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Sample records for concanavalin-a-primed baboon lymphocytes

  1. Increased lymphoid tissue apoptosis in baboons with bacteremic shock.

    Science.gov (United States)

    Efron, Philip A; Tinsley, Kevin; Minnich, Douglas J; Monterroso, Victor; Wagner, J; Lainée, Pierre; Lorré, Katrien; Swanson, Paul E; Hotchkiss, Richard; Moldawer, Lyle L

    2004-06-01

    The molecular mechanisms of immune cell apoptosis during sepsis remain unclear. Two young adult baboons (Papio sp.) received a lethal dose of live Escherichia coli and were sacrificed at either 16 (for animal welfare concerns) or 24 h post-septic shock. An additional baboon, which received no bacteria, served as a control. Necropsy was performed immediately with subsequent immunohistochemical staining of lymphoid tissue. Immunohistologic analysis of tissues from the septic baboons revealed marked systemic lymphocyte apoptosis occurring in all lymphoid tissues examined. Focally, pyknotic and karyorrhectic lymphocytes demonstrated activation of a mitochondrial-dependent cell death pathway (active caspase 9 and apoptosis-inducing factor). Other regions demonstrated apoptotic lymphocytes with activation of a death receptor-dependent cell pathway (Fas ligand). Thus, we have demonstrated for the first time in primates that overwhelming gram-negative bacteremia produces an early and profound lymphocyte death that occurs through multiple cell death pathways. Bacteremic shock in the baboon may be an appropriate model for studying experimental therapies aimed at blocking lymphocyte apoptosis because their response appears comparable to humans dying from sepsis.

  2. Immunological compatibility between the chacma baboon and man.

    Science.gov (United States)

    Stark, J H; Smit, J A; Neethling, F A; Nortman, P J; Myburgh, J A

    1991-12-01

    Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.

  3. The baboon syndrome

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hjorth, N; Menné, T

    1984-01-01

    The catchword "baboon syndrome" is used to denote a characteristic distribution pattern of systemic allergic contact dermatitis. Diffuse erythema of the buttocks, upper inner surface of the thighs, and axillae are characteristic features. We describe 3 cases provoked by ampicillin, nickel...... and mercury. The condition may be overlooked and suspected of being a textile dermatitis or seborrhoeic dermatitis of the elderly....

  4. Giant cell lichenoid dermatitis in a patient with baboon syndrome.

    Science.gov (United States)

    Khelifa-Hamdani, Elhem; Touati-Serraj, Monia; Perriard, Jacqueline; Chavaz, Pierre; Saurat, Jean-Hilaire; Kaya, Gürkan

    2008-10-01

    Giant cell lichenoid dermatitis is a recently described pathological entity, which can be seen as an unusual lichenoid drug eruption, a manifestation of sarcoidosis or within herpes zoster scars. Histopathological findings include focal vacuolar alteration of the basal layer with cytoid bodies, dermal and intraepidermal multinucleated giant cells and a mixed chronic inflammatory infiltrate with a lichenoid pattern consisting of lymphocytes, histiocytes, eosinophils and plasma cells. Here, we report a giant cell lichenoid dermatitis in a 41-year-old male patient who developed, 3 days after intravenous treatment with amoxicillin-clavulanic acid for erysipelas of the left leg, a clinical picture suggesting a baboon syndrome characterized by an erythematous and pruritic eruption on the axillary, inguinal and popliteal areas and the anterior side of elbows. This is the first reported case of giant cell lichenoid dermatitis in a patient with baboon syndrome.

  5. Seed size selection by olive baboons.

    Science.gov (United States)

    Kunz, Britta Kerstin; Linsenmair, Karl Eduard

    2008-10-01

    Seed size is an important plant fitness trait that can influence several steps between fruiting and the establishment of a plant's offspring. Seed size varies considerably within many plant species, yet the relevance of the trait for intra-specific fruit choice by primates has received little attention. Primates may select certain seed sizes within a species for a number of reasons, e.g. to decrease indigestible seed load or increase pulp intake per fruit. Olive baboons (Papio anubis, Cercopithecidae) are known to select seed size in unripe and mature pods of Parkia biglobosa (Mimosaceae) differentially, so that pods with small seeds, and an intermediate seed number, contribute most to dispersal by baboons. We tested whether olive baboons likewise select for smaller ripe seeds within each of nine additional fruit species whose fruit pulp baboons commonly consume, and for larger seeds in one species in which baboons feed on the seeds. Species differed in fruit type and seed number per fruit. For five of these species, baboons dispersed seeds that were significantly smaller than seeds extracted manually from randomly collected fresh fruits. In contrast, for three species, baboons swallowed seeds that were significantly longer and/or wider than seeds from fresh fruits. In two species, sizes of ingested seeds and seeds from fresh fruits did not differ significantly. Baboons frequently spat out seeds of Drypetes floribunda (Euphorbiaceae) but not those of other plant species having seeds of equal size. Oral processing of D. floribunda seeds depended on seed size: seeds that were spat out were significantly larger and swallowed seeds smaller, than seeds from randomly collected fresh fruits. We argue that seed size selection in baboons is influenced, among other traits, by the amount of pulp rewarded per fruit relative to seed load, which is likely to vary with fruit and seed shape.

  6. vaginal histological changes of the baboon

    African Journals Online (AJOL)

    2009-04-04

    Apr 4, 2009 ... baboon is a good model for investigating possible effects of hormonal contraceptives on vaginal epithelium .... folding. The placard and rosette arrangement of cells remained high. .... A randomized, double-blind trial. Mauritas.

  7. The discrimination of baboon grunt calls and human vowel sounds by baboons

    Science.gov (United States)

    Hienz, Robert D.; Jones, April M.; Weerts, Elise M.

    2004-09-01

    The ability of baboons to discriminate changes in the formant structures of a synthetic baboon grunt call and an acoustically similar human vowel (/eh/) was examined to determine how comparable baboons are to humans in discriminating small changes in vowel sounds, and whether or not any species-specific advantage in discriminability might exist when baboons discriminate their own vocalizations. Baboons were trained to press and hold down a lever to produce a pulsed train of a standard sound (e.g., /eh/ or a baboon grunt call), and to release the lever only when a variant of the sound occurred. Synthetic variants of each sound had the same first and third through fifth formants (F1 and F3-5), but varied in the location of the second formant (F2). Thresholds for F2 frequency changes were 55 and 67 Hz for the grunt and vowel stimuli, respectively, and were not statistically different from one another. Baboons discriminated changes in vowel formant structures comparable to those discriminated by humans. No distinct advantages in discrimination performances were observed when the baboons discriminated these synthetic grunt vocalizations.

  8. Epizootic pertussis focus of hamadryad baboons

    Directory of Open Access Journals (Sweden)

    A. Yu. Medkova

    2015-01-01

    Full Text Available The absence of an adequate experimental animal model makes difficult study of immunity against whooping cough and its pathogenesis. Experimental whooping cough reported by us earlier in pubescent non-human primates of the Old World was accompanied by specific clinical and laboratory marks in the absence of cough. The possibility of pertussis modelling while experimental whooping cough in impuberal hamadryad baboons was investigated. In the process of selection of monkeys for the further studies for perfecting of experimental model for pertussis research unexpectedly were detected specific pertussis antibodies in impuberal hamadryad baboons.The aim of the study: revealing of source of infection and transmission of pertussis to hamadryad baboons and investigation of response of antibody-positive impuberal hamadryad baboons to secondary contagion by B. pertussis bacteria while experimental infection.Results. 18 veterinary checked, somatically healthy hamadryad baboons of various gender managed in two neighboring cages. Specific pertussis IgM and IgG antibodies were found in blood serum of all the animals and one of the monkey keepers. By real-time PCR in nasopharyngeal swabs of the monkey keeper and three 7- and 9-month-old hamadryad baboons were registered single B. pertussis genom equivalents. Seropositive impuberal hamadryad baboons were experimentally challenged by virulent B. pertussis 475 strain. Quantity of B. pertussis genom equivalents and percentage of IgM and IgG antibodies in impuberal hamadryad baboons after experimental infection were detected. These results were comparable with such received after secondary experimental challenge of monkeys by B. pertussis. Humoral immuneresponse was characterized by booster effect and rapid B. pertussis elimination.Conclusion. The case of transmission of B.pertussis bacteria to hamadryad baboons by natural contagion and epizootic focus of pertussis in apery conditions

  9. Deep learning of orthographic representations in baboons.

    Science.gov (United States)

    Hannagan, Thomas; Ziegler, Johannes C; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process.

  10. Taxonomy Icon Data: hamadryas baboon [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available hamadryas baboon Papio hamadryas Chordata/Vertebrata/Mammalia/Theria/Eutheria/Primate Papio_hamadry...as_L.png Papio_hamadryas_NL.png Papio_hamadryas_S.png Papio_hamadryas_NS.png http://bioscien...cedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadry...as&t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&...t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=186 ...

  11. Renal histopathology of a baboon model with type 2 diabetes.

    Science.gov (United States)

    Rincon-Choles, Hernan; Abboud, Hanna E; Lee, Shuko; Shade, Robert E; Rice, Karen S; Carey, K Dee; Comuzzie, Anthony G; Barnes, Jeffrey L

    2012-10-01

    Naturally occurring type 2 diabetes has been found in a colony of baboons. Ongoing characterization of the baboon colony maintained at the Southwest National Primate Research Center has revealed a significant range of glucose sensitivity with some animals clearly diabetic.   Seven baboons, four with diabetes and three without diabetes, underwent histopathological investigation. Three diabetic animals were diagnosed using fasting blood glucose, hemoglobin A1C, and intravenous glucose tolerance test, and a fourth one was known to have hyperglycemia. One control baboon and three baboons with diabetes had microalbuminuria. On kidney biopsy, diabetic baboons had thickening of the glomerular basement membrane and mesangial matrix expansion compared to controls. Immunohistochemistry showed the diabetic animals had increased mesangial expression of cellular fibronectin ED-A. Two diabetic animals with microalbuminuria had evidence of mesangiolysis with the formation of an early nodule. One diabetic animal had a Kimmestiel-Wilson nodule. We conclude that the baboon represents a useful primate model of diabetes and nephropathy that resembles the nephropathy associated with type 2 diabetes in humans.

  12. [Grooming and group structure in hamadryas baboons].

    Science.gov (United States)

    2010-09-01

    The results of 3-year observation on coral living hamadryas baboons transported from natural habitat in Tuapse reservation have been presented. Despite of the fact that grooming between males and females accounted for 73% of total cases of grooming in adult individual pairs, only the relationships of males with high-ranked females of their harems fully corresponded to a star-shaped sociogram. The high-ranked females were not different from all the other females either according to a total number of grooming cases with their female partners or according to a proportion of a performed and received grooming. Grooming between the related females was noted predominantly in the cases when they belonged to the same harem. Grooming between the related males accounted for 59% of all the cases of grooming between the male partners.

  13. Charting the neglected West: The social system of Guinea baboons.

    Science.gov (United States)

    Fischer, Julia; Kopp, Gisela H; Dal Pesco, Federica; Goffe, Adeelia; Hammerschmidt, Kurt; Kalbitzer, Urs; Klapproth, Matthias; Maciej, Peter; Ndao, Ibrahima; Patzelt, Annika; Zinner, Dietmar

    2017-01-01

    Primate social systems are remarkably diverse, and thus play a central role in understanding social evolution, including the biological origin of human societies. Although baboons have been prominently featured in this context, historically little was known about the westernmost member of the genus, the Guinea baboon (Papio papio). Here, we summarize the findings from the first years of observations at the field site CRP Simenti in the Niokolo Koba National Park in Senegal. Guinea baboons reveal a nested multi-level social organization, with reproductive units comprising one "primary" male, one to several females, young, and occasionally "secondary" males at the base of the society. Three to five units form "parties," which team up with other parties to form a "gang." Different gangs have largely overlapping home ranges and agonistic interactions between different parties or gangs are rare. Some but not all strongly socially bonded males are highly related, and population genetic and behavioral evidence indicate female-biased dispersal. Females play an important role in intersexual bond formation and maintenance, and female tenure length varies between a few weeks to several years. While the social organization resembles that of hamadryas baboons (P. hamadryas), the social structure differs considerably, specifically in terms of low male aggressiveness and female freedom. Despite substantial differences in social organization and social structure, the acoustic structure of Guinea baboon vocalizations does not differ substantially from that of other baboon taxa. With its multi-level organization, stable bonds between males and females, as well as a high-degree of male-male cooperation and tolerance, Guinea baboons constitute an intriguing model for reconstructing human social evolution. © 2017 American Association of Physical Anthropologists.

  14. What baboons can (not) tell us about natural language grammars.

    Science.gov (United States)

    Poletiek, Fenna H; Fitz, Hartmut; Bocanegra, Bruno R

    2016-06-01

    Rey et al. (2012) present data from a study with baboons that they interpret in support of the idea that center-embedded structures in human language have their origin in low level memory mechanisms and associative learning. Critically, the authors claim that the baboons showed a behavioral preference that is consistent with center-embedded sequences over other types of sequences. We argue that the baboons' response patterns suggest that two mechanisms are involved: first, they can be trained to associate a particular response with a particular stimulus, and, second, when faced with two conditioned stimuli in a row, they respond to the most recent one first, copying behavior they had been rewarded for during training. Although Rey et al. (2012) 'experiment shows that the baboons' behavior is driven by low level mechanisms, it is not clear how the animal behavior reported, bears on the phenomenon of Center Embedded structures in human syntax. Hence, (1) natural language syntax may indeed have been shaped by low level mechanisms, and (2) the baboons' behavior is driven by low level stimulus response learning, as Rey et al. propose. But is the second evidence for the first? We will discuss in what ways this study can and cannot give evidential value for explaining the origin of Center Embedded recursion in human grammar. More generally, their study provokes an interesting reflection on the use of animal studies in order to understand features of the human linguistic system. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The baboon kidney transcriptome: analysis of transcript sequence, splice variants, and abundance.

    Directory of Open Access Journals (Sweden)

    Kimberly D Spradling

    Full Text Available The baboon is an invaluable model for the study of human health and disease, including many complex diseases of the kidney. Although scientists have made great progress in developing this animal as a model for numerous areas of biomedical research, genomic resources for the baboon, such as a quality annotated genome, are still lacking. To this end, we characterized the baboon kidney transcriptome using high-throughput cDNA sequencing (RNA-Seq to identify genes, gene variants, single nucleotide polymorphisms (SNPs, insertion-deletion polymorphisms (InDels, cellular functions, and key pathways in the baboon kidney to provide a genomic resource for the baboon. Analysis of our sequencing data revealed 45,499 high-confidence SNPs and 29,813 InDels comparing baboon cDNA sequences with the human hg18 reference assembly and identified 35,900 cDNAs in the baboon kidney, including 35,150 transcripts representing 15,369 genic genes that are novel for the baboon. Gene ontology analysis of our sequencing dataset also identified numerous biological functions and canonical pathways that were significant in the baboon kidney, including a large number of metabolic pathways that support known functions of the kidney. The results presented in this study catalogues the transcribed mRNAs, noncoding RNAs, and hypothetical proteins in the baboon kidney and establishes a genomic resource for scientists using the baboon as an experimental model.

  16. The Baboon (Papio spp. as a Model of Human Ebola Virus Infection

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    Gary L.White

    2012-10-01

    Full Text Available Baboons are susceptible to natural Ebola virus (EBOV infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.

  17. Metabolism of bupropion by baboon hepatic and placental microsomes

    OpenAIRE

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-...

  18. Metabolism of bupropion by baboon hepatic and placental microsomes.

    Science.gov (United States)

    Wang, Xiaoming; Abdelrahman, Doaa R; Fokina, Valentina M; Hankins, Gary D V; Ahmed, Mahmoud S; Nanovskaya, Tatiana N

    2011-08-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36±6 μM, Vmax 258±32 pmol mg protein(-1) min(-1)), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.

  19. Inherently analog quantity representations in olive baboons (Papio anubis

    Directory of Open Access Journals (Sweden)

    Allison M Barnard

    2013-05-01

    Full Text Available Strong evidence indicates that non-human primates possess a numerical representation system, but the inherent nature of that system is still debated. Two cognitive mechanisms have been proposed to account for non-human primate numerical performance: (1 a discrete object-file system limited to quantities <4, and (2 an analog system which represents quantities comparatively but is limited by the ratio between two quantities. To test the underlying nature of non-human primate quantification, we asked eight experiment -naive olive baboons (Papio anubis to discriminate between number pairs containing small (<4, large (>4, or span (small vs. large numbers of food items presented simultaneously or sequentially. The prediction from the object-file hypothesis is that baboons will only accurately choose the larger quantity in small pairs, but not large or span pairs. Conversely, the analog system predicts that baboons will be successful with all numbers, and that success will be dependent on numerical ratio. We found that baboons successfully discriminated all pair types at above chance levels. In addition, performance significantly correlated with the ratio between the numerical values. Although performance was better for simultaneous trials than sequential trials, evidence favoring analog numerical representation emerged from both conditions, and was present even in the first exposure to number pairs. Together, these data favor the interpretation that a single, coherent analog representation system underlies spontaneous quantitative abilities in primates.

  20. Influence of dehydration on locally mediated hindlimb vasodilation in baboons.

    Science.gov (United States)

    Thornton, R M; Proppe, D W

    1988-08-01

    Previous studies indicate that the heat stress-induced cutaneous vasodilation in baboons is attenuated during dehydration by mechanisms other than the well-known neurohumoral vasoconstrictor mechanisms. Therefore, this study sought to determine whether dehydration also attenuates locally mediated maximum hindlimb blood flow and vascular conductance in baboons. Five baboons were chronically instrumented to measure arterial blood pressure and mean external iliac artery blood flow (MIBF). Hindlimb vasodilation was induced by occlusions of the external iliac artery for 2.5, 5.0, 7.5, and 10.0 min and by close-arterial injections of acetylcholine (ACh) and sodium nitroprusside (NP) in graded doses. These vasodilatory stimuli were applied in euhydrated and dehydrated states, the latter being produced by water deprivation for 64-68 h. Maximum MIBF and iliac vascular conductance (IVC) after arterial occlusion were reduced by 67-70% during dehydration. Also, maximum MIBF and IVC produced by ACh in the dehydrated state were 46-52% lower than in the euhydrated state. A similar reduction in the responses to NP occurred during dehydration. It is concluded that the maximum hindlimb blood flow and vascular conductance produced by local, nonneurohumoral mechanisms are attenuated in the baboon during dehydration.

  1. Focused grooming networks and stress alleviation in wild female baboons.

    Science.gov (United States)

    Wittig, Roman M; Crockford, Catherine; Lehmann, Julia; Whitten, Patricia L; Seyfarth, Robert M; Cheney, Dorothy L

    2008-06-01

    We examine the relationship between glucocorticoid (GC) levels and grooming behavior in wild female baboons during a period of instability in the alpha male rank position. All females' GC levels rose significantly at the onset of the unstable period, though levels in females who were at lower risk of infanticide began to decrease sooner in the following weeks. Three factors suggest that females relied on a focused grooming network as a coping mechanism to alleviate stress. First, all females' grooming networks became less diverse in the weeks following the initial upheaval. Second, females whose grooming had already focused on a few predictable partners showed a less dramatic rise in GC levels than females whose grooming network had been more diverse. Third, females who contracted their grooming network the most experienced a greater decrease in GC levels in the following week. We conclude that close bonds with a few preferred partners allow female baboons to alleviate the stress associated with social instability.

  2. Detective mice assess relatedness in baboons using olfactory cues.

    Science.gov (United States)

    Célérier, Aurélie; Huchard, Elise; Alvergne, Alexandra; Féjan, Delphine; Plard, Floriane; Cowlishaw, Guy; Raymond, Michel; Knapp, Leslie A; Bonadonna, Francesco

    2010-05-01

    The assessment of relatedness may be crucial in the evolution of socio-sexual behaviour, because it can be associated with fitness benefits mediated by both nepotism and inbreeding avoidance. In this context, one proposed mechanism for kin recognition is 'phenotype matching'; animals might compare phenotypic similarities between themselves and others in order to assess the probability that they are related. Among cues potentially used for kin discrimination, body odours constitute interesting candidates that have been poorly investigated in anthropoid primates so far, because of a mixture of theoretical considerations and methodological/experimental constraints. In this study, we used an indirect approach to examine the similarity in odour signals emitted by related individuals from a natural population of chacma baboons (Papio ursinus). For that purpose, we designed an innovative behavioural tool using mice olfactory abilities in a habituation-discrimination paradigm. We show that: (i) mice can detect odour differences between individuals of same sex and age class in another mammal species, and (ii) mice perceive a higher odour similarity between related baboons than between unrelated baboons. These results suggest that odours may play a role in both the signalling of individual characteristics and of relatedness among individuals in an anthropoid primate. The 'biological olfactometer' developed in this study offers new perspectives to the exploration of olfactory signals from a range of species.

  3. Baboon feeding ecology informs the dietary niche of Paranthropus boisei.

    Directory of Open Access Journals (Sweden)

    Gabriele A Macho

    Full Text Available Hominins are generally considered eclectic omnivores like baboons, but recent isotope studies call into question the generalist status of some hominins. Paranthropus boisei and Australopithecus bahrelghazali derived 75%-80% of their tissues' δ(13C from C4 sources, i.e. mainly low-quality foods like grasses and sedges. Here I consider the energetics of P. boisei and the nutritional value of C4 foods, taking into account scaling issues between the volume of food consumed and body mass, and P. boisei's food preference as inferred from dento-cranial morphology. Underlying the models are empirical data for Papio cynocephalus dietary ecology. Paranthropus boisei only needed to spend some 37%-42% of its daily feeding time (conservative estimate on C4 sources to meet 80% of its daily requirements of calories, and all its requirements for protein. The energetic requirements of 2-4 times the basal metabolic rate (BMR common to mammals could therefore have been met within a 6-hour feeding/foraging day. The findings highlight the high nutritional yield of many C4 foods eaten by baboons (and presumably hominins, explain the evolutionary success of P. boisei, and indicate that P. boisei was probably a generalist like other hominins. The diet proposed is consistent with the species' derived morphology and unique microwear textures. Finally, the results highlight the importance of baboon/hominin hand in food acquisition and preparation.

  4. Efficacy of fenbendazole and milbemycin oxime for treating baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

    Science.gov (United States)

    Reichard, Mason V; Wolf, Roman F; Carey, David W; Garrett, Jennifer Jane; Briscoe, Heather A

    2007-03-01

    We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO.

  5. Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon

    DEFF Research Database (Denmark)

    Strandgaard, S; Jones, J V; MacKenzie, E T;

    1975-01-01

    The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons....... In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow...... remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure....

  6. NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon.

    Science.gov (United States)

    Mezquita, P; Beard, B C; Kiem, H-P

    2008-11-01

    We have previously compared the repopulation ability of gene-modified baboon CD34+ cells in an autologous transplantation versus a xenotransplant model in irradiated nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Baboon CD34-selected marrow cells were transduced with a gammaretrovirus vector and infused into irradiated baboons and NOD/SCID mice. A limited integration-site analysis could only detect two common retrovirus integration sites in the NOD/SCID and monkey. Here, we performed locus-specific PCR on 30 clones recovered from NOD/SCID beta2-microglobulin mice reconstituted with transduced baboon CD34+ cells. We identified five common integrants in the baboon early after transplant (2-6 weeks) but none during the long-term follow-up (6 and 12 months). These results confirm that repopulating cells in the NOD/SCID mouse contribute only to short-term repopulation in a clinically relevant large animal model.

  7. Taste responses to neohesperidin dihydrochalcone in rats and baboon monkeys.

    Science.gov (United States)

    Naim, M; Rogatka, H; Yamamoto, T; Zehavi, U

    1982-06-01

    Preference-aversion behavior to solutions containing neohesperidin dihydrochalcone (NHDHC) was studied rats and baboon monkeys. Electrophysiological responses evoked by application of NHDHC solutions to taste receptors innervated by the chorda tympani and the glossopharyngeal nerves were also measured. As a group, rats were indifferent to solutions containing up to 1.2 x 10(-3) M NHDHC in short and long-term preference tests. A solution containing the very high concentration of 8.2 x 10(-3) M NHDHC was consumed less than water by all rats. The aversive behavior of rats to the 8.2 x 10(-3) M NHDHC solution appeared to be due to taste quality rather than olfaction. When percent preferences were calculated on an individual basis for the long-term preference tests, 59% of the rats were indifferent to solutions containing up to 1.2 x 10(-3) M NHDHC, 33% of the animals found this solution aversive and less than 8% showed preference. Behavioral responses to a solution of 3.4 x 10(-4) M aspartame also varied considerably among rats. The electrophysiological data were in line with the behavioral responses suggesting weak taste responses for NHDHC in rats. More pronounced responses observed in the glossopharyngeal nerve as compared to the chorda tympani. Baboon monkeys showed a strong preference for solutions containing 1.6 x 10(-5) M-1.6 x 10(-3) M NHDHC. A solution of 1.6 x 10(-2) M was consumed to a lesser extent than water. It is concluded that baboon monkeys present a better experimental model than rats for investigating the sweetness of NHDHC.

  8. Learning of spatial statistics in nonhuman primates: contextual cueing in baboons (Papio papio).

    Science.gov (United States)

    Goujon, Annabelle; Fagot, Joel

    2013-06-15

    A growing number of theories of cognition suggest that many of our behaviors result from the ability to implicitly extract and use statistical redundancies present in complex environments. In an attempt to develop an animal model of statistical learning mechanisms in humans, the current study investigated spatial contextual cueing (CC) in nonhuman primates. Twenty-five baboons (Papio papio) were trained to search for a target (T) embedded within configurations of distrators (L) that were either predictive or non-predictive of the target location. Baboons exhibited an early CC effect, which remained intact after a 6-week delay and stable across extensive training of 20,000 trials. These results demonstrate the baboons' ability to learn spatial contingencies, as well as the robustness of CC as a cognitive phenomenon across species. Nevertheless, in both the youngest and oldest baboons, CC required many more trials to emerge than in baboons of intermediate age. As a whole, these results reveal strong similarities between CC in humans and baboons, suggesting similar statistical learning mechanisms in these two species. Therefore, baboons provide a valid model to investigate how statistical learning mechanisms develop and/or age during the life span, as well as how these mechanisms are implemented in neural networks, and how they have evolved throughout the phylogeny.

  9. Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine liver sinusoidal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Qiang Peng

    Full Text Available BACKGROUND: Baboons receiving xenogeneic livers from wild type and transgenic pigs survive less than 10 days. One of the major issues is the early development of profound thrombocytopenia that results in fatal hemorrhage. Histological examination of xenotransplanted livers has shown baboon platelet activation, phagocytosis and sequestration within the sinusoids. In order to study the mechanisms of platelet consumption in liver xenotransplantation, we have developed an in vitro system to examine the interaction between pig endothelial cells with baboon platelets and to thereby identify molecular mechanisms and therapies. METHODS: Fresh pig hepatocytes, liver sinusoidal and aortic endothelial cells were isolated by collagenase digestion of livers and processing of aortae from GTKO and Gal+ MGH-miniature swine. These primary cell cultures were then tested for the differential ability to induce baboon or pig platelet aggregation. Phagocytosis was evaluated by direct observation of CFSE labeled-platelets, which are incubated with endothelial cells under confocal light microscopy. Aurintricarboxylic acid (GpIb antagonist blocking interactions with von Willebrand factor/vWF, eptifibatide (Gp IIb/IIIa antagonist, and anti-Mac-1 Ab (anti-α(Mβ(2 integrin Ab were tested for the ability to inhibit phagocytosis. RESULTS: None of the pig cells induced aggregation or phagocytosis of porcine platelets. However, pig hepatocytes, liver sinusoidal and aortic endothelial cells (GTKO and Gal+ all induced moderate aggregation of baboon platelets. Importantly, pig liver sinusoidal endothelial cells efficiently phagocytosed baboon platelets, while pig aortic endothelial cells and hepatocytes had minimal effects on platelet numbers. Anti-MAC-1 Ab, aurintricarboxylic acid or eptifibatide, significantly decreased baboon platelet phagocytosis by pig liver endothelial cells (P<0.01. CONCLUSIONS: Although pig hepatocytes and aortic endothelial cells directly caused

  10. Out of Africa, but how and when? The case of hamadryas baboons (Papio hamadryas).

    Science.gov (United States)

    Kopp, Gisela H; Roos, Christian; Butynski, Thomas M; Wildman, Derek E; Alagaili, Abdulaziz N; Groeneveld, Linn F; Zinner, Dietmar

    2014-11-01

    Many species of Arabian mammals are considered to be of Afrotropical origin and for most of them the Red Sea has constituted an obstacle for dispersal since the Miocene-Pliocene transition. There are two possible routes, the 'northern' and the 'southern', for terrestrial mammals (including humans) to move between Africa and Arabia. The 'northern route', crossing the Sinai Peninsula, is confirmed for several taxa by an extensive fossil record, especially from northern Egypt and the Levant, whereas the 'southern route', across the Bab-el-Mandab Strait, which links the Red Sea with the Gulf of Aden, is more controversial, although post-Pliocene terrestrial crossings of the Red Sea might have been possible during glacial maxima when sea levels were low. Hamadryas baboons (Papio hamadryas) are the only baboon taxon to disperse out of Africa and still inhabit Arabia. In this study, we investigate the origin of Arabian hamadryas baboons using mitochondrial sequence data from 294 samples collected in Arabia and Northeast Africa. Through the analysis of the geographic distribution of genetic diversity, the timing of population expansions, and divergence time estimates combined with palaeoecological data, we test: (i) if Arabian and African hamadryas baboons are genetically distinct; (ii) if Arabian baboons exhibit population substructure; and (iii) when, and via which route, baboons colonized Arabia. Our results suggest that hamadryas baboons colonized Arabia during the Late Pleistocene (130-12 kya [thousands of years ago]) and also moved back to Africa. We reject the hypothesis that hamadryas baboons were introduced to Arabia by humans, because the initial colonization considerably predates the earliest records of human seafaring in this region. Our results strongly suggest that the 'southern route' from Africa to Arabia could have been used by hamadryas baboons during the same time period as proposed for modern humans. Copyright © 2014 The Authors. Published by Elsevier

  11. Sexual swellings advertise female quality in wild baboons.

    Science.gov (United States)

    Domb, L G; Pagel, M

    2001-03-08

    The females of many Old World primate species produce prominent and conspicuous swellings of the perineal skin around the time of ovulation. These sexual swellings have been proposed to increase competition among males for females or to increase the likelihood of a female getting fertilized, by signalling either a female's general reproductive status, or the timing of her ovulation. Here we show that sexual swellings in wild baboons reliably advertise a female's reproductive value over her lifetime, in accordance with a theoretical model of honest signalling. Females with larger swellings attained sexual maturity earlier, produced both more offspring and more surviving offspring per year than females with smaller swellings, and had a higher overall proportion of their offspring survive. Male baboons use the size of the sexual swelling to determine their mating effort, fighting more aggressively to consort females with larger swellings, and spending more time grooming these females. Our results document an unusual case of a sexually selected ornament in females, and show how males, by mating selectively on the basis of the size of the sexual swelling, increase their probability of mating with females more likely to produce surviving offspring.

  12. Baboons, like humans, solve analogy by categorical abstraction of relations.

    Science.gov (United States)

    Flemming, Timothy M; Thompson, Roger K R; Fagot, Joël

    2013-05-01

    Reasoning by analogy is one of the most complex and highly adaptive cognitive processes in abstract thinking. For humans, analogical reasoning entails the judgment and conceptual mapping of relations-between-relations and is facilitated by language (Gentner in Cogn Sci 7:155-170, 1983; Premack in Thought without language, Oxford University Press, New York, 1986). Recent evidence, however, shows that monkeys like "language-trained" apes exhibit similar capacity to match relations-between-relations (Fagot and Thompson in Psychol Sci 22:1304-1309, 2011; Flemming et al. in J Exp Psychol: Anim Behav Process 37:353-360, 2011; Truppa et al. in Plos One 6(8):e23809, 2011). Whether this behavior is driven by the abstraction of categorical relations or alternatively by direct perception of variability (entropy) is crucial to the debate as to whether nonhuman animals are capable of analogical reasoning. In the current study, we presented baboons (Papio papio) and humans (Homo sapiens) with a computerized same/different relational-matching task that in principle could be solved by either strategy. Both baboons and humans produced markedly similar patterns of responding. Both species responded different when the perceptual variability of a stimulus array fell exactly between or even closer to that of a same display. Overall, these results demonstrate that categorical abstraction trumped perceptual properties and, like humans, Old World monkeys can solve the analogical matching task by judging the categorical abstract equivalence of same/different relations-between-relations.

  13. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    NARCIS (Netherlands)

    D.J. Janssen; V.P. Carnielli (Virgilio); P.E. Cogo (Paola); S.R. Seidner; I.H.I. Luijendijk; J.L.D. Wattimena (Josias); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)

    2002-01-01

    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing

  14. GROUP DECISIONS. Shared decision-making drives collective movement in wild baboons.

    Science.gov (United States)

    Strandburg-Peshkin, Ariana; Farine, Damien R; Couzin, Iain D; Crofoot, Margaret C

    2015-06-19

    Conflicts of interest about where to go and what to do are a primary challenge of group living. However, it remains unclear how consensus is achieved in stable groups with stratified social relationships. Tracking wild baboons with a high-resolution global positioning system and analyzing their movements relative to one another reveals that a process of shared decision-making governs baboon movement. Rather than preferentially following dominant individuals, baboons are more likely to follow when multiple initiators agree. When conflicts arise over the direction of movement, baboons choose one direction over the other when the angle between them is large, but they compromise if it is not. These results are consistent with models of collective motion, suggesting that democratic collective action emerging from simple rules is widespread, even in complex, socially stratified societies.

  15. Studies on the cerebral circulation of the baboon in acutely induced hypertension

    DEFF Research Database (Denmark)

    Strandgaard, S; MacKenzie, E T; Jones, J V

    1976-01-01

    The upper limit autoregulation of cerebral blood flow was investigated in eight young baboons with the intracarotid 133xenon clearance method. Blood pressure was increased by intravenous angiotensin infusion. Autoregulation was effective during blood pressure increase from normotensive levels...

  16. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio).

