bluuebunny/crossref_metadata_2025 huggingface dataset:
Off‐label intravenous thrombolysis in acute stroke
Authors: Guillan M. , Alonso‐Canovas A. , Garcia‐Caldentey J. , Sanchez‐Gonzalez V. , Hernandez‐Medrano I. , DeFelipe‐Mimbrera A. , Matute M. C. , Alonso‐Arias M. A. , Alonso de Leciñana M. , Masjuan J.
Published: September 2011

Background and purpose:  Therapy for stroke with intravenous tissue plasminogen activator (IV‐tPA) is hampered by tight licensing restrictions; some of them have been discussed in recent literature. We assessed the safety and effectiveness of off‐label IV‐tPA in the clinical settings.

Methods:  Retrospective analysis of all the patients treated with IV‐tPA at our Stroke Unit. Patients were divided into two groups by licence criteria [on‐label group (OnLG), off‐label group (OffLG)]. Primary outcome measures were symptomatic intracranial haemorrhages (sICH), major systemic haemorrhages, modified Rankin scale (mRS) and mortality rate at 3 months.

Results:  Five hundred and five patients were registered, 269 (53.2%) were assigned to OnLG and 236 (46.9%) to OffLG. Inclusion criteria for the OffLG were aged >80 years (129 patients), time from onset of symptoms to treatment over 3 h (111), prior oral anticoagulant treatment with International Normalised Ratio ≤ 1.7 (41), combination of previous stroke and diabetes mellitus (14), surgery or severe trauma within 3 months of stroke (13), National Institutes of Health Stroke Scale score over 25 (11), intracranial tumours (5), systemic diseases with risk of bleeding (7) and seizure at the onset of stroke (2). No significant differences were identified between both groups regarding the proportion of sICH (OnLG 2.2% vs. OffLG 1.6%, P = 0.78) or the 3‐month mortality rate (11.1% vs. 19%: odds ratio (OR), 1.49; 95% CI, 0.86–2.55; P = 0.14). Multivariate analysis showed no significant differences in functional independence at 3 months between both groups (mRS <3 64.3% vs. 50.4%: OR mRS >2 1.7; 95% CI, 0.96–2.5; P = 0.07).

Conclusion:  Intravenous thrombolysis may be safe and efficacious beyond its current label restrictions.
Mass univariate analysis of event‐related brain potentials/fields I: A critical tutorial review
Authors: Groppe David M. , Urbach Thomas P. , Kutas Marta
Published: September 2011

Event‐related potentials (ERPs) and magnetic fields (ERFs) are typically analyzed via ANOVAs on mean activity in a priori windows. Advances in computing power and statistics have produced an alternative, mass univariate analyses consisting of thousands of statistical tests and powerful corrections for multiple comparisons. Such analyses are most useful when one has little a priori knowledge of effect locations or latencies, and for delineating effect boundaries. Mass univariate analyses complement and, at times, obviate traditional analyses. Here we review this approach as applied to ERP/ERF data and four methods for multiple comparison correction: strong control of the familywise error rate (FWER) via permutation tests, weak control of FWER via cluster‐based permutation tests, false discovery rate control, and control of the generalized FWER. We end with recommendations for their use and introduce free MATLAB software for their implementation.
Parsing relationships between dimensions of anxiety and action monitoring brain potentials in female undergraduates
Authors: Moser Jason S. , Moran Tim P. , Jendrusina Alexander A.
Published: September 2011

Anxiety is associated with enhanced action monitoring. Research to date, however, has employed extreme group designs that fail to address the full spectrum of anxiety, and in which overlapping and co‐occurring symptoms obscure the exact nature of the relationships between anxiety and action monitoring. To address these limitations, relationships between distinct dimensions of anxiety and neural indicators of action monitoring were examined in a sample of female undergraduates. Results revealed that higher anxious apprehension (i.e., worry) was associated with enhanced early action monitoring activity, as indexed by the error‐related negativity/correct‐response negativity. Anxious arousal (i.e., somatic tension) on the other hand, was unrelated to measures of action monitoring. These findings suggest that the anxiety‐action monitoring link holds along the continuum of severity and is specific to the worry component of anxiety.
Monitoring force errors: Medial‐frontal negativity in a unimanual force‐production task
Authors: Armbrecht Anne‐Simone , Gibbons Henning , Stahl Jutta
Published: September 2011

The effects of force production on medial‐frontal negativity (MFN), reflecting the activity of an internal action‐monitoring system, were investigated in a force‐production task. A precue indicated a low or high force before a stimulus signaled the execution of the same or opposite force. An incorrectly exerted force was assumed to involve an error of force selection if the opposite force was required (invalid precue), and an error of force execution if the same force was required (valid precue). The task was repeated to examine any improvements in monitoring sensitivity. No force‐related effects were observed on MFN amplitude. Although performance improved, there was no evidence of a force‐error sensitive monitoring system. As the MFN and motor activity were affected by the precue invalidity regardless of the response outcome, the MFN might reflect the activity of a general action‐evaluation system that is indirectly related to motor activation.
Intra‐operative frozen section analysis for suspected early‐stage ovarian cancer: 11 years of Gateshead Cancer Centre experience
Authors: Cross PA , Naik R , Patel A , Nayar AGN , Hemming JD , Williamson SLH , Henry JA , Edmondson RJ , Godfrey KA , Galaal K , Kucukmetin A , Lopes AD
Published: September 2011

Please cite this paper as: Cross P, Naik R, Patel A, Nayar A, Hemming J, Williamson S, Henry J, Edmondson R, Godfrey K, Galaal K, Kucukmetin A, Lopes A. Intra‐operative frozen section analysis for suspected early‐stage ovarian cancer: 11 years of Gateshead Cancer Centre experience. BJOG 2012;119:194–201.

