for HJV in hepatoma-derived cell lines, and that all 3 of these ligands are expressed in human liver. We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. Interestingly, ActRIIA is the predominant BMP type II receptor expressed in human liver. While HJV can use all 3 BMP type I receptors (ALK2, ALK3, and ALK6) in vitro, only ALK2 and ALK3 are detected in human liver. Finally, we show that HJV-induced BMP signaling and hepcidin expression are not altered by neogenin overexpression or by inhibition of endogenous neogenin expression. Thus, HJV-mediated BMP signaling and hepcidin regulation occur via a distinct subset of BMP ligands and BMP receptors, independently of neogenin.
The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate
Authors: Schüler Andrea , Schwieger Maike , Engelmann Afra , Weber Kristoffer , Horn Stefan , Müller Ursula , Arnold Michael A. , Olson Eric N. , Stocking Carol
Published: March 2008

Mef2c is a MADS (MCM1-agamous–deficient serum response factor) transcription factor best known for its role in muscle and cardiovascular development. A causal role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia (AML) has recently been demonstrated. Due to the pronounced monocytic component observed in Mef2c-induced AML, this study was designed to assess the importance of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells manipulated to constitutively express Mef2c demonstrated increased monopoiesis at the expense of granulopoiesis, whereas BM isolated from Mef2cΔ/− mice showed reduced levels of monocytic differentiation in response to cytokines. Mechanistic studies showed that loss of Mef2c expression correlated with reduced levels of transcripts encoding c-Jun, but not PU.1, C/EBPα, or JunB transcription factors. Inhibiting Jun expression by short-interfering RNA impaired Mef2c-mediated inhibition of granulocyte development. Moreover, retroviral expression of c-Jun in BM cells promoted monocytic differentiation. The ability of Mef2c to modulate cell-fate decisions between monocyte and granulocyte differentiation, coupled with its functional sensitivity to extracellular stimuli, demonstrate an important role in immunity—and, consistent with findings of other myeloid transcription factors, a target of oncogenic lesions in AML.
Calcitonin receptor-like receptor guides arterial differentiation in zebrafish
Authors: Nicoli Stefania , Tobia Chiara , Gualandi Laura , De Sena Giulia , Presta Marco
Published: March 2008

The calcitonin receptor-like receptor (crlr) is a major endothelial cell receptor for adrenomedullin, a peptide vasodilator involved in cardiovascular development, homeostasis, and disease. Here, we used the zebrafish (Danio rerio) model to characterize the role of crlr in vascular development. Crlr is expressed within somites from the 4- to the 13-somite stage and by arterial progenitors and axial vessels during zebrafish development. Loss of crlr results in profound alterations in vascular development and angiogenesis, including atrophic trunk dorsal aorta and interruption of anterior aortic bifurcation, delay in intersomitic vessel development, and lack of blood circulation. Remarkably, crlr morphants are characterized by the loss of arterial endothelial cell identity in dorsal aorta, as shown by the lack of expression of the arterial markers ephrin-B2a, DeltaC, and notch5. Down-regulation of crlr affects vascular endothelial growth factor (vegf) expression, whereas vegf overexpression is sufficient to rescue arterial differentiation in crlr morphants. Finally, genetic and biochemical evidences indicate that somitic crlr expression is under the control of sonic hedgehog. These data demonstrate that crlr plays a nonredundant role in arterial differentiation, representing a novel element of the sonic hedgehog–vegf-notch signaling cascade that controls arterial/venous fate.
Dysregulation of TGF-β signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease
Authors: Grant Christian , Oh Unsong , Yao Karen , Yamano Yoshihisa , Jacobson Steven
Published: March 2008