    Science.gov (United States)

    Knauf, Sascha; Barnett, Ulrike; Maciej, Peter; Klapproth, Matthias; Ndao, Ibrahima; Frischmann, Sieghard; Fischer, Julia; Zinner, Dietmar; Liu, Hsi

    2015-01-01

    The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum), yaws (ssp. pertenue), and endemic syphilis (ssp. endemicum) in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio) at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90%) baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560) versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7). Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication campaign with

  17. Transcervical administration of polidocanol foam prevents pregnancy in female baboons.

    Science.gov (United States)

    Jensen, Jeffrey T; Hanna, Carol; Yao, Shan; Thompson, Emily; Bauer, Cassondra; Slayden, Ov D

    2016-11-01

    Our objective was to conduct a pilot study to determine if transcervical administration of polidocanol foam (PF) with or without doxycycline or benzalkonium chloride (BZK) would prevent pregnancy in baboons. In study phase 1, adult cycling baboons underwent a hysterosalpingogram to evaluate tubal patency prior to transcervical infusion of 20 mL of 5% PF followed by 1 mL of saline containing 100 mg doxycycline (5%/doxy; n=5), 3% PF plus doxycycline (3%/doxy; n=4), 3% PF with 0.01% BZK (3%/BZK; n=4) or no additional treatment (control; n=9). Immediately following treatment, animals received intramuscular depot medroxyprogesterone acetate (DMPA, 2 mg/kg) to suppress cyclicity during healing and were then socially housed with males of proven fertility. The primary outcome was pregnancy within six cycles of resumption of menses (efficacy phase 1). During study phase 2, PF-treated females from study phase 1 contributed additional cycles (6-8) of exposure (efficacy phase 2), and 5 control females who had recovered from medical abortion (after study phase 1 pregnancy) were subsequently treated with 5% PF (with DMPA) and exposed to breeding (efficacy phase 1; n=3 six cycles, n=2 five cycles). All females resumed normal menstrual cycles and mating activity after DMPA. During efficacy phase 1, 7/9 (78%) control females became pregnant. In contrast, fewer pregnancies occurred in PF-treated females: 5% PF 0/5 (0%), 5%/doxy 1/5 (20%), 3%/doxy 1/4 (25%) and 3%/BZK 1/4 (25%). During efficacy phase 2, only one additional pregnancy occurred (3%/BZK). A single transcervical treatment with 5% PF prevented pregnancy in most baboons. Cotreatment with doxycycline or BZK did not improve results. Transcervical intrauterine administration of PF resulted in a high rate of tubal occlusion with prevention of pregnancy; refinements are needed to increase the contraceptive rate following a single treatment to near 100%. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights

  18. VIP innervation: sharp contrast in fetal sheep and baboon adrenal glands suggests differences in developmental regulation.

    Science.gov (United States)

    Berghorn, K A; Li, C; Nathanielsz, P W; McDonald, T J

    2000-09-22

    Immunocytochemical technique and light microscopy were used to ascertain the relationship between vasoactive intestinal polypeptide (VIP) and tyrosine hydroxylase in fetal sheep and fetal baboon adrenal cortices and medullae at 85% of gestation. VIP immunostaining was extremely robust in fetal sheep adrenal cortical neurofibers and cells while weak in fibers and nonexistent in cells of fetal baboon. Also, tyrosine hydroxylase-immunopositive cells, present throughout the adrenal cortices of both fetal sheep and baboons, were heavily innervated by VIP-immunoreactive neurofibers in fetal sheep, but not in fetal baboons. Adrenal cortical VIP-immunopositive fibers occurred in greater (Psection (127.85+/-5.16 vs. 74.53+/-4.93 microm). VIP immunogenicity in cells (ganglion and chromaffin) and fibers was robust in fetal adrenal medulla of sheep while nonexistent in baboons. VIP fibers in fetal sheep medulla were smaller in diameter compared to fetal sheep cortex (1.22+/-0.13 vs. 2.93+/-0.34 microm, Pmedullary neurofibers derive primarily from extrinsic sources while cortical fibers arise from cortical ganglion cells. We conclude that at 85% of gestation the potential for VIP neural control of paracrine (e.g., glucocorticoid/catecholamine) interactions in both adrenal cortex and medulla is much greater in fetal sheep compared to fetal baboons.

  19. Metabolism of 17alpha-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons.

    Science.gov (United States)

    Yan, Ru; Nanovskaya, Tatiana N; Zharikova, Olga L; Mattison, Donald R; Hankins, Gary D V; Ahmed, Mahmoud S

    2008-05-01

    Recent data from our laboratory revealed the formation of an unknown metabolite of 17 hydroxyprogesterone caproate (17-HPC), used for treatment of preterm deliveries, during its perfusion across the dually perfused human placental lobule. Previously, we demonstrated that the drug is not hydrolyzed, neither in vivo nor in vitro, to progesterone and caproate. Therefore, the hypothesis for this investigation is that 17-HPC is actively metabolized by human and baboon (Papio cynocephalus) hepatic and placental microsomes. Baboon hepatic and placental microsomes were investigated to validate the nonhuman primate as an animal model for drug use during pregnancy. Data presented here indicate that human and baboon hepatic microsomes formed several mono-, di-, and tri-hydroxylated derivatives of 17-HPC. However, microsomes of human and baboon placentas metabolized 17-HPC to its mono-hydroxylated derivatives only in quantities that were a fraction of those formed by their respective livers, except for two metabolites (M16' and M17') that are unique for placenta and contributed to 25% and 75% of the total metabolites formed by human and baboon, respectively. The amounts of metabolites formed, relative to each other, by human and baboon microsomes were different suggesting that the affinity of 17-HPC to CYP enzymes and their activity could be species-dependent.

  20. Age Effects on Transfer Index Performance and Executive Control in Baboons (Papio papio

    Directory of Open Access Journals (Sweden)

    Elodie eBonté

    2014-03-01

    Full Text Available Reversal performance in the transfer index (TI task is known to improve from prosimians to apes, suggesting that this task is a marker of cognitive evolution within the primate taxa (Rumbaugh, 1970. However, the cognitive processes recruited by this task remain unclear. In the present study, 19 socially-housed baboons (Papio papio from 1.6 to 14.3 years were tested on a computerized version of the TI task, using an automated self-testing procedure. Age was a significant factor in the level of success, with the younger baboons outperforming the adults. The younger baboons also learned the pre-reversal discrimination faster and improved their post-reversal performance more rapidly than adult baboons. As the same baboons had been tested in previous studies on inhibitory control and cognitive flexibility tasks, comparison across tasks provide indicators of the underlying cognitive processes. Age variations in performance were similar between the TI task and in an adaptation of the Wisconsin Card Sorting Task measuring cognitive flexibility (Bonté, Flemming and Fagot, 2011. This contrasts previous results from a task requiring motor inhibitory control (Fagot, Bonté and Hopkins, 2013. Therefore, these findings suggest that cognitive flexibility was a central component of the cognitive system that evolved within nonhuman primates. They also implicate a decline in executive control with age that begins during early adulthood in the baboon species.

  1. Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

    Science.gov (United States)

    Kwiecien, Timothy D; Sy, Christopher; Ding, Yuchuan

    2014-05-01

    Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

  2. DSCR9 gene simultaneous expression in placental, testicular and renal tissues from baboon (papio hamadryas

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    Rodriguez-Sanchez Irám

    2012-06-01

    Full Text Available Abstract Background In 2002 Takamatsu and co-workers described the human DSCR9 gene and observed that it was transcriptionally active in human testicular tissue, but no protein was identified as a product of this transcript. Similar results were obtained in chimpanzee tissue. This gene has not been detected in species other than primates, suggesting that DSCR9 is exclusively found in these mammals. Results We report evidence of DSCR9 expression in placenta, testis and kidney of baboon (Papio hamadryas. We used primers specific for DSCR9 to amplify transcripts through reverse transcription (RT coupled to polymerase chain reaction (PCR. Furthermore, PCR was used to amplify the complete DSCR9 gene from genomic DNA from three baboons. We amplified and sequenced five overlapping segments that were assembled into the 3284 bp baboon DSCR9 gene, including the putative promoter and the entire transcriptional unit (5'-UTR, CDS and 3'-UTR. Conclusions The baboon DSCR9 gene is highly similar to the human counterpart. The isolated transcripts from baboon tissues (placenta, testis and kidney of three different baboons correspond to the human orthologous gene.

  3. Unusually high predation on chacma baboons (Papio ursinus) by female leopards (Panthera pardus) in the Waterberg Mountains, South Africa.

    Science.gov (United States)

    Jooste, E; Pitman, R T; van Hoven, W; Swanepoel, L H

    2012-01-01

    Leopards do not preferentially favour baboons as prey, but they are considered the primary predators of baboons across Africa. Even in areas where baboons are abundant, their contribution to leopard diet seldom exceeds 5% of biomass. It is suggested that the extreme aggressiveness of baboons, group vigilance and their high mobility when escaping may limit leopard predation. Male baboons are particularly aggressive, and retaliation often leads to the death of the leopard. However, evidence suggests that leopards may learn to catch and kill certain dangerous prey. This study reports predation on chacma baboons by 3 female leopards on a private game reserve in the Waterberg Mountains of South Africa. Potential leopard feeding sites were identified using global positioning system (GPS) location clusters obtained from GPS collars. Over a 5-month period, we investigated 200 potential leopard feeding sites and located 96 leopard feeding/kill sites. Baboons constituted 18.7% of the leopards' biomass intake. The majority of baboons preyed upon were adults and 70% of the kills were diurnal. In terms of the measured variables, there were no significant differences in the way the leopards preyed upon baboons, compared to the rest of the prey species.

  4. Social networks predict gut microbiome composition in wild baboons.

    Science.gov (United States)

    Tung, Jenny; Barreiro, Luis B; Burns, Michael B; Grenier, Jean-Christophe; Lynch, Josh; Grieneisen, Laura E; Altmann, Jeanne; Alberts, Susan C; Blekhman, Ran; Archie, Elizabeth A

    2015-01-01

    Social relationships have profound effects on health in humans and other primates, but the mechanisms that explain this relationship are not well understood. Using shotgun metagenomic data from wild baboons, we found that social group membership and social network relationships predicted both the taxonomic structure of the gut microbiome and the structure of genes encoded by gut microbial species. Rates of interaction directly explained variation in the gut microbiome, even after controlling for diet, kinship, and shared environments. They therefore strongly implicate direct physical contact among social partners in the transmission of gut microbial species. We identified 51 socially structured taxa, which were significantly enriched for anaerobic and non-spore-forming lifestyles. Our results argue that social interactions are an important determinant of gut microbiome composition in natural animal populations-a relationship with important ramifications for understanding how social relationships influence health, as well as the evolution of group living.

  5. Cumulative early life adversity predicts longevity in wild baboons.

    Science.gov (United States)

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-04-19

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

  6. Baboons' response speed is biased by their moods.

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    Yousri Marzouki

    Full Text Available The affect-as-information hypothesis (e.g., Schwarz & Clore, 2003, predicts that the positive or negative valence of our mood differentially affects our processing of the details of the environment. However, this hypothesis has only been tested with mood induction procedures and fairly complex cognitive tasks in humans. Here, six baboons (Papio papio living in a social group had free access to a computerized visual search task on which they were over-trained. Trials that immediately followed a spontaneously expressed emotional behavior were analyzed, ruling out possible biases due to induction procedures. RTs following negatively valenced behaviors are slower than those following neutral and positively valenced behaviors, respectively. Thus, moods affect the performance of nonhuman primates tested in highly automatized tasks, as it does in humans during tasks with much higher cognitive demands. These findings reveal a presumably universal and adaptive mechanism by which moods influence performance in various ecological contexts.

  7. Genetic integration of molar cusp size variation in baboons

    Science.gov (United States)

    Koh, Christina; Bates, Elizabeth; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

    2010-01-01

    Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded our study to include data from the maxillary molar cusps. Here we report on these later analyses, as well as inter-arch comparisons with the mandibular data. We analyzed variation in two-dimensional maxillary molar cusp size using data collected from a captive pedigreed breeding colony of baboons, Papio hamadryas, housed at the Southwest National Primate Research Center. These analyses show that variation in maxillary molar cusp size is heritable and sexually dimorphic. We also estimated additive genetic correlations between cusps on the same crown, homologous cusps along the tooth row, and maxillary and mandibular cusps. The pattern for maxillary molars yields genetic correlations of one between the paracone-metacone and protocone-hypocone. Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that are high or not significantly different from one. Between dental arcades, the non-occluding cusps consistently yield high genetic correlations, especially the metaconid-paracone and metaconid-metacone. This pattern of genetic correlation does not immediately accord with the pattern of development and/or calcification, however these results do follow predictions that can be made from the evolutionary history of the tribosphenic molar. PMID:20034010

  8. Sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons and their perceptual discrimination by baboon listeners

    Science.gov (United States)

    Rendall, Drew; Owren, Michael J.; Weerts, Elise; Hienz, Robert D.

    2004-01-01

    This study quantifies sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons (Papio spp.) and tests the basic perceptual discriminability of these differences to baboon listeners. Acoustic analyses were performed on 1028 grunts recorded from 27 adult baboons (11 males and 16 females) in southern Africa, focusing specifically on the fundamental frequency (F0) and formant frequencies. The mean F0 and the mean frequencies of the first three formants were all significantly lower in males than they were in females, more dramatically so for F0. Experiments using standard psychophysical procedures subsequently tested the discriminability of adult male and adult female grunts. After learning to discriminate the grunt of one male from that of one female, five baboon subjects subsequently generalized this discrimination both to new call tokens from the same individuals and to grunts from novel males and females. These results are discussed in the context of both the possible vocal anatomical basis for sex differences in call structure and the potential perceptual mechanisms involved in their processing by listeners, particularly as these relate to analogous issues in human speech production and perception.

  9. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    Directory of Open Access Journals (Sweden)

    Marco Valente

    Full Text Available In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI and partial-body irradiation (PBI to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS and need hematologic support (i.e., mostly TBI victims. To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18 were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI. More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6 and PBI (n = 12, for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  10. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    Science.gov (United States)

    Valente, Marco; Denis, Josiane; Grenier, Nancy; Arvers, Philippe; Foucher, Barbara; Desangles, François; Martigne, Patrick; Chaussard, Hervé; Drouet, Michel; Abend, Michael; Hérodin, Francis

    2015-01-01

    In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  11. Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

    Energy Technology Data Exchange (ETDEWEB)

    Damian, R.T.; Powell, M.R.; Roberts, M.L. (Georgia Univ., Athens (USA). Dept. of Zoology); Clark, J.D. (Georgia Univ., Athens (USA). Lab. Animal Medicine); Stirewalt, M.A.; Lewis, F.A. (Biomedical Research Inst., Rockville, MD (USA))

    1985-06-01

    Young baboons (Papio cynocephalus) were vaccinated with ..gamma..-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines.

  12. Bomb-spike dating of a mummified baboon in Ludwig Cave, Namibia

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    Hodgins Greg

    2007-01-01

    Full Text Available In 1982 a mummified adult female baboon was discovered on a ledge in Ludwig Cave in Namibia. A toe bone was removed for dating in July 1995. AMS radiocarbon dating of bone collagen, tendon, and skin indicates a post-modern age. Application of the atomic bomb-spike calibration curve suggests death in late 1977 and an age at death of around 19 years. Baboons roost in the cave and the mummified female, along with a mummified juvenile male discovered in 2002 and three rotting corpses discovered in 1995, were probably chased by other baboons or by leopards down a ca. 6 m drop during the rainy season, and were unable to climb the steep and very slippery slope to escape. The large number of baboons trapped in the cave in less than 20 years, and mummification of two individuals on dry, dusty ledges in the cave, may explain why large numbers of baboon skeletons have been discovered in ancient bone breccias (up to 4 Ma old in a number of caves throughout Southern Africa.

  13. Comparing responses of four ungulate species to playbacks of baboon alarm calls.

    Science.gov (United States)

    Kitchen, Dawn M; Bergman, Thore J; Cheney, Dorothy L; Nicholson, James R; Seyfarth, Robert M

    2010-11-01

    A growing body of evidence suggests that a wide range of animals can recognize and respond appropriately to calls produced by other species. Social learning has been implicated as a possible mechanism by which heterospecific call recognition might develop. To examine whether familiarity and/or shared vulnerability with the calling species might influence the ability of sympatric species to distinguish heterospecific alarm calls, we tested whether four ungulate species (impala: Aepyceros melampus; tsessebe: Damaliscus lunatus; zebra: Equus burchelli; wildebeest: Connochaetes taurinus) could distinguish baboon (Papio hamadryas ursinus) alarm calls from other loud baboon calls produced during intra-specific aggressive interactions ('contest' calls). Overall, subjects' responses were stronger following playback of alarm calls than contest calls. Of the species tested, impala showed the strongest responses and the greatest difference in composite response scores, suggesting they were best able to differentiate call types. Compared with the other ungulate species, impala are the most frequent associates of baboons. Moreover, like baboons, they are susceptible to both lion and leopard attacks, whereas leopards rarely take the larger ungulates. Although it seems possible that high rates of association and/or shared vulnerability may influence impala's greater ability to distinguish among baboon call types, our results point to a stronger influence of familiarity. Ours is the first study to compare such abilities among several community members with variable natural histories, and we discuss future experiments that would more systematically examine development of these skills in young ungulates.

  14. Performance of juvenile baboons on neuropsychological tests assessing associative learning, motivation and attention.

    Science.gov (United States)

    Zürcher, Nicole R; Rodriguez, Jesse S; Jenkins, Sue L; Keenan, Kate; Bartlett, Thad Q; McDonald, Thomas J; Nathanielsz, Peter W; Nijland, Mark J

    2010-05-15

    The CANTAB (Cambridge Neuropsychological Test Automated Battery), a system developed for human neuropsychological testing, has previously been used to assess cognitive function in two species of nonhuman primates, common marmoset monkeys and rhesus macaques. We describe the application of the system to the juvenile baboon, a nonhuman primate species offering specific investigative advantages. Juvenile baboons were trained and tested on a progressive ratio task to assess motivation, simple discrimination and simple reversal tasks to assess associative learning, and intra- and extra-dimensional set-shifting tasks to assess selective attention and attentional set-shifting, respectively. Study subjects were 8 juvenile baboons (Papio sp.), 4 females and 4 males aged 3.0+/-0.1 (mean+SEM) years and weight 8.2+/-0.4 kg. All baboons were easily trained, readily learned the neuropsychological tests and exhibited a stable performance. Applying a method such as the CANTAB has significant implications for expanding on the translational utility of the baboon in studies of neurodevelopment.

  15. Human infants and baboons show the same pattern of handedness for a communicative gesture.

    Directory of Open Access Journals (Sweden)

    Helene Meunier

    Full Text Available To test the role of gestures in the origin of language, we studied hand preferences for grasping or pointing to objects at several spatial positions in human infants and adult baboons. If the roots of language are indeed in gestural communication, we expect that human infants and baboons will present a comparable difference in their pattern of laterality according to task: both should be more right-hand/left-hemisphere specialized when communicating by pointing than when simply grasping objects. Our study is the first to test both human infants and baboons on the same communicative task. Our results show remarkable convergence in the distribution of the two species' hand biases on the two kinds of tasks: In both human infants and baboons, right-hand preference was significantly stronger for the communicative task than for grasping objects. Our findings support the hypothesis that left-lateralized language may be derived from a gestural communication system that was present in the common ancestor of baboons and humans.

  16. Effect of sodium depletion on peripheral vascular responses to heat stress in baboons.

    Science.gov (United States)

    Proppe, D W

    1987-04-01

    The cutaneous vasodilation and renal vasoconstriction in baboons during environmental heating (EH) appear to be produced predominantly by sympathetic vasoconstrictor withdrawal and activation of the renin-angiotensin system, respectively. Since these mechanisms may be influenced differently by sodium depletion, this study examined the hypothesis that sodium depletion would have a differential effect on cutaneous and renal vascular responses to EH. Sodium depletion was produced in chronically instrumented baboons by placing them on low-salt intake for 8-19 days along with diuretic administration. EH consisted of exposing the baboon to an ambient temperature of 40-42 degrees C until core temperature (Tc) reached 39.8-40.0 degrees C. Both control plasma renin activity (PRA) and the rise in PRA with Tc during EH were considerably larger in sodium-depleted baboons. However, the magnitudes of the progressive increases in iliac vascular conductance (used as an index of hindlimb cutaneous vasodilation) and renal vascular resistance with rising Tc during EH were unaltered by sodium depletion. Therefore, neither cutaneous nor renal vascular responses to EH are influenced by elevated PRA and other changes accompanying sodium depletion in the baboon.

  17. Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation.

    Science.gov (United States)

    Platenberg, R C; Hubbard, G B; Ehler, W J; Hixson, C J

    2001-10-01

    Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P discs seen by MRI were in baboons 14 years of age or older.

  18. S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis

    Directory of Open Access Journals (Sweden)

    Banzon Virryan

    2010-10-01

    Full Text Available Abstract Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.

  19. Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea and retina

    Science.gov (United States)

    Rodríguez-Sánchez, Iràm Pablo; Garza-Rodríguez, Maria Lourdes; Mohamed-Noriega, Karim; Voruganti, Venkata Saroja; Tejero, Maria Elizabeth; Delgado-Enciso, Ivan; Ibave, Diana Cristina Perez; Schlabritz-Loutsevitch, Natalia E.; Mohamed-Noriega, Jibran; Martinez-Fierro, Margarita L; Reséndez-Pérez, Diana; Cole, Shelley A; Cavazos-Adame, Humberto; Comuzzie, Anthony G.; Mohamed-Hamsho, Jesús; Barrera-Saldaña, Hugo Alberto

    2013-01-01

    Background Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, the orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve. Methods OLFML3 amplification was performed by RT-PCR from human and baboon ocular tissues. The products were cloned and sequenced. Results We report OFML3 expression in human and baboon eye. The full CDS has 1221 bp, from which a OFR of 406 amino acid was obtained. The baboon OLFML3 gene nucleotidic sequence has 98%, and amino acidic 99% similarity with humans. Conclusions OLFML3 expression in human and baboon ocular tissues and its high similarity make the baboon a powerful model to deduce the physiological and/or metabolic function of this protein in the eye. PMID:23398349

  20. Threats to Gelada Baboon (Theropithecus gelada around Debre Libanos, Northwest Shewa Zone, Ethiopia

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    Kassahun Abie

    2016-01-01

    Full Text Available This study was aimed at determining threats to gelada baboon around Debre Libanos, Northwest Shewa Zone, Ethiopia. This was investigated based on questionnaire, informant interview, focus group discussion, and direct observation methods from August 2012 to March 2013. Data were analyzed using descriptive statistics, and responses were compared using chi-square test. Habitat destruction (95%, livestock grazing (91.67%, expansion of agricultural land (88.33%, expansion of invasive species (58.33% in the area that reduces the availability and quality of gelada baboon’s food, inappropriate investment activity (75%, and depredation (66.67% were the major threats to gelada baboons in the study area. All these challenges could cause a short and long-term effect on gelada baboon population size and growth rate.

  1. Male-driven grooming bouts in mixed-sex dyads of Kinda baboons (Papio kindae).

    Science.gov (United States)

    Weyher, Anna H; Phillips-Conroy, Jane E; Fourrier, Marc S; Jolly, Clifford J

    2014-01-01

    The behavior of the Central African Kinda baboon (Papio kindae) is not well documented. Having previously noted distinctive grooming behavior in several Kinda baboon populations, we investigated the topic more systematically in the Kafue National Park, Zambia. We recorded the duration and details of male-female dyadic interactions (approaches, withdrawals and time spent grooming) in the early morning and late afternoon. Such interactions were more often initiated by the male and terminated by the female partner. The male groomed the female more often, and longer, than she groomed him, regardless of the female's reproductive state or the presence of an infant. The bias towards male grooming was stronger in morning than evening interactions. These behaviors, whose function is not immediately obvious, and which are unlike those previously reported in baboons, further exemplify the distinctiveness of the taxon.

  2. A non-Levy random walk in chacma baboons: what does it mean?

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    Cédric Sueur

    Full Text Available The Lévy walk is found from amoebas to humans and has been described as the optimal strategy for food research. Recent results, however, have generated controversy about this conclusion since animals also display alternatives to the Lévy walk such as the Brownian walk or mental maps and because movement patterns found in some species only seem to depend on food patches distribution. Here I show that movement patterns of chacma baboons do not follow a Lévy walk but a Brownian process. Moreover this Brownian walk is not the main process responsible for movement patterns of baboons. Findings about their speed and trajectories show that baboons use metal maps and memory to find resources. Thus the Brownian process found in this species appears to be more dependent on the environment or might be an alternative when known food patches are depleted and when animals have to find new resources.

  3. Population structure and habitat use of baboons (Papio hamadryas ursinus in the Blyde Canyon Nature Reserve

    Directory of Open Access Journals (Sweden)

    A.J. Marais

    2006-12-01

    Full Text Available Baboons are highly intelligent and ecologically flexible animals with attributes that allow them to exploit diverse habitats. As a result of their dietary flexibility they often exploit human habitats, causing damage to crops and forest plantations as well as to human dwellings. In the South African context this has led to baboons being regarded as problem animals and attempted extirpation is the most common approach to the damage they cause. This perception of and attitude toward baboons gives many conservationists cause for concern since all southern African cercopithecine primates are CITES listed and it has not been proven that this strategy is the best long-term solution. As part of a research programme focusing on the damage done by chacma baboons in pine plantations along the Drakensberg escarpment in Mpumalanga, a single troop in the Blyde Canyon Nature Reserve was studied to describe their patterns of habitat use. Vegetation and habitat surveys were conducted within the home range of the troop. The troop was habituated and each member’s activity, location and food items utilised were recorded over a 12 month period. The results of this study indicate that baboons utilised plant communities based on food production and availability rather than size in hectares. The results also indicate that the group size, foraging and food search strategies of this troop resembles that of the Drakensberg troops previously studied. The study troop employs two different forage modes of engagement depending on where they choose to forage while they avoid utilising an easily accessible pine plantation. Due to the troop’s long inter-birth intervals it is likely that the current forestry practice of extirpation may have a negative influence on baboon population viability in these areas.

  4. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide

    Science.gov (United States)

    Dalli, Jesmond; Kraft, Bryan D.; Colas, Romain A.; Shinohara, Masakazu; Fredenburgh, Laura E.; Hess, Dean R.; Chiang, Nan; Welty-Wolf, Karen; Choi, Augustine M.; Piantadosi, Claude A.

    2015-01-01

    Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined “specialized proresolving mediators” (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae–infected (n = 5–6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200–300 ppm for 60–90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM–SPM levels, including eicosapentaenoic acid–derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution. PMID:25568926

  5. Microsomal drug-metabolizing enzymes in the olive baboon (papio anabis)

    DEFF Research Database (Denmark)

    1975-01-01

    1.1. The activity of microsomal drug-metabolizing enzymes—azo reductase, nitroreductase, p-hydroxylation, N-demethylation, O-demethylation, NADPH cytochrome c reductase and cytochrome P P-450—in the olive baboon are lower than in other animal species, e.g. mouse, rat, guinea-pig. 2. 2. The level...... is comparable with the level in man for N-demethylation, azo reductase, O-demethylation and NADPH cytochrome c reductase. 3. 3. The ratio of the activity of the p-hydroxylation as compared with cytochrome P-450 is very similar in baboon and man. 4. 4. Arylsulfatase is localized in the lysosomal fraction...

  6. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio.

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    Sascha Knauf

    Full Text Available The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum, yaws (ssp. pertenue, and endemic syphilis (ssp. endemicum in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90% baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560 versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7. Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication

  7. Are there advantages in the use of specific pathogen-free baboons in pig organ xenotransplantation models?

    Science.gov (United States)

    Zhou, Huidong; Iwase, Hayato; Wolf, Roman F; Ekser, Burcin; Ezzelarab, Mohamed; Hara, Hidetaka; White, Gary; Cooper, David K C

    2014-01-01

    Baboons have natural antibodies against pig antigens. We have investigated whether there are differences in anti-non-Gal pig antibody levels between baboons maintained under specific pathogen-free (SPF) conditions and those housed under conventional conditions (non-SPF) that might be associated with improved outcome after pig-to-baboon organ transplantation. Baboons (n = 40) were housed indoors (SPF n = 8) or in indoor/outdoor pens (non-SPF n = 32) in colonies of similar size and structure. Non-SPF colonies harbor a number of pathogens common to non-human primate species, whereas many of these pathogens have been eliminated from the SPF colony. Complete blood cell counts (CBC), blood chemistry, and anti-non-Gal IgM and IgG levels were monitored. There were no significant differences in CBC or blood chemistry between SPF and non-SPF baboons. Anti-non-Gal IgM levels were significantly lower in the SPF baboons than in the non-SPF baboons (MFI 7.1 vs. 8.8, P 20; if these three baboons are omitted, the mean MFIs were 4.8 (SPF) vs. 7.5 (non-SPF) (P xenotransplantation studies as the initial binding of anti-pig IgM to an α1,3-galactosyltransferase gene-knockout pig organ may be less, thus resulting in less complement and/or endothelial cell activation. However, even under identical SPF conditions, an occasional baboon will express a high level of anti-non-Gal IgM, the reason for which remains uncertain.

  8. Heritability of lumbar trabecular bone mechanical properties in baboons.

    Science.gov (United States)

    Havill, L M; Allen, M R; Bredbenner, T L; Burr, D B; Nicolella, D P; Turner, C H; Warren, D M; Mahaney, M C

    2010-03-01

    Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6-32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h(2)) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h(2)=0.58), toughness (h(2)=0.64), and BV/TV (h(2)=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures.

  9. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  10. Rank and grooming reciprocity among females in a mixed-sex group of captive hamadryas baboons

    NARCIS (Netherlands)

    Leinfelder, I.; Vries, Han de; Deleu, R.; Nelissen, M.

    2001-01-01

    In a mixed-sex, captive group of hamadryas baboons (Papio hamadryas hamadryas) we investigated whether female grooming relationships are affected by their dominance ranks. Seyfarths [1977] grooming for support model and Barrett et al.s [1999] biological market model both predict that in primate grou

  11. Inferential reasoning and modality dependent discrimination learning in olive baboons (Papio hamadryas anubis).

    Science.gov (United States)

    Schmitt, Vanessa; Fischer, Julia

    2009-08-01

    Apes use inferential reasoning by exclusion to locate food both in the visual and auditory domain. To test whether olive baboons (Papio hamadryas anubis) show similar abilities as the apes object choice experiments with differing information about food located in 1 of 2 cups were conducted in the visual and auditory modality. Although all baboons (N = 7) were able to locate the reward when they had previously seen it, they failed to make use of auditory cues or arbitrary acoustic signals. When only partial information was given (i.e., only 1 cup was opened) 4 of the baboons were apparently able to infer the location of the reward by reasoning, whereas the other 3 may have adopted an alternative strategy ("avoid the empty cup"). In addition, 3 of the baboons were able to use arbitrary visual markers to locate the food reward. The results suggest that inferential reasoning is not restricted to apes but is shared with Old World monkeys. Furthermore, they also highlight some important differences in the processing of auditory versus visual information in operant conditioning settings.

  12. Baboons as a model to study genetics and epigenetics of human disease.

    Science.gov (United States)

    Cox, Laura A; Comuzzie, Anthony G; Havill, Lorena M; Karere, Genesio M; Spradling, Kimberly D; Mahaney, Michael C; Nathanielsz, Peter W; Nicolella, Daniel P; Shade, Robert E; Voruganti, Saroja; VandeBerg, John L

    2013-01-01

    A major challenge for understanding susceptibility to common human diseases is determining genetic and environmental factors that influence mechanisms underlying variation in disease-related traits. The most common diseases afflicting the US population are complex diseases that develop as a result of defects in multiple genetically controlled systems in response to environmental challenges. Unraveling the etiology of these diseases is exceedingly difficult because of the many genetic and environmental factors involved. Studies of complex disease genetics in humans are challenging because it is not possible to control pedigree structure and often not practical to control environmental conditions over an extended period of time. Furthermore, access to tissues relevant to many diseases from healthy individuals is quite limited. The baboon is a well-established research model for the study of a wide array of common complex diseases, including dyslipidemia, hypertension, obesity, and osteoporosis. It is possible to acquire tissues from healthy, genetically characterized baboons that have been exposed to defined environmental stimuli. In this review, we describe the genetic and physiologic similarity of baboons with humans, the ability and usefulness of controlling environment and breeding, and current genetic and genomic resources. We discuss studies on genetics of heart disease, obesity, diabetes, metabolic syndrome, hypertension, osteoporosis, osteoarthritis, and intrauterine growth restriction using the baboon as a model for human disease. We also summarize new studies and resources under development, providing examples of potential translational studies for targeted interventions and therapies for human disease.

  13. Mapping cocaine binding sites in human and baboon brain in vivo.

    Science.gov (United States)

    Fowler, J S; Volkow, N D; Wolf, A P; Dewey, S L; Schlyer, D J; Macgregor, R R; Hitzemann, R; Logan, J; Bendriem, B; Gatley, S J

    1989-01-01

    The first direct measurements of cocaine binding in the brain of normal human volunteers and baboons have been made by using positron emission tomography (PET) and tracer doses of [N-11C-methyl]-(-)-cocaine ([11C]cocaine). Cocaine's binding and release from brain are rapid with the highest regional uptake of carbon-11 occurring in the corpus striatum at 4-10 minutes after intravenous injection of labeled cocaine. This was followed by a clearance to half the peak value at about 25 minutes with the overall time course paralleling the previously documented time course of the euphoria experienced after intravenous cocaine administration. Blockade of the dopamine reuptake sites with nomifensine reduced the striatal but not the cerebellar uptake of [11C]cocaine in baboons indicating that cocaine binding is associated with the dopamine reuptake site in the corpus striatum. A comparison of labeled metabolites of cocaine in human and baboon plasma showed that while cocaine is rapidly metabolized in both species, the profile of labeled metabolites is different, with baboon plasma containing significant amounts of labeled carbon dioxide, and human plasma containing no significant labeled carbon dioxide. These studies demonstrate the feasibility of using [11C]cocaine and PET to map binding sites for cocaine in human brain, to monitor its kinetics, and to characterize its binding mechanism by using appropriate pharmacological challenges.

  14. Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G. Cutroneo

    2015-06-01

    Full Text Available The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

  15. Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study.

    Science.gov (United States)

    Cutroneo, G; Centofanti, A; Speciale, F; Rizzo, G; Favaloro, A; Santoro, G; Bruschetta, D; Milardi, D; Micali, A; Di Mauro, D; Vermiglio, G; Anastasi, G; Trimarchi, F

    2015-06-05

    The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

  16. Methoxychlor and its metabolites inhibit growth and induce atresia of baboon antral follicles.

    Science.gov (United States)

    Gupta, Rupesh K; Aberdeen, Graham; Babus, Janice K; Albrecht, Eugene D; Flaws, Jodi A

    2007-08-01

    Methoxychlor (MXC), an organochlorine pesticide, inhibits growth and induces atresia of antral follicles in rodents. MXC metabolites, mono-OH MXC (mono-OH) and bis-OH MXC (HPTE), are thought to be more toxic than the parent compound. Although studies have examined effects of MXC in rodents, few studies have evaluated the effects of MXC in primates. Therefore, the present study tested the hypothesis that MXC, mono-OH, and HPTE inhibit growth and induce atresia of baboon antral follicles. To test this hypothesis, antral follicles were isolated from adult baboon ovaries and cultured with vehicle (dimethylsulfoxide; DMSO), MXC (1-100 micro g/ml), mono-OH (0.1-10 micro g/ml), or HPTE (0.1-10 micro g/ml) for 96 hr. Growth was monitored at 24 hr intervals. After culture, follicles were processed for histological evaluation of atresia. MXC, mono-OH, and HPTE significantly inhibited follicular growth and increased atresia compared to DMSO. Moreover, the adverse effects of MXC and its metabolites on growth and atresia in baboon antral follicles were observed at lower (100-fold) doses than those causing similar effects in rodents. These data suggest that MXC and its metabolites inhibit growth and induce atresia of baboon antral follicles, and that primate follicles are more sensitive to MXC than rodent follicles.