Objective  In centres in which intra‐operative frozen section (FS) analysis is not performed, ‘apparent’ early‐stage ovarian cancer diagnosed after surgery on paraffin section may require further restaging laparotomy or adjuvant chemotherapy. Previous studies on FS analysis have reported high sensitivity, specificity and overall accuracy. The objective of this article is to present the largest published dataset on the accuracy of FS analysis over an 11‐year period from a single institution.

Design  Diagnostic test accuracy.

Setting  Northern Gynaecological Oncology Centre and Department of Cellular Pathology, Gateshead, UK.

Population  1439 intra‐operative FS analyses performed between January 2000 and December 2010 for suspected ovarian cancer.

Methods  Prospectively collected data on FS analysis were compared with gold standard paraffin section.

Main outcome measures  Sensitivity, specificity, likelihood ratios and post‐test probability.

Results  The overall sensitivity and specificity of FS analysis were 91.2% and 98.6%, respectively. Positive and negative likelihood ratios were 64.7% and 0.09%, respectively. The pre‐test probability of an ovarian tumour being borderline or malignant was 45.8%. When FS analysis was reported to be positive, the post‐test probability increased to 98% (confidence interval, 97–99%). Conversely, when FS analysis was reported to be negative, the post‐test probability decreased to 7% (confidence interval, 6–9%). The majority of false test results were either borderline tumours or of mucinous differentiation.

Conclusions  Intra‐operative FS analysis has excellent diagnostic test accuracy and assists gynaecological oncologists to perform the appropriate surgery in 95% of cases, thereby preventing the morbidity of surgical staging in benign cases and the morbidity of restaging procedures or chemotherapy in early‐stage malignant tumours.
Preclinical development of CAT‐354, an IL‐13 neutralizing antibody, for the treatment of severe uncontrolled asthma
Authors: May RD , Monk PD , Cohen ES , Manuel D , Dempsey F , Davis NHE , Dodd AJ , Corkill DJ , Woods J , Joberty‐Candotti C , Conroy LA , Koentgen F , Martin EC , Wilson R , Brennan N , Powell J , Anderson IK
Published: September 2011

BACKGROUND AND PURPOSE IL‐13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. Here we describe the preclinical in vitro and in vivo characterization of CAT‐354, an IL‐13‐neutralizing IgG4 monoclonal antibody (mAb), currently in clinical development.

EXPERIMENTAL APPROACH In vitro the potency, specificity and species selectivity of CAT‐354 was assayed in TF‐1 cells, human umbilical vein endothelial cells and HDLM‐2 cells. The ability of CAT‐354 to modulate disease‐relevant mechanisms was tested in human cells measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin generation by normal lung fibroblasts, CD23 upregulation in peripheral blood mononuclear cells and IgE production by B cells. In vivo CAT‐354 was tested on human IL‐13‐induced air pouch inflammation in mice, ovalbumin‐sensitization and challenge in IL‐13 humanized mice and antigen challenge in cynomolgus monkeys.

KEY RESULTS CAT‐354 has a 165 pM affinity for human IL‐13 and functionally neutralized human, human variant associated with asthma and atopy (R130Q) and cynomolgus monkey, but not mouse, IL‐13. CAT‐354 did not neutralize human IL‐4. In vitro CAT‐354 functionally inhibited IL‐13‐induced eotaxin production, an analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE production. In vivo in humanized mouse and cynomolgus monkey antigen challenge models CAT‐354 inhibited airways hyperresponsiveness and bronchoalveolar lavage eosinophilia.

CONCLUSIONS AND IMPLICATIONS CAT‐354 is a potent and selective IL‐13‐neutralizing IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate to severe uncontrolled asthma.
The melting pot of science and belief: studying Vesuvius in seventeenth‐century Naples
Authors: EVERSON JANE E.
Published: September 2011

In December 1631, after more than 300 years of inactivity, Vesuvius erupted causing widespread damage. These were the first eruptions of Vesuvius in early modern times, and they coincided with the birth of modern scientific enquiry. They were also the first eruptions to occur after the upheavals of the Reformation and the reassertion of traditional Catholic doctrine and piety following the Council of Trent. The eruptions provoked a considerable number of publications ranging from theoretical treatises to philosophical dialogues, journals giving eyewitness accounts, and poems in both Latin and Italian. Many of these publications emanated from the numerous academies of Naples and were dedicated to leading figures in the politics and culture of the Regno. There is some sound scientific discussion in these publications, but they also testify in different ways and with varying emphases to the persistence of both orthodox Catholic belief and popular superstition. In this article I consider the relative emphases in a select number of these publications between serious science, the persistence of orthodox religious belief and the continuing humanist debt to classical literature.
Alcohol Dependence is Related to Overall Internalizing Psychopathology Load Rather than to Particular Internalizing Disorders: Evidence from a National Sample
Authors: Kushner Matt G. , Wall Melanie M. , Krueger Robert F. , Sher Kenneth J. , Maurer Eric , Thuras Paul , Lee Susanne
Published: September 2011

Background:  Alcohol dependence is more prevalent among those with any one of several anxiety or depressive (“internalizing”) disorders than among those in the general population. However, because internalizing disorders are highly intercorrelated, it is ambiguous whether alcohol dependence is related to internalizing psychopathology components that are: (i) unique to a particular internalizing disorder (“specific”); versus (ii) shared across a number of internalizing disorders (“general”). To clarify this ambiguity, we employed structural equation and logistic models to decompose the specific versus general components of internalizing psychopathology and then related these components separately to alcohol dependence.