We previously demonstrated that CD4+CD25+ T regulatory cells (Tregs), important for the maintenance of immune tolerance and prevention of autoimmune disease, from patients with human T lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) exhibit reduced Foxp3 expression and Treg suppressor function compared with healthy donors. Since TGF-β signaling has been previously reported to be critical for both Foxp3 expression and Treg function, we examined whether this signaling pathway was dysregulated in patients with HAM/TSP. Levels of TGF-β receptor II (TGF-βRII) as well as Smad7 (a TGF-β–inducible gene) were significantly reduced in CD4+ T cells in patients with HAM/TSP compared with healthy donors, and the expression of TGF-βRII inversely correlated with the HTLV-I tax proviral load. Importantly, both CD4+CD25+ and CD4+CD25− T cells from HAM/TSP patients exhibited reduced TGF-βRII expression compared with healthy donors, which was associated with functional deficits in vitro, including a block in TGF-β–inducible Foxp3 expression that inversely correlated with the HTLV-I tax proviral load, loss of Treg suppressor function, and escape of effector T cells from Treg-mediated control. This evidence suggests that a virus-induced breakdown of immune tolerance affecting both regulatory and effector T cells contributes to the pathogenesis of HAM/TSP.
Development and dynamics of robust T-cell responses to CML under imatinib treatment
Authors: Chen Christiane I-U. , Maecker Holden T. , Lee Peter P.
Published: March 2008

Novel molecular targeted therapies, such as imatinib for chronic myelogenous leukemia (CML), represent the first agents that inhibit cancer cells more than other dividing cells, such as immune cells. We hypothesize that imatinib may create a window in which the immune response is partially restored while apoptotic leukemic cells are present, thus rendering leukemic cells immunogenic as patients enter remission. To detect and quantify antileukemia immune responses in an antigen-unbiased way, we used cryopreserved autologous pretreatment blood samples (representing predominantly leukemic cells) as stimulators to detect antileukemia T-cell responses in CML patients in remission on imatinib. We studied patients over time to address the dynamics of such responses. Our data show that antileukemia T-cell responses develop in the majority of CML patients (9 of 14) in remission and that CD4+ T cells producing tumor necrosis factor-α (median 17.6%) represent the major response over interferon-γ. This confirms the immune system's ability to respond to leukemia under certain conditions. Such responses may be further amplified as a potential therapy that synergizes with imatinib for improved control of CML.
Use of IGHV3–21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post–germinal center leukemogenic selection
Authors: Ghia Emanuela M. , Jain Sonia , Widhopf George F. , Rassenti Laura Z. , Keating Michael J. , Wierda William G. , Gribben John G. , Brown Jennifer R. , Rai Kanti R. , Byrd John C. , Kay Neil E. , Greaves Andrew W. , Kipps Thomas J.
Published: March 2008

We examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV), IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity-determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH with HCDR3 motif-1 or motif-2, respectively, was paired with Ig light chains (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median time from diagnosis to initial therapy comparable with that of cases without a defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3-21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that apparently had incurred antigendriven somatic mutations and subsequent rearrangement with KDE. This study reveals that CLL cells expressing IGHV3-21/IGLV3-21 most likely were derived from B cells that had experienced somatic mutation and germinal-center maturation in an apparent antigen-driven immune response before undergoing Ig-receptor editing and after germinal-center leukemogenic selection.
Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts
Authors: Walter Roland B. , Boyle Kelli M. , Appelbaum Frederick R. , Bernstein Irwin D. , Pagel John M.
Published: March 2008

Targeting CD33 or CD45 is currently exploited for immunotherapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate of an anti-CD33 antibody that facilitates cellular uptake of a toxic calicheamicin-γ1 derivative, induces complete remissions in a subset of patients with AML. We herein tested whether simultaneous targeting of CD45 could improve GO cytotoxicity against AML cell lines and primary AML cells. We found that the anti-CD45 antibody, BC8, dose-dependently increased cytotoxicity induced by GO, and, to a lesser degree, free calicheamicin-γ1. BC8 promoted CD33 endocytosis, suggesting that its effect on GO cytotoxicity may be, at least partly, due to increased uptake and intracellular GO availability. Finally, compared with either agent alone, BC8 combined with GO resulted in marked tumor growth inhibition and superior survival rates of mice bearing human AML xenografts. These data suggest that further study of this antibody combination for clinical use in AML is warranted.
Different effects of femoral and tibial rotation on the different measurements of patella tilting: An axial computed tomography study
Authors: Lin Yeong-Fwu , Jan Mei-Hwa , Lin Da-Hon , Cheng Cheng-Kung
Published: March 2008

Background

The various measurements of patellar tilting failed to isolate patellar tilting from the confounding effect of its neighboring bone rotation (femoral and tibial rotation) in people sustaining patellofemoral pain (PFPS). Abnormal motions of the tibia and the femur are believed to have an effect on patellofemoral mechanics and therefore PFPS. The current work is to explore the various effects of neighboring bone rotation on the various measurements of patellar tilting, through an axial computed tomography study, to help selecting a better parameter for patella tilting and implement a rationale for the necessary intervention at controlling the limb alignment in the therapeutic regime of PFPS.