  17. Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.-Y.; Vallabhahosula, Shankar; Wolf, Alfred P.; Dewey, Stephen L.; Fowler, Joanna S.; Schlyer, David J.; Arnett, Carroll D.; Zhou Yiguo

    1997-02-01

    No-carrier-added (NCA)[{sup 11}C]({+-})-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [{sup 11}C]H{sub 3}I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/{mu}mole at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [{sup 11}C]ketamine may not be an ideal tracer for studying NMDA receptor with PET.

  18. Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

    Directory of Open Access Journals (Sweden)

    Riashna Sithaldeen

    Full Text Available Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp. supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

  19. Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions.

    Directory of Open Access Journals (Sweden)

    Mohamed B F Hawash

    Full Text Available The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates.We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related.Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates.

  20. Kinetics of glyburide metabolism by hepatic and placental microsomes of human and baboon.

    Science.gov (United States)

    Zharikova, Olga L; Ravindran, Selvan; Nanovskaya, Tatiana N; Hill, Ronald A; Hankins, Gary D V; Ahmed, Mahmoud S

    2007-06-15

    Glyburide (glibenclamide) is under investigation for treatment of gestational diabetes. Two metabolites of glyburide have been previously identified in patients, namely, 4-trans-(M1) and 3-cis-(M2) hydroxycyclohexyl glyburide. Recently, the metabolism of glyburide by microsomes of liver and placenta from humans and baboons revealed the formation of four additional metabolites: 4-cis-(M2a), 3-trans-(M3), and 2-trans-(M4) hydroxycyclohexyl glyburide, and ethyl-hydroxy glyburide (M5). The aim of this investigation was to determine the kinetics for the metabolism of glyburide by cytochrome P450 (CYP) isozymes of human and baboon placental and hepatic microsomes. The metabolism of glyburide by microsomes from the four organs revealed saturation kinetics and apparent K(m) values between 4 and 12 microM. However, the rates for formation of the metabolites varied between organs and species. M1 was the major metabolite (36% of total), formed by human hepatic microsomes with V(max) of 80+/-13 pmol mg protein(-1)min(-1), and together with M2, accounted for only 51% of the total. M5 was the major metabolite (87%) formed by human placental microsomes with V(max) of 11 pmol mg protein(-1)min(-1). In baboon liver, M5 had the highest rate of formation (V(max) 135+/-32 pmol mg protein(-1)min(-1), 39% of total), and in its placenta, was M4 (V(max) 0.7+/-0.1 pmol mg protein(-1)min(-1), 65%). The activity of human and baboon hepatic microsomes in metabolizing glyburide was similar, but the activity of human and baboon placental microsomes was 7% and 0.3% of their respective hepatic microsomes. The data obtained suggest that more than 1 CYP isozyme is responsible for catalyzing the hydroxylation of glyburide.

  1. Road and Street Centerlines, Baboon Peak, Published in 2007, 1:24000 (1in=2000ft) scale, Iron County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — , published at 1:24000 (1in=2000ft) scale, was produced all or in part from Other information as of 2007. It is described as 'Baboon Peak'. The extent of these data...

  2. Experimental infections of baboons (Papio spp. and vervet monkeys (Cercopithecus aethiops with Trichinella zimbabwensis and successful treatment with ivermectin

    Directory of Open Access Journals (Sweden)

    S. Mukaratirwa

    2008-08-01

    Full Text Available Experimental Trichinella zimbabwensis infections were established in three baboons (Papios p.and four vervet monkeys (Cercopithecuase thiops and the clinical-pathological manifestations assessed. The infected animals showed clinical signs ranging from fever, diarrhoea, periorbitaol edema and muscular pain in varying degrees. One baboon became blind due to the infection. Levels of creatinine phosphokinase and lactated ehydrogenase increased to reach a peak on Day 42 post-infection(pifor both baboons and monkeys. Blood parameters such as packed cell volume, levels of red blood cells and white blood cells did not change significantly from the normal ranges except for the levels of eosinophils which peaked above the normal ranges at Day 28 and 56 pi in baboons and at Day 56 pi in monkeys.

  3. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. Brucella papionis sp. nov., isolated from baboons (Papio spp.).

    Science.gov (United States)

    Whatmore, Adrian M; Davison, Nicholas; Cloeckaert, Axel; Al Dahouk, Sascha; Zygmunt, Michel S; Brew, Simon D; Perrett, Lorraine L; Koylass, Mark S; Vergnaud, Gilles; Quance, Christine; Scholz, Holger C; Dick, Edward J; Hubbard, Gene; Schlabritz-Loutsevitch, Natalia E

    2014-12-01

    Two Gram-negative, non-motile, non-spore-forming coccoid bacteria (strains F8/08-60(T) and F8/08-61) isolated from clinical specimens obtained from baboons (Papio spp.) that had delivered stillborn offspring were subjected to a polyphasic taxonomic study. On the basis of 16S rRNA gene sequence similarities, both strains, which possessed identical sequences, were assigned to the genus Brucella. This placement was confirmed by extended multilocus sequence analysis (MLSA), where both strains possessed identical sequences, and whole-genome sequencing of a representative isolate. All of the above analyses suggested that the two strains represent a novel lineage within the genus Brucella. The strains also possessed a unique profile when subjected to the phenotyping approach classically used to separate species of the genus Brucella, reacting only with Brucella A monospecific antiserum, being sensitive to the dyes thionin and fuchsin, being lysed by bacteriophage Wb, Bk2 and Fi phage at routine test dilution (RTD) but only partially sensitive to bacteriophage Tb, and with no requirement for CO2 and no production of H2S but strong urease activity. Biochemical profiling revealed a pattern of enzyme activity and metabolic capabilities distinct from existing species of the genus Brucella. Molecular analysis of the omp2 locus genes showed that both strains had a novel combination of two highly similar omp2b gene copies. The two strains shared a unique fingerprint profile of the multiple-copy Brucella-specific element IS711. Like MLSA, a multilocus variable number of tandem repeat analysis (MLVA) showed that the isolates clustered together very closely, but represent a distinct group within the genus Brucella. Isolates F8/08-60(T) and F8/08-61 could be distinguished clearly from all known species of the genus Brucella and their biovars by both phenotypic and molecular properties. Therefore, by applying the species concept for the genus Brucella suggested by the ICSP

  5. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  6. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  7. Baboon syndrome: an unusual complication arising from antibiotic treatment of tonsillitis and review of the literature.

    Science.gov (United States)

    Blackmur, James Peter; Lammy, Simon; Baring, David E C

    2013-11-28

    A 40-year-old man presented with sore throat and fevers associated with bilaterally enlarged and inflamed tonsils. A clinical diagnosis of tonsillitis was made and the patient received intravenous benzylpenicillin. Over subsequent days, the patient developed a macular rash over both groins, buttocks and axillae, with necrotic patches in the groins. An assumptive diagnosis of necrotising fasciitis was made. The patient underwent urgent groin biopsy and was started on broad spectrum antibiotics. No organisms were seen on Gram stain. Following a multidisciplinary discussion, the patient was diagnosed with baboon syndrome (symmetrical drug-related intertriginous and flexural exanthema). He was treated with oral steroid along with topical agents. Baboon syndrome can develop following penicillin administration. Given the widespread use of penicillin antibiotics to treat tonsillitis and many other conditions, it is important that medical staff recognise the side effects of these medications.

  8. Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

    DEFF Research Database (Denmark)

    Nyakundi, Ruth K; Nyamongo, Onkoba; Maamun, Jeneby

    2016-01-01

    Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal...... models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni...... cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe...

  9. Role of Grooming in Reducing Tick Load in Wild Baboons (Papio cynocephalus).

    Science.gov (United States)

    Akinyi, Mercy Y; Tung, Jenny; Jeneby, Maamun; Patel, Nilesh B; Altmann, Jeanne; Alberts, Susan C

    2013-03-01

    Nonhuman primate species spend a conspicuous amount of time grooming during social interactions, a behavior that probably serves both social and health-related functions. While the social implications of grooming have been relatively well studied, less attention has been paid to the health benefits, especially the removal of ectoparasites, which may act as vectors in disease transmission. In this study, we examined the relationship between grooming behavior, tick load (number of ticks), and haemoprotozoan infection status in a population of wild free-ranging baboons (Papio cynocephalus). We found that the amount of grooming received was influenced by an individual's age, sex and dominance rank. The amount of grooming received, in turn, affected the tick load of an individual. Baboons with higher tick loads had lower packed red cell volume (PCV or haematocrit), one general measure of health status. We detected a tick-borne haemoprotozoan, Babesia microti, but its low prevalence in the population precluded identifying sources of variance in infection.

  10. Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation.

    Science.gov (United States)

    Mueller, Nicolas J; Livingston, Christine; Knosalla, Christoph; Barth, Rolf N; Yamamoto, Shin; Gollackner, Bernd; Dor, Frank J M F; Buhler, Leo; Sachs, David H; Yamada, Kazuhiko; Cooper, David K C; Fishman, Jay A

    2004-05-01

    Tissue-invasive disease due to porcine cytomegalovirus (PCMV) has been demonstrated after pig-to-baboon solid-organ xenotransplantation. Porcine lymphotropic herpesvirus (PLHV)-1 is associated with B cell proliferation and posttransplant lymphoproliferative disorder after allogeneic bone marrow transplantation in swine but has not been observed in pig-to-primate xenotransplantation. Activation of PCMV and PLHV-1 was investigated in 22 pig-to-baboon xenotransplants by use of quantitative polymerase chain reaction. PCMV was found in all xenografts; increased viral replication occurred in 68% of xenografts during immunosuppression. PLHV-1 was found in 12 xenografts (55%); no increases in viral replication occurred during immunosuppression. Control immunosuppressed swine coinfected with PCMV and PLHV-1 had activation of PCMV but not PLHV-1. PCMV, but not PLHV-1, is activated in solid-organ xenotransplantation.

  11. Mitochondrial genome analyses suggest multiple Trichuris species in humans, baboons, and pigs from different geographical regions

    DEFF Research Database (Denmark)

    Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.;

    2015-01-01

    BACKGROUND: The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found...... in primates. METHODS AND FINDINGS: We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes...... of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively...

  12. Distribution of immunoglobulin allotypes among local populations of Kenya olive baboons.

    Science.gov (United States)

    Oliver, T J; Coppenhaver, D H; Steinberg, A G

    1986-05-01

    In this paper we report on the distributions of immunoglobulin allotypes among 564 olive baboons collected at six localities in Kenya. The sample localities and sizes are 1) Lake Magadi, N = 107; 2) Nanyuki, N = 77; 3) Lake Baringo, N = 55; 4) Mosiro, N = 132; 5) Isiolo, N = 36; 6) Gilgil, N = 157. Gm allotypes 1, 10, 13, 15, and 17 are polymorphic among these samples. Gm(11) and Km(3) were present in all samples, and Gm(2,3,5,6,14,16,21,24,26) and Km(1) were absent from all samples. The proportions of individuals positive for polymorphic allotypes varied substantially between different local samples, as did the arrays and estimated frequencies of haplotypes. Allotype frequencies in local samples do not appear to be simply related to either geographic location or habitat characteristics of the localities. Our data suggest that much of the geographic variability in Kenya olive baboon populations occurs between populations separated by small geographic distances.

  13. Zoledronic acid-associated symmetrical drug-related intertriginous and flexural exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent metastatic breast cancer after receiving zoledronic acid

    OpenAIRE

    Cohen, Philip R.

    2015-01-01

    Background:  Baboon syndrome is a distinctive skin reaction in which the patient typically develops erythematous buttocks that appear similar to those of a baboon.  The non-contact allergenic variant of baboon syndrome is also referred to as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE).  Zoledronic acid is a bisphosphonate that is used in patients with metastatic cancer to prevent bone complications. Purpose:  Zoledronic acid-associated baboon syndrome is ...

  14. The Ontogeny of the Endocrine Pancreas in the Fetal/Newborn Baboon

    Science.gov (United States)

    Quinn, Amy R.; Blanco, Cynthia L.; Perego, Carla; Finzi, Giovanna; La Rosa, Stefano; Capella, Carlo; Guardado-Mendoza, Rodolfo; Casiraghi, Francesca; Gastaldelli, Amalia; Johnson, Marney; Dick, Edward J.; Folli, Franco

    2013-01-01

    Background Erratic regulation of glucose metabolism including hyperglycemia is a common condition of premature infants and is associated with increased morbidity and mortality. Objective To examine histological and ultra-structural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons. Methods Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140dGA, or 175dGA. Eight animals were delivered at term (185dGA); half were fed for 5d. Seventy-three non-diabetic adult baboons were used for comparison. Pancreatic tissue was studied utilizing light microscopy, confocal imaging and electron microscopy. Results The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of α-β-δ-cell type were similar within each fetal and newborn GA (NS), but were higher than the adults (P<0.05) regardless of GA. The ratio of β-cells within the islet (whole and core) increased with gestation (P<0.01). Neonatal baboons who survived for 5 days (feeding), had a 2.5-fold increase in pancreas weight compared to their counterparts euthanized at birth (P=0.01). Endocrine cells were found amongst exocrine ductal and acinar cells in 125,140 and 175dGA fetuses. Subpopulation of cells that co-expressed trypsin and glucagon/insulin show the presence of cells with mixed endo-exocrine lineage in fetuses. Conclusions The fetal endocrine pancreas has no prevalence of a of α-β-δ-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long term implications. PMID:22723715

  15. Serum Vitamin D Concentrations in Baboons (Papio spp.) during Pregnancy and Obesity

    OpenAIRE

    Schlabritz-Loutsevitch, Natalia E.; Comuzzie, Anthony G.; Mahaney, Michael M; Hubbard, Gene B.; DICK, EDWARD J.; Kocak, Mehmet; Gupta, Sonali; Carrillo, Maira; Schenone, Mauro; Postlethwaite, Arnold; Slominski, Andrzej

    2016-01-01

    Obesity is associated with vitamin D deficiency, which can lead to serious problems during pregnancy. However, the mechanisms of the deficiency and guidelines for vitamin D supplementation during pregnancy are not established yet, and variations in environmental exposures combined with the difficulties of performing research in pregnant women are obstacles in the evaluation of vitamin D metabolism. Baboons (Papio spp.) are an excellent, well-established model for reproductive research and rep...

  16. Antenatal Corticosteroids Alter Insulin Signaling Pathways in Fetal Baboon Skeletal Muscle

    Science.gov (United States)

    BLANCO, Cynthia L.; MOREIRA, Alvaro G.; McGILL, Lisa L.; ANZUETO, Diana G.; NATHANIELSZ, Peter; MUSI, Nicolas

    2015-01-01

    Objective We hypothesize that prenatal exposure to glucocorticoids (GCs) will negatively alter the insulin signal transduction pathway and has differing effects on the fetus according to gestational age at exposure. Methods Twenty-three fetal baboons were delivered from twenty-three healthy, non-diabetic mothers. Twelve preterm (0.67 gestational age) and eleven near term (0.95 gestational age) baboons were euthanized immediately after delivery. Half of the pregnant baboons at each gestation received two doses of intramuscular betamethasone 24-hours apart (170 μg.kg−1) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure protein content and gene expression of insulin receptor (IR)-β, IR-β Tyr 1361 phosphorylation (pIR-β), IR substate-1 (IRS-1), IRS-1 tyrosine phosphorylation (pIRS-1), p85 subunit of PI3-kinase (p85), Akt (Protein Kinase B), phospho-Akt Ser473 (pAkt), Akt-1, Akt-2, and glucose transporters (GLUT1 and GLUT4). Results Skeletal muscle from preterm baboons exposed to glucocorticoids had markedly reduced protein content of Akt and Akt-1 (respectively, 73% and 72% from 0.67 gestational age Control, P<0.001); IR-β and pIR-β were decreased (respectively, 94% and 85%, P<0.01) in the muscle of premature GC exposed fetuses, but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased 6.0 fold in term animals after GC exposure (P<0.05). Conclusion Exposure to a single course of antenatal GCs during fetal life alters the insulin-signaling pathway in fetal muscle in a manner dependent on the stage of gestation. PMID:24756099

  17. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/CON-20042915 . Mayo Clinic Footer Legal Conditions and ...

  18. Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

    Science.gov (United States)

    Harper, Kristin N; Fyumagwa, Robert D; Hoare, Richard; Wambura, Philemon N; Coppenhaver, Dorian H; Sapolsky, Robert M; Alberts, Susan C; Tung, Jenny; Rogers, Jeffrey; Kilewo, Morris; Batamuzi, Emmanuel K; Leendertz, Fabian H; Armelagos, George J; Knauf, Sascha

    2012-01-01

    It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.

  19. Homeothermy and primate bipedalism: is water shortage or solar radiation the main threat to baboon (Papio hamadryas) homeothermy?

    Science.gov (United States)

    Mitchell, Duncan; Fuller, Andrea; Maloney, Shane K

    2009-05-01

    Other than the hominin lineage, baboons are the diurnally active primates that have colonized the arid plains of Africa most successfully. While the hominin lineage adopted bipedalism before colonizing the open, dry plains, baboons retained a quadrupedal mode of locomotion. Because bipedalism has been considered to reduce the thermoregulatory stress of inhabiting open dry plains, we investigated how baboons cope with thermal loads and water restriction. Using implanted data loggers, we measured abdominal temperature every 5 min in six unrestrained baboons while they were exposed to simulated desert conditions (15 degrees C at night rising to 35 degrees C during the day, with and without extra radiant heating), or an ambient temperature of 22 degrees C. At 22 degrees C, core temperature averaged 37.9 degrees C and cycled nychthemerally by 1.7 degrees C. Mean, minimum, and maximum daily core temperatures in euhydrated baboons in the simulated desert environments did not differ from the temperatures displayed in the 22 degrees C environment, even when radiant heating was applied. At 22 degrees C, restricting water intake did not affect core temperature. During the desert simulations, maximum core temperature increased significantly on each day of water deprivation, with the highest temperatures (>40 degrees C) on the third day in the simulation that included radiant heat. When drinking water heated to 38 degrees C was returned, core temperature decreased rapidly to a level lower than normal for that time of day. We conclude that baboons with access to water can maintain homeothermy in the face of high air temperatures and radiant heat loads, but that a lack of access to drinking water poses a major threat to baboon homeothermy. We speculate that any competitive thermoregulatory advantage of bipedalism in early hominins was related to coping with water shortage in hot environments, and that their freed hands might have enabled them to transport enough water to avoid

  20. Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

    Directory of Open Access Journals (Sweden)

    Kristin N Harper

    Full Text Available It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum, yaws (subsp. pertenue, and bejel (subsp. endemicum in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.

  1. Mental maps in chacma baboons (Papio ursinus): using inter-group encounters as a natural experiment.

    Science.gov (United States)

    Noser, Rahel; Byrne, Richard W

    2007-07-01

    Encounters between groups of wild chacma baboons (Papio ursinus) can be viewed as a natural experiment to investigate the nature of these primates' mental representations of large-scale space. During a 16-month field study in a high population density habitat we recorded the foraging routes and the most important resources of a group of 25 individuals. Also, we estimated the locations of additional baboon groups relative to the study group. Routes were less linear, travel speed was higher, and inter-resource distances were larger when other groups were present within 500 m of the focal group; thus, the study group avoided others by taking detours. We predicted that evasive manoeuvres would be characteristic of different possible orientation mechanisms, and compared them with our observations. We analysed 34 evasive manoeuvres in detail. In an area that lacked prominent landmarks, detours were small; larger detours occurred when resources were directly visible, or in the vicinity of a hill offering conspicuous landmarks. In areas without prominent landmarks, detours were along familiar routes and waiting bouts of up to 60 min occurred; on one occasion the study group aborted their entire day's journey. We discuss these findings in the light of time and energy costs and suggest that the baboons lack the ability to compute Euclidean relations among locations, but use network maps to find their way to out-of-sight locations.

  2. Relationship between canine dimorphism and mandibular morphology in the hamadryas baboon and the Japanese monkey.

    Science.gov (United States)

    Fukase, Hitoshi

    2011-04-01

    To examine morphological interrelationships between canine size and mandibular corpus shape, inter-sex comparisons were made in the hamadryas baboon and the Japanese monkey, known to display extreme and moderate canine dimorphism, respectively. Results of adult comparisons showed that all mandibular dimensions were significantly larger in the males than in the females in both species. In the hamadryas baboon, the males also exhibited a higher ratio of anterior to posterior corpus height than the females. This sex difference in corpus shape was not significant in the Japanese monkey, indicating lack of involvement of canine dimorphism. Analysis of mandibular growth patterns in the hamadryas baboon demonstrated that significant sexual size difference did not occur before incisor eruption, and that the anteriorly high corpus of the adult male mandible was associated with a rapidly increasing symphyseal height after incisor eruption. It was also shown that the female canine started to erupt shortly after incisor eruption, while the forming male canine continued to stay near the mandibular base and developed further in size until eruption. The relative positions of the incisors kept shifting upwards even after eruption in the males, while they hardly changed in the females. It is therefore suggested that the prolonged development and size increase of the male canine is accompanied by further enlargement of the symphysis, resulting in the higher anterior corpus of the adult males compared to the adult females. The results thus indicate the importance of understanding the spatial relationships of the developing teeth in interpreting mandibular morphology.

  3. A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

    Science.gov (United States)

    Barbaud, A; Tréchot, P; Granel, F; Lonchamp, P; Faure, G; Schmutz, J L; Béné, M C

    1999-01-01

    Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

  4. Serum Vitamin D Concentrations in Baboons (Papio spp.) during Pregnancy and Obesity.

    Science.gov (United States)

    Schlabritz-Loutsevitch, Natalia E; Comuzzie, Anthony G; Mahaney, Michael M; Hubbard, Gene B; Dick, Edward J; Kocak, Mehmet; Gupta, Sonali; Carrillo, Maira; Schenone, Mauro; Postlethwaite, Arnold; Slominski, Andrzej

    2016-04-01

    Obesity is associated with vitamin D deficiency, which can lead to serious problems during pregnancy. However, the mechanisms of the deficiency and guidelines for vitamin D supplementation during pregnancy are not established yet, and variations in environmental exposures combined with the difficulties of performing research in pregnant women are obstacles in the evaluation of vitamin D metabolism. Baboons (Papio spp.) are an excellent, well-established model for reproductive research and represent a unique opportunity to study vitamin D metabolism in a controlled environment. This study used secondary data and specimen analysis as well as a novel experimental design to evaluate pregnant and nonpregnant baboons that were or were not exposed to sunlight while they were obese and after weight reduction. Daily D3 intake was 71% higher in nonpregnant obese baboons than in their nonobese counterparts, but serum vitamin D concentrations did not differ between these populations. In addition, serum 25-hydroxyvitamin D concentrations correlated negatively with the obesity index. This report is the first to show the effect of obesity and pregnancy on vitamin D concentrations in a NHP population. These data underline the importance of adequate vitamin D supplementation in obese animals.

  5. When good neighbors don't need fences: Temporal landscape partitioning among baboon social groups.

    Science.gov (United States)

    Markham, A Catherine; Guttal, Vishwesha; Alberts, Susan C; Altmann, Jeanne

    2013-06-01

    Intraspecific competition is a key factor shaping space-use strategies and movement decisions in many species, yet how and when neighbors utilize shared areas while exhibiting active avoidance of one another is largely unknown. Here we investigated temporal landscape partitioning in a population of wild baboons (Papio cynocephalus). We used global positioning system (GPS) collars to synchronously record the hourly locations of 5 baboon social groups for ~900 days, and we used behavioral, demographic, and life history data to measure factors affecting use of overlap areas. Annual home ranges of neighboring groups overlapped substantially, as predicted (baboons are considered non-territorial), but home ranges overlapped less when space use was assessed over shorter time scales. Moreover, neighboring groups were in close spatial proximity to one another on fewer days than predicted by a null model, suggesting an avoidance-based spacing pattern. At all time scales examined (monthly, biweekly, and weekly), time spent in overlap areas was greater during time periods when groups fed on evenly dispersed, low-quality foods. The percent of fertile females in social groups was negatively correlated with time spent in overlap areas only during weekly time intervals. This suggests that broad temporal changes in ecological resources are a major predictor of how intensively overlap areas are used, and groups modify these ecologically driven spacing patterns at short time scales based on female reproductive status. Together these findings offer insight into the economics of territoriality by highlighting the dynamics of spacing patterns at differing time scales.

  6. Control of plasma renin activity in heat-stressed baboons on varied salt intake.

    Science.gov (United States)

    Proppe, D W

    1987-04-01

    The characteristics and control of the increase in plasma renin activity (PRA) during environmental heating (EH) were determined in 12 unanesthetized, chronically catheterized baboons. Each EH experiment consisted of a 1.5- to 4-h exposure to an ambient temperature of 39-44 degrees C until core temperature (Tc) reached 39.5-40.0 degrees C. These EH experiments were done on the baboon in an unblocked state and during beta-adrenergic receptor blockade produced by propranolol when on normal-to-high salt intake (NHSI) and on low-salt intake (LSI). PRA rose linearly with Tc during EH, but the increase in PRA was considerably larger when the baboon was on LSI. The PRA-Tc linear regression coefficients were 2.32 and 5.98 ng angiotensin I X ml-1 X h-1 X degrees C-1 in NHSI and LSI states, respectively. This rise in PRA during EH was completely eliminated during beta-blockade in both NHSI and LSI states. It is concluded that heat stress activates the sympathetic nervous system to stimulate beta-receptor-mediated renin secretion by the kidney, this activation is controlled primarily by internal thermoreceptors, and variations in salt intake alters only the magnitude of the increase in PRA during heat stress, not the mechanisms that produce it.

  7. Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons.

    Science.gov (United States)

    Ryan, K L; Thornton, R M; Proppe, D W

    1989-02-01

    This study primarily sought to determine whether the role of vasopressin (VP) in maintenance of arterial blood pressure is enhanced in awake, chronically instrumented baboons after 68-72 h of dehydration. This question was approached by pharmacologically blocking vasopressin V1-receptors in euhydrated and dehydrated baboons with or without a normally functioning renin-angiotensin system (RAS). VP blockade during dehydration produced a rapidly occurring (within 5 min), statistically significant (P less than 0.05) decrease in mean arterial pressure (MAP) of 5 +/- 1 mmHg in the RAS-intact condition and an identical decline in MAP (5 +/- 1 mmHg) during blockade of the RAS by captopril, an angiotensin I-converting enzyme inhibitor. At 15 min after induction of VP blockade, heart rate was elevated by 9 +/- 2 beats/min in the RAS-intact condition and by 20 +/- 5 beats/min in the RAS-blocked condition. In addition, VP blockade in the dehydrated state produced small and equal increases in hindlimb vascular conductance in RAS-intact and RAS-blocked conditions. None of these cardiovascular changes were produced by VP blockade in the euhydrated state. RAS blockade produced modest declines in MAP in both hydration states, but the fall was larger by 7 +/- 4 mmHg in the dehydrated state. Thus both VP and the RAS contribute to the maintenance of arterial blood pressure during dehydration in the conscious baboon.

  8. Synergy between angiotensin and aldosterone in evoking sodium appetite in baboons.

    Science.gov (United States)

    Shade, R E; Blair-West, J R; Carey, K D; Madden, L J; Weisinger, R S; Denton, D A

    2002-11-01

    The synergy between ANG II and aldosterone (Aldo) in the induction of salt appetite, extensively studied in rats, has been tested in baboons. ANG II was infused intracerebroventricularly at 0.5 or 1.0 microg/h; Aldo was infused subcutaneously at 20 microg/h. Separate infusions over 7 days had no significant effect on the daily intake of 300 mM NaCl. Concurrent infusions, however, increased daily NaCl intake approximately 10-fold and daily water intake approximately 2.5-fold. In addition, the combined infusions caused 1) a reduction in daily food intake, 2) changes in blood composition indicative of increased vasopressin release, and 3) changes of urinary excretion rates of cortisol and Aldo indicative of increased ACTH release. Arterial blood pressure, measured in two baboons, rose during concurrent ANG II and Aldo treatment. These results indicate a potent synergy between central ANG II and peripheral Aldo in stimulating salt appetite in baboons. At the same time, other ANG II-specific brain mechanisms concerned with water intake, food intake, vasopressin release, ACTH release, and blood pressure regulation appear to have been activated by the same type of synergy. These central enhancement processes have never been previously demonstrated in primates.

  9. Efficacy of fenbendazole formulated in a commercial primate diet for treating specific pathogen-free baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

    Science.gov (United States)

    Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

    2008-11-01

    Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura.

  10. Follow up of infection of chacma baboons with inoculum containing a and non-a genotypes of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Marina Baptista; Anna Kramvis; Saffie Jammeh; Jocelyn Naicker; Jacqueline S.Galpin; Michael C.Kew

    2003-01-01

    AIM: To determine whether one genotype (A or non-A genotypes of HBV) predominated over the other during the course of HBV infection.METHODS: Four baboons were inoculated with HBV. DNA was extracted from serum obtained at monthly intervals postinoculation for 52 weeks and HBV DNA was amplified using primers specific for the core region containing an insert characteristic of genotype A (nt 2 354-2 359, numbering from the EcoRI site). The amplicons were cloned into PCRScriptTM and a minimum of 15 clones per time point were sequenced in both directions.RESULTS: Both genotypes persisted for the entire followup period of 52 weeks. Genotype non-A predominated in two baboons and genotype A in one baboon. Neither genotype predominated in the fourth baboon, as shown at a 5 % level of testing.CONCLUSION: No conclusions concerning the dominance of either genotype or the natural progression or replication rates of HBV could be drawn because the pattern of the genotypes found may have been caused by sampling fluctuations at the time of DNA extraction and cloning as a result of the very low viral loads in the baboon sera.

  11. Gaze following in baboons (Papio anubis): juveniles adjust their gaze and body position to human's head redirections.

    Science.gov (United States)

    Parron, Carole; Meguerditchian, Adrien

    2016-12-01

    Gaze following, the ability to follow the gaze of other individuals, has been widely studied in non-human primate species, mostly in adult individuals. Yet, the literature on gaze following revealed a quite variability across the different findings, some of it might reflect true inter-species differences, while others might be related to methodological differences, or to an underestimation of the factors involved in the expression of gaze following. In the current study, we tested 54 captive olive baboons (Papio anubis), housed in social groups, to assess how juvenile and adult baboons would spontaneously react to a sudden change in the direction of a human experimenter's head. First, our results showed that juveniles, more than adult baboons, co-oriented their gaze with the experimenter's gaze. We also observed a strong habituation effect in adult baboons but not in juveniles, as the adults' response vanished at the second exposure to a change of direction of the experimenter's head. Second, our results showed that juveniles subsequently adopted an original strategy when the experimenter's head indicated some new directions: they reliably adjusted their spatial body position to keep a gaze contact with the experimenter's line of sight. We discussed how the age class and the individual expertise of the baboons could lead to some modulations in terms of attentiveness, motivation, or cognitive abilities, and thus likely influence gaze following.

  12. Establishment and Characterization of Baboon Embryonic Stem Cell Lines An Old World Primate Model for Regeneration and Transplantation Research

    Science.gov (United States)

    Simerly, Calvin R.; Navara, Christopher S.; Castro, Carlos A.; Turpin, Janet C.; Redinger, Carrie J.; Mich-Basso, Jocelyn D.; Jacoby, Ethan S.; Grund, Kevin J.; McFarland, David A.; Oliver, Stacie L.; Ben-Yehudah, Ahmi; Carlisle, Diane L.; Frost, Patricia; Penedo, Cecilia; Hewitson, Laura; Schatten, Gerald

    2010-01-01

    Here we have developed protocols using the baboon as a complementary alternative Old World Primate to rhesus and other macaques which have severe limitations in their availability. Baboons are not limited as research resources, they are evolutionarily closer to humans and the multiple generations of pedigreed colonies which display complex human disease phenotypes all support their further optimization an invaluable primate model. Since neither baboon assisted reproductive technologies nor baboon embryonic stem cells (ESCs) have been reported, here we describe the first derivations and characterization of baboon ESC lines from IVF-generated blastocysts. Two ESCs lines (BabESC-4 and BabESC-15) display ESC morphology, express pluripotency markers (Oct-4, hTert, Nanog, Sox-2, Rex-1, TRA1–60, TRA1–81), and maintain stable euploid female karyotypes with parentage confirmed independently. They have been grown continuously for >430 and 290 days, respectively. Teratomas from both lines have all three germ layers. Availabilities of these BabESCs represent another important resource for stem cell biologists. PMID:19393591

  13. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  14. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  15. Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy.

    Science.gov (United States)

    Kobayashi, T; Taniguchi, S; Neethling, F A; Rose, A G; Hancock, W W; Ye, Y; Niekrasz, M; Kosanke, S; Wright, L J; White, D J; Cooper, D K

    1997-11-15

    This study sought to (i) investigate the efficacy of cobra venom factor (CVF) in preventing hyperacute rejection (HAR) after pig-to-baboon heart transplantation, (ii) examine the effect of additional splenectomy (Spx) and pharmacologic immunosuppression (IS), and (iii) study delayed graft rejection when HAR is avoided by complement depletion. Eleven recipient baboons received heterotopic pig heart transplants. Three received either no therapy or IS (cyclosporine + methylprednisolone +/- cyclophosphamide +/- methotrexate) at clinically well-tolerated doses, with graft survival for only 40, 32, and 15 min, respectively. Two received CVF+/-Spx, which extended survival to 5 and 6 days, respectively. Six underwent Spx + CVF therapy + IS; graft survival was 3 hr (technical complication), 6 days (death from sepsis), 10, 12, and 22 days (vascular rejection), and <25 days (euthanized for viral pneumonia with a functioning graft that showed histopathologic features of vascular rejection). Dense deposition of IgM and, to a lesser extent, IgG and IgA were seen on the endothelial cells within 1 hr of transplantation, but only trace levels of complement deposition were present in CVF-treated recipients. Within approximately 5-12 days, cardiac xenografts showed progressive infiltration by mononuclear cells, consisting primarily of activated macrophages producing tumor necrosis factor-alpha and small numbers of natural killer cells; T and B cells were absent. We conclude that (i) CVF prevents HAR, (ii) the addition of Spx + IS delays rejection, but (iii) the early deposition of antibody leads to progressive graft injury, resulting in (iv) delayed vascular rejection. Our findings indicate that the features of delayed xenograft rejection described in small animal models also occur in the pig-to-baboon model, and that rejection may occur in a complement-independent manner from the effects of antibody and/or host macrophages.