Methods:  The data were based on face‐to‐face interviews of U.S. community residents collected in the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093).

Results:  Both analytic approaches demonstrated that increases in the general internalizing psychopathology load are accompanied by increases in the prevalence of alcohol dependence. Once the general internalizing psychopathology load is accounted for, knowing whether a particular internalizing disorder is present or absent provides little additional information regarding the prevalence of alcohol dependence.

Conclusions:  The components of internalizing psychopathology that are associated with alcohol dependence are shared and cumulative among common anxiety and depressive disorders. These findings have the potential to influence clinical and scientific conceptualizations of the association between alcohol dependence and internalizing psychopathology.
Opioidergic Modulation of Ethanol Self‐Administration in the Ventral Pallidum
Authors: Kemppainen Heidi , Raivio Noora , Suo‐Yrjo Ville , Kiianmaa Kalervo
Published: September 2011

Background:  Striatopallidal medium spiny neurons have been viewed as a final common path for drug reward and the ventral pallidum as an essential convergent point for hedonic and motivational signaling in the brain. The medium spiny neurons are GABAergic, but they colocalize enkephalin. Purpose of this study was to investigate the role of the opioidergic mechanisms of the ventral pallidum in ethanol self‐administration behavior.

Methods:  Effects of bilateral microinjections of μ‐, δ‐, and κ‐opioid receptor agonists and antagonists into the ventral pallidum on voluntary ethanol consumption were monitored in alcohol‐preferring Alko Alcohol (AA) rats using the 90‐minute limited access paradigm.

Results:  Stimulation of μ‐opioid receptors with DAMGO (0.01 to 0.1 μg) or morphine (1 to 10 μg) in the ventral pallidum decreased ethanol intake dose‐dependently. Conversely, blocking μ‐receptors with CTOP (0.3 to 3 μg) increased ethanol intake significantly. Unlike CTOP, DAMGO also increased locomotor activity. Consumption of ethanol was not modified significantly by a broad‐spectrum opioid receptor antagonist naltrexone, by δ‐opioid receptor agonist DPDPE or antagonist naltrindole, or by a κ‐opioid receptor agonist U50,488H or antagonist nor‐BNI.

Conclusions:  The study provides evidence for μ‐ but not δ‐ or κ‐opioid receptors in the ventral pallidum playing a role in the regulation of voluntary ethanol consumption. Furthermore, present findings give support to earlier work, suggesting an essential role of pallidal opioidergic transmission in drug reward.
To Approach or Avoid Alcohol? Automatic and Self‐Reported Motivational Tendencies in Alcohol Dependence
Authors: Barkby Helen , Dickson Joanne M. , Roper Louise , Field Matt
Published: September 2011

Background:  Motivational conflict is central to alcohol dependence, with patients reporting motivation to limit their drinking at the same time as urges to drink alcohol. In addition, dual process models of addiction emphasise the power of automatic cognitive processes, particularly automatic approach responses elicited by alcohol‐related cues, as determinants of drinking behavior. We aimed to examine the strength of automatic and self‐reported alcohol approach and avoidance tendencies among alcohol‐dependent inpatients relative to matched controls.

Methods:enbsp; A total of 63 alcohol‐dependent patients undergoing detoxification and 64 light‐drinking controls completed a stimulus‐response compatibility (SRC) task, which assesses the speed of categorization of alcohol‐related pictures by making symbolic approach and avoidance movements. We also included modified versions of the SRC task to assess automatic motivational conflict, that is, strong approach and avoidance tendencies elicited simultaneously by alcohol‐related cues.

Results:  There were no differences between alcohol‐dependent patients and controls on the SRC task, although individual differences in the quantity of alcohol consumed before entering treatment were significantly positively correlated with the strength of approach (but not avoidance) tendencies elicited by alcohol‐related cues. Automatic approach tendencies were also positively correlated with self‐reported “approach” inclinations and negatively correlated with self‐reported “avoidance” inclinations.

Conclusions:  Although alcohol‐dependent patients and matched controls did not differ on automatic approach and avoidance tendencies elicited by alcohol‐related cues, individual differences in the quantity of alcohol consumed before entering treatment were associated with the strength of automatic approach tendencies elicited by alcohol cues.
TRAP Abortion Laws and Partisan Political Party Control of State Government
Authors: MEDOFF MARSHALL H. , DENNIS CHRISTOPHER
Published: September 2011

Abstract

Targeted Regulation of Abortion Providers (or TRAP) laws impose medically unnecessary and burdensome regulations solely on abortion providers in order to make abortion services more expensive and difficult to obtain. Using event history analysis, this article examines the determinants of the enactment of a TRAP law by states over the period 1974–2008. The empirical results find that Republican institutional control of a state's legislative/executive branches is positively associated with a state enacting a TRAP law, while Democratic institutional control is negatively associated with a state enacting a TRAP law. The percentage of a state's population that is Catholic, public anti‐abortion attitudes, state political ideology, and the abortion rate in a state are statistically insignificant predictors of a state enacting a TRAP law. The empirical results are consistent with the hypothesis that abortion is a redistributive issue and not a morality issue.
Land Rent and Housing Policy: A Case Study of the San Francisco Bay Area Rental Housing Market
Authors: BARTON STEPHEN E.
Published: September 2011