Methods

Forty seven patients (90 knees), comprising of 34 females and 11 males, participated in this study. Forty five knees, from randomly selected sides of bilaterally painful knees and the painful knees of unilaterally painful knees, were enrolled into the study. From the axial CT images in the subject knees in extension with quadriceps relaxed, the measurements of femoral rotation, tibial rotation, femoral rotation relative to tibia, and 3 parameters for patella tilting were obtained and analyzed to explore the relationship between the different measurements of patella tilt angle and the measurements of its neighboring bone rotation (femoral, tibial rotation, and femoral rotation relative to tibia).

Results

The effect of femoral, tibial rotation, and femoral rotation relative to tibia on patella tilting varied with the difference in the way of measuring the patella tilt angle. Patella tilt angle of Grelsamer increased with increase in femoral rotation, and tibial rotation. Patella tilt angle of Sasaki was stationary with change in femoral rotation, tibial rotation, or femoral rotation relative to tibia. While, modified patella tilt angle of Fulkerson decreased with increase in femoral rotation, tibial rotation, or femoral rotation relative to tibia.

Conclusion

The current study has demonstrated various effects of regional bony alignment on the different measurements of the patellar tilt. And the influence of bony malalignment on the patellar tilt might draw a clinical implication that patellar malalignment can not be treated, separately, independent of the related limb alignment. This clinical implication has to be verified by further works, with a comprehensive evaluation of the various treatments of patellar malalignment.
Large isoform of MRJ (DNAJB6) reduces malignant activity of breast cancer
Authors: Mitra Aparna , Fillmore Rebecca A , Metge Brandon J , Rajesh Mathur , Xi Yaguang , King Judy , Ju Jingfang , Pannell Lewis , Shevde Lalita A , Samant Rajeev S
Published: March 2008

Introduction

Mammalian relative of DnaJ (MRJ [DNAJB6]), a novel member of the human DnaJ family, has two isoforms. The smaller isoform, MRJ(S), is studied mainly for its possible role in Huntington's disease. There are no reports of any biologic activity of the longer isoform, MRJ(L). We investigated whether this molecule plays any role in breast cancer. Our studies were prompted by interesting observations we made regarding the expression of MRJ in breast cancer cell lines and breast cancer tissue microarrays, as described below.

Methods

Expression of MRJ(L) from several breast cancer cell lines was evaluated using real-time PCR. Relative levels of the small and large isoforms in breast cancer cell lines were studied using Western blot analysis. A breast cancer progression tissue microarray was probed using anti-MRJ antibody. MRJ(L) was ectopically expressed in two breast cancer cell lines. These cell lines were evaluated for their in vitro correlates of tumor aggressiveness, such as invasion, migration, and anchorage independence. The cell lines were also evaluated for in vivo tumor growth and metastasis. The secreted proteome of the MRJ(L) expressors was analyzed to elucidate the biochemical changes brought about by re-expression of MRJ(L).

Results

We found that MRJ(L) is expressed at a significantly lower level in aggressive breast cancer cell lines compared with normal breast. Furthermore, in clinical cases of breast cancer expression of MRJ is lost as the grade of infiltrating ductal carcinoma advances. Importantly, MRJ staining is lost in those cases that also had lymph node metastasis. We report that MRJ(L) is a protein with a functional nuclear localization sequence. Expression of MRJ(L) via an exogenous promoter in breast cancer cell line MDA-MB-231 and in MDA-MB-435 (a cell line that metastasizes from the mammary fat pad) decreases their migration and invasion, reduces their motility, and significantly reduces orthotopic tumor growth in nude mice. Moreover, the secreted proteome of the MRJ(L)-expressing cells exhibited reduced levels of tumor progression and metastasis promoting secreted proteins, such as SPP1 (osteopontin), AZGP1 (zinc binding α2-glycoprotein 1), SPARC (osteonectin), NPM1 (nucleophosmin) and VGF (VGF nerve growth factor inducible). On the other hand, levels of the secreted metastasis-suppressor KiSS1 (melanoma metastasis suppressor) were increased in the secreted proteome of the MRJ(L)-expressing cells. We confirmed by quantitative RT-PCR analysis that the secreted profile reflected altered transcription of the respective genes.