  16. Training experience in gestures affects the display of social gaze in baboons' communication with a human.

    Science.gov (United States)

    Bourjade, Marie; Canteloup, Charlotte; Meguerditchian, Adrien; Vauclair, Jacques; Gaunet, Florence

    2015-01-01

    Gaze behaviour, notably the alternation of gaze between distal objects and social partners that accompanies primates' gestural communication is considered a standard indicator of intentionality. However, the developmental precursors of gaze behaviour in primates' communication are not well understood. Here, we capitalized on the training in gestures dispensed to olive baboons (Papio anubis) as a way of manipulating individual communicative experience with humans. We aimed to delineate the effects of such a training experience on gaze behaviour displayed by the monkeys in relation with gestural requests. Using a food-requesting paradigm, we compared subjects trained in requesting gestures (i.e. trained subjects) to naïve subjects (i.e. control subjects) for their occurrences of (1) gaze behaviour, (2) requesting gestures and (3) temporal combination of gaze alternation with gestures. We found that training did not affect the frequencies of looking at the human's face, looking at food or alternating gaze. Hence, social gaze behaviour occurs independently from the amount of communicative experience with humans. However, trained baboons-gesturing more than control subjects-exhibited most gaze alternation combined with gestures, whereas control baboons did not. By reinforcing the display of gaze alternation along with gestures, we suggest that training may have served to enhance the communicative function of hand gestures. Finally, this study brings the first quantitative report of monkeys producing requesting gestures without explicit training by humans (controls). These results may open a window on the developmental mechanisms (i.e. incidental learning vs. training) underpinning gestural intentional communication in primates.

  17. Complement inhibition decreases early fibrogenic events in the lung of septic baboons

    Science.gov (United States)

    Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

    2015-01-01

    Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 109 cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. PMID:26337158

  18. Acute Lung Injury and Fibrosis in a Baboon Model of Escherichia coli Sepsis

    Science.gov (United States)

    Keshari, Ravi S.; Silasi-Mansat, Robert; Zhu, Hua; Popescu, Narcis I.; Peer, Glenn; Chaaban, Hala; Lambris, John D.; Polf, Holly; Lupu, Cristina; Kinasewitz, Gary

    2014-01-01

    Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrosis. The pathology of ARDS is complex and poorly understood, and the therapeutic approaches are limited. We used a baboon model of Escherichia coli sepsis that mimics the complexity of human disease to study the pathophysiology of ARDS. We performed extensive biochemical, histological, and functional analyses to characterize the disease progression and the long-term effects of sepsis on the lung structure and function. Similar to humans, sepsis-induced ARDS in baboons displays an early inflammatory exudative phase, with extensive necrosis. This is followed by a regenerative phase dominated by proliferation of type 2 epithelial cells, expression of epithelial-to-mesenchymal transition markers, myofibroblast migration and proliferation, and collagen synthesis. Baboons that survived sepsis showed persistent inflammation and collagen deposition 6–27 months after the acute episodes. Long-term survivors had almost double the amount of collagen in the lung as compared with age-matched control animals. Immunostaining for procollagens showed persistent active collagen synthesis within the fibroblastic foci and interalveolar septa. Fibroblasts expressed markers of transforming growth factor-β and platelet-derived growth factor signaling, suggesting their potential role as mediators of myofibroblast migration and proliferation, and collagen deposition. In parallel, up-regulation of the inhibitors of extracellular proteases supports a deregulated matrix remodeling that may contribute to fibrosis. The primate model of sepsis-induced ARDS mimics the disease progression in humans, including chronic inflammation and long-lasting fibrosis. This model helps our understanding of the pathophysiology of fibrosis and the testing of new therapies. PMID:24066737

  19. LYMPHOCYTE APOPTOSIS IN PSORIASIS

    Directory of Open Access Journals (Sweden)

    О. M. Kapuler

    2006-01-01

    Full Text Available Abstract. Forty-two patients with progressive vulgar psoriasis (PASI = 19.7 ± 1.5 and 40 healthy volunteers were under investigation. Psoriatic patients were characterized by increased number of CD4+ CD95+ peripheral blood T lymphocytes, which correlates with clinical psoriatic score, and by increased levels of soluble Fas (sFas in serum, as compared to controls (resp., 1868.1 ± 186.8 pg/ml vs. 1281.4 ± 142.5 pg/ml, PLSD = 0.019. The levels of spontaneous lymphocyte apoptosis and anti-Fas (Mab-induced apoptosis in psoriatic patients did not differ from the controls. However, apoptosis induced by “oxidative stress” (50 M Н202, 4 hrs was depressed in the patients. Moreover, a simultaneous assessment of cell cycle structure (metachromatic staining with Acridine Orange, apoptosis and Fas receptor expression (AnnV-FITC/antiFas mAbs-PE staining following a short-term mitogenic stimulation (PHA-P, 5 µg/ml, 24 hrs were performed. We found no marked differences in mitogenic reactivity, activation-induced apoptosis, and activation-induced Fas receptor expression when studying lymphocytes from healthy donors and psoriatic patients. However, PHA-activated lymphocytes from psoriatic patients displayed a significantly decreased ratio of AnnV+CD95+ to the total AnnV+ subpopulation, thus suggesting a decreased role of Fas-dependent mechanisms of apoptosis during the cell activation. The data obtained confirm a view, that an abnormal lymphocyte “apoptotic reactivity”, which plays a crucial role in the mechanisms of autoimmunity, may also of importance in the pathogenesis of psoriasis.

  20. Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline. [/sup 133/Xe tracer technique, baboons

    Energy Technology Data Exchange (ETDEWEB)

    McCalden, T.A.; Eidelman, B.H.; Mendelow, A.D.

    1977-10-01

    Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.

  1. Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad.

    Science.gov (United States)

    Harrison, R A; Bickle, Q D; Kiare, S; James, E R; Andrews, B J; Sturrock, R F; Taylor, M G; Webbe, G

    1990-01-01

    We have shown previously that baboons (Papio anubis) develop high levels (greater than 80%) of protection against challenge infection following immunization with Schistosoma haematobium cercariae irradiated with 20 krad. In the present study baboons were immunized with schistosomula irradiated with either 20 krad or 60 krad, with variations in the timing and number of larvae comprising each vaccination. Baboons immunized 2 or 3 times with schistosomula irradiated with 20 krad were significantly more protected (85-90%) against challenge infection than baboons similarly immunized with larvae receiving 60 krad (56-50% protection). Baboons immunized with schistosomula irradiated with 20 krad were better protected against challenge infection at 8 weeks after immunization than at 28 weeks after immunization. Protection was manifest by a reduction in worm numbers, tissue and excreta egg counts, gross pathology and, to a lesser extent, by stability of body weight and haematological indices following challenge. Enzyme-linked immunosorbent assay (ELISA) results of selected baboon sera showed few differences related to irradiation dose alone, but titres were higher in baboons receiving booster immunizations, and there was a significant correlation between titres immediately preceding challenge and the degree of resistance. Examination of responses to individual schistosomular surface antigens by immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed no correlation between the pattern of antigens recognized and resistance status. As with the ELISA assay, an anamnestic response was detected after vaccination, while the amount of antibody present declined markedly with increasing time after individual immunizations.

  2. Monkey Management: Using Spatial Ecology to Understand the Extent and Severity of Human-Baboon Conflict in the Cape Peninsula, South Africa

    Directory of Open Access Journals (Sweden)

    Tali S. Hoffman

    2012-09-01

    Full Text Available Conflict with humans poses one of the greatest threats to the persistence and survival of all wildlife. In the Cape Peninsula, South Africa, human-baboon conflict levels remain high despite substantial investment by conservation authorities in a variety of mitigation measures. Here we explore how spatial ecology can inform wildlife managers on the extent and severity of both current and projected human-baboon conflict. We apply conservative and generous densities - 2.3 and 5.9 baboons/km2 - to hypothetical landscape management scenarios to estimate whether the chacma baboon (Papio ursinus population in the Cape Peninsula is currently overabundant. We correlate conflict indices with spatial variables to explain intertroop differences in conflict levels. We investigate how an understanding of key elements of baboon ecology, including sleeping-site characteristics and intertroop territoriality, can direct management efforts and mitigate conflict. Our findings suggest that the current population of 475 baboons is below even the most conservative density estimate and that the area could potentially sustain up to 799 baboons. Conflict levels correlated positively with the loss of access to low-lying land through habitat transformation (Pearson r = 0.77, p = 0.015, n = 9 troops, and negatively with the distance of sleeping sites from the urban edge (Pearson r = 0.81, p = 0.001, n = 9 troops. Despite the availability of suitable sleeping sites elsewhere, more than half of all troops slept

  3. Immunohistochemical localisation of TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney.

    Science.gov (United States)

    Gubhaju, Lina; Laslett, Andrew; Bertram, John F; Zulli, Anthony; Black, M Jane

    2008-05-01

    The baboon is an ideal animal model to study human kidney development. The aim of the current study was to use immunohistochemistry to localise the antigens TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney where nephrogenesis was still on-going and in kidneys where nephrogenesis was complete. Fixed kidney sections from baboons delivered at 125, 140, 175 and 185 days gestation (term = 185 days) were immuno-labelled with antibodies directed against TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin. In kidneys with on-going nephrogenesis (125 and 140 days gestation), TRA-1-60, TRA-1-81 and GCTM-2 were specifically localised to the apical plasma membrane of the epithelium of the ureteric ampullae and the collecting ducts, while podocalyxin immunostaining was not detected. In kidneys where nephrogenesis was complete (175 and 185 days gestation) localisation of these markers was again very specifically localised to the collecting ducts. In conclusion, although further experimentation is required to confirm the identity of the specific cell types marked by these antibodies, this study provides new insight into the distribution of commonly utilised stem cell antibodies in the developing baboon kidney.

  4. Endogenous type C viral gene expression in cultures of fetal diploid baboon cells treated with 5'-bromodeoxyuridine

    Energy Technology Data Exchange (ETDEWEB)

    Lavelle, G.; Kennel, S.J.; Foote, L.J.

    1981-04-30

    Cultures of fetal diploid baboon fibroblasts treated with 5-bromodeoxyuridine synthesized protein antigenically related to baboon endogenous type C viral gag gene product, p28. Radioimmunoassays detected p28 antigenic specificities indistinguishable from those of purified virus. However, viral RNA-dependent DNA polymerase was not detected in culture fluids, and infectious virus was rarely recovered by cocultivation with susceptible heterologous cells. Extracellular particles containing p28 were not readily detected, further indicating that viral gag gene-coded proteins were synthesized independently of whole virus. Normal cultures of the same baboon cells exhibited endogenous expression of a glycoprotein antigenically related to BEV gp70, suggesting differential regulation of the endogenous gag and env gene-coded products. Baboon cell cultures exogenously infected with BEV produced extracellular particles having viral p28 and gp70 as measured by radioimmunoassays of culture fluids. Since induced cultures have about 10% positive cells versus close to 100% for infected culture, the amount of p28 per producing cell was about the same in both cell populations.

  5. Other better versus self better in baboons: an evolutionary approach of social comparison.

    Science.gov (United States)

    Dumas, F; Fagot, J; Davranche, K; Claidière, N

    2017-05-31

    Comparing oneself with others is an important characteristic of human social life, but the link between human and non-human forms of social comparison remains largely unknown. The present study used a computerized task presented in a social context to explore psychological mechanisms supporting social comparison in baboons and compare major findings with those usually observed in humans. We found that the effects of social comparison on subject's performance were guided both by similarity (same versus different sex) and by task complexity. Comparing oneself with a better-off other (upward comparison) increased performance when the other was similar rather than dissimilar, and a reverse effect was obtained when the self was better (downward comparison). Furthermore, when the other was similar, upward comparison led to a better performance than downward comparison. Interestingly, the beneficial effect of upward comparison on baboons' performance was only observed during simple task. Our results support the hypothesis of shared social comparison mechanisms in human and non-human primates. © 2017 The Author(s).

  6. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Science.gov (United States)

    Galbany, Jordi; Tung, Jenny; Altmann, Jeanne; Alberts, Susan C

    2015-01-01

    Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  7. Behavioral measurement of temperament in male nursery-raised infant macaques and baboons.

    Science.gov (United States)

    Heath-Lange, S; Ha, J C; Sackett, G P

    1999-01-01

    We define temperament as an individual's set of characteristic behavioral responses to novel or challenging stimuli. This study adapted a temperament scale used with rhesus macaques by Schneider and colleagues [American Journal of Primatology 25:137-155, 1991] for use with male pigtailed macaque (Macaca nemestrina, n = 7), longtailed macaque (M. fascicularis, n = 3), and baboon infants (Papio cynocephalus anubis, n = 4). Subjects were evaluated twice weekly for the first 5 months of age during routine removal from their cages for weighing. Behavioral measures were based on the subject's interactions with a familiar human caretaker and included predominant state before capture, response to capture, contact latency, resistance to tester's hold, degree of clinging, attention to environment, defecation/urination, consolability, facial expression, vocalizations, and irritability. Species differences indicated that baboons were more active than macaques in establishing or terminating contact with the tester. Temperament scores decreased over time for the variables Response to Capture and Contact Latency, indicating that as they grew older, subjects became less reactive and more bold in their interactions with the tester. Temperament scores changed slowly with age, with greater change occurring at younger ages. The retention of variability in reactivity between and within species may be advantageous for primates, reflecting the flexibility necessary to survive in a changing environment.

  8. Pathology resulting from the administration of a live attenuated anti-Schistosoma haematobium vaccine in baboons.

    Science.gov (United States)

    Byram, J E; Harrison, R A; von Lichtenberg, F; Webbe, G; Sturrock, R F

    1989-01-01

    Baboons (Papio anubis) were injected in the leg muscle with 18,000 20 Krad irradiated schistosomula of Schistosoma haematobium. Four protocols were followed: single, primary injection; single injection into animals primed by patent S. haematobium infection; secondary vaccine injection following an earlier injection; and single injection following praziquantel treatment of infected animals. Injection of the putative vaccine elicited localized mixed inflammatory infiltration at the site of injection which was both intense and prolonged. Three grades of tissue reaction were seen: the relatively mild primary response; the response in infected animals which had enhanced tissue eosinophilia; and the response in animals primed by prior injection and drug-treated prior infection. The latter 2 showed intensification of eosinophilia, stellate abscesses in the lesion centers, and perischistosomular Hoeppli precipitates. Intramuscular lesions peaked at 14 days for the primary response and at 7 days for all secondary responses. Traces of the milder lesions persisted beyond 4 weeks; more severe reactions healed more rapidly. Some schistosomula survived for 14 days in the milder reactions. A few larvae were deposited in the skin by backflushing of the injectate which produced local inflammation. Compared to mice, live schistosome vaccines injected into baboons elicited greater local inflammation; however, while evidence suggested that sporadic vaccine schistosomula did reach the lymphatic nodes draining the injection sites, no systemic lesions were found and the injection sites healed in approximately 5-6 weeks without permanent damage.

  9. Cardiac output by Doppler echocardiography in the premature baboon: comparison with radiolabeled microspheres.

    Science.gov (United States)

    Kinsella, J P; Morrow, W R; Gerstmann, D R; Taylor, A F; deLemos, R A

    1991-04-01

    Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). We conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress.

  10. CM 40907: a structurally novel anticonvulsant in mice, rats and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Chambon, J.P.; Brochard, J.; Hallot, A.; Heaulme, M.; Brodin, R.; Roncucci, R.; Biziere, K.

    1985-06-01

    CM 40907 (3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine) is a chemically original compound which possesses the pharmacological properties of a potent, p.o. active anticonvulsant. The anticonvulsant activity of CM 40907 was examined in mice, rats and photosensitive Papio-papio baboons and compared to that of phenobarbital, diphenylhydantoin, carbamazepine, sodium valproate and ethosuximide. In mice, CM 40907 antagonized electroconvulsive shock and chemically induced seizures with an overall potency comparable to that of carbamazepine and a therapeutic ratio (ED50 rotorod/ED50 electroshock) superior to that of ethosuximide, sodium valproate, phenobarbital and carbamazepine. In the rat CM 40907 suppressed completed kindled amygdaloid seizures and was approximately as active as phenobarbital. In naturally photosensitive Senegalese Papio-papio baboons CM 40907 antagonized myoclonus and cortical paroxysmal discharges. In this model CM 40907 was approximately one-fourth as potent as phenobarbital, twice as potent as carbamazepine and 6 times more potent than sodium valproate. In mice CM 40907, at anticonvulsant doses, increased the affinity of (/sup 3/H)flunitrazepam for its central receptor site. Based on these results it is postulated that CM 40907 is a potent and relatively nonsedative anticonvulsant and may be of therapeutic benefit in epileptic disorders.

  11. Effect of water or saline intake on heat-induced limb vasodilation in dehydrated baboons.

    Science.gov (United States)

    Ryan, K L; Proppe, D W

    1990-02-01

    Dehydration markedly attenuates the increase in hindlimb blood flow elicited by environmental heating (EH) in baboons. This study sought to determine the importance of gradually produced increases in body fluid osmolality and decreases in body fluid volume in producing this attenuation. The hindlimb blood flow increases during EH of seven unanesthetized chronically instrumented baboons were examined during euhydration, dehydration (64-68 h of water deprivation), and after ad libitum oral rehydration with either water or a hyperosmotic saline solution. EH consisted of acute exposure to ambient temperatures of 38-42 degrees C until internal temperature reached 39.5 degrees C. Dehydration depressed the maximal external iliac artery blood flow (MIBF) and iliac vascular conductance (IVC) attained during EH in the euhydrated state by 37 and 43%, respectively. Rehydration with either water or saline solution, however, restored maximal MIBF and IVC to euhydrated levels. Because plasma osmolality remained at dehydrated levels after rehydration with saline, hyperosmolality does not produce the dehydration-induced attenuation in hindlimb blood flow.

  12. Effects of hyperosmolality and diuretics on heat-induced limb vasodilation in baboons.

    Science.gov (United States)

    Proppe, D W

    1990-02-01

    Dehydration attenuates the increase in limb skin blood flow elicited by environmental heating (EH). This study sought to determine which of the two primary effects of dehydration, increased body fluid osmolality or decreased body fluid volume, was primarily responsible for this cutaneous vasoconstrictor bias in baboons. Unanesthetized chronically instrumented baboons were exposed to EH while in euhydrated state, after 65-69 h of water deprivation (dehydration), after infusion of a small volume of hypertonic (20%) saline to raise plasma osmolality and sodium concentration to dehydration levels, and after injections of the diuretic furosemide over a 64-h period to produce an isosmotic fall in extracellular fluid volume. EH consisted of an acute elevation of ambient temperature to 39.5-42.0 degrees C until internal temperature reached 39.5-39.8 degrees C. The normal increases in external iliac artery blood flow and iliac vascular conductance during EH were unchanged by hyperosmolality but were attenuated by 39 and 31%, respectively, after furosemide treatment and by 42 and 46%, respectively, during dehydration. Thus the fall in extracellular fluid volume is the component of dehydration that attenuates the increase in hindlimb blood flow during EH in the same way as dehydration itself.

  13. alpha-Adrenergic control of intestinal circulation in heat-stressed baboons.

    Science.gov (United States)

    Proppe, D W

    1980-05-01

    The mechanisms involved in producing intestinal vasoconstriction during a hyperthermia-producing intestinal vasoconstriction during a hyperthermia-producing environmental heat stress are unknown. Five conscious baboons (Papio anubis), each with chronically implanted catheters and a flow probe around the superior mesenteric artery, were subjected to environmental heating (Ta 40-45 degrees C) to raise their arterial blood temperature (Tbl) 2.0-2.6 degrees C to approximately 39.5 degrees C. Accompanying the gradual rise in Tbl was a fall in mean superior mesenteric artery blood flow (MSMF) and a progressive rise in superior mesenteric vascular resistance (SMR). At peak Tbl, MSMF had fallen 28.8 +/- 0.6% (mean +/- SE) and SMR had risen 50.2 +/- 4.2%. To determine the involvement of the sympathetic nervous system in producing this intestinal vasoconstriction, the baboon was subjected to environmental heating after induction of alpha-adrenergic receptor blockade by phenoxybenzamine or phentolamine. In this state, the rise in Tbl was accompanied by no change in MSMF and a slight, but not statistically significant, rise (7.8 +/- 3.8%) in SMR. Since alpha-receptor blockade nearly completely abolishes intestinal vasoconstriction during heat stress, this intestinal vasoconstriction must be mediated primarily by elevated sympathetic outflow.

  14. Temporal dynamics of gene expression in the lung in a baboon model of E. coli sepsis

    Directory of Open Access Journals (Sweden)

    Zhu Hua

    2007-02-01

    Full Text Available Abstract Background Bacterial invasion during sepsis induces disregulated systemic responses that could lead to fatal lung failure. The purpose of this study was to relate the temporal dynamics of gene expression to the pathophysiological changes in the lung during the first and second stages of E. coli sepsis in baboons. Results Using human oligonucleotide microarrays, we have explored the temporal changes of gene expression in the lung of baboons challenged with sublethal doses of E. coli. Temporal expression pattern and biological significance of the differentially expressed genes were explored using clustering and pathway analysis software. Expression of selected genes was validated by real-time PCR. Cytokine levels in tissue and plasma were assayed by multiplex ELISA. Changes in lung ultrastructure were visualized by electron microscopy. We found that genes involved in primary inflammation, innate immune response, and apoptosis peaked at 2 hrs. Inflammatory and immune response genes that function in the stimulation of monocytes, natural killer and T-cells, and in the modulation of cell adhesion peaked at 8 hrs, while genes involved in wound healing and functional recovery were upregulated at 24 hrs. Conclusion The analysis of gene expression modulation in response to sepsis provides the baseline information that is crucial for the understanding of the pathophysiology of systemic inflammation and may facilitate the development of future approaches for sepsis therapy.

  15. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Directory of Open Access Journals (Sweden)

    Jordi Galbany

    Full Text Available Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank, but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  16. Knockouts of high-ranking males have limited impact on baboon social networks.

    Science.gov (United States)

    Franz, Mathias; Altmann, Jeanne; Alberts, Susan C

    Social network structures can crucially impact complex social processes such as collective behaviour or the transmission of information and diseases. However, currently it is poorly understood how social networks change over time. Previous studies on primates suggest that `knockouts' (due to death or dispersal) of high-ranking individuals might be important drivers for structural changes in animal social networks. Here we test this hypothesis using long-term data on a natural population of baboons, examining the effects of 29 natural knockouts of alpha or beta males on adult female social networks. We investigated whether and how knockouts affected (1) changes in grooming and association rates among adult females, and (2) changes in mean degree and global clustering coefficient in these networks. The only significant effect that we found was a decrease in mean degree in grooming networks in the first month after knockouts, but this decrease was rather small, and grooming networks rebounded to baseline levels by the second month after knockouts. Taken together our results indicate that the removal of high-ranking males has only limited or no lasting effects on social networks of adult female baboons. This finding calls into question the hypothesis that the removal of high-ranking individuals has a destabilizing effect on social network structures in social animals.

  17. Evidence for varying social strategies across the day in chacma baboons.

    Science.gov (United States)

    Sick, Claudia; Carter, Alecia J; Marshall, Harry H; Knapp, Leslie A; Dabelsteen, Torben; Cowlishaw, Guy

    2014-07-01

    Strong social bonds can make an important contribution to individual fitness, but we still have only a limited understanding of the temporal period relevant to the adjustment of social relationships. While there is growing recognition of the importance of strong bonds that persist for years, social relationships can also vary over weeks and months, suggesting that social strategies may be optimized over shorter timescales. Using biological market theory as a framework, we explore whether temporal variation in the benefits of social relationships might be sufficient to generate daily adjustments of social strategies in wild baboons. Data on grooming, one measure of social relationships, were collected from 60 chacma baboons (Papio ursinus) across two troops over a six month period. Our analyses suggest that social strategies can show diurnal variation, with subordinates preferentially grooming more dominant individuals earlier in the day compared with later in the day. These findings indicate that group-living animals may optimize certain elements of their social strategies over relatively short time periods.

  18. Effect of the antiestrogen ethamoxytriphetol (MER-25) on placental low density lipoprotein uptake and degradation in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Henson, M.C.; Babischkin, J.S.; Pepe, G.J.; Albrecht, E.D.

    1988-05-01

    The present study determined if the decline in placental progesterone (P4) production that results from administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons results from a change in placental low density lipoprotein (LDL) uptake and/or degradation. Pregnant baboons (Papio anubis) were untreated (n = 10) or received MER-25 (25 mg/kg BW, orally; n = 10) daily on days 140-170 of gestation (term, 184 days). Placentas were removed by cesarean section on day 170 of gestation, and villous tissue was dispersed with 0.1% collagenase at 37 C for 40 min. Placental cells (10(6)) were incubated in medium 199 (pH 7.2) for 12 h at 37 C with increasing amounts (5-100 micrograms) of (125I)LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SE) peripheral serum P4 concentrations on days 140-170 of gestation were 51% lower (P less than 0.01) in MER-25-treated (5.7 +/- 0.3 ng/ml) than in untreated (11.6 +/- 0.5 ng/ml) baboons. The uptake of LDL was 56% lower (P less than 0.01) in placental cells from antiestrogen-treated (6.3 +/- 1.6 ng/micrograms cell protein) than in those from untreated (14.4 +/- 1.9 ng/micrograms cell protein) baboons. The dissociation constants for placental LDL uptake, as assessed by Scatchard analysis, however, were similar in untreated (0.80 microgram/ml) and MER-25-treated (0.76 microgram/ml) animals. The amount of (125I)LDL concomitantly degraded by cells from baboons that received MER-25 was 54% of that degraded by cells from untreated controls. The relative decline in LDL degradation by cells of antiestrogen-treated baboons was proportionate to the decline in overall LDL uptake. The results indicate, therefore, that antiestrogen treatment decreased the amount of placental LDL uptake, but did not change the affinity for the lipoprotein.

  19. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  20. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  1. Anti-GaL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation.

    Science.gov (United States)

    Minanov, O P; Itescu, S; Neethling, F A; Morgenthau, A S; Kwiatkowski, P; Cooper, D K; Michler, R E

    1997-01-27

    We have previously demonstrated that hyperacute rejection does not occur in a pig-to-newborn baboon heart transplant model, presumably because of low levels of cytotoxic antipig antibodies present in the serum of newborn baboons. Cytotoxic antipig antibodies are primarily directed to alpha-1,3-galactosyl (alpha Gal) residues on endothelial cell surface structures Twenty-one full-term humans and 5 full-term baboons were tested for complement mediated lysis (CML) of pig kidney (PK-15) cells and anti-alpha Gal activity with an ELISA using BSA-conjugated alpha Gal residues as target. To evaluate the significance of the anti-alpha Gal titers in vivo 5 newborn baboons underwent heterotopic pig cardiac xenotransplantation. Six of 21 human samples and 1 of 5 baboon samples demonstrated significant cytotoxicity to PK-15 cells. Twelve of 21 newborn humans had anti-alpha Gal IgG antibodies at titers of 1:80 or greater. None of the samples had anti-alpha Gal IgM. In newborn baboons, 1 of 5 sera had anti-alpha Gal IgG antibodies at titers greater than 1:80 and none of these samples had anti-alpha Gal IgM. Xenografts survived for an average of 3.6 days, even in the baboon with high anti-alpha Gal IgG titers. Analysis of the explanted grafts showed minimal evidence of complement-mediated hyperacute rejection (HAR), but prominent mononuclear cell infiltrates. In serum tested posttransplant there was an induced anti-alpha Gal response with cytotoxicity against PK-15 cells. These results show that anti-alpha Gal IgM is absent in newborn human and baboon sera, allowing pig grafts to avoid HAR. However, the presence of anti-alpha Gal IgG may be associated with mononuclear cell infiltration of the xenograft and its subsequent rejection.

  2. A note on the efficacy of a new class of compounds, 9-acridanone-hydrazones, against Schistosoma mansoni in a primate--the baboon.

    Science.gov (United States)

    Sturrock, R F; Otieno, M; James, E R; Webbe, G

    1985-01-01

    Five 9-acridanone-hydrazone compounds were tested against moderately heavy Schistosoma mansoni infections in baboons. They were administered as a single oral dose at a rate of 50 mg/kg body-weight. Compared with results from an untreated control baboon, four of the compounds showed high levels of activity judged by the reduction or elimination of faecal egg production, adult worms and tissue eggs.

  3. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  4. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.

    2015-01-01

    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact...

  5. Lymphocytic Interstitial Pneumonia.

    Science.gov (United States)

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  6. Chronic lymphocytic leukaemia

    Science.gov (United States)

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  7. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    Science.gov (United States)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  8. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

    2010-01-12

    Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

  9. The baboon (Papio anubis extracranial carotid artery: An anatomical guide for endovascular experimentation

    Directory of Open Access Journals (Sweden)

    Laufer Ilya

    2001-12-01

    Full Text Available Abstract Background As novel endovascular strategies are developed for treating neurological disease, there is an increasing need to evaluate these techniques in relevant preclinical models. The use of non-human primates is especially critical given their structural and physiological homology with humans. In order to conduct primate endovascular studies, a comprehensive understanding of the carotid anatomy is necessary. We therefore performed a detailed examination of the vessel lengths, lumen diameters and angles of origin of the baboon extracranial carotid system. Methods We characterized the extracranial carotid system often male baboons (Papio anubis, range 15.1–28.4 kg by early post-mortem dissection. Photographic documentation of vessel lengths, lumen diameters, and angles of origin were measured for each segment of the carotid bilaterally. Results The common carotid arteries averaged 94.7 ± 1.7 mm (left and 87.1 ± 1.6 mm (right in length. The average minimal common carotid lumen diameters were 3.0 ± 0.3 mm (left and 2.9 ± 0.2 mm (right. Each animal had a common brachiocephalic artery arising from the aorta which bifurcated into the left common carotid artery and right braciocephalic artery after 21.5 ± 1.6 mm. The vascular anatomy was found to be consistent among animals despite a wide range of animal weights. Conclusions The consistency in the Papio anubis extracranial carotid system may promote the use of this species in the preclinical investigation of neuro-interventional therapies.

  10. White monkey syndrome and presumptive copper deficiency in wild savannah baboons.

    Science.gov (United States)

    Markham, A Catherine; Gesquiere, Laurence R; Bellenger, Jean-Philippe; Alberts, Susan C; Altmann, Jeanne

    2011-11-01

    In immature wild savannah baboons (Papio cynocephalus), we observed symptoms consistent with copper (Cu) deficiency and, more specifically, with a disorder referred to as white monkey syndrome (WMS) in laboratory primates. The objectives of this study were to characterize this pathology, and test three hypotheses that (1) Cu deficiency may have been induced by zinc (Zn) toxicity, (2) it may have been induced by molybdenum (Mo) toxicity, and (3) cumulative rainfall during the perinatal period and particularly during gestation is an ecological factor distinguishing infants afflicted with WMS from non-WMS infants. During 2001-2009, we observed 22 instances of WMS out of a total 377 live births in the study population. Visible symptoms exhibited by WMS infants included whitening of the animal's fur and/or impaired mobility characterized by an apparent "stiffening" of the hindlimbs. Occurrence of WMS did not vary significantly by gender. However, among individuals that survived at least 180 days, WMS males had a significantly lower survivorship probability than non-WMS males. Zn/Cu ratios assessed from hair samples of adult female baboons were higher in females who had produced at least one WMS offspring relative to females who had not had a WMS offspring. This was true even when the hair sample was collected long after the birth of the female's afflicted infant. We consider this potentially indicative of a robust tendency for low Cu levels induced by elevated Zn intake in some individuals. No significant differences of Mo/Cu ratios were observed. Cumulative rainfall during gestation (∼179 days) was 50% lower for WMS infants relative to non-WMS infants. In contrast, rainfall for the two classes of infants did not differ in the 180 days before conception or in the 180 days following birth. This finding highlights the importance of prenatal ecological conditions in healthy fetal development with regard to WMS.

  11. Paternity alone does not predict long-term investment in juveniles by male baboons.

    Science.gov (United States)

    Moscovice, Liza R; Heesen, Marlies; Di Fiore, Anthony; Seyfarth, Robert M; Cheney, Dorothy L

    2009-08-01

    Adult male chacma baboons (Papio hamadryas ursinus) form preferential associations, or friendships, with particular lactating females. Males exhibit high levels of affiliative contact with their friends' infants and defend them from potentially infanticidal attacks (Palombit et al. 1997). Little is known about males' associations with juveniles once they have passed the period of infanticidal risk. We conducted an observational, experimental, and genetic study of adult male and juvenile chacma baboons in the Moremi Reserve, Botswana. We identified preferential associations between males and juveniles and used behavioral data and a playback experiment to explore whether those associations have potential fitness benefits for juveniles. We determined whether males preferentially invest in care of their own offspring. We also determined how often males invest in care of their former friends' offspring. The majority of juveniles exhibited preferential associations with one or two males, who had almost always been their mother's friend during infancy. However, in only a subset of these relationships was the male the actual father, in part because many fathers died or disappeared before their offspring were weaned. Male caretakers intervened on behalf of their juvenile associates in social conflicts more often than they intervened on behalf of unconnected juveniles, and they did not appear to differentiate between genetic offspring and unrelated associates. Playbacks of juveniles' distress calls elicited a stronger response from their caretakers than from control males. Chacma males may provide care to unrelated offspring of former friends because the costs associated with such care are low compared with the potentially high fitness costs of refusing aid to a juvenile who is a possible offspring.

  12. Baboons, water, and the ecology of oxygen stable isotopes in an arid hybrid zone.

    Science.gov (United States)

    Moritz, Gillian L; Fourie, Nicolaas; Yeakel, Justin D; Phillips-Conroy, Jane E; Jolly, Clifford J; Koch, Paul L; Dominy, Nathaniel J

    2012-01-01

    Baboons regularly drink surface waters derived from atmospheric precipitation, or meteoric water. As a result, the oxygen isotope (δ(18)O) composition of their tissues is expected to reflect that of local meteoric waters. Animal proxies of the oxygen isotope composition of meteoric water have practical applications as paleoenvironmental recorders because they can be used to infer aridity and temperature in historic and fossil systems. To explore this premise, we measured the δ(18)O values of hair from two baboon species, Papio anubis and Papio hamadryas, inhabiting Awash National Park, Ethiopia. The hybridizing taxa differ in their ranging behavior and physiological response to heat. Papio hamadryas ranges more widely in the arid thornbush and is inferred to ingest a greater proportion of leaf water that is enriched in (18)O as a result of evaporative fractionation. It is also better able to conserve body water, which reduces its dependence on meteoric waters depleted in (18)O. Taken together, these factors would predict relatively higher δ(18)O values in the hair (δ(18)O(hair)) of P. hamadryas. We found that the δ(18)O(hair) values of P. hamadryas were higher than those of P. anubis, yet the magnitude of the difference was marginal. We attribute this result to a common source of drinking water, the Awash River, and the longer drinking bouts of P. hamadryas. Our findings suggest that differences in δ(18)O values among populations of Papio (modern or ancient) reflect different sources of drinking water (which might have ecological significance) and, further, that Papio has practical value as a paleoenvironmental recorder.