Abstract

In the San Francisco Bay Area, where residential rent is among the highest in the United States, an analysis of data from several sources demonstrates that high rent cannot be accounted for by higher quality, higher operating costs, or higher construction costs. At least one‐third of the total rent paid is land rent. Despite increases in real incomes, very‐low‐income tenants in the Bay Area today have less income remaining after payment of rent than tenants did in 1960. High land rent is a long‐term feature of the Bay Area rental market that results mostly from its geography, the density of its urban centers, and a strong economy, rather than from regulatory barriers to new multifamily construction. Deregulation is not a sufficient response to the effects of land rent on low‐income tenants. Government should subsidize non‐profit housing organizations, particularly land trusts that remove residential land from the market. Taxes on land rent would be a particularly appropriate funding source.
Moral Capitalism: A Biblical Perspective
Authors: FRIEDMAN HERSHEY H. , ADLER WILLIAM D.
Published: September 2011

Abstract

We argue that laissez‐faire capitalism in its current form is unsustainable, and that if it is to survive, we need to develop a new moral capitalism. An underexplored source on the subject that may provide insight into current difficulties is the Hebrew Bible. We explicate four basic principles of the Hebrew Bible and Talmud on economic affairs, and show how these ancient ideas can be used to create a more moral economic system.
Regulatory T cell: a protection for tumour cells
Authors: Wang Yi , Ma Yushui , Fang Ying , Wu Shengdi , Liu Lili , Fu Da , Shen Xizhong
Published: September 2011

Introduction

The mechanisms of Tregs stimulating metastasis and mediating       immunosuppression

   ‐   Tregs stimulate cancer metastasis through RANKL‐RANK signal

   ‐   TGF‐b inhibits anti‐tumour immunity in tumour    microenvironment

   ‐   Immunosuppression of Tregs can be abolished by neutralized    or knocked out IL‐10

   ‐   CTLA‐4 participates in the suppression of Tregs

   ‐   Blocking GITR weakens the immunosuppression of Tregs

   ‐   Others

The manners of Tregs in tumour stroma

   ‐   Tregs proliferate in tumour microenvironment

   ‐   Tumours secrete chemokines recruiting Tregs from    peripheral blood

   ‐   Non‐regulatory T cells converse into Tregs in tumour stroma

The target cells of Tregs in tumour microenvironment

   ‐   Tregs weaken body immune surveillance by inhibiting DCs

   ‐   Tregs suppress non‐regulatory CD4+ T cells

   ‐   Tregs inhibit the proliferation and anti‐tumour capacity    of CD8+ T cells

   ‐  Tregs suppress the lysis of NK cells

   ‐   Tregs inhibit the proliferation of B cells

   ‐   Tregs inhibit function of macrophage directly

A new immunotherapeutic target

   ‐   Depletion of Tregs leads to tumour regression

   ‐   Inhibiting the immunosuppression of Tregs improves    the prognosis of cancer patients

   ‐   Combination immunotherapy may be the best choice

Conclusions

Characterized by immunosuppression regulatory T cells (Tregs) play a key role in maintaining immune tolerance. A growing number of tumours have been found with Tregs accumulating in microenvironment and patients with high density of Tregs in tumour stroma get a worse prognosis, which suggests that Tregs may inhibit anti‐tumour immunity in stroma, resulting in a poor prognosis. In this paper, we demonstrate the accumulation of Tregs in tumour stroma and the possible suppressive mechanisms. We also state the immunotherapy that has being used in animal and clinical trials.
Dental service utilization by Europeans aged 50 plus
Authors: Listl Stefan , Moran Valerie , Maurer Jürgen , Faggion Clovis M.
Published: September 2011

Listl S, Moran V, Maurer J, Faggion CM Jr. Dental service utilization by Europeans aged 50 plus. Community Dent Oral Epidemiol 2012; 40: 164–174. © 2011 John Wiley & Sons A/S

Objectives:  To describe variations in the utilization of dental services by persons aged 50+ from 14 European countries and to identify the extent to which such variations are attributable to differences in oral health need and in accessibility of dental care.

Methods:  We use data from the Survey of Health, Ageing, and Retirement in Europe (SHARE Waves 2 and 3) and estimate a series of multivariate logistic regression models to analyze variations in dental service utilization (overall dental attendance, preventive treatment and/or operative treatment, dental attendance in early life years)

Results:  Overall dental attendance and incidence of solely preventive treatment are comparatively high in the Netherlands, Sweden, Denmark, Germany, and Switzerland. In contrast, overall dental attendance is relatively low in Spain, Italy, France, Greece, Poland, and Ireland. Moreover, a high incidence of solely operative treatment is observed in Austria, Italy, and France, whereas in the Netherlands, Sweden, Denmark, Switzerland, and Ireland, the incidence of solely operative treatment is comparably low. By and large, these variations persist even when controlling for cross‐country differences in oral health need and in accessibility of dental care.

Conclusions:  In comparison with other European regions, there is a tendency toward more frequent and preventive dental treatment of the elderly populations residing in Scandinavia and Western Europe. Such utilization patterns appear only partially attributable to differences in need for and accessibility of dental care.
The mitogen‐induced generation of interferon‐gamma producing cells in cultures of rhesus monkey peripheral blood mononuclear cells is age‐dependent
Authors: van Besouw N.M. , van der Meide P.H. , Bakker N.P.M.
Published: September 2011

An enzyme‐linked immunoabsorbent spot (ELISPOT) assay has been developed for measuring the frequency of interferon‐gamma (IFN‐gamma) producing cells in rhesus monkeys.