Conclusion

Collectively, our data indicate an important role for a totally uncharacterized isoform of DNAJB6 in breast cancer. We show that MRJ(L) is a nuclear protein that is lost in breast cancer, that regulates several key players in tumor formation and metastasis, and that is functionally able to retard tumor growth.
Effects of two different anaesthetics on serum concentrations of cortisol and luteinizing hormone in barrows and gilts
Authors: Clapper Jeffrey A
Published: March 2008

To determine if administration of the anaesthetic cocktail, telazol–ketamine–xylazine (TKX) and pentothal (PEN) decreases serum concentrations of luteinizing hormone (LH) in pigs, the following experiment was performed. On day 1, eight gilts and six barrows of similar weight (75 kg) were anaesthetized with TKX (1 mL/22.5 kg body weight [BW] intramuscularly) and indwelling jugular catheters were inserted. On days 2, 6 and 8 blood samples were taken every 20 min, for 4 h before pigs were administered saline (day 2) or anaesthetized with TKX (day 6) and PEN (8.9 mg/kg BW intravenously, day 8). Blood samples were taken every 20 min for 4 h following administration of saline and anaesthetics. Mean serum concentrations of LH and cortisol did not differ ( P > 0.05) within barrows or gilts from before administration of saline (day 2) to following saline administration. Mean serum concentrations of LH and cortisol were not different ( P > 0.05) within barrows and gilts before administration of TKX (pre-TKX) or PEN compared with day 2 samples. Following administration of TKX (post-TKX), mean serum concentrations of LH decreased ( P < 0.05) and remained decreased for 140 min, while mean serum concentrations of cortisol increased ( P < 0.05) post-TKX and remained elevated for 140 min. In gilts, mean serum concentrations of LH did not differ ( P > 0.05) from pre- to post-TKX. However, mean serum concentrations of cortisol increased ( P < 0.05) post-TKX in gilts and remained elevated for 240 min. Following administration of PEN, mean serum concentrations of LH and cortisol within barrows and gilts were not different ( P > 0.05) from concentrations before administration of PEN. Administration of TKX to barrows and gilts increased serum concentrations of Cortisol, but transient decreases in serum concentrations of LH were observed only in barrows, indicating gonadal status and/or sex may influence the ability of TKX to alter circulating concentrations of LH in pigs.
EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery
Authors: Otto Klaus A
Published: March 2008

The first attempts to introduce computerized power spectrum analysis of the electroencephalogram (EEG) as an intraoperative anaesthesia monitoring device started approximately 30 years ago. Since that time, the effects of various anaesthetic agents, sedative and analgesic drugs on the EEG pattern have been addressed in numerous studies in human patients and different animal species. These studies revealed dose-dependent changes in the EEG power spectrum for many intravenous and volatile anaesthetics. Moreover, EEG responses evoked by surgical stimuli during relative light levels of surgical anaesthesia have been classified as ‘arousal’ and ‘paradoxical arousal’ reaction, previously referred to as ‘desynchronization’ and ‘synchronization’, respectively. Contrasting reports on the correlation between quantitative EEG (QEEG) variables derived from power spectrum analysis (i.e. spectral edge frequency, median frequency) and simultaneously recorded clinical signs such as movement and haemodynamic responses, however, limited the routine use of intraoperative EEG monitoring. In addition, the appearance of EEG burst suppression pattern and isoelectricity at clinically relevant concentrations/doses of newer general anaesthetics (i.e. isoflurane, sevoflurane, propofol) may have weakened the dose-related EEG changes previously reported. Despite these findings, the EEG power spectrum analysis may still provide valuable information during intraoperative monitoring in the individual subject. The information obtained from EEG power spectrum analysis may be further supplemented by newer EEG indices such as bispectral index and approximate entropy or other neurophysiological monitors including auditory evoked potentials or somatosensory evoked potentials.
Prevalence of herpes B virus genome in the trigeminal ganglia of seropositive cynomolgus macaques
Authors: Oya C , Ochiai Y , Taniuchi Y , Takano T , Fujima A , Ueda F , Hondo R , Yoshikawa Y
Published: March 2008