  13. Endothelial reconstitution by CD34+ progenitors derived from baboon embryonic stem cells.

    Science.gov (United States)

    Shi, Qiang; Schatten, Gerald; Hodara, Vida; Simerly, Calvin; VandeBerg, John L

    2013-02-01

    In this study, we used a large non-human primate model, the baboon, to establish a step-wise protocol to generate CD34+ endothelial progenitor cells (EPCs) from embryonic stem cells (ESCs) and to demonstrate their reparative effects. Baboon ESCs were sequentially differentiated from embryoid body cultures for 9 days and then were specified into EPCs by culturing them in monolayer for 12 days. The resulting EPCs expressed CD34, CXCR4 and UEA-1, but neither CD31 nor CD117. The EPCs were able to form intact lumen structures when seeded on Matrigel, took up Dil-LDL, and responded to TNF-α. Angioblasts specified in EGM-2 medium and ECGS medium had 6.41 ± 1.16% (n = 3) and 9.32 ± 3.73% CD34+ cells (n = 3). The efficiency of generating CD34+ EPCs did not differ significantly from ECGS to EGM-2 culture media, however, angioblasts specified in ECGS medium expressed a higher percentage of CD34+/CXCR4+ cells (3.49 ± 1.32%, n = 3) than those specified in EGM-2 medium (0.49 ± 0.52%, n = 3). To observe their reparative capacity, we purified CD34+ progenitors after specification by EGM-2 medium; inoculated fluorescently labelled CD34+ EPCs into an arterial segment denuded of endothelium in an ex vivo system. After 14 days of ex vivo culture, the grafted cells had attached and integrated to the denuded surface; in addition, they had matured further and expressed terminally differentiated endothelial markers including CD31 and CD146. In conclusion, we have proved that specified CD34+ EPCs are promising therapeutic agents for repairing damaged vasculature.

  14. Pulp response to ferric sulfate, diluted formocresol and IRM in pulpotomized primary baboon teeth.

    Science.gov (United States)

    Fuks, A B; Eidelman, E; Cleaton-Jones, P; Michaeli, Y

    1997-01-01

    This study investigated the pulp response to a 15.5 percent ferric sulfate solution (FS) and a 20 percent dilution of formocresol (DFC) in pulpotomized primary teeth of baboons, after four and eight weeks. Pulpotomies were performed in seventy-nine primary teeth of 4 baboons. After coronal pulp resection, the pulp stumps were painted with ferric sulfate for fifteen seconds, in thirty-two teeth (group 1); in another thirty-two teeth, a cotton pellet moistened with dilution of formocresol was placed over the pulp stumps for five minutes, and removed (group 2). In fifteen teeth, IRM was placed directly over the pulp stumps after hemostasis (group 3--control). The teeth of all groups were sealed with IRM, and examined for inflammatory changes under a microscope by two blinded examiners. Seventy-seven teeth were assessed. Mild or no inflammation was found in 58 percent (18/31) of the teeth of group 1, in 48 percent (15/31) of those of group 2, and in 73 percent (11/15) of those of group 3. Severe inflammation was found in 35 percent (11/31) of group 1, 29 percent (9/31) of group 2, and in 7 percent (1/15) of group 3. No statistically significant difference between the three groups was observed for degree of inflammation, periradicular or interradicular abscess or inflammatory root resorption (chi-square p > 0.05). Dentin bridges were observed in 52 percent (16/31) of the teeth in group 1, 52 percent (16/31) of those of group 2, and in 73 percent (11/15) of those of group 3. No difference was found between the experimental and control groups for the presence of dentin bridge, (p > 0.05). Ferric sulfate produced pulp responses that compared favorably to those of diluted formocresol.

  15. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  16. Derivation and characterization of novel nonhuman primate embryonic stem cell lines from in vitro-fertilized baboon preimplantation embryos.

    Science.gov (United States)

    Chang, Tien-Cheng; Liu, Ya-Guang; Eddy, Carlton A; Jacoby, Ethan S; Binkley, Peter A; Brzyski, Robert G; Schenken, Robert S

    2011-06-01

    The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol. The inner cell mass of blastocyst was laser-dissected and plated on mouse embryonic fibroblast feeder cell monolayer in the NHP ESC culture medium. Three cell lines with characteristic ESC morphology have been cultured through an extended period (>14 months), with 2 male cell lines (UT-1 and -2) and 1 female cell line (UT-3) displaying normal baboon karyotypes. Reverse transcription-polymerase chain reaction analysis confirmed that all 3 lines express primate ESC pluripotency markers, including OCT-4, NANOG, SOX-2, TERT, TDGF, LEFTYA, and REX-1. All 3 lines demonstrated positive immunocytochemical staining for OCT-4, stage-specific embryonic antigen-3, stage-specific embryonic antigen-4, TRA-1-60, and TRA-1-81. Baboon ESCs injected into NOD/SCID mice formed teratomas with all 3 germ layers. In addition, embryoid body-like spherical structures were derived and initial outgrowth was observed when embedded into extracellular matrix Matrigel. The ESC lines established in this NHP model have the potential to extend our knowledge in the fields of developmental biology, regenerative medicine, and future applications, including preclinical safety assessment of in vivo stem cell therapy.

  17. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    Science.gov (United States)

    Chavez, Alberto O; Gastaldelli, Amalia; Guardado-Mendoza, Rodolfo; Lopez-Alvarenga, Juan C; Leland, M Michelle; Tejero, M Elizabeth; Sorice, GianPio; Casiraghi, Francesca; Davalli, Alberto; Bastarrachea, Raúl A; Comuzzie, Anthony G; DeFronzo, Ralph A; Folli, Franco

    2009-01-01

    Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp. Results In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001). Conclusion In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus. PMID:19389241

  18. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    Directory of Open Access Journals (Sweden)

    Bastarrachea Raúl A

    2009-04-01

    Full Text Available Abstract Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c. However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159, a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI derived from the clamp. Results In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd. A second model, which included fasting plasma insulin (log transformed and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p Conclusion In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference, plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus.

  19. Immunisation of baboons against Schistosoma mansoni using irradiated S. mansoni cercariae and schistosomula and non-irradiated S. rodhaini cercariae.

    Science.gov (United States)

    Taylor, M G; James, E R; Nelson, G S; Bickle, Q; Andrews, B J; Dobinson, A R; Webbe, G

    1976-09-01

    In an attempt to develop a non-pathogenic procedure for immunising baboons against S. mansoni, groups of five baboons were exposed to three doses of 5000 6 Kr-irradiated S. mansoni cercariae or to similar numbers of normal S. rodhaini cercariae and challenged at week 15 with 500 normal S. mansoni cercariae. Faecal egg counts, worm and tissue egg counts, and histopathological examination, showed that neither of the immunising schedules had produced significant protection. In the second experiment baboons were injected by the intramuscular route with 31000 schistosomula of S. mansoni in three doses and the irradiation dose was reduced to near the minimum required for worm sterilisation (2-1--2-4 Kr). Challenge with 3500 normal cercariae of S. mansoni 21 weeks after the first immunising dose again showed no significant protection, although reductions of 20--30% were found in egg and worm counts resulting from the challenge. These results indicate that it may be difficult to develop an effective live vaccine for S. mansoni unless the antigenicity of the immunising larvae can be greatly increased.

  20. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  1. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2007-10-01

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  2. Influence of heat stress on arterial baroreflex control of heart rate in the baboon.

    Science.gov (United States)

    Gorman, A J; Proppe, D W

    1982-07-01

    The influence of environmental heat stress on the arterial baroreflex control of heart rate (HR) was studied in eight conscious, chronically instrumented baboons. Inflations of balloon occluders around the inferior vena cava (IVC) and thoracic descending aorta (DA) were used to produce acute, graded changes in mean arterial blood pressure (MABP) in 5 mm Hg intervals ranging from +/- 5 to +/- 25 mm Hg. After determination of the HR responses to changes in MABP in the normothermic baboon (blood temperature less than or equal to 37.6 degrees C), the animal was subjected to environmental heating to produce hyperthermia. When blood temperature reached approximately 39.5 degrees C, HR responses to graded DA and IVC occlusions were again determined. During hyperthermia, the HR sensitivity (delta HR/ delta MABP) to MABP changes was markedly diminished for reductions in MABP and significantly enhanced for increases in MABP. To determine whether these alterations in the HR response to changes in MABP were due to an alteration of the baroreflex control of HR, full, sigmoid-shaped HR-MABP curves for both the normothermic and hyperthermic states were constructed and characterized by total HR range, estimated slope of the steep portion of the curve, and MABP at the midpoint of the HR range (BP50). During hyperthermia (1) the whole HR-MABP curve shifted significantly upward by 35-40 beats/min, (2) total HR range, the estimated slope, and BP50 did not change, and (3) the control point (pre-occlusion HR-MABP value) curves were also constructed during either beta-adrenergic blockade or cholinergic (Ch)-receptor blockade in the normothermic and hyperthermic state. Similar to that seen for the unblocked heart, the whole HR-MABP curves were also shifted upward during hyperthermia in this group of baboons with no alteration in the total HR range, the estimated slope, or BP50. The upward shift in the HR-MABP curve during Ch-receptor blockade, unlike during beta-receptor blockade, was

  3. Initiation of lymphocyte DNA synthesis.

    Science.gov (United States)

    Coffman, F D; Fresa, K L; Cohen, S

    1991-01-01

    The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.

  4. Effects of ozone on cyclooxygenase metabolites in the baboon tracheobronchial tree

    Energy Technology Data Exchange (ETDEWEB)

    Fouke, J.M.; DeLemos, R.A.; Dunn, M.J.; McFadden, E.R. Jr. (Southwest Foundation for Biomedical Research, San Antonio, TX (USA))

    1990-07-01

    Short-term exposure to 0.5 parts per million (ppm) ozone has been shown to cause an increase in respiratory resistance in primates that can be diminished by 50% with pretreatment with cromolyn sodium. Because of the known membrane-stabilizing effects of cromolyn and the resultant inhibition of mediator production, we hypothesized a role for the products of arachidonic acid (AA) metabolism in these events. We exposed five adult male baboons to 0.5 ppm ozone on two occasions, once with cromolyn pretreatment and once without. Pulmonary resistance (RL) was monitored and bronchoalveolar lavage (BAL) was performed before and after each exposure. The BAL was analyzed for a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin (PG) F1 alpha, PGE2, a stable hydrolysis product of thromboxane (Tx) A2, TxB2, and PGF2 alpha. RL increased after ozone exposure (1.62 +/- 0.23 to 3.77 +/- 0.51 cmH2O.l-1.s, difference 2.15; P less than 0.02), and this effect was partially blocked by cromolyn (1.93 +/- 0.09 to 3.18 +/- 0.40 cmH2O.l-1.s, difference 1.25; P less than 0.02). The base-line levels of the metabolites of AA in the BAL were as follows (in pg/ml): 6-keto-PGF1 alpha 72.78 +/- 12.6, PGE2 145.92 +/- 30.52, TxB2 52.52 +/- 9.56, and PGF2 alpha 22.28 +/- 5.42. Ozone exposure had no effect on the level of any of these prostanoids (P = NS). These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from baboon lungs and demonstrate that changes in the levels of these mediators in BAL are not prerequisites for ozone-induced increases in respiratory resistance.

  5. Papio Cranium from the Hominin-Bearing Site of Malapa: Implications for the Evolution of Modern Baboon Cranial Morphology and South African Plio-Pleistocene Biochronology.

    Directory of Open Access Journals (Sweden)

    Christopher C Gilbert

    Full Text Available A new partial cranium (UW 88-886 of the Plio-Pleistocene baboon Papio angusticeps from Malapa is identified, described and discussed. UW 88-886 represents the only non-hominin primate yet recovered from Malapa and is important both in the context of baboon evolution as well as South African hominin site biochronology. The new specimen may represent the first appearance of modern baboon anatomy and coincides almost perfectly with molecular divergence date estimates for the origin of the modern P. hamadryas radiation. The fact that the Malapa specimen is dated between ~2.026-2.36 million years ago (Ma also has implications for the biochronology of other South African Plio-Pleistocene sites where P. angusticeps is found.

  6. Crowding increases salivary cortisol but not self-directed behavior in captive baboons.

    Science.gov (United States)

    Pearson, Brandon L; Reeder, DeeAnn M; Judge, Peter G

    2015-04-01

    Reduced space can lead to crowding in social animals. Crowding increases the risk of agonistic interactions that, in turn, may require additional physiological defensive coping mechanisms affecting health. To determine the stress induced from increased social density in a group of nineteen baboons living in an indoor/outdoor enclosure, saliva cortisol levels and rates of anxiety-related behavior were analyzed across two unique crowding episodes. Initially, mean salivary cortisol levels when animals were restricted to their indoor quarters were compared to those when they also had access to their larger outdoor enclosure. Then, mean cortisol levels were compared before, during, and after two distinct crowding periods of long and short duration. Crowding resulted in significantly elevated cortisol during crowding periods compared to non-crowded periods. Cortisol levels returned to baseline following two crowding episodes contrasting in their length and ambient climate conditions. These cortisol elevations indicate greater metabolic costs of maintaining homeostasis under social stress resulting from reduced space. Self-directed behavior, conversely, was not reliably elevated during crowding. Results suggest that the potential for negative social interactions, and/or the uncertainty associated with social threat can cause physiological stress responses detected by salivary cortisol. Self-directed behavioral measures of stress may constitute inadequate indicators of social stress in colony-housed monkeys or represent subjective emotional arousal unrelated to hypothalamic-pituitary adrenal axis activation.

  7. Behavioural processes in social context: female abductions, male herding and female grooming in hamadryas baboons.

    Science.gov (United States)

    Polo, Pablo; Colmenares, Fernando

    2012-06-01

    The formation of bonds between strangers is an event that occurs routinely in many social animals, including humans, and, as social bonds in general, they affect the individuals' welfare and biological fitness. The present study was motivated by an interest in the behavioural processes that drive bond formation in a social context of hostility, in which the incumbent partners vary greatly in physical power and reproductive interests, a situation in which individuals of many group-living species find themselves often throughout their lives. We focused on the quantitative analysis of female abductions via male aggressive herding in a nonhuman primate, the hamadryas baboon, in which intersexual bonds are known to be strong. We tested three hypotheses informed by sexual conflict/sexual coercion theory (male herding-as-conditioning and female grooming-as-appeasement) and by socioecological theory (unit size and female competition). The results supported the predictions: males resorted to coercive tactics (aggressive herding) with abducted females, and abducted females elevated the amount of grooming directed at their new unit males; in fact, they escaped from the otherwise negative effect of unit size on female-to-male grooming. These findings reveal that conflicts of interest are natural ingredients underpinning social bonds and that resorting to coercive aggression may be an option especially when partners differ greatly in their physical power.

  8. Ozone treatment of alveolar bone in the cape chacma baboon does not enhance healing following trauma.

    Science.gov (United States)

    Kotze, Marthinus; Bütow, Kürt-W; Olorunju, Steve A; Kotze, Harry F

    2014-06-01

    In the international literature, the role of Ozone (O3) in the advancement in alveolar bone healing in the absence of bone pathology was not tested before. The purpose of this study was to evaluate alveolar bone regeneration after a bone defect was created and treated with a single topical administration of O3. Alveolar bone defects were created on five healthy chacma baboons. One side of the maxilla and mandible was topically treated with a single treatment of an O3/O2 mixture (3,5-4 % O3), while the opposite sides were not treated and thus served as control. Regeneration was measured radiologically, using a standardized gray scale, as the increase in bone density in the treatment area at 3 and 6 weeks post-operative and was statistically analyzed using multivariate analysis of variance (MANOVA). There were no significant differences in densities observed between the O3/O2 mixture treatment and the control (p > 0.05). A single O3 treatment did not increase alveolar bone healing over a 3- and 6-week period in the mandible and the maxilla.

  9. Whole body [{sup 11}C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, Rajan [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Harris, Paul; Leibel, Rudolph [Columbia University College of Physicians and Surgeons, Department of Medicine, New York, NY (United States); Simpson, Norman; Parsey, Ramin [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Van Heertum, Ronald [Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Mann, J.J. [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States)

    2008-04-15

    Vesicular monoamine transporter type 2 abundance quantified using the radiotracer [{sup 11}C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis and pathogenesis of dementia and psychiatric disorders in humans. In addition, it may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful for longitudinal measurements using positron emission tomography to track progression of autoimmune diabetes. To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [{sup 11}C]-DTBZ in humans. Five baboon studies were acquired using a Siemens ECAT camera. After transmission scanning, 165-210 MBq of [{sup 11}C]-DTBZ were injected, and dynamic whole body emission scans were conducted. Time-activity data were used to obtain residence times and estimate absorbed radiation dose according to the MIRD model. Most of the injected tracer localized to the liver and the lungs, followed by the intestines, brain, and kidneys. The highest estimated absorbed radiation dose was in the stomach wall. The largest radiation dose from [{sup 11}C]-DTBZ is to the stomach wall. This dose estimate, as well as the radiation dose to other radiosensitive organs, must be considered in evaluating the risks of multiple administrations. (orig.)

  10. Selective inhibition by a synthetic hirudin peptide of fibrin-dependent thrombosis in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Cadroy, Y.; Hanson, S.R.; Harker, L.A. (Emory Univ., Atlanta, GA (United States)); Maraganore, J.M. (Biogen Inc., Cambridge, MA (United States))

    1991-02-15

    To determine the importance of the thrombin substrate recognition exosite for fibrinogen binding in the formation of both arterial and venous thrombi the authors evaluated the antithrombotic effects of the tyrosine-sulfated dodecapeptide from residues 53-64 of hirudin (H peptide) in a nonhuman primate model. This peptide was studied because it inhibits thrombin cleavages of fibrinogen by simple competition without blocking enzyme catalytic-site function. When an exteriorized arteriovenous access shunt model was used in baboons (Papio anubis), thrombus formation was induced by placing a thrombogenic device made of (i) a segment of tubing coated covalently with type I collagen, which generated platelet-rich thrombi under arterial flow conditions, and (ii) two subsequent annular regions of flow expansion that produced fibrin-rich thrombi typically associated with venous valves and veins. Thrombus formation was quantified by measurements of {sup 111}In-labeled platelet and {sup 125}I-labeled fibrinogen deposition in both arterial-flow and venous-flow portions of the device. These finding suggest that, by competitive inhibition of fibrinogen binding to thrombin, fibrin-rich venous-type thrombus formation may be selectively prevented. This strategy may be therapeutically attractive for preserving normal platelet function when conventional anticoagulant therapy is contraindicated.

  11. Social environment influences the relationship between genotype and gene expression in wild baboons.

    Science.gov (United States)

    Runcie, Daniel E; Wiedmann, Ralph T; Archie, Elizabeth A; Altmann, Jeanne; Wray, Gregory A; Alberts, Susan C; Tung, Jenny

    2013-05-19

    Variation in the social environment can have profound effects on survival and reproduction in wild social mammals. However, we know little about the degree to which these effects are influenced by genetic differences among individuals, and conversely, the degree to which social environmental variation mediates genetic reaction norms. To better understand these relationships, we investigated the potential for dominance rank, social connectedness and group size to modify the effects of genetic variation on gene expression in the wild baboons of the Amboseli basin. We found evidence for a number of gene-environment interactions (GEIs) associated with variation in the social environment, encompassing social environments experienced in adulthood as well as persistent effects of early life social environment. Social connectedness, maternal dominance rank and group size all interacted with genotype to influence gene expression in at least one sex, and either in early life or in adulthood. These results suggest that social and behavioural variation, akin to other factors such as age and sex, can impact the genotype-phenotype relationship. We conclude that GEIs mediated by the social environment are important in the evolution and maintenance of individual differences in wild social mammals, including individual differences in responses to social stressors.

  12. UniPron is A Fully Effective Non-hormonal Reversible Contraceptive in Baboon Model(Papio Anubis)

    Institute of Scientific and Technical Information of China (English)

    Jael A.Obiero; Maureen N.Mburu; Benson M.Ndung'u; Kenneth K.Waititu; Isaac Mulei; Idle O.Farah; Peter G.Mwethera

    2008-01-01

    Objective To determine the safety and efficacy of UniPron as a reversible contraceptive.Methods Vaginal swabs were obtained before and after UniPron administration.cultured onto appropriate culture media and bacteria identification was done based on type of media used,Gram stain reactions,colony morphology and biochemical tests.Vaginal biopsy tissues were processed using paraffin wax method,stained with hematoxylin and eosin and examined under light microscopy to determine the effect of the product on vaginal tissues.The effect of UniPron on sperm was examined by mixing the product with electroejaculated spermatozoa in vitro at different concentrations.For efficacy studies,male baboons of proven fertility were mated with UniPron treated or untreated females of proven fertility during the fertile stages.Results All the five females(100%)that were treated with UniPron did not conceive and they regained total fertitity when the treatment was stopped while all the controls conceived.At a concentration of 40%,UniPron completely immobilized spermatozoa in an in-vitro system.UniPron mechanism of action was by lowering the vaginal pH and on application in baboon,the pH was lowered for at least 3 h after which it went back to normal.Conclusions As we plan for a study to test UniPron as a microbicide to prevent STIs including HIV,our current study has established that this novel product is effective in contraception and harmless to vaginal tissues and vaginal microbial flora in a baboon model(Papio anubis).

  13. Quantitation of fibroblast activation protein (FAP-specific protease activity in mouse, baboon and human fluids and organs

    Directory of Open Access Journals (Sweden)

    Fiona M. Keane

    2014-01-01

    Full Text Available The protease fibroblast activation protein (FAP is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

  14. The role of cromakalim and a nitric oxide synthase blocker in cardiac arrhythmia in the intact baboon model.

    Science.gov (United States)

    Hay, L; Schutte, P J; Du Plooy, W J; Kahler, C P

    2000-02-01

    The arrhythmogenic effect of adenosine triphosphate (ATP)-sensitive potassium channel openers is controversial and may be dependent on the type of animal model used. Information on the effect of these drugs in the normal primate model is limited. The purpose of this study was first to determine the arrhythmogenic properties of cromakalim in the baboon and second to determine whether N-omega-nitro-L-arginine methyl ester (L-NAME) has any effect on the induced arrhythmia. Adult (2-4 years old) baboons (Papio ursinus) were anesthetized with a continuous i.v. infusion of ketamine (100 mg/ ml), diazepam (5 mg/ml), and saline (ratio 2:2:50) at a rate of 40-60 ml/h. Sympathetic responses were inhibited by administration of propranolol (1 mg/kg) before the start of the experiments. Cromakalim (30 microg/kg) was administered before and after L-NAME (7.5 mg/kg), and the parameters were monitored for 15 min after each intervention. A Millar double-tipped microcatheter was used to record left ventricular and aortic pressures. Lead II of the ECG was monitored. During a 15-min period after administration of cromakalim, 22.3 +/- 6.0 abnormal ventricular complexes were recorded. L-NAME administration significantly reduced these abnormal complexes to 4.5 +/- 2 (paired t test, p < or = 0.05). We therefore conclude that cromakalim has arrhythmogenic properties in the baboon and that these can be attenuated by L-NAME.

  15. The enzyme linked immunosorbent assay (ELISA) for the determination of circulating antigen and antibody in Schistosoma haematobium-infected baboons.

    Science.gov (United States)

    Ismail, M M; James, C; Webbe, G

    1981-01-01

    The ELISA was used to measure circulating antigen and antibody in four baboons of which three were treated. The circulating antigen appeared earlier after infection than the antibody which eventually, however, reached a higher level. Both antigen and antibody levels increased slightly after treatment and thereafter declined to reach background levels eight weeks later. It is concluded that the ELISA has a potentially useful role in detecting both antibody and circulating antigen and that it may be successfully used in evaluating the efficacy of schistosomicides.

  16. Pulp response to collagen and glutaraldehyde in pulpotomized primary teeth of baboons.

    Science.gov (United States)

    Fuks, A B; Jones, P C; Michaeli, Y; Bimstein, E

    1991-01-01

    This investigation assessed histologically the pulp tissue reaction to glutaraldehyde (GA) and to a commercial collagen preparation in pulpotomized primary teeth of baboons. One hundred and eighty-eight primary teeth were pulpotomized; in half of them inflammation was induced prior to the treatment. The teeth were divided into five groups: in three of them GA was used as a pulp dressing and applied for 1 min (group 1), 5 min (group 2), or mixed into the paste (group 3); collagen was used in group 4 and in group 5 (control) IRM was placed directly over the pulp stumps. Follow-up times were two, eight, and 24 weeks. Total necrosis was observed only in the collagen group. Partial necrosis and severe inflammation also were seen mainly in this group, and when the GA was incorporated into the paste. Slight to moderate inflammation was evident in all groups two and eight weeks postoperatively; however, 78% of the teeth of group 2 (GA 5 min) were inflammation-free after 24 weeks. Partial dentin bridges were seen in 92% of the teeth of the control group, in 82% of group 2, and 50% each of groups 1 and 3 eight weeks postoperatively. Dentin bridges were present in only 4% of the collagen group. After 24 weeks, all the teeth in group 2 and 83% of group 1 had dentin bridges. We conclude that Zyderm (Colagen Corp. Palo Alto, CA) led to unacceptable results, 5 min application of GA presented the best healing response, and GA 1 min and IRM also were satisfactory.

  17. The effect of excluding juveniles on apparent adult olive baboons (Papio anubis) social networks

    Science.gov (United States)

    Fedurek, Piotr; Lehmann, Julia

    2017-01-01

    In recent years there has been much interest in investigating the social structure of group living animals using social network analysis. Many studies so far have focused on the social networks of adults, often excluding younger, immature group members. This potentially may lead to a biased view of group social structure as multiple recent studies have shown that younger group members can significantly contribute to group structure. As proof of the concept, we address this issue by investigating social network structure with and without juveniles in wild olive baboons (Papio anubis) at Gashaka Gumti National Park, Nigeria. Two social networks including all independently moving individuals (i.e., excluding dependent juveniles) were created based on aggressive and grooming behaviour. We used knockout simulations based on the random removal of individuals from the network in order to investigate to what extent the exclusion of juveniles affects the resulting network structure and our interpretation of age-sex specific social roles. We found that juvenile social patterns differed from those of adults and that the exclusion of juveniles from the network significantly altered the resulting overall network structure. Moreover, the removal of juveniles from the network affected individuals in specific age-sex classes differently: for example, including juveniles in the grooming network increased network centrality of adult females while decreasing centrality of adult males. These results suggest that excluding juveniles from the analysis may not only result in a distorted picture of the overall social structure but also may mask some of the social roles of individuals belonging to different age-sex classes. PMID:28323851

  18. Intracellular maturation of apolipoprotein[a] and assembly of lipoprotein[a] in primary baboon hepatocytes.

    Science.gov (United States)

    White, A L; Rainwater, D L; Lanford, R E

    1993-03-01

    The glycoprotein apolipoprotein[a] (apo[a]) is present in plasma at highly variable concentrations and appears as a number of genetically determined size isoforms (400-800 kDa), disulfide linked to apoB-100 in low density lipoprotein to produce lipoprotein [a](Lp[a]). Apo[a] is synthesized by the liver, but the site of association of apo[a] and apoB and factors that regulate its production are unknown. To examine the morphogenesis of the Lp[a] particle, baboon hepatocytes expressing a single, low molecular weight isoform of apo[a] were labeled with [35S]cysteine and methionine, and apo[a] was analyzed by immunoprecipitation and SDS-PAGE. Steady-state labeling revealed two molecular weight forms of apo[a] inside the cell. Only the large form was recovered from the culture medium. Pulse-chase studies and endoglycosidase treatment revealed that the lower molecular weight form of apo[a] represented a precursor with a prolonged residence time in the endoplasmic reticulum or an early Golgi compartment, after which it was processed to the mature form. A proportion of the mature form of apo[a] was rapidly secreted after synthesis, whereas the remainder had a prolonged residence time in a late Golgi compartment. In all experiments, apoB co-precipitated with apo[a] from the culture medium, but not from cell lysates. Density gradient ultracentrifugation and immunoblot analysis revealed that the majority of apo[a] was secreted into the medium in a free form, suggesting that the association between apo[a] and apoB occurred after secretion. Regulation of the movement of apo[a] between intracellular compartments may be one mechanism by which the plasma levels of Lp[a] are influenced.

  19. Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia

    Science.gov (United States)

    Kraft, Bryan D.; Hess, Dean R.; Harris, R. Scott; Wolf, Monroe A.; Suliman, Hagir B.; Roggli, Victor L.; Davies, John D.; Winkler, Tilo; Stenzler, Alex; Baron, Rebecca M.; Thompson, B. Taylor; Choi, Augustine M.; Welty-Wolf, Karen E.; Piantadosi, Claude A.

    2015-01-01

    Inhaled carbon monoxide (CO) gas has therapeutic potential for patients with acute respiratory distress syndrome if a safe, evidence-based dosing strategy and a ventilator-compatible CO delivery system can be developed. In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (108-109 CFU) (n = 14) or saline vehicle (n = 5); in a subset with pneumonia (n = 5), we administered low-dose, inhaled CO gas (100–300 ppm × 60–90 min) at 0, 6, 24, and/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6–8% with ambient CO levels ≤ 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model. PMID:26320156

  20. Studies on rabbit lymphocytes in vitro

    Science.gov (United States)

    Sell, S.; Gell, P. G. H.

    1969-01-01

    Anti-allotypic sera that have no known allotypic determinants other than those also present in the genotype of the lymphocyte donor are as able to induce lymphocyte `blast' transformation in vitro as are anti-allotypic sera that do have allotypic determinants that are not present in the lymphocyte donor. Therefore, anti-allotypic sera do not appear to function in the stimulation of blast transformation by providing access for any of the known allotypic determinants into lymphocytes. PMID:5769980

  1. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    Science.gov (United States)

    Shibue, Kimitaka; Fujii, Toshihito; Goto, Hisanori; Yamashita, Yui; Sugimura, Yoshihisa; Tanji, Masahiro; Yasoda, Akihiro; Inagaki, Nobuya

    2017-01-01

    Abstract Rationale: Lymphocytic hypophysitis is a relatively rare autoimmune disease defined by lymphocytic infiltration to the pituitary. Its rarity and wide spectrum of clinical manifestations make clarification of the pathology difficult. Here, we describe a case we examined from the primary diagnosis to final discharge, showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. Patient concerns: Polyuria, General fatigue and Nausea/Vomiting. Diagnoses: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). Interventions: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. Outcomes: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. Lessons: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint. PMID:28248860

  2. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  3. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Liu, Xin; O' Connell, Jeff; Peng, Ze; Krauss, Ronald M.; Rainwater, David L.; VandeBerg, John L.; Rubin, Edward M.; Cheng, Jan-Fang; Pennacchio, Len A.

    2003-09-15

    Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however, whether independently arising polymorphisms in orthologous regions of non-human primates leads to similar variation in a quantitative trait found in both species. To explore this paradigm, we studied a baboon apolipoprotein gene cluster (APOA1/C3/A4/A5) for which the human gene orthologs have well established roles in influencing plasma HDL-cholesterol and triglyceride concentrations. Our extensive polymorphism analysis of this 68 kb gene cluster in 96 pedigreed baboons identified several haplotype blocks each with limited diversity, consistent with haplotype findings in humans. To determine whether baboons, like humans, also have particular haplotypes associated with lipid phenotypes, we genotyped 634 well characterized baboons using 16 haplotype tagging SNPs. Genetic analysis of single SNPs, as well as haplotypes, revealed an association of APOA5 and APOC3 variants with HDL cholesterol and triglyceride concentrations, respectively. Thus, independent variation in orthologous genomic intervals does associate with similar quantitative lipid traits in both species, supporting the possibility of uncovering human QTL genes in a highly controlled non-human primate model.

  4. Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein.

    Science.gov (United States)

    Azimzadeh, Agnes M; Kelishadi, Sean S; Ezzelarab, Mohamed B; Singh, Avneesh K; Stoddard, Tiffany; Iwase, Hayato; Zhang, Tianshu; Burdorf, Lars; Sievert, Evelyn; Avon, Chris; Cheng, Xiangfei; Ayares, David; Horvath, Keith A; Corcoran, Philip C; Mohiuddin, Muhammad M; Barth, Rolf N; Cooper, David K C; Pierson, Richard N

    2015-01-01

    We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3 days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway-regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life-supporting GalTKO kidney (n = 7) or heterotopic heart (n = 14) grafts received either no immunosuppression (n = 4), or one of several partial or full immunosuppressive regimens (n = 17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n = 5) or heart (n = 9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P organs in which EGF developed (P organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.

  5. Testing the function of reconciliation and third-party affiliation for aggressors in hamadryas baboons (Papio hamadryas hamadryas).

    Science.gov (United States)

    Romero, Teresa; Colmenares, Fernando; Aureli, Filippo

    2009-01-01

    In social groups, agonistic conflicts can have different negative consequences. Several post-conflict interactions have been suggested as post-conflict management behaviors to mitigate those negative effects. In this study, we investigated the function of two post-conflict behaviors--reconciliation and aggressor-initiated third-party affiliation--on the aggressor's levels of post-conflict anxiety and aggression in a large colony of hamadryas baboons. We also examined variation in the aggressor's levels of post-conflict anxiety as a function of relationship quality between the opponents as predicted by the Integrated Hypothesis. We found that after conflicts hamadryas baboon aggressors showed increased rates of anxiety-related behaviors and that they were also more likely to be involved in renewed aggressive interactions. Although both reconciliation and aggressor-initiated third-party affiliation reduced the probability of receiving post-conflict aggression, only reconciliation reduced the rates of anxiety-related behaviors, suggesting that the aggressors' post-conflict anxiety might be owing mainly to the damage that the conflict causes to their relationship with the victim. Furthermore, aggressor's rates of post-conflict anxiety were higher after conflicts with individuals with whom they had a high-quality relationship, supporting the idea that levels of post-conflict anxiety mediate the occurrence of reconciliation depending on the quality of the relationship with former opponent as predicted by the Integrated Hypothesis.

  6. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

    Science.gov (United States)

    Albuquerque-Silva, Iolanda; Vecellio, Laurent; Durand, Marc; Avet, John; Le Pennec, Déborah; de Monte, Michèle; Montharu, Jérôme; Diot, Patrice; Cottier, Michèle; Dubois, Francis; Pourchez, Jérémie

    2014-01-01

    To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region) of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]). Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%). The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%). Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

  7. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

    Directory of Open Access Journals (Sweden)

    Iolanda Albuquerque-Silva

    Full Text Available To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]. Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%. The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%. Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

  8. In vivo imaging of brain aromatase in female baboons: [11C]vorozole kinetics and effect of the menstrual cycle.

    Science.gov (United States)

    Pareto, Deborah; Biegon, Anat; Alexoff, David; Carter, Pauline; Shea, Coreen; Muench, Lisa; Xu, Youwen; Fowler, Joanna S; Kim, Sunny W; Logan, Jean

    2013-01-01

    The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [11C]vorozole using three different quantification methods for estimating the total distribution volume (V(T)): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R  =  .988; p  =  .0001). [11C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V(T). The highest uptake of [11C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V(T). The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V(T).