Aged monkeys revealed, upon mitogenic stimulation, a significantly higher percentage of IFN‐gamma secreting peripheral blood mononuclear cells (PBMC) compared to young animals. No correlation was found between the frequency of IFN‐gamma producing PBMC and the mitogen‐driven proliferation, indicating that in rhesus monkeys no direct correlation exists between these two activation parameters.
Chimpanzees in AIDS research: A biomedical and bioethical perspective
Authors: van Akker R. , Balls M. , Eichberg J.W. , Goodall J. , Heeney J.L. , Qsterhaus A.D.M.E. , Prince A.M. , Spruit I.
Published: September 2011

The present article represents a consensus view of the appropriate utilization of chimpanzees in AIDS research arrived at as a result of a meeting of a group of scientists involved in AIDS research with chimpanzees and bioethicists. The paper considers which types of studies are scientifically justifiable in this species, the conditions under which such studies should be carried out, and the conditions which should be encouraged for post‐experimental retirement of these animals.
Immunization with whole inactivated vaccine protects from infection by SIV grown in human but not macaque cells
Authors: Goldstein Simoy , Elkins William R. , London William T. , Hahn Anna , Goeken Robert , Martin Jennifer E. , Hirsch Vanessa M.
Published: September 2011

Homologous SIVsm stocks were generated by passage of a macaque isolate of SIVsm (SIVsm/E660) in human CEM × 174 cells or macaque peripheral blood mononuclear cells. Macaques were immunized with whole inactivated SIV vaccine consisting of virus generated by transfection of CEM × 174 cells with the SIVsmH4 clone and were challenged with either cell‐free stock. Only vaccinees challenged with virus generated in human cells were protected from infection. This confirms the species‐specificity of whole inactivated vaccine‐mediated protection.
Ultrastructural and immunohistochemical studies in callitrichid renal glomeruli
Authors: Brack M. , Weber M.
Published: September 2011

The “normal” mesangium of callitrichids exhibits certain features pointing to enhanced activity. Protrusions of the mesangial cellular cytoplasm (blebs) into the capillary lumen were observed very frequently as were electron‐dense granules in mesangial matrix channels. Histochemical, α‐actin expression was invariably observed in the mesangial cells of callitrichids.
VCAM‐1 expression and leukocyte trafficking to the CNS occur early in infection with pathogenic isolates of SIV
Authors: Sasseville Vito G. , Lane Joan H. , Walsh Dennis , Ringler Douglas J. , Lackner Andrew A.
Published: September 2011

Abstract: This study reports on the endothelial expression of vascular cell adhesion molecule‐1 (VCAM‐1) in the central nervous system (CNS) early after experimental infection of rhesus monkeys (Macaca mulatta) with pathogenic and nonpathogenic simian immunodeficiency virus (SIV). Diffuse endothelial expression of VCAM‐1 was observed in the CNS in all animals receiving pathogenic SIV These findings demonstrate the rapidity with which pathogenic SIV is able to enter the CNS and induce endothelial cell activation.
Red cell polymorphisms in nonhuman primates: A review
Authors: Socha Wladyslaw W. , Blancher Antoine , Moor‐Jankowski Jan
Published: September 2011

Abstract: Development as well as current status of the knowledge of nonhuman primate blood groups are discussed together with some practical implications of the red cell antigen polymorphisms in anthropoid apes, Old and New World monkeys and prosimians. Recent data on molecular biology and genetics throw light on the relationships among simian and human red cell antigens and their evolutionary pathways.
The history of simian AIDS
Authors: Gardner Murray B.
Published: September 2011

Abstract: Gardner MB. The history of simian AIDS. J Med Primatol 1996; 25:148–157. Munksgaard, Copenhagen

Retrospective data indicate that two separate outbreaks of simian AIDS and associated lymphoma were caused by Simian Immunodeficiency Virus (SIVmac and SIVstm, respectively) in group‐housed macaques at the California Regional Primate Research Center (CRPRC) in the early and mid‐1970s. Because these epizootics were not then recognized as infectious in nature, surviving healthy SIV carriers were sent to other primate centers where they transmitted the viruses to resident macaques. The source of SIV at the CRPRC was by contact with co‐housed seropositive sooty mangabeys. Spread of SIV via saliva and blood while fighting most likely accounted for these epizootics. Separate outbreaks of a somewhat different version of simian AIDS, caused by the simian Type D retrovirus (SRV‐1), and spread from healthy carriers via saliva and blood also occurred in the late 1970s and early 1980s in group‐housed macaques at the CRPRC. Initially, these SRV‐1 outbreaks were also not recognized as infectious.
Initial characterization of viral sequences from a SHIV‐inoculated pig‐tailed macaque that developed AIDS
Authors: Stephens E.B. , Joag S.V. , Sheffer D. , Liu Z.Q. , Zhao L. , Mukherjee S. , Foresman L. , Adany I. , Li Z. , Pinson D. , Narayan O.
Published: September 2011