Herpes B virus infection is almost asymptomatic in macaques ( Macaca spp.), which are the natural hosts of this pathogen, but is the cause of high mortality in humans. Reactivation of the latent virus in the trigeminal ganglia (TG) results in the shedding of infectious particles into the oral mucosal membrane. Saliva contaminated with the reactivated virus from the ganglia of the natural host is considered to be important for viral transmission to humans and other monkeys. In the present study, we investigated the prevalence of the herpes B virus genome in the left and right TG of seropositive asymptomatic cynomolgus macaques. The latent virus genome was detected using a polymerase chain reaction and microplate hybridization assay. We found that the virus DNA was present in one or both TG of 12 of the 30 macaques (40%) tested, with the virus being detected from both TG in five of the 12 macaques and from a single TG in the remaining seven.
Changes in minimal alveolar concentration of isoflurane following treatment with medetomidine and tiletamine/zolazepam, epidural morphine or systemic buprenorphine in pigs
Authors: Malavasi L M , Jensen-Waern M , Augustsson H , Nyman G
Published: March 2008

The aim of this study was to determine the changes in minimal alveolar concentration (MAC) of isoflurane after treatment with medetomidine and tiletamine/zolazepam (MTZ), epidural morphine or systemic buprenorphine in 11 healthy crossbred pigs. The first part of this study was to measure the baseline values in pigs induced with isoflurane (5%) by face mask and maintained with isoflurane in air and oxygen for 2 h (ISO). Baseline isoflurane MAC was determined using mechanical stimulation. Thereafter, each pig was randomly chosen for a crossover test in which the same animal received three different treatments with at least one week in between treatments. The three treatments were as follows: induction of anaesthesia with medetomidine (0.05 mg kg–1) and tiletamine/zolazepam (2.5 mg kg–1 each) given intramuscularly (MTZ); MTZ followed by epidural morphine (0.1 mg kg–1; MTZ/M); and MTZ followed by intramuscular buprenorphine (0.1 mg kg–1; MTZ/B). All pigs were maintained with isoflurane in oxygen and air for 2 h and their lungs were mechanically ventilated. The end-tidal isoflurane concentration, respiratory rate, inspiratory and expiratory O2 and CO2 concentrations, heart rate (HR) and arterial blood pressure were recorded every 10 min. Arterial blood gases were analysed every 20 min. Among the treatment groups, differences in isoflurane MAC were tested using GLM and Tukey's method for further comparison; P < 0.05 was adopted as significant. Isoflurane MAC was 1.9 ± 0.3%. MTZ reduced isoflurane MAC to 0.6 ± 0.1%. Additional morphine or buprenorphine reduced the MTZ isoflurane MAC further to 0.4 ± 0.2 and 0.3 ± 0.1%, respectively. During MTZ, MTZ/M and MTZ/B mean arterial blood pressure was higher and the alveolar-arterial oxygen tension difference was lower compared with ISO. In conclusion, induction of anaesthesia with MTZ reduced the isoflurane MAC in pigs by 68%. Additional epidural morphine or systemic buprenorphine decreased MTZ isoflurane MAC by 33 and 50%, respectively.
Aggression in cataract-bearing α-1,3-galactosyltransferase knockout mice
Authors: SØRensen Dorte Bratbo , Dahl Kirsten , Ersbøll Annette Kjær , Kirkeby Svend , D'apice Anthony J F , Hansen Axel Kornerup
Published: March 2008

The Galα1-3Galβ1-4GlcNAc epitope is the key antigen in the hyperacute rejection of pig-toman xenotransplantation. In the α-1,3-galactosyltransferase knockout (α-1,3GT-KO) mouse – a model for xenograft donor pigs – a targeted mutation of the α-1,3 galactosyltransferase gene (Ggta1) has been constructed. These mice are depleted of the carbohydrate antigen and besides the mice are also known to develop cortical cataracts. The present study aimed at evaluating the morphology and the degree of the cataract in a population of α-GT KO mice, its age of onset, its progression and the impact the cataract may have on aggression, anxiety and perception of light. The α-gal epitope could be shown in the lenses with lectin GS1 B4 in all wild-type and none of the α-GT KO mice. Histology showed apparent cataract in all α-GT KO mice from six weeks of age. Apart from a single wild-type mouse with a small degree of microscopically visible cataract without epithelial involvement at the age of 30 weeks none of the wild-type mice showed signs of cataract. Behavioural testing demonstrated significantly more mounting behaviour and a longer duration of attacking in the α-GT KO mice. Apart from this, the agonistic behaviour was not influenced by genotype. Neither did the genotype affect anxiety or perception of light.