  9. In vivo regulation of hepatic LDL receptor mRNA in the baboon. Differential effects of saturated and unsaturated fat.

    Science.gov (United States)

    Fox, J C; McGill, H C; Carey, K D; Getz, G S

    1987-05-25

    The effects of diets enriched with cholesterol and different fats upon plasma lipoproteins and hepatic low density lipoprotein (LDL) receptor mRNA levels were studied in a group of 18 normal baboons. Animals were fed diets containing 1% cholesterol and 25% fat as either coconut oil, peanut oil, or olive oil for a period of 20 weeks. Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, beta-lipoprotein (LDL + very low density lipoprotein) cholesterol, apolipoprotein B and apolipoprotein A-I were measured in samples obtained at 4-week intervals. All three diet groups demonstrated a statistically significant increase in plasma cholesterol as compared to base line throughout the experiment. Hepatic LDL receptor (LDL-R) mRNA levels were quantified by dot blot hybridization in serial liver biopsies. Animals fed saturated fat sustained a significant reduction in hepatic LDL-R mRNA as compared to those fed either monounsaturated or polyunsaturated fat. A strong negative correlation between LDL-R mRNA and plasma total cholesterol (r = -0.71), HDL cholesterol (r = -0.76), and plasma apo A-I (r = -0.77) was observed only in those animals fed coconut oil. Weak negative correlations between LDL-R mRNA and other plasma parameters did not achieve statistical significance. We conclude that saturated and unsaturated oils may influence plasma cholesterol levels in part through differential effects on LDL receptor biosynthesis in baboons.

  10. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  11. Social affiliation matters: both same-sex and opposite-sex relationships predict survival in wild female baboons.

    Science.gov (United States)

    Archie, Elizabeth A; Tung, Jenny; Clark, Michael; Altmann, Jeanne; Alberts, Susan C

    2014-10-22

    Social integration and support can have profound effects on human survival. The extent of this phenomenon in non-human animals is largely unknown, but such knowledge is important to understanding the evolution of both lifespan and sociality. Here, we report evidence that levels of affiliative social behaviour (i.e. 'social connectedness') with both same-sex and opposite-sex conspecifics predict adult survival in wild female baboons. In the Amboseli ecosystem in Kenya, adult female baboons that were socially connected to either adult males or adult females lived longer than females who were socially isolated from both sexes--females with strong connectedness to individuals of both sexes lived the longest. Female social connectedness to males was predicted by high dominance rank, indicating that males are a limited resource for females, and females compete for access to male social partners. To date, only a handful of animal studies have found that social relationships may affect survival. This study extends those findings by examining relationships to both sexes in by far the largest dataset yet examined for any animal. Our results support the idea that social effects on survival are evolutionarily conserved in social mammals.

  12. Transcriptional regulation of proteoglycan 4 by 17β-estradiol in immortalized baboon temporomandibular joint disc cells.

    Science.gov (United States)

    McDaniel, Jennifer S; Akula Suresh Babu, Ramya; Navarro, Mary M; LeBaron, Richard G

    2014-04-01

    Temporomandibular joint disorders (TMDs) affect a significant portion of the population of the USA, with the majority of those seeking treatment being women of childbearing age. Owing to this striking sexual dimorphism it has been postulated that sex hormones play a role in the maintenance of normal temporomandibular joint (TMJ) function. Proteoglycan 4 (PRG4) is a secreted lubricating molecule required for maintaining low frictional levels within articular joints; however, its role in the TMJ is not well characterized. In this study we describe the development of immortalized baboon cells isolated from specific regions of the TMJ disc and their use in the investigation of PRG4 expression and localization patterns in the TMJ. We identified conserved estrogen response elements within the 5' flanking region of the PRG4 gene of several species, and found that treatment of baboon TMJ disc cells with estrogen led to reduced PRG4 promoter activity and reduced expression of PRG4 mRNA in vitro. The observed negative regulation of PRG4 by estrogen could lead to increased friction and degradation of joint components over time. This study, for the first time, provides evidence of the regulatory potential of estrogen on PRG4 gene expression and suggests a novel etiology for the gender disparity observed among TMD patients.

  13. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

  14. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  15. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D. (Eastern Virginia Medical School, Norfolk (USA))

    1990-12-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of (3H)F/(14C)E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production.

  16. Vegetation classification as the basis for baboon management in the Bourke’s Luck Section of the Blyde Canyon Nature Reserve, Mpumalanga

    Directory of Open Access Journals (Sweden)

    L.R. Brown

    2005-12-01

    Full Text Available The Blyde Canyon Nature Reserve (BCNR was identified as an important conservation area due to of its extraordinary diversity of plant species. Plant communities represent ecosystems and form the basis of any management plan for natural areas. If these ecosystems and their different potentials are unknown, they cannot be managed successfully. Baboons exploit diverse habitats including human environments where they often cause damage to crops and forest plantations. Baboons are regarded as particularly problematic residents of protected areas as conventional fences do not readily enclose them, their eclectic diets allow them to benefit from a range of agricultural endeavours, and they are behaviourally opportunistic. Thus as a first step to implementing a conservation policy to manage chacma baboons in the BCNR, it was necessary to have some understanding of their exploitation of natural habitats adjacent to areas where they do cause problems. Although a broad vegetation map of the BCNR exists, no detailed vegetation studies have been conducted on the largest part of the reserve. It was therefore decided to ndertake a detailed vegetation study of the home range of a single baboon troop within the Bourke’s Luck section of the BCNR. From a TWINSPAN classification, refined by Braun-Blanquet procedures, 13 plant communities, which can be grouped into seven major groups, were identified. A classification and description of these communities, as well as a vegetation map are presented. Data collected as part of this study also revealed that the baboons show preference to certain communities whilst avoiding others. These have important consequences in terms of the management strategies followed on the reserve.

  17. Transuteroplacental metabolism of cortisol and cortisone during mid- and late gestation in the baboon

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Albrecht, E.D.

    1984-11-01

    We measured uterine extraction (i.e. metabolism) and transuteroplacental interconversion of cortisol (F) and cortisone (E) to determine whether metabolism across the uterus changes during pregnancy and contributes to the MCR of these corticosteroids. On day 100 (n . 4) or 170 (n . 3) of pregnancy (term . day 184), baboons (Papio anubis; 14-18 kg) were sedated with ketamine, and a constant infusion (0.38 ml/min) of 8-12 microCi (/sup 3/H)F and 9-15 microCi (/sup 14/C)E in 80 ml 0.9% NaCl-1% ethanol was initiated (time zero) via a maternal antecubital vein. At 60 min, animals were laparotomized, and at 70, 80, and 90 min, blood samples were obtained from right and left uterine veins and from a maternal saphenous vein. At 95 min, a transverse incision was made in the uterus, the fetus was isolated, and blood samples were obtained from the umbilical vein and artery. The cord was then clamped, and the fetus was delivered. Radio-labeled F and E were extracted from serum and purified by sequential paper chromatography, and metabolic parameters were calculated. Endogenous F and E levels were determined by RIA. In the mother, the percent conversions of E to F at midgestation (mean +/- SE; 72 +/- 4) and late gestation (65 +/- 3) were similar and exceeded (P less than 0.01) respective values for oxidation of F to E (51 +/- 7 and 46 +/- 7, respectively), indicating that maternal corticosteroid metabolism favors F formation and is unchanged during the second half of gestation. In contrast, corticosteroid metabolism across the uterus and placenta (transuteroplacental) was altered during pregnancy. At midgestation, transuteroplacental conversion of E to F (37 +/- 9) exceeded (P less than 0.05) the reverse reaction (18 +/- 3), whereas oxidation of F to E at term (28 +/- 4) was 7-fold greater (P less than 0.05) than reduction of E to F (4 +/- 1).

  18. Seroprevalence of Zika Virus in Wild African Green Monkeys and Baboons

    Science.gov (United States)

    Buechler, Connor R.; Bailey, Adam L.; Weiler, Andrea M.; Barry, Gabrielle L.; Breitbach, Meghan E.; Stewart, Laurel M.; Jasinska, Anna J.; Freimer, Nelson B.; Apetrei, Cristian; Phillips-Conroy, Jane E.; Jolly, Clifford J.; Rogers, Jeffrey; Friedrich, Thomas C.

    2017-01-01

    ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and

  19. Evaluation of 6-([{sup 18}F]fluoroacetamido)-1-hexanoicanilide for PET imaging of histone deacetylase in the baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Reid, Alicia E. [National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892 (United States); Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: areid@bnl.gov; Hooker, Jacob; Shumay, Elena; Logan, Jean; Shea, Colleen; Kim, Sung Won [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Collins, Shanika [School of Science, Health and Technology Medgar Evers College, Brooklyn, NY 11225 (United States); Xu Youwen [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Volkow, Nora [National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892 (United States); National Institute on Drug Abuse, Bethesda, MD 20892 (United States); Fowler, Joanna S. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2009-04-15

    Introduction: Histone deacetylases (HDACs) are enzymes involved in epigenetic modifications that shift the balance toward chromatin condensation and silencing of gene expression. Here, we evaluate the utility of 6-([{sup 18}F]fluoroacetamido)-1-hexanoicanilide ([{sup 18}F]FAHA) for positron emission tomography imaging of HDAC activity in the baboon brain. For this purpose, we assessed its in vivo biodistribution, sensitivity to HDAC inhibition, metabolic stability and the distribution of the putative metabolite [{sup 18}F]fluoroacetate ([{sup 18}F]FAC). Methods: [{sup 18}F]FAHA and its metabolite [{sup 18}F]FAC were prepared, and their in vivo biodistribution and pharmacokinetics were determined in baboons. [{sup 18}F]FAHA metabolism and its sensitivity to HDAC inhibition using suberanilohydroxamic acid (SAHA) were assessed in arterial plasma and by in vitro incubation studies. The chemical form of F-18 in rodent brain was assessed by ex vivo studies. Distribution volumes for [{sup 18}F]FAHA in the brain were derived. Results: [{sup 18}F]FAHA was rapidly metabolized to [{sup 18}F]FAC, and both labeled compounds entered the brain. [{sup 18}F]FAHA exhibited regional differences in brain uptake and kinetics. In contrast, [{sup 18}F]FAC showed little variation in regional brain uptake and kinetics. A kinetic analysis that takes into account the uptake of peripherally produced [{sup 18}F]FAC indicated that SAHA inhibited binding of [{sup 18}F]FAHA in the baboon brain dose-dependently. In vitro studies demonstrated SAHA-sensitive metabolism of [{sup 18}F]FAHA to [{sup 18}F]FAC within the cell and diffusion of [{sup 18}F]FAC out of the cell. All radioactivity in brain homogenate from rodents was [{sup 18}F]FAC at 7 min postinjection of [{sup 18}F]FAHA. Conclusion: The rapid metabolism of [{sup 18}F]FAHA to [{sup 18}F]FAC in the periphery complicates the quantitative analysis of HDAC in the brain. However, dose-dependent blocking studies with SAHA and kinetic modeling

  20. Opinion: Interactions of innate and adaptive lymphocytes

    Science.gov (United States)

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

  1. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

    Science.gov (United States)

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-01

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care.

  2. Baboons' hand preference resists to spatial factors for a communicative gesture but not for a simple manipulative action.

    Science.gov (United States)

    Bourjade, Marie; Meunier, Hélène; Blois-Heulin, Catherine; Vauclair, Jacques

    2013-09-01

    Olive baboons (Papio anubis) do acquire and use intentional requesting gestures in experimental contexts. Individual's hand preference for these gestures is consistent with that observed for typical communicative gestures, but not for manipulative actions. Here, we examine whether the strength of hand preference may also be a good marker of hemispheric specialization for communicative gestures, hence differing from the strength of hand preference for manipulative actions. We compared the consistency of individuals' hand preference with regard to the variation in space of either (i) a communicative partner or (ii) a food item to grasp using a controlled set-up. We report more consistent hand preference for communicative gestures than for grasping actions. Established hand preference in the midline was stronger for gesturing than for grasping and allowed to predict the consistency of hand preference across positions. We found no significant relation between the direction of hand preference and the task.

  3. Application of piecewise hierarchical linear growth modeling to the study of continuity in behavioral development of baboons (Papio hamadryas).

    Science.gov (United States)

    Hernández-Lloreda, María Victoria; Colmenares, Fernando; Martínez-Arias, Rosario

    2004-09-01

    In behavioral science, developmental discontinuities are thought to arise when the association between an outcome measure and the underlying process changes over time. Sudden changes in behavior across time are often taken to indicate that a reorganization in the outcome-process relationship may have occurred. The authors proposed in this article the use of piecewise hierarchical linear growth modeling as a statistical methodology to search for discontinuities in behavioral development and illustrated its possibilities by applying 2-piece hierarchical linear models to the study of developmental trajectories of baboon (Papio hamadryas) mothers' behavior during their infants' 1st year of life. The authors provided empirical evidence that piecewise growth modeling can be used to determine whether abrupt changes in development trajectories are tied to changes in the underlying process. ((c) 2004 APA, all rights reserved).

  4. Evidence of a Vocalic Proto-System in the Baboon (Papio papio) Suggests Pre-Hominin Speech Precursors

    Science.gov (United States)

    Boë, Louis-Jean; Berthommier, Frédéric; Legou, Thierry; Captier, Guillaume; Kemp, Caralyn; Sawallis, Thomas R.; Becker, Yannick; Rey, Arnaud; Fagot, Joël

    2017-01-01

    Language is a distinguishing characteristic of our species, and the course of its evolution is one of the hardest problems in science. It has long been generally considered that human speech requires a low larynx, and that the high larynx of nonhuman primates should preclude their producing the vowel systems universally found in human language. Examining the vocalizations through acoustic analyses, tongue anatomy, and modeling of acoustic potential, we found that baboons (Papio papio) produce sounds sharing the F1/F2 formant structure of the human [ɨ æ ɑ ɔ u] vowels, and that similarly with humans those vocalic qualities are organized as a system on two acoustic-anatomic axes. This confirms that hominoids can produce contrasting vowel qualities despite a high larynx. It suggests that spoken languages evolved from ancient articulatory skills already present in our last common ancestor with Cercopithecoidea, about 25 MYA. PMID:28076426

  5. Male takeovers are reproductively costly to females in hamadryas baboons: a test of the sexual coercion hypothesis.

    Directory of Open Access Journals (Sweden)

    Pablo Polo

    Full Text Available During male takeovers, in addition to fighting off the female's current mating partner, males may exhibit intense aggressive mate guarding of the newly acquired females. Recent studies indicate that coercive sexual aggression by males is an important strategy through which sexual conflict is expressed. Previous tests of the sexual coercion hypothesis in primates have focused on assessing if female mate choice is effectively reduced by male aggression, however, only one recent study has tested a critical prediction of this hypothesis, namely, that male coercion is reproductively costly to victim females. The present study uses 15 years of data on inter-birth intervals from a large multilevel colony of baboons, mostly Papio h. hamadryas, with a mating system based on harem-defence polygyny to examine if male takeovers impact the length of the abducted females' inter-birth intervals. Our analysis of 121 inter-birth intervals from 45 adult females indicates that male takeovers are reproductively costly to abducted females as they are associated with an increase in the time they take to conceive and a lengthening of the inter-birth intervals. We discuss how several factors may contribute to this reproductive cost, including male-female sexual conflict, male-male competition, and female-female competition. Our findings suggest that the male's aggressive herding is the main contributor to the abducted females' immediate reproductive cost. We argue that although some of the male's aggressive herding may be driven by male-male competition, nonetheless, it serves a coercive function as it both constrains the female's mate choice options and hampers her immediate breeding performance. This conclusion is backed up by results obtained in the only other study that has tested the same prediction and which has been carried out in a wild population of hamadryas baboons.

  6. Male takeovers are reproductively costly to females in hamadryas baboons: a test of the sexual coercion hypothesis.

    Science.gov (United States)

    Polo, Pablo; Hernández-Lloreda, Victoria; Colmenares, Fernando

    2014-01-01

    During male takeovers, in addition to fighting off the female's current mating partner, males may exhibit intense aggressive mate guarding of the newly acquired females. Recent studies indicate that coercive sexual aggression by males is an important strategy through which sexual conflict is expressed. Previous tests of the sexual coercion hypothesis in primates have focused on assessing if female mate choice is effectively reduced by male aggression, however, only one recent study has tested a critical prediction of this hypothesis, namely, that male coercion is reproductively costly to victim females. The present study uses 15 years of data on inter-birth intervals from a large multilevel colony of baboons, mostly Papio h. hamadryas, with a mating system based on harem-defence polygyny to examine if male takeovers impact the length of the abducted females' inter-birth intervals. Our analysis of 121 inter-birth intervals from 45 adult females indicates that male takeovers are reproductively costly to abducted females as they are associated with an increase in the time they take to conceive and a lengthening of the inter-birth intervals. We discuss how several factors may contribute to this reproductive cost, including male-female sexual conflict, male-male competition, and female-female competition. Our findings suggest that the male's aggressive herding is the main contributor to the abducted females' immediate reproductive cost. We argue that although some of the male's aggressive herding may be driven by male-male competition, nonetheless, it serves a coercive function as it both constrains the female's mate choice options and hampers her immediate breeding performance. This conclusion is backed up by results obtained in the only other study that has tested the same prediction and which has been carried out in a wild population of hamadryas baboons.

  7. INITIAL IN VIVO EXPERIENCE OF PIG ARTERY PATCH TRANSPLANTATION IN BABOONS USING MUTANT MHC (CIITA-DN) PIGS

    Science.gov (United States)

    Iwase, H; Ekser, B; Satyananda, V; Zhou, H; Hara, H; Bajona, P; Wijkstrom, M; Bhama, JK; Long, C; Veroux, M; Wang, Y; Dai, Y; Phelps, C; Ayares, D; Ezzelarab, MB; Cooper, DKC

    2015-01-01

    Background In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. Methods As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept+anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. Results When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. Conclusion Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons. PMID:25687023

  8. Behavioral effects and pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) after intragastric administration to baboons.

    Science.gov (United States)

    Goodwin, Amy K; Mueller, Melanie; Shell, Courtney D; Ricaurte, George A; Ator, Nancy A

    2013-06-01

    (±)-3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32-7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N = 4). Effects of MDMA on food-maintained responding were assessed over a 20-hour period, whereas untrained behaviors and fine-motor coordination were characterized every 30 minutes until 3 hours postadministration. Levels of MDMA and metabolites in plasma were measured in the same animals (n = 3) after dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-hour period, and systematic behavioral observations revealed increased frequency of bruxism as the dose of MDMA was increased. Drug blood level determinations showed no MDMA after the lower doses of MDMA tested (0.32-1.0 mg/kg) and modest levels after higher MDMA doses (3.2-7.8 mg/kg). High levels of 3,4-dihydroxymethamphetamine (HHMA) were detected after all doses of MDMA, suggesting extensive first-pass metabolism of MDMA in the baboon. The present results demonstrate that MDMA administered via an intragastric catheter produced behavioral effects that have also been reported in humans. Similar to humans, blood levels of MDMA after oral administration may not be predictive of the behavioral effects of MDMA. Metabolites, particularly HHMA, may play a significant role in the behavioral effects of MDMA.

  9. Characterization of very-low-density lipoproteins isolated from baboons, and fractionated using heparin-Sepharose chromatography.

    Science.gov (United States)

    Rainwater, D L; Kushwaha, R S

    1988-02-19

    Plasma very-low-density lipoproteins (VLDL) (d less than 1.006 g/ml) were purified from baboons by repeated ultracentrifugation. The weight composition of VLDL purified from these animals was 59% triacylglycerol, 17% phospholipid, 13% cholesterol plus cholesteryl esters, and 11% protein. When purified VLDL was fractionated using heparin-Sepharose chromatography, an average of 33% of the total recovered proteins were unbound in a saline solution, and 67% (range, 31 to 92%) were bound by the column, but could be eluted with 3 M NaCl. Recoveries of starting protein and the major classes of lipids in the two fractions were 70-80%. The two fractions differed in both apolipoprotein and lipid compositions. Analysis of sodium dodecyl sulfate-treated apolipoproteins using 3-21.5% acrylamide gradient gel electrophoresis indicated that both VLDL fractions contained apolipoprotein B, but only the bound fraction possessed significant amounts of apolipoprotein E. On a weight percent basis, the apolipoprotein-E-rich (bound) VLDL fraction contained significantly more cholesterol and cholesteryl esters (P less than 0.001) and less phospholipids (P less than 0.005) compared to the apolipoprotein E-poor (unbound) VLDL. Apolipoprotein-E-poor VLDL had shorter retention times than E-rich VLDL upon gel filtration chromatography, suggesting a larger size. There was no significant correlation between plasma levels of apolipoprotein-E-poor VLDL and levels of apolipoprotein B. These results demonstrate that baboons possess VLDL which can be separated into apolipoprotein-E-poor and E-rich fractions and these fractions differ in protein and lipid composition and in size.

  10. Parasitological, Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa in the Baboon (Papio anubis.

    Directory of Open Access Journals (Sweden)

    Samuel Wanji

    2015-11-01

    Full Text Available Loiasis, a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae (mf following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation.Fifteen baboons (Papio anubis were infected with 600 infective larvae (L3 isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1-2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4-8 months, with a majority (60% of animals becoming patent by 5 months post infection (MPI; all animals were patent by 8 MPI. Microfilarial loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000 mf/mL with 50% of these animals with mf >50,000 mf/mL. Absolute eosinophil, creatinine, Ca2+ and K+ levels were generally above normal values (NV. Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca2+, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels.Infection of splenectomised baboons with L. loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans.

  11. Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.

    Science.gov (United States)

    Iwase, H; Ekser, B; Satyananda, V; Zhou, H; Hara, H; Bajona, P; Wijkstrom, M; Bhama, J K; Long, C; Veroux, M; Wang, Y; Dai, Y; Phelps, C; Ayares, D; Ezzelarab, M B; Cooper, D K C

    2015-03-01

    In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. [Adoptive transfer of T lymphocytes].

    Science.gov (United States)

    Vié, H; Clémenceau, B

    2017-09-01

    Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells. Indeed, the management of patients is made very complex both for medical reasons, because the toxicities associated with these treatments are important, and for technical reasons, because the preparation of T lymphocytes for therapeutic use requires dedicated structures. During this same period, knowledge of the mechanisms of regulation of T lymphocytes and the possibilities offered by synthetic biology and techniques of genome engineering have progressed considerably. Combined, they allow envisaging a true "programming" of the T lymphocytes, intended to improve the efficiency of the treatments and the safety of the patients. Medical and industrial perspectives and the role of these approaches in the arsenal of cancer therapies will depend largely on two conditions: the emergence of a robust demonstration of their effectiveness in solid tumors, and the establishment of an acceptable production and distribution model 1. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Lymphocyte subpopulations in Sheehan's syndrome.

    Science.gov (United States)

    Atmaca, Hulusi; Araslı, Mehmet; Yazıcı, Zihni Acar; Armutçu, Ferah; Tekin, Ishak Özel

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

  14. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  15. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  16. Lymphocyte-platelet crosstalk in Graves' disease.

    Science.gov (United States)

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

  17. Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

    NARCIS (Netherlands)

    Ormai, S.; Hagenbeek, A.; Palkovits, M.; Bekkum, D.W. van

    1973-01-01

    The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administra

  18. Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons

    Science.gov (United States)

    Guardado-Mendoza, Rodolfo; Davalli, Alberto M.; Chavez, Alberto O.; Hubbard, Gene B.; Dick, Edward J.; Majluf-Cruz, Abraham; Tene-Perez, Carlos E.; Goldschmidt, Lukasz; Hart, John; Perego, Carla; Comuzzie, Anthony G.; Tejero, Maria Elizabeth; Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo; Halff, Glenn; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco

    2009-01-01

    β-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative β-cell volume, and increased relative α-cell volume and hyperglucagonemia. These results strongly support the concept that IA and β-cell apoptosis in concert with α-cell proliferation and hypertrophy are key determinants of islets of Langerhans “dysfunctional remodeling” and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R2 = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. PMID:19666551

  19. Interpretation of NCCN Guideline: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017

    Directory of Open Access Journals (Sweden)

    Lei XIA

    2016-12-01

    Full Text Available Chronic lymphocytic leukemia (CLL is a kind of chronic lymphocyte proliferative disease with corresponding clinical symptoms caused by the accumulation of mature B lymphocytes in peripheral blood, bone marrow and lymphatic tissues. In recent years, great achievements have been reached on the basic research, new prognostic markers, diagnostic criteria and therapeutic methods in CLL. This study mainly interpreted the corresponding diagnosis and treatment of CLL in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017.

  20. Genetics Home Reference: bare lymphocyte syndrome type I

    Science.gov (United States)

    ... Home Health Conditions bare lymphocyte syndrome type I bare lymphocyte syndrome type I Enable Javascript to view ... boxes. Download PDF Open All Close All Description Bare lymphocyte syndrome type I (BLS I) is an ...

  1. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

    2016-01-01

    AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  2. Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis endometrium

    Directory of Open Access Journals (Sweden)

    Fazleabas Asgerally T

    2008-01-01

    Full Text Available Abstract Background The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro. Methods Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG. Results Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected. The inhibitory effects of insulin on IGFBP-1 were more evident in explants of non-pregnant tissue or tissue away from the implantation site. In the absence of insulin, synthesis of IGFBP-1 was induced in explants with low levels of de novo synthesis whereas IGFBP-2 synthesis was inhibited. This effect was potentiated by steroids and hCG in the explant cultures. Conclusion Insulin differentially regulates endometrial IGFBP-1 and IGFBP-2 secretion in the baboon.

  3. The influence of baboon predation and time in water on germination and early establishment of Opuntia stricta (Australian pest pear in the Kruger National Park

    Directory of Open Access Journals (Sweden)

    W.D. Lotter

    1999-01-01

    Full Text Available The alien invader weed, Opuntia stricta Haw (family Cactaceae, is seriously threatening biodiversity in veld habitats of the Kruger National Park. Basic biological and ecological information on the establishment, growth and reproduction of the species is necessary for the development of effective strategies for its control. The rapid spread of the plant is apparently mainly due to seed dispersal by baboon (Papio ursinus. Sixty percent of seed taken from baboon faeces resulted in seedlings that established. Although palatability criteria for ripe fruit were more favourable than for unripe or medium-ripe fruit, seed from fruit at all three degrees of ripeness germinated equally well, and seedling establishment was similar. Despite their lower acidity, as well as higher total soluble sugar content and pH, cladodes are not subject to herbivory to near the extent that ripe fruit are. Freshly collected seed kept in Sabie River water showed significantly better germination/emergence after seven days submersion (83 than at 14 or 28 days (52 and 66 , respectively. Results suggest that seed dispersal of the species by animals, principally baboon, is an important cause of rapidly expanding infestations, and that dissipation in water will intensify the problem. Current findings should contribute toward the development of long-term weed management strategies aimed at con- tainment/eradication of the weed.

  4. Lenalidomide and Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Ana Pilar González-Rodríguez

    2013-01-01

    Full Text Available Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS and tumor flare reaction (TFR, that make its management different from other hematologic malignancies.

  5. [Evolution and phylogeny of B lymphocytes].

    Science.gov (United States)

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

    B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  6. [{sup 11}C]d-threo-Methylphenidate, a new radiotracer for the dopamine transporter. Characterization in baboon and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Volkow, N.D.; Fowler, J.S. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

    1995-05-01

    dl-threo Methylphenidate (MP, Ritalin) is a psychostimulant drug which binds to the dopamine transporter (DAT). We evaluated [{sup 11}C]d-threo-methylphenidate ([{sup 11}C]d-MP), the more active enantiomer, as a radiotracer for the DAT in baboons and human brain. Stereoselectivity, saturability and pharmacological specificity and reproducibility were examined. Stereoselectivity was examined in baboons by comparing [{sup 11C}]d-MP,[{sup 11}C]l-MP and [{sup 11}C]dl-MP. Unlabeled MP was used to assess the reversibility and saturability of the binding. GBR 12909,{beta}-(4-iodophenyl)tropane-2-carboxylic acid methyl ester ({beta}-CIT), tomoxetine and citalopram were used to assess the specificity of the binding. The ratios between the radioactivity in the striatum to that in cerebellum (ST/CB) were 3.3,2.2 and 1.1 for [{sup 11}C]d-MP,[{sup 11}C]dl-MP and [{sup 11}C]l-MP respectively. Most of the striatal binding of [{sup 11}C]d-threo-MP was displaced by injection of nonradioactive MP demonstrating reversibility. Pretreatment with MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) or {beta}-CIT (0.3 mg/kg) reduced ST/CB by about 60% and the ratios of distribution volumes at the steady-state for the triatum to cerebellum (DV{sub st/}DV{sub cb}) by about 50%. Pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg), inhibitors of the norepinephrine and serotonin transporter, had no effect. Studies of [{sup 11}C]d-MP in the human brain showed highest uptake in basal ganglia with a half clearance time of about 60 minutes. Repeated studies in 6 normal human subjects showed differences in DV{sub st/}DV{sub cb} between -7% and 8%. MP pretreatment decreased BG but no cortical or cerebellar binding and reduced Bmax/Kd by 91%.

  7. Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons

    Science.gov (United States)

    Lim, Keunpoong; Labaree, David; Ropchan, Jim; Harris, Paul; Huang, Yiyun; Ichise, Masanori; Carson, Richard E.; Cline, Gary W.

    2017-01-01

    Introduction 18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(−)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. Methods PET scans were conducted for up to 4 h with (+) and (−) enantiomers. Displacement experiments using unlabeled (+) and (−) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F-FP-(−)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90 min post-injection. Results Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(−)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND. Conclusions VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume

  8. Metabolism of peripheral lymphocytes, interleukin-2-activated lymphocytes and tumor-infiltrating lymphocytes from sup 31 P NMR studies

    Energy Technology Data Exchange (ETDEWEB)

    Kaplan, O.; Cohen, J.S.; Aebersold, P.

    1989-11-20

    {sup 31}O NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly diefferent form those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase in ATP levels. In all lumphocytes the phosphomonoester (PME) region is dominated by phosphoethanolamine (PE), while there is an unusual absence of phosphocholine (PC). Perfusion of these cells with high concentrations of choline caused only a minimal increase in PC, indicating that choline kinase is not the rate limiting step of lecithin synthesis in lymphocytes. (author). 13 refs.; 3 figs.; 1 tab.

  9. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  10. Chronic lymphocytic leukemia: present status.

    Science.gov (United States)

    Montserrat, E; Rozman, C

    1995-03-01

    Chronic lymphocytic leukemia (CLL) is the form of leukemia which occurs most frequently in Western countries. Its etiology is unknown, and no relationship with viruses or genes has been demonstrated. Epidemiological data suggest that genetic and ambiental factors might be of some significance. Clinical features of CLL are due to the accumulation of leukemic cells in bone marrow and lymphoid organs as well as the immune disturbances that accompany the disease. The prognosis of patients with CLL varies. Treatment is usually indicated by the risk of the individual patient, which is clearly reflected by the stage of the disease. In the early stage (Binet A, Rai O) it is reasonable to defer therapy until disease progression is observed. By contrast, because their median survival is less than five years, patients with more advanced stages require therapy. For almost 50 years, no major advances in the management of CLL, which has revolved around the use of alkylating agents, have been made. In recent years, the therapeutic approach in patients with CLL has changed as a result of the introduction of combination chemotherapy regimens and, in particular, purine analogues. The latter are already the treatment of choice for patients not responding to standard therapies, and their role as front-line therapy is being investigated. Bone marrow transplants are also being increasingly used. It is to be hoped that in years to come the outcome of patients with CLL will be improved by these advances.

  11. Lymphocyte subsets in pediatric migraine.

    Science.gov (United States)

    Cseh, Aron; Farkas, Kristof Mark; Derzbach, Laszlo; Muller, Katalin; Vasarhelyi, Barna; Szalay, Balazs; Treszl, Andras; Farkas, Viktor

    2013-07-01

    Aseptic inflammation due to activated immune cells has been implicated in the pathomechanism of migraine. We measured the prevalence of regulatory T cells (Tregs), along with that of CD4(+)/CD8(+) lymphocytes and their Th1/Th2 commitment in pediatric migraine. Children and adolescents suffering from migraine without aura, migraine with aura and hemiplegic migraine ictally (n = 53, 27, and 20, respectively), also interictally (n = 33) were recruited and compared to 24 healthy children. Our results indicated comparable prevalence of Tregs, CD4(+) and Th1/Th2 committed cells. CD8(+) prevalence was lower, and CD4(+)/CD8(+) ratio was higher in ictal phase irrespective of the subtype of migraine. No association between CD8(+) prevalence and gender, body weight, disease onset and attack duration in migraine subtypes was found. CD8(+) prevalence was normal in patients in interictal phase. These results suggest the absence of major systemic alteration of adaptive immunity in children and adolescents suffering from migraine; however, a transient decrease of CD8(+) prevalence during the ictal phase was detected irrespective of the subtype of migraine.

  12. Obinutuzumab for chronic lymphocytic leukemia.

    Science.gov (United States)

    Rioufol, Catherine; Salles, Gilles

    2014-10-01

    Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents.

  13. How T lymphocytes see antigen

    Science.gov (United States)

    Chakraborty, Arup K.

    2009-03-01

    Complex organisms, like humans, have an adaptive immune system that enables us to do battle with diverse pathogens. This flexible system can also go awry, and many diseases are the direct consequence of the adaptive immune system failing to discriminate between markers of self and non-self. The orchestrators of adaptive immunity are a class of cells called T lymphocytes (T cells). T cells recognize minute numbers of molecular signatures of pathogens, and T cell recognition of these molecular markers of non-self is both specific and degenerate. The specific (yet, cross-reactive), diverse, and self-tolerant T cell repertoire is designed in the thymus. I will describe how an approach that brings together theoretical and computational studies (rooted in statistical physics) with experiments (carried out by key collaborators) has allowed us to shed light on the mechanistic principles underlying how T cells respond to pathogens in a digital fashion (``on'' or ``off''), and how this molecular machinery coupled with frustration (a la spin glasses) plays a key role in designing the special properties of the T cell repertoire during development in the thymus.

  14. Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, S.R.; Paxton, L.D.; Harker, L.A.

    1986-09-01

    To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous /sup 111/In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located /sup 111/In source implanted at the time of surgery. In five animals, /sup 111/In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of /sup 111/In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced /sup 111/In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, /sup 111/In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy.

  15. Bilateral dacryoadenitis complicated by lymphocytic hypophysitis.

    Science.gov (United States)

    Baoke, Hou; Shihui, Wei; Maonian, Zhang; Zhaohui, Li; Zhitong, Zou; Zhigang, Song; Yan, Hei

    2009-09-01

    Three patients developed dacryoadenitis (DA) or lymphocytic pneumonitis before the diagnosis of lymphocytic hypophysitis (LyH). There were two previous reports of concurrence of DA and LyH. Our patients add support to the idea that DA and LyH are manifestations of a systemic autoimmune disease. We suggest that the discovery of DA should prompt imaging and endocrine investigation of LyH.

  16. Expression of tenascin in lymphocytic autoimmune thyroiditis.

    OpenAIRE

    Back, W; Heubner, C; Winter, J.; Bleyl, U

    1997-01-01

    AIMS: To study the distribution of tenascin by immunocytochemistry in autoimmune diseases of the thyroid. METHODS: Thyroids from patients with inflammatory lesions of the thyroid (lymphocytic thyroiditis Hashimoto, Grave's disease, thyroiditis DeQuervain) were studied by immunocytochemistry using antibodies against tenascin, collagen III, and collagen IV. RESULTS: In autoimmune lymphocytic thyroiditis Hashimoto there was a characteristic corona-like staining pattern of tenascin around all act...

  17. Lymphocyte migration into syngeneic implanted lymph nodes

    Energy Technology Data Exchange (ETDEWEB)

    Gordeeva, M.S.