Abstract: In this study, we report on the derivation of a pathogenic SIV‐HIV chimeric virus (SHIV) and the initial characterization of the viral sequences from the first (macaque PPc) of a series of pig‐tailed macaques that developed CD4+ T cell loss and AIDS. Viral genes were amplified by PCR from the brain, lymphoid, and kidney tissues and their sequences compared to the original SHIV used to initiate passages in macaques. Our results show that the vpu gene, which was nonfunctional in the original SHIV, now coded for functional protein in macaque PPc. The tat and rev genes had no consensus changes but the nef gene had 4–5 consensus changes, depending on the tissue examined. The gp 120 gene had the highest number of nucleotide and amino acid substitution rates that varied from 0.64% to 1.44% and 1.17% to 3.71%, respectively, again depending on the tissue examined. These results suggest that a constellation of changes accumulated at the genomic level during the derivation of a SHIV that was pathogenic for pig‐tailed macaques.
The immunopathogenesis of retroviral diseases: No immunophenotypic alterations in T, B, and NK cell subsets in SIVmac239‐challenged rhesus macaques protected by SIVΔnef vaccination
Authors: Giorgi Janis V. , Hultin Lance E. , Desrosiers Ronald C.
Published: September 2011

Abstract: Immunophenotype analysis was used to characterize circulating lymphocyte subset levels in both rhesus monkeys that were chronically infected with SIVmac239 and in those that had resisted SIVmac239 infection as a result of prior vaccination with an attenuated SIV strain. Alterations in T, NK, and B cell subsets were compared with those previously identified in humans chronically infected with HIV [8–11, 14, 22]. The well‐known decrease in CD4+ cell levels was observed in the SIVmac239‐infected animals. However, these animals had relatively little activation of circulating CD8+ T cells as compared with uninfected monkeys. This contrasts with chronically HIV‐infected humans who have substantial activation of circulating CD8+ cells as evidenced by elevated HLA‐DR and CD38 antigen expression on CD8+ cells as well as substantially increased percentages and numbers of total CD8+ cells. NK cells of the SIVmac239‐infected animals, on the other hand, demonstrated the same changes recently described in HIV‐infected humans, i.e., a decrease in circulating percentages and a decreased amount of FcRIII (CD 16). B cell percentages were markedly increased in the SIVmac239‐infected animals, a finding also noted in some children with HIV infection but not in HIV‐infected adults. SIVΔnef‐vaccinated/SIVmac239‐challenged animals showed none of the immune alterations found in the SIVmac239‐infected monkeys, providing further confirmation of lack of SIV disease in these vaccinated animals.
Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells
Authors: Polacino Patricia S. , Pinchuk Lesya M. , Sidorenko Svetlana P. , Clark Edward A.
Published: September 2011

Abstract: We explored the relationship between T cell activation signals and dendritic cells (DC) in the replication cycle of immunodeficiency viruses. First we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on SIV reverse transcription, circularization, and integration in macaque resting T cells stimulated with anti‐CD3 mAb at the time of infection. The formation of SIV LTR circles was blocked by the G1 inhibitor mimosine. The G1/S inhibitor aphidicolin neither affected circularization nor integration of SIV DNA. Therefore, the induction of SIV LTR circle production is likely to be mediated by signaling events normally regulating the G1 to S transition. We further characterized DC‐dependent HIV‐expression in human T cells. We examined the effect of ligating two novel receptors, IPO‐3 and Bgp95, on DC‐dependent HIV‐1 expression. Activation of DCs through IPO‐3 receptors, and to a lesser extent Bgp95 ligation, upregulated HIV spread in these cells. The mechanisms by which IPO‐3 vs. Bgp95 increase HIV‐1 levels appear to be different. In particular, IPO‐3 ligation alone on T cells also increased HIV‐1 levels. Activation of T cells via defined surface receptors or with DCs is required for establishing HIV/SIV cDNA synthesis in T cells.
Occurrence and frequency of transmission of naturally occurring simian retroviral infections (SIV, STLV, and SRV) at the CIRMF Primate Center, Gabon
Authors: Georges‐Courbot M.C. , Moisson P. , Leroy E. , Pingard A.M. , Nerrienet E. , Dubreuil G. , Wickings E.J. , Debels F. , Bedjabaga I. , Poaty‐Mavoungou V. , Hahn N. T. , Georges A.J.
Published: September 2011

Abstract: Among the primates held at the CIRMF Primate Center, Gabon, no serological sign of SIV infection could be demonstrated in 68 cynomolgus monkeys, 60 chimpanzees, nine gorillas, and 12 sun‐tailed monkeys, while seven of 102 mandrills and six of 24 vervets were infected with SIV. Six mandrills, seven vervets and ten cynomolgus monkeys exhibited a full HTLV type 1 Western blot profile. The sera of two gorillas and one chimpanzee presented with a positive but not typical HTLV Western blot profile. The sera of the gorillas lacked p24 antibodies, and the chimpanzee had a Western blot profile evocative of HTLV‐II. All attempts to amplify viruses from these animals by PCR were unsuccessful. Two other chimpanzees and seven gorillas presented with indeterminate HTLV Western blot profiles. In the mandrill colony, only male animals were STLV seropositive and no sexual transmission to females was observed. SIV infection was also more frequent in male than female mandrills and sexual transmission appeared to be a rare event. No SRV infection was observed in macaques.
Identification of rhesus macaques with spontaneous endometriosis
Authors: Rippy M.K. , Lee D.R. , Pearson S.L. , Bernal J.C. , Kuehl T.J.
Published: September 2011