    1986-03-01

    To judge the functional activity of lymphocytes of an implanted lymph node (LN), the proliferative response of lymphocytes of the implanted organ in the blast-transformation reaction in vitro and their ability to induce a local graft versus host reaction (GVHR) were determined. The lymphocyte suspension for labeling with /sup 51/Cr was obtained from peripheral LN in different situations from syngeneic mice. The resulting lymphocyte suspension was labeled with a solution of sodium chromate-/sup 51/Cr in a concentration of 20-40 microCi/100.10/sup 6/ cells in 1 ml for 40 min at 37/sup 0/C. The proliferative activity of a suspension of lymphocytes was estimated as incorporation of /sup 3/H-thymidine into DNA during incubation of the cell suspension for 3 days. Data on migration of /sup 51/Cr-labeled cells and the results of the morphological observations revealed marked ability of lymphocytes of the peripheral pool to colonize the regenerating stroma.

  18. Prenatal ontogeny of lymphocyte subpopulations in pigs.

    Science.gov (United States)

    Sinkora, M; Sinkora, J; Reháková, Z; Splíchal, I; Yang, H; Parkhouse, R M; Trebichavsk, I

    1998-12-01

    Although porcine lymphocytes have been classified into numerous subpopulations in postnatal animals, little is known about the ontogeny of these complex cell subsets. Using double- and triple-colour flow cytometry (FCM), we investigated the surface phenotype of fetal lymphoid cells in the thymus, cord blood, spleen and mesenteric lymph nodes at different stages of gestation. It was found that the major lymphocyte subpopulations started to appear at the beginning of the second third of the gestation period, with B cells being the earliest lymphocyte subpopulation to appear in the periphery. The T-cell receptor (TCR) gamma delta+ cells were the earliest detectable T-cell subset, developing first in the thymus and subsequently arriving in the periphery. Later in ontogeny, however, the number of TCRalpha beta+ lymphocytes rapidly increased, becoming the predominant T cells both in the thymus and in the periphery. Cells with the phenotype of adult natural killer cells were also identified in pig fetuses, though their nature and functional roles remain to be investigated. In addition, CD2 was expressed on most B cells whilst very few CD4+ TCRalpha beta+ cells or CD2+ TCRgamma delta+ cells expressed CD8, suggesting that the expression of CD2 and CD8 may reflect the functional status of the cells in postnatal animals. Taken together, this study has provided a systematic analysis of fetal porcine lymphocyte subpopulations and may provide the base for studies to establish the physiological roles of these lymphocyte subsets.

  19. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  20. Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-07-24

    Anemia; B-Cell Prolymphocytic Leukemia; Fatigue; Fever; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Hairy Cell Leukemia; Lymphadenopathy; Lymphocytosis; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Night Sweats; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Richter Syndrome; Splenomegaly; Thrombocytopenia; Weight Loss

  1. Synthesis, radiolabeling and baboon SPECT imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl)tropane ([{sup 123}I]YP256) as a serotonin transporter radiotracer

    Energy Technology Data Exchange (ETDEWEB)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Kula, Nora; Baldessarini, Ross [Department of Psychiatry and Neuroscience Program, Harvard Medical School, Mailman Research Center McLean Division of Massachusetts General Hospital, Belmont, MA 02478 (United States); Innis, Robert B.; Staley, Julie K. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Tamagnan, Gilles D. [Yale University, School of Medicine, VA Connecticut HCS (116A2), West Haven, CT 06516 (United States); Institute for Neurodegenerative Disorders, New Haven, CT 06510 (United States)], E-mail: gtamagnan@indd.org

    2008-01-15

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson's disease, Alzheimer's disease and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2{beta}-carbomethoxy-3{beta}-(3'-[{sup 123}I]iodophenyl) tropane (YP256, ). The radiolabeling was performed by iododestannylation using sodium [{sup 123}I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo.

  2. Synthesis, radiolabeling, and baboon SPECT imaging of 2β-carbomethoxy-3β-(3′-[123I]iodophenyl)tropane ([123I]YP256) as a serotonin transporter radiotracer.([123I]YP256) a potential serotonin transporter radiotracer)

    Science.gov (United States)

    Bois, Frederic; Baldwin, Ronald M.; Amici, Louis; Al-Tikriti, Mohammed S.; Kula, Nora; Baldessarini, Ross; Innis, Robert B.; Staley, Julie K.; Tamagnan., Gilles D.

    2008-01-01

    To develop a potential SPECT probe to evaluate the integrity of the serotoninergic system (5-HTT) whose dysfunction is linked to several disease conditions such as Parkinson’s, Alzheimer’s diseases and depression, we report the synthesis, radiolabeling and in vivo baboon imaging of 2β-carbomethoxy-3β-(3′-[123I]iodophenyl) tropane (YP256, 6). The radiolabeling was performed by iododestannylation using sodium [123I]iodide and peracetic acid. Although the ligand displayed high selectivity for 5-HTT over dopamine transporter (DAT) in vitro, SPECT imaging in baboons did not reveal selective 5-HTT accumulation in brain in vivo. PMID:18158943

  3. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  4. Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI study of fetal brain development in pregnant baboons

    Directory of Open Access Journals (Sweden)

    Peter Kochunov

    2010-05-01

    Full Text Available The global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (PG; weeks 17-25 of 26 weeks total gestation. Studying pregnant baboons using high-resolution MRI in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of ten primary cortical sulci. Seven normally developing fetuses were imaged in two animals longitudinally and sequentially. We compared these results to those on PG that from the ferret studies and analyzed them in the context of our recent studies of phylogenetics of cerebral gyrification. We observed that in both primates and non-primates, the cerebrum undergoes a very rapid transformation into the gyrencephalic state, subsequently accompanied by an accelerated growth in brain volume and cortical surface area. However, PG trends in baboons exhibited some critical differences from those observed in ferrets. For example, in baboons, the growth along the long (length axis of cortical sulci was unrelated to the growth along the short (depth axis and far outpaced it. Additionally, the correlation between the rate of growth along the short sulcal axis and heritability of sulcal depth was negative and approached significance (r=-0.60;p<.10, while the same trend for long axis was positive and not significant (p=0.3;p=0.40. These findings, in an animal that shares a highly orchestrated pattern of PG with humans, suggest that ontogenic processes that influence changes in sulcal length and depth are diverse and possibly driven by different factors in primates than in non-primates.

  5. Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures

    DEFF Research Database (Denmark)

    Hokland, M; Hokland, P; Heron, I

    1983-01-01

    Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T...

  6. A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: {sup 99m}Tc-HMPAO vs {sup 123}I(IMP)

    Energy Technology Data Exchange (ETDEWEB)

    Dormehl, I.C.; Oliver, D.W.; Hugo, N.; Rossouw, D

    1995-04-01

    Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from {sup 99m}Tc-HMPAO and {sup 123}I-iodoamphetamine [{sup 123}I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for {sup 123}I(IMP), which could have diagnostic implications.

  7. Immunization of baboons with attenuated schistosomula of Schistosoma haematobium: levels of protection induced by immunization with larvae irradiated with 20 and 60 krad

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, R.A. (US Naval Medical Research Unit No. 3, Cairo (Egypt) Wellcome Trust Research Labs., Nairobi (Kenya)); Bickle, Q.D.; Sturrock, R.F.; Taylor, M.G.; Webbe, G. (London School of Hygiene and Tropical Medicine (UK)); Kiare, S. (Wellcome Trust Research Labs., Nairobi (Kenya) Institute of Primate Research, Nairobi (Kenya)); James, E.R. (Medical Univ. of South Carolina, Charleston, SC (USA). Dept. of Ophthalmology); Andrews, B.J. (Bergen Univ. (Norway). Medical Dept. B)

    1990-01-01

    The authors have demonstrated that baboons can be immunized with S. haemotobium schistosomula irradiated with 20 krad in a regimen that induces 90% protection. While this high level of protection has stimulated a discussion on the feasibility of a human volunteer trial (Von Lichtenberg, 1985), results of further studies particularly on (i) the pathogensis of immunization per se (Byram et al., 1989), (ii) the longevity of protection, and (iii) the protective efficacy of cryopreserved irradiated S. haemotobium schistosomula (R. Harrison et al., in preparation), prevent recommending this form of vaccination for human application. (author).

  8. Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.

    Directory of Open Access Journals (Sweden)

    Tejero M Elizabeth

    2010-10-01

    Full Text Available Abstract Background Baboons (Papio hamadryas Sp. develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers. Methods We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9 ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6 was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period. Results Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004, triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,, and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001 and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002. Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002 also increased in the intervention group. Conclusions Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.

  9. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

    Full Text Available Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

  10. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  11. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

    Directory of Open Access Journals (Sweden)

    Yutaro Shiota

    2000-01-01

    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  12. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  13. Stability of cardiodynamic and some blood parameters in the baboon following intravenous anaesthesia with ketamine and diazepam

    Directory of Open Access Journals (Sweden)

    W.J. Du Plooy

    1998-07-01

    Full Text Available The stability of cardiodynamic and some blood parameters during a slow, continuous infusion of a combination of ketamine and diazepam is reported. Contractility (dP/dt, myocardial relaxation (Tln, left ventricular end-diastolic pressure (LVEDP, left ventricular systolic pressure (LVSP, arterial blood pressure and certain blood parameters were assessed in 3 male and 3 female juvenile baboons (Papio ursinus. Anaesthesia was induced with 15 mg/kg ketamine IM and maintained with a continuous IV infusion (40-60 mℓ/h of ketamine and diazepam. The mixture consisted of 2 mℓ ketamine (100 mg/mℓ, 2 mℓ diazepam (5 mg/mℓ and 50 mℓ saline. A period of 75 + 10 min was allowed for preparation of the animals, after which lead II of the ECG, femoral artery blood pressure and left ventricular pressure were recorded at 15-min intervals for a period of 2 h: the total duration of anaesthesia was 195 min. Arterial blood samples were analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin. Left ventricular parameters were derived from the left ventricular pressure curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p < 0.037 at the 195-min interval. No arrhythmias or ECG changes were seen, while blood pressure decreased gradually. Serum calcium concentration decreased and blood glucose levels increased gradually over time. Anaesthesia and analgesia were sufficient and no other drugs were necessary. The animals appeared sedated and dazed 60-80 min after the procedure. A continuous infusion of a combination of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia for cardiodynamic measurements.

  14. Nodular lymphocyte-predominant Hodgkin lymphoma.

    Science.gov (United States)

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL.

  15. T cell immunity using transgenic B lymphocytes

    Science.gov (United States)

    Gerloni, Mara; Rizzi, Marta; Castiglioni, Paola; Zanetti, Maurizio

    2004-03-01

    Adaptive immunity exists in all vertebrates and plays a defense role against microbial pathogens and tumors. T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells and differentiate into effector cells. Currently, dendritic cells are considered the only cells capable of stimulating T lymphocytes. Here, we show that mature naïve B lymphocytes can be genetically programmed by using nonviral DNA and turned into powerful antigen-presenting cells with a dual capacity of synthesis and presentation of antigen to T cells in vivo. A single i.v. injection of transgenic lymphocytes activates T cell responses reproducibly and specifically even at very low cell doses (102). We also demonstrate that T cell priming can occur in the absence of dendritic cells and results in immunological memory with protective effector functions. These findings disclose aspects in the regulation of adaptive immunity and indicate possibilities for vaccination against viruses and cancer in humans.

  16. An intrinsic GABAergic system in human lymphocytes.

    Science.gov (United States)

    Dionisio, Leonardo; José De Rosa, María; Bouzat, Cecilia; Esandi, María Del Carmen

    2011-01-01

    γ-amino butyric acid (GABA) is an ubiquitous neurotransmitter in the central nervous system and it is also present in non-neuronal cells. In this study we investigated the presence of neuronal components of the GABAergic system in lymphocytes and its functional significance. By using RT-PCR we detected mRNA expression of different components of the GABAergic system in resting and mitogen-activated lymphocytes: i) GAD67, an isoform of the enzyme that synthetizes GABA; ii) VIAAT, the vesicular protein involved in GABA storage; iii) GABA transporters (GAT-1 and GAT-2); iv) GABA-T, the enzyme that catabolizes GABA; and v) subunits that conform ionotropic GABA receptors. The presence of VIAAT protein in resting and activated cells was confirmed by immunocytochemistry. The functionality of GABA transporters was evaluated by measuring the uptake of radioactive GABA. The results show that [(3)H]GABA uptake is 5-fold higher in activated than in resting lymphocytes. To determine if GABA subunits assemble into functional channels, we performed whole-cell recordings in activated lymphocytes. GABA and muscimol, a specific agonist of ionotropic GABA receptors, elicit macroscopic currents in about 10-15% of the cells. Finally, by using [(3)H]thymidine incorporation assays, we determined that the presence of agonists of GABA receptor during activation inhibits lymphocyte proliferation. Our results reveal that lymphocytes have a functional GABAergic system, similar to the neuronal one, which may operate as a modulator of T-cell activation. Pharmacological modulation of this system may provide new approaches for regulation of T-cell response. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Lymphocytic adenohypophysitis: skull radiographs and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Saiwai, S.; Miyamoto, T. [Department of Radiology, Kobe Central Municipal Hospital, Hyogo (Japan); Inoue, Y.; Nemoto, Y.; Tashiro, T. [Department of Radiology, Osaka City University Medical School (Japan); Ishihara, T. [Department of Endocrinology, Kobe Central Municipal Hospital, Hyogo (Japan); Matsumoto, S. [Department of Neurosurgery, Kobe Central Municipal Hospital, Hyogo (Japan); Hakuba, A. [Department of Neurosurgery, Osaka City University Medical School, 1-5-7 Asahimachi, Abeno, Osaka, 545 (Japan)

    1998-02-01

    We report the skull radiograph, CT and MRI findings in three patients with lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were associated with pregnancy. CT demonstrated a pituitary mass but did not differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull radiographs showed either a normal sella turcica or minimal abnormalities; they did not show ballooning or destruction. The MRI appearances were distinctive: relatively low signal on T1-weighted images; preservation of the bright posterior pituitary lobe despite the presence of a relatively large pituitary mass, less common in macroadenomas; marked contrast enhancement compared with pituitary macroadenomas; and dural enhancement adjacent to a pituitary mass. (orig.) With 3 figs., 1 tab., 40 refs.

  18. Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS Are Active In Vivo in Anemic Baboons and Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Michael S Boosalis

    Full Text Available High-level fetal (γ globin expression ameliorates clinical severity of the beta (β hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

  19. Schistosoma haematobium in the baboon (Papio anubis): effect of vaccination with irradiated larvae on the subsequent infection with percutaneously applied cercariae.

    Science.gov (United States)

    Webbe, G; Sturrock, R F; James, E R; James, C

    1982-01-01

    Groups of five baboons were vaccinated three times at approximately six-weekly intervals at a rate of 1,000 organisms per kg of gamma-irradiated Schistosoma haematobium larvae. Five vaccines were tested: 3 and 20 Krad cercariae applied percutaneously; fresh 3 and 20 Krad mechanically transformed schistosomula injected intramuscularly; and cryopreserved 20 Krad schistosomula injected intramuscularly. These five groups and an unvaccinated control group were challenged percutaneously with 7,500 S. haematobium cercariae three months after the last vaccination. The efficacy of the vaccines was judged by faecal egg excretion, and by adult worm and tissue egg recoveries at necropsy 4.5 months after challenge. Significant protection, with 64 to 89% reductions in worm burden and parallel reductions in egg production, was achieved by all but the cryopreserved vaccine, although egg production was not significantly reduced in those female worms which did mature. Cercariae tended to give more protection than schistosomula and 20 Krad more protection than 3 Krad. No significant pathology could be detected in an additional baboon vaccinated with 20 Krad schistosomula but not challenged with cercariae. This is an encouraging result for the development of a live vaccine against S. haematobium.

  20. dSno facilitates baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad and toward dSmad2.

    Science.gov (United States)

    Takaesu, Norma T; Hyman-Walsh, Cathy; Ye, Ying; Wisotzkey, Robert G; Stinchfield, Michael J; O'connor, Michael B; Wotton, David; Newfeld, Stuart J

    2006-11-01

    A screen for modifiers of Dpp adult phenotypes led to the identification of the Drosophila homolog of the Sno oncogene (dSno). The dSno locus is large, transcriptionally complex and contains a recent retrotransposon insertion that may be essential for dSno function, an intriguing possibility from the perspective of developmental evolution. dSno is highly transcribed in the embryonic central nervous system and transcripts are most abundant in third instar larvae. dSno mutant larvae have proliferation defects in the optic lobe of the brain very similar to those seen in baboon (Activin type I receptor) and dSmad2 mutants. This suggests that dSno is a mediator of Baboon signaling. dSno binds to Medea and Medea/dSno complexes have enhanced affinity for dSmad2. Alternatively, Medea/dSno complexes have reduced affinity for Mad such that, in the presence of dSno, Dpp signaling is antagonized. We propose that dSno functions as a switch in optic lobe development, shunting Medea from the Dpp pathway to the Activin pathway to ensure proper proliferation. Pathway switching in target cells is a previously unreported mechanism for regulating TGFbeta signaling and a novel function for Sno/Ski family proteins.

  1. Up-regulation of the fetal baboon hypothalamo-pituitary-adrenal axis in intrauterine growth restriction: coincidence with hypothalamic glucocorticoid receptor insensitivity and leptin receptor down-regulation.

    Science.gov (United States)

    Li, Cun; Ramahi, Emma; Nijland, Mark J; Choi, Jaeyhek; Myers, Dean A; Nathanielsz, Peter W; McDonald, Thomas J

    2013-07-01

    Intrauterine growth restriction (IUGR) is an important fetal developmental problem resulting from 2 broad causes: maternal undernutrition and/or decreased fetal nutrient delivery to the fetus via placental insufficiency. IUGR is often accompanied by up-regulation of the hypothalamo-pituitary-adrenal axis (HPAA). Sheep studies show fetal HPAA autonomy in late gestation. We hypothesized that IUGR, resulting from poor fetal nutrient delivery, up-regulates the fetal baboon HPAA in late gestation, driven by hypothalamo-pituitary glucocorticoid receptor (GR) insensitivity and decreased fetal leptin in peripheral plasma. Maternal baboons were fed as ad libitum controls or nutrient restricted to produce IUGR (fed 70% of the control diet) from 0.16 to 0.9 gestation. Peripheral ACTH, cortisol, and leptin were measured by immunoassays. CRH, arginine vasopressin (AVP), GR, leptin receptor (ObRb), and pro-opiomelanocortin peptide expression were determined immunohistochemically. IUGR fetal peripheral cortisol and ACTH, but not leptin, were increased (P HPAA activation was aided by GR insensitivity and decreased ObRb expression in the PVN, and (3) the anterior pituitary is not a site for ObRb effects on the HPAA.

  2. Short-term effects of high-dose khat on sperm parameters and reproductive hormonal levels in olive baboons (Papio anubis).

    Science.gov (United States)

    Nyachieo, Atunga; Kiraithe, Muthamia M; Spiessens, Carl; Chai, Daniel C; Kiulia, Nicholas M; D'Hooghe, Thomas M; Mwenda, Jason M

    2013-01-01

    The biological effects of khat (Catha edulis) on reproduction and fertility are inadequately investigated and controversial, hence we determined the effects of oral administration of high-dose khat on sperm parameters and male hormonal levels in olive baboons. In this study, 6 male baboons received a high dose of khat (500 g/week) during 1 month. Electroejaculation for sperm studies (concentration, motility and chromatin integrity) and plasma collection for hormonal analysis (testosterone, prolactin and cortisol) were done weekly during 1 month before and 1 month during khat administration as well as 2 weeks after the last dose of khat administration. Administration of khat extract induced a significant reduction in sperm motility (p = 0.008), sperm count (p = 0.041), sperm chromatin integrity (p = 0.0003), testosterone levels (p = 0.035) and prolactin levels (p = 0.0115), but not in cortisol levels and sperm volume (p > 0.05). The results suggest that high-dose khat decreases sperm quality and testosterone and hence may contribute to male infertility.

  3. The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

    Science.gov (United States)

    Hill, Bridget T.; Harrap, K. R.

    1972-01-01

    It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy. PMID:4647395

  4. Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle dog.

    Science.gov (United States)

    Doi, Takuya; Tomonari, Yuki; Kawasako, Kazufumi; Yamada, Naoaki; Tsuchitani, Minoru

    2017-02-04

    Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the medulla of the bilateral adrenal glands was observed in an 18-month-old male laboratory beagle dog. It might be that the present lymphocytic adrenal medullitis is an autoimmune-mediated disease as the histological characteristics are consistent with an autoimmune pathogenesis. However, the actual cause remains unclear as the existence of serum autoantibodies against the adrenal medulla could not be confirmed. Although this dog also contracted lymphocytic thyroiditis along with serum thyroglobulin autoantibodies, indicating that the thyroiditis occurred with an autoimmune basis; the relation between the adrenal medullitis and thyroiditis is unknown.

  5. Uterine receptivity and implantation: The regulation and action of insulin-like growth factor binding protein-1 (IGFBP-1, HOXA10 and forkhead transcription factor-1 (FOXO-1 in the baboon endometrium

    Directory of Open Access Journals (Sweden)

    Fazleabas Asgerally T

    2004-06-01

    Full Text Available Abstract In primates, the phase of the menstrual cycle when the uterus becomes receptive is initially dependent on estrogen and progesterone. Further morphological and biochemical changes are induced as a result of biochemical signals between the embryo and the maternal endometrium. Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation and is similar to that described for the rhesus macaque. In the baboon, when chorionic gonadotropin is infused in a manner that mimics blastocyst transit, this has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. Decidualization, is the major change that occurs in the primate endometrium after conception. During this process the fibroblast-like stromal cells change morphologically into polygonal cells and express specific decidual proteins. Studies in the baboon demonstrated that insulin-like growth factor binding protein-1 (IGFBP-1 gene expression is a conceptus-mediated response. Subsequent studies in vitro established that IGFBP-1 is transcriptionally regulated by FOXO1 and HOXA10 which together upregulate the IGFBP-1 promoter activity. A baboon endometriosis model was utilized to determine if the changes observed during uterine receptivity in normally cycling animals were compromised. The data suggests that in animals with disease, markers of uterine receptivity are not appropriately expressed in the eutopic endometrium. It is possible that these differences influence the fertility of the animals with disease and the baboon could be used as a primate model to study

  6. Dual character of interaction between lymphocytes and allogeneic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Kochetkova, M.O.; Nikolaeva, I.S.

    1986-10-01

    The mechanisms of stimulation of colony formation by small doses of allogeneic lymphocytes were studied in mice. When interaction of lymphocytes with allogeneic stem cells was studied, bone marrow cells of mice were injected into lethally irradiated recipients in the control, and mixtures of bone marrow cells with varied numbers of lymphocytes were injected in the experiment. Dependence of the inactivation indices on the number of lymphocytes injected, based on the results of counting macro- and microcolonies in the spleen, is shown.

  7. Morphometric Characterization of Small Cell Lymphocytic Lymphoma

    Directory of Open Access Journals (Sweden)

    Chisoi Anca

    2014-11-01

    Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

  8. Targeting cytotoxic T lymphocytes for cancer immunotherapy

    OpenAIRE

    Maher, J; Davies, E. T.

    2004-01-01

    In light of their preeminent role in cellular immunity, there is considerable interest in targeting of cytotoxic T-lymphocytes to cancer. This review summarises the active and passive immunotherapeutic approaches under development to achieve this goal, emphasising how recent advances in tumour immunology and gene transfer have impacted upon this field.

  9. Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

    Directory of Open Access Journals (Sweden)

    Caroline Boda

    Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

  10. SnapShot: chronic lymphocytic leukemia.

    Science.gov (United States)

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  11. Regulatory T-lymphocytes in asthma

    NARCIS (Netherlands)

    van Oosterhout, AJM; Bloksma, N

    2005-01-01

    T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. However, little is known about immunoregulatory mechanisms that determine susceptibility to, severity of, or persistence of asthma. The concept of a dist

  12. Lymphocyte dynamics in health and disease

    NARCIS (Netherlands)

    van Gent, R.

    2009-01-01

    Following immune depletion, it is vital that the immune system recovers rapidly to avoid severe or life-threatening infections. In adults, full recovery of CD4+ and CD8+ T-cell counts, important cell types of the immune system, may take years. Similar to other lymphocytes, T cells start their develo

  13. Peripheral lymphocyte subpopulations in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P

    1991-01-01

    Peripheral lymphocyte subsets--T-helper (CD4+), T-suppressor/cytotoxic (CD8+), and naive/virgin T cells/natural killer cells (CD45RA)--were studied quantitatively in 30 patients with recurrent aphthous ulceration (RAU) and 29 sex- and age-matched RAU-free control donors. The CD4+ percentage was s...

  14. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  15. Rosette formation of pig T lymphocytes with sheep erythrocytes.

    Science.gov (United States)

    Escajadillo, C; Binns, R M

    1975-01-01

    The relationship of sheep RBC rosette formation to density of thymus and blood lymphocytes was investigated. Thymocyte density was unimodal and cells of all densities rosetted equally. Blood lymphocyte density was bimodal with most rosette-forming cells in the denser ficoll layers. Papain treatment of SRBC increases rosette formation with blood lymphocytes while apparently maintaining specificity of T cells.

  16. 21 CFR 864.8500 - Lymphocyte separation medium.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864.8500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes from...

  17. DMPD: Developmental plasticity of lymphocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18472258 Developmental plasticity of lymphocytes. Cobaleda C, Busslinger M. Curr Op...in Immunol. 2008 Apr;20(2):139-48. Epub 2008 May 9. (.png) (.svg) (.html) (.csml) Show Developmental plastic...ity of lymphocytes. PubmedID 18472258 Title Developmental plasticity of lymphocytes. Authors Cobaleda C, Bus

  18. Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

    2008-11-15

    We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

  19. NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

    OpenAIRE

    Cukic, Vesna

    2016-01-01

    Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surg...

  20. Lymphocytic colitis: A clue to bacterial etiology

    Institute of Scientific and Technical Information of China (English)

    Thanaa EA Helal; Naglaa S Ahmed; Osama Abo El Fotoh

    2005-01-01

    AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis.METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain.RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli(14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coliwas associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coliin their biopsy cultures.Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coliin their specimen's culture. None of the controls showed these bacteria in histopathological sections.CONCLUSION: This preliminary study reports an association between E coliand lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coliin the pathogenesis of lymphocytic colitis.

  1. Lymphocyte transformation studies in drug hypersensitivity.

    Science.gov (United States)

    Warrington, R J; Tse, K S

    1979-05-05

    In a group of patients with clinically diagnosed drug hypersensitivity the in vitro lymphocyte response to the suspected drug was assessed by the lymphocyte transformation test. The test gave positive results in all 15 patients with penicillin-induced immediate or accelerated allergic reactions and positive immediate skin-test reactivity to the major or the minor antigenic determinant of penicillin, or both, but in only 3 of the 12 patients with delayed-onset maculopapular rashes induced by penicillin, despite positive immediate reactivity to the skin-test reagents.Lymphocyte stimulation greater than five times the control level was demonstrated for five patients with penicillin-induced erythroderma, Stevens-Johnson syndrome or a serum-sickness-like illness, or with methicillin-induced interstitial nephritis, all of whom had negative reactions to the appropriate skin-test reagents. A low level of stimulation was seen in eight other skin-test-negative patients with possible allergic reactions induced by penicillins. However, in all subjects tested the stimulation was significantly greater than the mean for control subjects.For 9 of 11 patients with isoniazid-induced hepatitis or maculopapular rashes, but for only 8 of 31 patients with eruptions induced by a variety of drugs other than penicillins and isoniazid, significant stimulation occurred in the lymphocyte transformation test.It is concluded that the lymphocyte transformation test is useful in the detection of hypersensitivity to the penicillins (although in IgE-mediated reactions skin testing is clearly preferable) and isoniazid but is of limited value in the demonstration of hypersensitivity to other drugs.

  2. Is lymphocytic (hashimoto) thyroiditis associated with suicide?

    Science.gov (United States)

    Cina, Stephen J; Perper, Joshua A

    2009-09-01

    The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in

  3. Mean dose to lymphocytes during radiotherapy treatments

    Energy Technology Data Exchange (ETDEWEB)

    Brandan, M.E.; Perez-Pastenes, M.A. [Instituto de Fisica (Mexico); Ostrosky-Wegman, P.; Gonsebatt, M.E. [Instituto de Investigaciones Biomedicas (Mexico); Diaz-Perches, R. [Hospital General de Mexico (Mexico)

    1994-10-01

    Using a probabilistic model with parameters from four radiotherapy protocols used in Mexican hospitals for the treatment of cervical cancer, the authors have calculated the distribution of dose to cells in peripheral blood of patients. Values of the mean dose to the lymphocytes during and after a {sup 60}Co treatment are compared to estimates from an in vivo chromosome aberration study performed on five patients. Calculations indicate that the mean dose to the circulating blood is about 2% of the tumor dose, while the mean dose to recirculating lymphocytes may reach up to 7% of the tumor dose. Differences up to a factor of two in the dose to the blood are predicted for different protocols delivering equal tumor doses. The data suggest mean doses higher than the predictions of the model. 10 refs., 3 figs., 2 tabs.

  4. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Ch(a)vez-Gal(a)n L; Arenas-Del Angel MC; Zenteno E; Ch(a)vez R; Lascurain R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lyric molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

  5. Bioluminescent assay for human lymphocyte blast transformation.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Romanova, N A; Brovko LYu; Ugarova, N N

    1995-05-01

    One of the basic tests of in vitro evaluation of immune cell functional activity is a proliferative response of lymphocytes on the action of external stimuli such as mitogenic lectines, antigens, etc. We compared two methods used to assess the lymphocyte functional status. (1) [3H]thymidine incorporation and (2) bioluminescence for determination of intracellular ATP in blast cells. Comparison has been done for healthy donors and patients with proven low immunological status. The proposed bioluminescent method for evaluation of the proliferative response was shown to be sensitive enough for diagnostic purposes. This method allows one to process a large number of samples at the same time and correlates highly with the radionuclide test use hazardous radioactive materials.

  6. Lymphocyte transformation in presumed ocular histoplasmosis

    Energy Technology Data Exchange (ETDEWEB)

    Ganley, J.P.; Nemo, G.J.; Comstock, G.W.; Brody, J.A.

    1981-08-01

    Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

  7. Obinutuzumab for previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Abraham, Jame; Stegner, Mark

    2014-04-01

    Obinutuzumab was approved by the Food and Drug Administration in late 2013 for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). The approval was based on results of an open-label phase 3 trial that showed improved progression-free survival (PFS) with the combination of obinutuzumab plus chlorambucil compared with chlorambucil alone. Obinutuzumab is a monoclonal antibody that targets CD20 antigen expressed on the surface of pre B- and mature B-lymphocytes. After binding to CD20, obinutuzumab mediates B-cell lysis by engaging immune effector cells, directly activating intracellular death signaling pathways, and activating the complement cascade. Immune effector cell activities include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

  8. The Danish National Chronic Lymphocytic Leukemia Registry

    DEFF Research Database (Denmark)

    da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth;

    2016-01-01

    , and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. DESCRIPTIVE DATA: To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National......, 3,082 patients have been registered. CONCLUSION: The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark......AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

  9. Metabolism pathways in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilai, Merav; Keating, Michael J; Estrov, Zeev

    2016-01-01

    Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

  10. B cell acute lymphocytic leukemia in pregnancy.

    Science.gov (United States)

    Bottsford-Miller, Justin; Haeri, Sina; Baker, Arthur M; Boles, Jeremiah; Brown, Mark

    2011-08-01

    Acute lymphocytic leukemia (ALL) is a rare occurrence in pregnancy and can be rapidly fatal if left untreated. The need for immediate treatment of ALL, coupled with the maternal-fetal risks from the chemotherapy regimen render a therapeutic dilemma in pregnant women with ALL. We report a case of ALL diagnosed in the 24th week of pregnancy to outline our management strategy, to demonstrate the feasibility of treatment with multi-agent chemotherapy, and to provide a review of the literature.

  11. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

  12. Centre-embedded structures are a by-product of associative learning and working memory constraints: evidence from baboons (Papio Papio).

    Science.gov (United States)

    Rey, Arnaud; Perruchet, Pierre; Fagot, Joël

    2012-04-01

    Influential theories have claimed that the ability for recursion forms the computational core of human language faculty distinguishing our communication system from that of other animals (Hauser, Chomsky, & Fitch, 2002). In the present study, we consider an alternative view on recursion by studying the contribution of associative and working memory processes. After an intensive paired-associate training with visual shapes, we observed that baboons spontaneously ordered their responses in keeping with a recursive, centre-embedded structure. This result suggests that the human ability for recursion might partly if not entirely originate from fundamental processing constraints already present in nonhuman primates and that the critical distinction between animal communication and human language should more likely be found in working memory capacities than in an ability to produce recursive structures per se.

  13. Lymphocytic hypophysitis masquerading as pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Rajneesh Mittal

    2012-01-01

    Full Text Available Introduction: Pituitary hypophysitis (PH is characterized by pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be autoimmune or secondary to systemic diseases or infections. Based on the histopathological findings PH is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous, necrotizing and Immunoglobulin- G4 (IgG4 plasmacytic types. Objective: To report a case of lymphocytic hypophysitis (LH. Case Report: A 15-year-old girl presented with history of headache, amenorrhea, and history of polyuria for past 4 months. Initial evaluation had suppressed follicular stimulating hormone (<0.01 mIU/ml, high prolactin levels (110.85 ng/ml and diabetes insipidus (DI. Magnetic resonance imaging of sella was suggestive of pituitary macroadenoma with partial compression over optic chiasma. Patient underwent surgical decompression. Yellowish firm tissue was evacuated and xanthochromic fluid was aspirated. Histopathology was suggestive of LH. She resumed her cycles postoperatively after 4 months, prolactin levels normalized, however, she continues to have DI and is on desmopressin spray. This case has been presented here for its rare presentation in an adolescent girl because it is mostly seen in young females and postpartum period and its unique presentation as an expanding pituitary mass with optic chiasma compression. Conclusion: Definitive diagnosis of LH is based on histopathological evaluation. Therapeutic approach should be based on the grade of suspicion and clinical manifestations of LH.

  14. [Circadian rhythm of human lymphocyte subpopulations].

    Science.gov (United States)

    Pasqualetti, P; Colantonio, D; Casale, R; Colangeli, S; Natali, G

    1988-01-01

    Circadian rhythm of lymphocyte subsets was investigated in four healthy subjects, males, aged 35-58 years old. After a period of ambiental synchronization, venous blood samples were taken during a span of a day at 0.00 a.m., 4.00 a.m., 8.00 a.m., noon, 4.00 p.m. and 8.00 p.m. Lymphocyte subsets (OKT3, OKT4, OKT8, OKB7, OKJa1) were determined by monoclonal antibodies method, and serum level of cortisol by radioimmunoassay method. The OKT4/OKT8 ratio was also calculated. Data were analyzed by chronograms (mean +/- 1SD) and by cosinor method. Results show a significant circadian rhythm for each lymphocyte subset and for serum cortisol levels. The lowest levels of all circulating subsets were seen between noon and 4.00 p.m. and the highest levels around midnight, inversely related with the circadian rhythm of serum cortisol. The OKT4/OKT8 ratio, on the contrary, was relatively constant during the day, without a significant circadian rhythm. These observations have laboratoristic, clinical, and therapeutic implications and should be considered in the course of immunological studies.