Abstract: Rhesus macaques (Macaca mulatta) with endometriosis were identified using reproductive histories, serum levels CA‐125, pelvic ultrasonography, laparoscopy, and histopathology. All animals were evaluated from a large breeding colony and had a history of infertility and/or spontaneous abortions. Laparoscopy and ultrasonography were performed on 40 macaques: 27 macaques from the breeding colony with elevated CA‐125 levels, ten macaques from the breeding colony with normal or low serum CA‐125 levels, and three macaques from another facility with previously diagnosed spontaneous endometriosis. Clinical endometriosis was diagnosed by laparoscopy in 16/37 (43%) macaques from the breeding colony and was confirmed by histologic examination in all animals biopsied. The disease was classified as minimal (40%), mild (25%), moderate (10%), or severe (25%). The most common sites of endometriosis were the serosal surface of the uterus (75%) and the posterior cul‐de‐sac (75%). In this study, CA‐125 levels were useful in identifying animals from the breeding colony with endometriosis. The rhesus macaque provides a valuable animal model to study endometriosis and potentially to assess efficacy of therapeutic agents for this disease condition.
The physiological and behavioral effects of radio music on singly housed baboons
Authors: Brent L. , Weaver O.
Published: September 2011

Abstract: The response of four singly caged baboons to radio music was measured using behavioral and physiological indices. Heart rate and blood pressure, measured through a tether system, as well as behavior, were recorded during a two‐week period in which radio music was available in half of the samples. The behavior of the subjects, as well as their blood pressure, did not vary in relation to radio music. Heart rate was significantly lower when the radio was on.
Pertussis toxin induces lymphocytosis in rhesus macaques
Authors: Hinds Paul W. , Yin Cheng , Salvato Maris S. , Pauza C. David
Published: September 2011

Abstract: Lymph nodes and other solid tissues of the immune system are the principal sites for antigen presentation and lymphocyte activation. Lymphocytes in peripheral blood recognize the high endothelial venules within lymphoid tissues and cross from blood to tissue by the process of extravasation. Pertussis toxin is known to block extravasation and cause lymphocytosis in murine models but has not been studied extensively in nonhuman primates. We used intravenous injection of soluble pertussis toxin to induce a transient lymphocytosis in rhesus monkeys. The increase in total white blood cells was proportionally greater for lymphocytes than for polymorphonuclear cells and the CD4+ lymphocyte subpopulation increased more than the CD8+ cell population. The presence of immature polymorphonuclear cells suggested some activation of bone marrow. Clinical chemistry studies revealed an effect of pertussis toxin on liver function. Pertussis toxin is a powerful immunomodulatory agent that can disrupt and reorganize solid lymphoid tissues.
Inflammatory arthritis in Pongo
Authors: Rothschild Bruce M. , Woods Robert J.
Published: September 2011

Abstract: As the arboreal ape, Pongo, has an unusual ground ambulation adaptation, it was of interest to assess the impact of Pongo gait on patterns of arthritis. While osteoarthritis was not identified in Pongo, 11% of individual skeletons were afflicted with an inflammatory, erosive arthritis. The presence of sacroiliac involvement and the nature and distribution of erosive lesions allowed definitive diagnosis of spondyloarthropathy. Character, distribution, and radiologic appearance revealed a picture distinguishable from spondyloarthropathy in other primates.
Cell tropism of the simian foamy virus type 1 (SFV‐1)
Authors: Mergia Ayalew , Leung Nancy J. , Blackwell Jeanne
Published: September 2011

Abstract: Several cell lines representing different species and cell types were tested for simian foamy virus type 1 (SFV‐1) infection. SFV‐1 infections were monitored by polymerase chain reaction, reverse transcriptase, cytopathology, and immunofluorescent assays. All cells tested were permissive for SFV‐1, demonstrating that SFV‐1 has a broad host range with respect to species and cell types. Infected fibroblasts, epithelial cells, and neural cells all showed extensive cytopathology that is characteristic of foamy virus infection. No cytopathology was induced in T cell‐derived Jurkats and Hut‐78 cell lines. The cytopathic effects in B and macrophage originated cells were delayed by several days. Cytopathology in these cell lines was not as dramatic as seen in the infected fibroblast and epithelial cells. The reverse transcriptase values in the SFV‐1 infected lymphoid and macrophage cell lines were severalfold lower than that of the fibroblasts and epithelial cells. Therefore, SFV‐1 appears to establish a low level persistent infection in lymphoid and macrophage cell lines.
Influences of blood sampling procedures on basal hypothalamic‐pituitary‐adrenal hormone levels and leukocyte values in rhesus macaques (Macaca mulatta)
Authors: Capitanio John P. , Mendoza Sally P. , McChesney Michael
Published: September 2011

Abstract: The influences of housing location and temporal factors on the results of blood sampling were examined to determine their contributions to levels of hypothalamic‐pituitary‐adrenal hormones, as well as leukocyte subset counts from peripheral blood in rhesus monkeys. Differences in housing location and the amount of room disturbance associated with blood sampling have a significant impact on cell counts, but not on ACTH or Cortisol levels.
Relation between phylogeny of African green monkey CD4 genes and their respective simian immunodeficiency virus genes
Authors: Fomsgaard Anders , Müller‐Trutwin Michaela C. , Diop Ousmane , Hansen Jan , Mathiot Christian , Corbet Sylvie , Barré‐Sinoussi Francoise , Allan Jonathan S.
Published: September 2011

Abstract: An apparent species‐specific relatedness of SIVagm suggests a coevolution with their natural hosts. However, the exact species or subspecies classification of African green monkeys, AGM, is uncertain because current classification schemes rely on phenotype markers, while more definitive genetic data are lacking. In this study, the CD4 protein involved in tissue type recognition was genetically cloned and sequenced from PBMC RNA from all AGM species, including Barbados green monkeys (BGM). Phylogenetic trees were constructed that also included genomic CD4 nucleotide sequences from patas, sooty mangabeys, rhesus and pig‐tail macaques, chimpanzees, and humans. Chimpanzees and humans consistently clustered together. Monkeys within the Cercopithecus genus formed a separate cluster which included pata monkeys, supporting its grouping as a member of Cercopithecus. Surprisingly, sooty mangabeys were genetically more closely related to Asian macaques than to other African species, which might explain why macaques are more susceptible to infection by the SIVsm group than to infection by SIVagm or HIV‐1 and why patas, on the other hand, are highly susceptible to SIVagm infection. Based on CD4 genetic data, tantalus, vervets, grivets, and sabaeus formed separate subgroups with BGM grouping closely with vervets. The branching order of the AGM species was related to that of their respective SIVagm env sequences. The study suggests a strong correlation between CD4 phylogeny and the susceptibility of the host species to infection by a specific lentivirus and supports the assumption of a coevolution of SIVagm and AGM. CD4 sequencing is suggested as a relevant method for genetic determination of primate species.
Nonsurgical embryo transfer in the common marmoset monkey
Authors: Marshall V.S. , Kalishman J. , Thomson J.A.
Published: September 2011

Abstract: A technique for nonsurgical embryo transfer in common marmosets was developed. Transfers were either synchronous (ST) or asynchronous (AT). Synchronous transfers (embryo donor and the embryo recipient ovulated on the same day) were performed 5 to 8 days post‐ovulation. Asynchronous transfers (embryo donor had ovulated at least 2 days before the embryo recipient) were performed when the recipient was 2 to 4 days post‐ovulation (donor was 6 to 8 days post‐ovulation). Four pregnancies from nine transfers (44%) were established by AT, and three pregnancies were carried to term. Only 1 of 11 transfers (9%) from ST resulted in a pregnancy, which was lost by Day 40 of gestation. Significantly more infants were born from AT (6 infants from 17 embryos; 35%) than from ST (0 infants from 22 embryos; 0%; p<0.005). This technique allows experimental analysis of primate postimplantation development and provides a tool for conservation of endangered Callithrichid species.
Seroprevalence of specific viral infections in confiscated orangutans (Pongo pygmaeus)
Authors: Warren K.S. , Niphuis H. , Heriyanto  , Verschoor E.J. , Swan R.A. , Heeney J.L.
Published: September 2011

A serological survey of confiscated orangutans was conducted to determine the prevalence of specific viral infections cross reacting with human viruses. Antibodies specific for human hepatitis A (HAV) and B (HBV) viruses, herpes simplex viruses (HSV), and human T‐lymphotropic virus (HTLV types I and II), as well as for the simian type D retroviruses (SRV types 1 to 3) and simian immunodeficiency virus (SIV) were tested in samples from 143 orangutans. Results revealed a high prevalence of potential pathogens. The most prevalent viral infection found was HBV (59.4% prevalence) of which 89.4% of infected individuals seroconverted to the non‐infectious state and 10.6% remained as chronic carriers. Antibodies to HAV, HSV, HTLV‐1, and SRV were also detected but at a lower prevalence. There was no evidence of lentiviral infections in this group of animals. The results confirm the importance of quarantine and the need for diagnostic differentiation of virus infections to determine if they are of human origin or unique orangutan viruses.
CD4/GP120mac251 interaction induces phospholipase A2 (PLA2) activation in cynomolgus monkey lymphocytes
Authors: Mavoungou Elie , Poaty‐Mavoungou Virginie
Published: September 2011

Cynomolgus monkey are susceptible to infection with select simian immunodeficiency virus (SIV). We investigated the early interactions between SIV envelope glycoproteins (gp120mac251) and macaque lymphocytes. Our results demonstrate that the soluble viral glycoprotein induce a specific phospholipase A2 (PLA2) activation in lymphocytes through CD4. This PLA2 activation, induced after envelope glycoprotein‐CD4 interaction, because of its locally destabilizing membrane effect, may have important implications for preparing the lymphocyte membrane for fusion with the viral particle. However, this effect is not sufficient to accomplish fusion. These data indicate that the specific step of fusion may be downstream from PLA2 activation.
Effects of 13‐cis‐retinoic acid on hindbrain and craniofacial morphogenesis in long‐tailed macaques (Macaca fascicularis)
Authors: Makori Norbert , Peterson Pamela E. , Blankenship Thomas N. , Dillard‐Telm Lisa , Hummler Hans , Hendrickx Andrew G.
Published: September 2011

Hindbrain and craniofacial development during early organogenesis was studied in normal and retinoic acid‐exposed Macaca fascicularis embryos. 13‐cis‐retinoic acid impaired hindbrain segmentation as evidenced by compression of rhombomeres 1 to 5. Immunolocalization with the Hoxb‐1 gene product along with quantitative measurements demonstrated that rhombomere 4 was particularly vulnerable to size reduction. Accompanying malformations of cranial neural crest cell migration patterns involved reduction and/or delay in pre‐ and post‐otic placode crest cell populations that contribute to the pharyngeal arches and provide the developmental framework for the craniofacial region. The first and second pharyngeal arches were partially fused and the second arch was markedly reduced in size. The otocyst was delayed in development and shifted rostrolaterally relative to the hindbrain. These combined changes in the hindbrain, neural crest, and pharyngeal arches contribute to the craniofacial malformations observed in the retinoic acid malformation syndrome manifested in the macaque fetus.