  15. Normal lymphocyte immunophenotype in an elderly population

    Directory of Open Access Journals (Sweden)

    Sâmia Macedo Queiroz Mota Castellão Tavares

    2014-06-01

    Full Text Available OBJECTIVE: The aim of this work was to evaluate the lymphocyte immunophenotype in an elderly population.METHODS: This study enrolled 35 over 60-year-old volunteers and a control group composed of 35 young adults. The study included elderly without diseases that might affect the functioning of the immune system. These individuals were consulted by doctors and after a physical examination, laboratory tests were performed using a Beckman Coulter (r flow cytometer. The GraphPad Prism computer program was employed for statistical analysis with the level of significance being set for p-values <0.05.RESULTS: There is a statistically significant reduction in the number of lymphocytes (CD8 +, CD2 + and CD3 + cells in the elderly compared to young adults. These low rates are explained by changes attributed to aging and may be partly responsible for the reduction in the cellular immune response, lower proliferative activity and the low cytotoxicity of lymphocytes.CONCLUSION: These parameters showed greater impairment of adaptive immunity in the elderly population and can therefore explain the greater fragility of the aged body to developing diseases.

  16. Sudden unexpected death associated with lymphocytic thyroiditis.

    Science.gov (United States)

    Vestergaard, Vibeke; Drostrup, Dorthe Høj; Thomsen, Jørgen L

    2007-04-01

    A forensic autopsy study comprising 125 cases was carried out retrospectively in order to evaluate pathological changes in the thyroid gland in different groups of death. The five groups selected consecutively were: (i) opiate addicts who died from an overdose, (ii) alcoholics who died as a result of their alcohol abuse, (iii) cases of fatal poisoning other than opiate addicts, (iv) unknown cause of death and (v) controls without prior disease. Tissue samples from the thyroid gland were cut and stained with haematoxylin and eosin and van Gieson. Histology examinations were subsequently performed blind with semiquantitative assessment of the following six parameters: (a) height of the follicular epithelium, (b) the amount of lymphocytes, (c) the presence of plasma cells, (d) hyperplastic follicular changes, (e) oxyphilic changes, and (f) fibrosis. The most striking result was the finding of extensive lymphocytic infiltration of the thyroid parenchyma in five of the 124 cases, of which four belonged in the group of 'unknown cause of death'. This discovery leads to reflections regarding lymphocytic thyroiditis as a cause of death, either by itself or in combination with other disorders. Silent (painless) thyroiditis, especially, is easily overlooked at autopsy as there are no macroscopic changes and often no prior symptoms or history of thyroid disease pointing towards this condition. Analyses of thyroid hormones are unreliable in predicting endocrine status in life. Routine microscopy of the thyroid gland is therefore advocated in cases of sudden unexpected death in order to diagnose thyroid disease, in particular silent (painless) thyroiditis.

  17. Decreased chronic-stage cortical C-11-flumazenil binding after focal ischemia-reperfusion in baboons - A marker of selective neuronal loss?

    Energy Technology Data Exchange (ETDEWEB)

    Giffard, C.; Landeau, B.; Kerrouche, N.; Young, A.R. [Univ Caen, INSERM Avenir, INSERM U320, INSERM E 0218, F-14032 Caen (France); Giffard, C.; Landeau, B.; Kerrouche, N.; Young, A.R. [Univ Caen, CYCERON, F-14032 Caen (France); Giffard, C.; Landeau, B. [Univ Caen, CYCERON, CEA LRV 10, F-14032 Caen (France); Baron, J.C. [Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 2QQ (United Kingdom)

    2008-07-01

    Background and Purpose - Although the penumbra can be saved by early reperfusion, in the rat it is consistently affected by selective neuronal loss. Mapping selective neuronal loss in the living primate would be desirable. Methods - Five young adult baboons underwent {sup 15}O positron emission tomography for cerebral blood flow, cerebral oxygen consumption, and oxygen extraction fraction mapping at baseline and serially during and after 20-hours temporary middle cerebral artery occlusion. At approximately day 30, {sup 11}C-flumazenil (FMZ), a potential positron emission tomography marker of selective neuronal loss, and structural magnetic resonance-based infarct mapping were obtained, and the brain was perfused-fixed. Reduced FMZ binding in non-infarcted cortical middle cerebral artery areas was searched voxel-wise, and specific binding was assessed using compartmental modeling of FMZ time-activity curves. Results - Visual inspection revealed reduced late FMZ uptake in the affected cortical territory, extending well beyond the infarct. Accordingly, the incidence of selected voxels was greater than chance, documenting mildly but significantly reduced FMZ uptake and specific binding. Serial {sup 15}O positron emission tomography revealed moderately severe acute ischemia followed by reperfusion. Histopathology documented only mild neuronal changes in or near the affected areas. Conclusions - We document moderate but definite late FMZ binding decrements in non-infarcted cortical areas in the baboon, consistent with previous rat and human studies. These were acutely characterized by moderate ischemia followed by reperfusion, consistent with neuronal damage from ischemic or reperfusion injury in the salvaged at-risk tissue. Only mild histopathological changes subtended these FMZ alterations suggesting subtle processes such as isolated dendrite or synapse loss. Whether these changes impact on clinical outcome deserves studying because they may be targeted by specific

  18. Up to 9-day survival and control of thrombocytopenia following alpha1,3-galactosyl transferase knockout swine liver xenotransplantation in baboons.

    Science.gov (United States)

    Kim, Karen; Schuetz, Christian; Elias, Nahel; Veillette, Gregory R; Wamala, Isaac; Varma, Manish; Smith, R Neal; Robson, Simon C; Cosimi, A Benedict; Sachs, David H; Hertl, Martin

    2012-01-01

    With standard miniature swine donors, survivals of only 3 days have been achieved in primate liver-transplant recipients. The recent production of alpha1,3-galactosyl transferase knockout (GalT-KO) miniature swine has made it possible to evaluate xenotransplantation of pig organs in clinically relevant pig-to-non-human primate models in the absence of the effects of natural anti-Gal antibodies. We are reporting our results using GalT-KO liver grafts. We performed GalT-KO liver transplants in baboons using an immunosuppressive regimen previously used by our group in xeno heart and kidney transplantation. Post-operative liver function was assessed by laboratory function tests, coagulation parameters and histology. In two hepatectomized recipients of GalT-KO grafts, post-transplant liver function returned rapidly to normal. Over the first few days, the synthetic products of the donor swine graft appeared to replace those of the baboon. The first recipient survived for 6 days and showed no histopathological evidence of rejection at the time of death from uncontrolled bleeding, probably caused by transfusion-refractory thrombocytopenia. Amicar treatment of the second and third recipients led to maintenance of platelet counts of over 40 000 per μl throughout their 9- and 8-day survivals, which represents the longest reported survival of pig-to-primate liver transplants to date. Both of the last two animals nevertheless succumbed to bleeding and enterococcal infection, without evidence of rejection. These observations suggest that thrombocytopenia after liver xenotransplantation may be overcome by Amicar therapy. The coagulopathy and sepsis that nevertheless occurred suggest that additional causes of coagulation disturbance must be addressed, along with better prevention of infection, to achieve long-term survival. © 2012 John Wiley & Sons A/S.

  19. Transfer of cholesterol from macrophages to lymphocytes in culture.

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

    A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage-derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from [4-14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes from 10(7) macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre-labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%-increase in the total cholesterol content of lymphocytes was found after co-cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated for 24 h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co-cultivated in a single-well chamber system (cells in direct contact), but also in a two-compartment system (where cells can communicate but not by direct contact). Co

  20. Alteration of peripheral blood lymphocyte subsets in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Miroslawa Pietruczuk; Milena I Dabrowska; Urszula Wereszczynska-Siemiatkowska; Andrzej Dabrowski

    2006-01-01

    AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP).METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5,10 and 30 by means of flow cytometry.RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of Tover B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28,CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5,IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells.CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

  1. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A

    1998-01-01

    We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58...... beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... of allospecific cytotoxic activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T cell-mediated immune functions....

  2. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma.

  3. Suppressive effects of antigens on the activity of specific activated lymphocytes: A test to define the specificity of activated lymphocytes

    Institute of Scientific and Technical Information of China (English)

    HU Jun; PAN Sheng-jun; CAI Zhen-jie; GUAN De-lin; LIU Xiao-cheng

    2006-01-01

    Objective:With the regular mixed lymphocytes culture (MLC) to detect the allograft rejection, the reactivity of the activated lymphocytes (primed lymphocytes) of a recipient shows sometimes increase and sometimes decrease against the antigens from the donor, which is inconsistent with the clinical results. In order to establish a convenient method for testing the specificity of the activated lymphocytes in vitro, so as to know the rejection occurred or not by testing the existence of the specific activated lymphocytes against donor's HLA antigens in the recipient's peripheral blood. Methods: Anti-IL-2 neutralizing monoclonal antibody (anti-IL-2 N-mAb) and immunosuppressors were introduced in this test system in the presence of specific stimulators and activated lymphocytes. Results: When the activated lymphocytes were chosen from the one-way MLC 4 d to undergo re-stimulation by specific stimulators, the activity of activated lymphocytes in the treatment group was suppressed significantly compared with that in the control group. The result of this test method is consistent with the biopsy in the clinical diagnosis of rejection.Conclusion :It suggests that the activated lymphocytes can be inactivated by specific antigens in certain conditions. This can be a useful tool to define the specificity of the activated lymphocytes.

  4. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  5. The association between chronic lymphocytic thyroiditis and thyroid tumors.

    Science.gov (United States)

    Tamimi, Dalal M

    2002-04-01

    An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To assess the relationship, a histopathologic analysis of surgically resected thyroid tumors together with the frequency and severity of chronic lymphocytic infiltration of the thyroid among patients with follicular adenoma, follicular carcinoma, and papillary carcinoma was performed. The prevalence of lymphocytic infiltrate, which is indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma (58%) than in patients with follicular carcinoma (20%) or follicular adenoma (14%). The lymphocytic infiltration within the tumor compared with the severity of thyroiditis in the nontumorous tissue. Therefore, the association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed. The possibility that an immunologic mechanism involved in the pathogenesis of papillary carcinoma stimulates lymphocytic infiltration in the thyroid tissue through an autoimmune mechanism is suggested.

  6. Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA.

    Science.gov (United States)

    Sturrock, R F; Bain, J; Webbe, G; Doenhoff, M J; Stohler, H

    1987-01-01

    Derivatives in the class of 9-acridanone-hydrazones were found to be highly active against Schistosoma mansoni in baboons. Single doses of 25 mg/kg were fully effective. Data are presented showing changes detected by ELISA in antibody levels against schistosome eggs which correlated positively with the effect of chemotherapy. This approach may help to evaluate the effects of treatment of human schistosomiasis where the detection of low egg counts is problematic.

  7. Chronic lymphocytic leukemia: case-based session.

    Science.gov (United States)

    Rai, K R; Döhner, H; Keating, M J; Montserrat, E

    2001-01-01

    Drs. Hartmut Döhner, Michael J. Keating, Kanti R. Rai and Emili Montserrat form the panel to review chronic lymphocytic leukemia (CLL) while focusing on the clinical features of a particular patient. The pace of progress in CLL has accelerated in the past decade. The pathophysiological nature of this disease, as had been known in the past, was based largely on the intuitive and empiric notions of two leaders in hematology, William Dameshek and David Galton. Now the works of a new generation of leaders are providing us with the scientific explanations of why CLL is a heterogeneous disease, perhaps consisting of at least two separate entities. In one form of CLL, the leukemic lymphocytes have a surface immunoglobulin (Ig) variable region gene that has undergone somatic mutations, with tell-tale markers suggesting that these cells had previously traversed the germinal centers. Such patients have a distinctly superior prognosis than their counterparts whose leukemic lymphocytes IgV genes have no mutations (these are indeed immunologically naive cells), who have a worse prognosis. The introduction of fluorescence in situ hybridization (FISH) technique has provided us with new insights into the diverse chromosomal abnormalities that can occur in CLL, and which have significant impact on the clinical behavior and prognosis of patients with this disease. Major advances in therapeutics of CLL also have occurred during the past decade. Two monoclonal antibodies, Campath-1H (anti-CD52) and rituximab (anti-CD20), and one nucleoside analogue, fludarabine, have emerged as three agents of most promise in the front-line treatment of this disease. Studies currently in progress reflect our attempts to find the most effective manner of combining these agents to improve the overall survival statistics for CLL patients. As in many other hematological malignancies, high dose chemotherapy followed by autologous or HLA-compatible allogeneic stem cells rescue strategies are under study as

  8. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    Science.gov (United States)

    2017-10-05

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  9. Phenotypic and Functional Analysis of Porcine T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    李华; 陈应华

    2001-01-01

    Porcine and other higher mammals express clusters of differentiation (CD) antigens on the surface of T lymphocytes, such as CD2, CD3, CD4, CD8, etc. However, in porcine, a high percentage of the CD4+ CD8-T lymphocyte subpopulation exist in the peripheral blood and the ratio of the CD4+ and CD8+ T lymphocyte subpopulations is reversed. These differences bring new challenges to better understanding of the phenotype and function of porcine T lymphocytes in antigen recognition and immune response.

  10. Recent advances in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    N Vyas

    2012-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL was largely considered to be a disease of slow progression, standard treatment with Chlorambucil and having almost similar prognosis. With the introduction of molecular methods for understanding the disease pathophysiology in CLL there has been a remarkable change in the approach towards the disease. The variation in B-cell receptor response and immunoglobulin heavy chain variable region (IGHV mutation, genetic aberration and defect in apoptosis and proliferation has had an impact on therapy initiation and prognosis. Early diagnosis of molecular variant is therefore necessary in CLL.

  11. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  12. Spinal epidural compression in chronic lymphocytic leukemia.

    Science.gov (United States)

    Michalevicz, R; Burstein, A; Razon, N; Reider, I; Ilie, B

    1989-11-01

    Spinal epidural compression is a rare neurologic complication in patients with lymphoma. It occurs mostly in those with intermediate-grade to high-grade malignancy disease. This type of neurologic involvement has not been described in chronic lymphocytic leukemia (CLL). A patient with a long, stable CLL course developed spinal epidural compression and consequently died. The frequency of spinal epidural compression in lymphoma, according to the histologic subtypes and the considerations in making the right choice of therapy are discussed in light of the presented case.

  13. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K

    1986-01-01

    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR...

  14. Characterization of the lymphocyte substance P receptor

    Energy Technology Data Exchange (ETDEWEB)

    McGillis, J.P.; Organist, M.L.; Payan, D.G.

    1986-03-01

    Recent studies have provided evidence that tissues of the immune and reticuloendothelial systems are influenced by various hormones and neuropeptides. While the interrelationship between these peptides and the immune system, and the physiological relevance of their effects is not clear, a variety of highly specific, receptor-mediated effects has been demonstrated. One neuropeptide for which immunomodulatory effects have been identified is substance P (SP). SP acts as a potent T-cell mitogen, and enhances the mitogenic effects of PHA. Radioreceptor and FACS binding studies suggest that the SP receptor is present on a discrete population of T-cells and has a Kd of 0.87 nM and a density of 24,000. Studies have been initiated to biochemically characterize the lymphocyte SP receptor on IM-9 lymphoblasts. (/sup 125/I)-labeled SP was covalently crosslinked to the receptor using disuccinimidyl suberate and solubilized. Two radioactive bands of m.w. 55,000 and 33,000 were seen when the solubilized crosslinked receptor was electrophoresed on SDS gels. The authors are currently using a combination of HPLC immunoaffinity and reverse-phase chromatography to purify the receptor. The initial studies indicate that the receptor can be purified to homogeneity using this approach. The biochemical characterization of this receptor should provide a better understanding of its importance not only on lymphocytes, but in other tissues as well.

  15. Benzene metabolites induce apoptosis in lymphocytes.

    Science.gov (United States)

    Martínez-Velázquez, M; Maldonado, V; Ortega, A; Meléndez-Zajgla, J; Albores, A

    2006-08-01

    Benzene is an important environmental pollutant with important health implications. Exposure to this aromatic hydrocarbon is associated with hematotoxicity, and bone marrow carcinogenic effects. It has been shown that benzene induces oxidative stress, cell cycle alterations, and programmed cell death in cultured cells. Hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. Nevertheless, there are no reports on the cellular effects of reactive intermediates derived from hepatic metabolism of benzene. Thus, the goal of this project was to determine the cellular alterations of benzene metabolites produced by the cultured hepatic cell line HepG2. Supernatants collected from these cells were applied to a culture of freshly isolated lymphocytes. A higher decrease in cell viability was found in cells exposed to these supernatants than to unmetabolized benzene. This viability decrease was due to apoptosis, as determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay and internucleosomal fragmentation of DNA. When supernatants were analyzed by HPLC, we found that not all the hydrocarbon was biotransformed, since a 28 microM concentration (37%) remained. The only metabolite found in the culture medium was muconic acid. The present results show that muconic acid derived from benzene metabolism is able to cooperate with the pollutant for the induction of apoptosis in rat lymphocytes.

  16. Spondylarthritis in the absence of B lymphocytes.

    Science.gov (United States)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P

    2008-03-01

    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.

  17. Secondary autoimmune cytopenias in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rogers, Kerry A; Woyach, Jennifer A

    2016-04-01

    Secondary autoimmune cytopenias in chronic lymphocytic leukemia are distinct clinical entities that require specific management. These autoimmune disorders have a complex pathogenesis that involves both the leukemic cells and the immune environment in which they exist. The mechanism is not the same in all cases, and to varying degrees involves the chronic lymphocytic leukemia (CLL) cells in antibody production, antigen presentation, and stimulation of T cells and bystander polyclonal B cells. Diagnosis of autoimmune cytopenias can be challenging as it is difficult to differentiate between autoimmunity and bone marrow failure due to disease progression. There is a need to distinguish these causes, as prognosis and treatment are not the same. Evidence regarding treatment of secondary autoimmune cytopenias is limited, but many effective options exist and treatment can be selected with severity of disease and patient factors in mind. With new agents to treat CLL coming into widespread clinical use, it will be important to understand how these will change the natural history and treatment of autoimmune cytopenias.

  18. The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N

    1987-01-01

    Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

  19. Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2017-10-09

    B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Diffuse Well-differentiated Lymphocytic Lymphoma; B Cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; B-Cell Diffuse Lymphoma

  20. 9 CFR 113.42 - Detection of lymphocytic choriomeningitis contamination.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Detection of lymphocytic choriomeningitis contamination. 113.42 Section 113.42 Animals and Animal Products ANIMAL AND PLANT HEALTH... contamination. The test for detection of lymphocytic choriomeningitis (LCM) virus provided in this section...

  1. Lymphocytes and liver fibrosis in HIV & HCV coinfection

    NARCIS (Netherlands)

    Feuth, M.|info:eu-repo/dai/nl/371501547

    2014-01-01

    Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat

  2. Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

    African Journals Online (AJOL)

    EL-HAKIM

    is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism ... Patients were subjected to clinical evaluation with special ... The percentage of CD95 on T-lymphocytes could not be ..... Correlation between CD3 lymphocytes and CD95 antigen .... control.36 On the other hand, Tchórzewski et al.1.

  3. Effect of praziquantel on human lymphocyte proliferation in vitro

    DEFF Research Database (Denmark)

    Odum, Niels; Theander, T G; Bygbjerg, I C

    1984-01-01

    The antischistosomal drugs tartar emetic and niridazole exert immunosuppression both in vitro and in vivo. In the present study the influence of praziquantel (Biltricide), a potent schistosomicidal drug, on human lymphocyte proliferation in vitro was investigated. Praziquantel 80 micrograms...... no suppressive effect on human lymphocyte proliferation in vitro....

  4. Carotenoid levels in human lymphocytes, measured by Raman microspectroscopy

    NARCIS (Netherlands)

    Ramanauskaite, R B; SegersNolten, IGMJ; DeGrauw, K J; Sijtsema, N M; VanderMaas, L; Greve, J; Otto, C; Figdor, C G

    1997-01-01

    Carotenoid levels in lymphocytes obtained from peripheral blood of healthy people have been investigated by Raman microspectroscopy. We observed that carotenoids are concentrated in so-called ''Gall bodies''. The level of carotenoids in living human lymphocytes was found to be age-dependent and to d

  5. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P;

    1989-01-01

    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control do...

  6. Lymphocytes and liver fibrosis in HIV & HCV coinfection

    NARCIS (Netherlands)

    Feuth, M.

    2014-01-01

    Coinfection with HIV has an important impact on immunity against hepatitis C virus (HCV). In the present dissertation, phenotypes of lymphocytes derived from the peripheral blood of HCV-infected patients were studied into detail, with special attention to changes in phenotype of lymphocytes associat

  7. Lymphocytes as a neural probe : potential for studying psychiatric disorders

    NARCIS (Netherlands)

    Gladkevich, A; Kauffman, HF; Korf, J

    There is an increasing body evidence pointing to a close integration between the central nervous system (CNS) and immunological functions with lymphocytes playing therein a central role. The authors provide arguments to consider blood lymphocytes as a convenient probe of-an albeit-limited number of

  8. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...

  9. Endothelial PI 3-kinase activity regulates lymphocyte diapedesis.

    Science.gov (United States)

    Nakhaei-Nejad, Maryam; Hussain, Amer M; Zhang, Qiu-Xia; Murray, Allan G

    2007-12-01

    Lymphocyte recruitment to sites of inflammation involves a bidirectional series of cues between the endothelial cell (EC) and the leukocyte that culminate in lymphocyte migration into the tissue. Remodeling of the EC F-actin cytoskeleton has been observed after leukocyte adhesion, but the signals to the EC remain poorly defined. We studied the dependence of peripheral blood lymphocyte transendothelial migration (TEM) through an EC monolayer in vitro on EC phosphatidylinositol 3-kinase (PI 3-kinase) activity. Lymphocytes were perfused over cytokine-activated EC using a parallel-plate laminar flow chamber. Inhibition of EC PI 3-kinase activity using LY-294002 or wortmannin decreased lymphocyte TEM (48 +/- 6 or 34 +/- 7%, respectively, vs. control; mean +/- SE; P structure" after intercellular adhesion molecule-1 ligation, whereas this was inhibited by jasplakinolide treatment. A similar fraction of lymphocytes migrated on control or LY-294002-treated EC and localized to interendothelial junctions. However, lymphocytes failed to extend processes below the level of vascular endothelial (VE)-cadherin on LY-294002-treated EC. Together these observations indicate that EC PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier.

  10. Effect of Schistosoma haematobium and N-butyl-N-(4-hydroxybutyl)nitrosamine on the development of urothelial neoplasia in the baboon.

    Science.gov (United States)

    Hicks, R M; James, C; Webbe, G

    1980-11-01

    Experiments were conducted to determine whether bladder cancer would develop in primates (Papio sp.) infected with S. haematobium and concurrently exposed to low initiating doses of the bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). To control for the systemic effects of schistosomiasis, 5 baboons were infected with S. mansoni, which does not lay its eggs in the bladder wall; to control for the effect of the carcinogen alone, 5 others were treated with BBN alone at the rate of 5 or 50 mg/kg per week for the duration of the experiment. Five animals were infected with S. haematobium and had no further treatment, and the main experimental group of 10 baboons was infected with S. haematobium and also treated weekly with 5 mg/kg BBN for up to 2½ years. Four of the 10 animals in the last group, but none in the three control groups developed neoplastic disease of the urothelium. Four animals with S. haematobium plus BBN treatment developed in situ carcinoma in the bladder (3 latent adenomatous lesions and 1 more advanced papillary tumour) and 2 of these animals plus 1 other had slightly dysplastic urothelial endophytic papillary growths of the ureter which penetrated the muscle layer. By contrast, none of the control animals developed urothelial carcinomas, though 4/5 of those with S. haematobium infection alone had inflamed bladders with polypoid lesions, and one individual had endophytic papillary hyperplasia of the ureter. The animals were killed after 2½ years while still relatively immature or adolescent, and it is possible that had they been allowed to survive longer some of the BBN-only group would have developed bladder cancer, and more of the latent lesions seen in the BBN + schistosomiasis group would have progressed to invasive carcinoma. It is postulated that, in this model for human bilharzial bladder cancer, schistosomiasis supplies the proliferative stimulus necessary to accelerate cancer growth from latent tumour foci produced by

  11. Lymphocytes in patients with psoriasis promote proliferation of keratinocytes

    Institute of Scientific and Technical Information of China (English)

    DENG An-mei; ZHONG Ren-qian; CHEN Sun-xiao; ZHOU Ye; KONG Xian-tao

    2002-01-01

    Objective: To analyze the effect of lymphocytes on proliferation of keratinocytes in patients with psoriasis. Methods: Lymphocytes in lesion and peripheral blood were isolated and amplified, then cultured together with normal keratinocytes. By MTT method, the living cells were quantified in the mixed culture.Results: Compared with normal controls, lymphocytes from lesion and peripheral blood of psoriasis both promote the proliferation of keratinocytes (P<0. 01 and P<0. 05 respectively). The concentrations of IL-2 and IFN-γ in the mixture of lesion lymphocytes and keratinocytes were significantly higher than that of controls.Tripterygium glycosides inhibited this promotion. Conclusion: Lymphocytes in patients with psoriasis (mainly Thl cell) play an important role in proliferation of keratinocytes. This psoriasis cell model is useful for studies on signal transduction in psoriasis.

  12. Lymphocyte respiration in children with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Aburawi Elhadi H

    2012-12-01

    Full Text Available Abstract Background This study measured lymphocyte mitochondrial O2 consumption (cellular respiration in children with trisomy 21. Methods Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O2] was determined as a function of time from the phosphorescence decay rates (1/τ of Pd (II-meso-tetra-(4-sulfonatophenyl-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O2] declined linearly with time, confirming the zero-order kinetics of O2 conversion to H2O by cytochrome oxidase. The rate of respiration (k, in μM O2 min-1, thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. Results For control children (age = 8.8 ± 5.6 years, n = 26, the mean (± SD value of kc (in μM O2 per min per 107 cells was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61. For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26, the values of kc were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80, pp6.1 mU/L. Fourteen of 26 (54% children with trisomy 21 had kc values of 0.20 to 0.60 (i.e., kc positively correlated with body-mass index (BMI, R >0.302, serum creatinine (R >0.507, blood urea nitrogen (BUN, R >0.535 and albumin (R >0.446. Conclusions Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.

  13. The Danish National Chronic Lymphocytic Leukemia Registry

    Directory of Open Access Journals (Sweden)

    da Cunha-Bang C

    2016-10-01

    Full Text Available Caspar da Cunha-Bang,1 Christian Hartmann Geisler,2 Lisbeth Enggaard,3 Christian Bjørn Poulsen,4 Peter de Nully Brown,2 Henrik Frederiksen,5 Olav Jonas Bergmann,6 Elisa Jacobsen Pulczynski,7 Robert Schou Pedersen,8 Linda Højberg Nielsen,9 Ilse Christiansen,10 Carsten Utoft Niemann2 1Department of Internal Medicine, Roskilde Hospital, Roskilde, Denmark; 2Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 3Department of Hematology, Herlev Hospital, Herlev, Denmark; 4Department of Hematology, Roskilde Hospital, Roskilde, Denmark; 5Department of Hematology, Odense University Hospital, Odense, Denmark; 6Department of Hematology, Vejle Hospital, Vejle, Denmark; 7Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 8Department of Hematology, Holstebro Hospital, Holstebro, Denmark; 9Department of Hematology, Esbjerg Hospital, Esbjerg, Denmark; 10Department of Hematology, Aalborg University Hospital, Aalborg, Denmark Aim: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL in Denmark. Secondarily, to evaluate adherence to national guidelines and to provide source data for research purposes. Study population: All patients diagnosed with CLL in Denmark from 2008 onward are included in the registry. Patients are followed in one of nine hematology centers. All centers participate in the registry and are all obliged to collect data. Main variables: Predefined data are collected at the time of diagnosis, and follow-up at the time of significant events: treatment, progression, transplantation, and death. Parameters included in the International Workshop on Chronic Lymphocytic Leukaemia criteria for diagnosis, and for decision on treatment initiation as well as characteristics included in the CLL

  14. Mitochondrial apoptosis of lymphocyte is induced in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Xu Hui; Chen Yanbo; Li Yanxiang; Xia Fangzhen; Han Bing; Zhang Huixin; Zhai Hualing

    2014-01-01

    Background Lymphocyte function and homeostasis is associated with immune defence to infection.Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia.The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.Methods Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study.Annexin V and propidiumiodide (Pl) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry.Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2,cytochrome c (Cyt-C),caspase-9 and caspase-3 were analyzed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR).Results Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P <0.05).Transmission electron microscopy showed lymphocyte shrinkage and breakage,chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9,caspase-3 and Cyt-C were elevated (P <0.05) in diabetic patients.Conclusions The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population.Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.

  15. Expression of protooncogenes during lymphocyte activation by growth factors.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

  16. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

    Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole

    2013-01-01

    . RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...... of cobalt ions in particular on T-cells with 2-year whole-blood cobalt regression coefficients for CD3+ of -0.10 (95% CI: -0.16 to -0.04) × 10(9) cells/parts per billion (ppb), for CD3+CD4+ of -0.06 (-0.09 to -0.03) × 10(9) cells/ppb, and for CD3(+)CD8(+) of -0.02 (-0.03 to -0.00) × 10(9) cells/ppb...

  17. Fungal natural products targeting chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Kildgaard, Sara; Knudsen, Peter Boldsen

    2012-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults from the western world. No curative treatments of CLL are presently known so the treatment strategy today is primarily to prolong patient survival,1 why we have initiated new activities towards discovery of novel compounds...... with potential tumor specificity. Our starting point is a diverse fungal collection of thousands of Penicillium and Aspergillus species. These fungi have proven to be a very rich source of various bioactive compounds and yet our dereplication investigations have demonstrated that there are still numerous unknown...... compounds to be identified within these species. Until now we have found that 11 out of 289 fungal extracts are active against CLL cells. Using our established chemotaxonomic discovery approach we have dereplicated and fractionated these extracts to track the activity into single fractions/compounds.2...

  18. Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Zusen Fan; Qixiang Zhang

    2005-01-01

    Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell.The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

  19. Role of angiogenesis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Letilovic, Tomislav; Vrhovac, Radovan; Verstovsek, Srdan; Jaksic, Branimir; Ferrajoli, Alessandra

    2006-09-01

    Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently. An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications.

  20. Chronic lymphocytic leukemia in African Americans.

    Science.gov (United States)

    Coombs, Catherine C; Falchi, Lorenzo; Weinberg, J Brice; Ferrajoli, Alessandra; Lanasa, Mark C

    2012-11-01

    Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States with almost 4390 attributable deaths per year. Epidemiologic data compiled by the Surveillance, Epidemiology and End Results (SEER) program identifies important differences in incidence and survival for African Americans with CLL. Although the incidence of CLL is lower among African Americans than among Caucasians (4.6 and 6.2 per 100 000 men, respectively), age-adjusted survival is inferior. African American patients with CLL are almost twice as likely to die from a CLL-related complication in the first 5 years after diagnosis as are Caucasian patients with CLL. The biologic basis for these observations is almost entirely unexplored, and a comprehensive clinical analysis of African American patients with CLL is lacking. This is the subject of the present review.

  1. Thyroid carcinoma: immunology, irradiation, and lymphocytic infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Shull, J.H.; Sharon, N.; Victor, T.A.; Scanlon, E.F.

    1979-06-01

    Patients undergoing thyroidectomies at Evanston (I11) Hospital, during a six-month period had immunological studies performed preoperatively. No differential could be found between those with carcinoma or benign pathologic findings. T- and B-cell distribution and lymphocytic response to mitogens varied widely. Quantitative immunoglobulins showed slightly increased levels of IgG in patients wih carcinoma and thyroiditis in comparison with those patients with adenomas. Antithyroglobulin antibodies were negative in all patients. Pathology slides from 107 patients with thyroid carcinoma between 1972 and 1978 at Evanston Hospital were reviewed for the presence of thyroiditis, either focal or diffuse. It was found that 50% of all carcinomas had either diffuse or focal thyroiditis. Diffuse thyroiditis was more common in patients with no history of irradiation and papillary carcinoma, and in younger age groups.

  2. Mediastinal irradiation for chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Sawitskii, A.; Rai, K.R.; Aral, I.; Silver, R.T.; Glicksman, A.S.; Carey, R.W.; Scialla, S.; Cornell, C.J. Jr.; Seligman, B.; Shapiro, L.

    1976-12-01

    Thirty-one patients with chronic lymphocytic leukemia were treated with mediastinal radiation. In none of the patients was complete remission achieved; either partial remission or clinical improvement was achieved in 52 percent, but the duration of response was short. The response rate was 77 percent for the patients receiving a total radiation dose greater than 3,000 rads and 45 percent for those receiving less than 3,000 rads. Severe life-threatening toxicity was noted in 11 patients and seven of these patients died; two patients died with progressive disease. Severe toxicity was manifested by one or more of the following: bone marrow aplasia, pancytopenia, gram-negative sepsis, generalized herpes zoster and severe esophagitis. Neither the total dose of radiation nor the dose per week correlated with the severity of reaction or death.

  3. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  4. Epigenetic repolarization of T lymphocytes from chronic lymphocytic leukemia patients using 5-aza-2'-deoxycytidine.

    Science.gov (United States)

    Dubovsky, Jason A; Powers, John J; Gao, Yang; Mariusso, Luis F; Sotomayor, Eduardo M; Pinilla-Ibarz, Javier A

    2011-09-01

    T cell immune dysfunction has an important role in the profound immune suppression that characterizes chronic lymphocytic leukemia (CLL). Improper polarization of T cells has been proposed as one of the mechanism involved. Mounting data implicates chromatin regulation, namely promoter methylation, in the plasticity of naïve human T cells. Recent in vitro evidence indicates that this plasticity may be phenotypically altered by using methylation inhibitors which are approved for clinical use in certain types of cancer. These results beg the question: can the ineffective polarization of T lymphocytes in the context of CLL be effectively modulated using methylation inhibitors in a sustainable therapeutic fashion? To answer this question our laboratory has studied the effects of 5-aza-2'-deoxycytidine (5A2) in helper and cytotoxic T lymphocytes from healthy donors and CLL patients in well characterized molecular and epigenetic signaling pathways involved in effective polarization. Moreover, we sought to investigate the consequences of methylation inhibitor treatment on lymphocyte survival, activation intensity, and naïve cell polarization. Our data indicates that 5A2 treatment can depolarize Th2 cells to effectively secrete interferon gamma, signal via T-bet, and achieve demethylation of critical Th1 specific promoters. Moreover, we demonstrate that 5A2 can force Th1 polarization of naïve T cells despite a strong IL-4 stimuli and a lack of IL-12. In conclusion our data seeks to define a modality in which improper or ineffective T cell polarization can be altered by 5AZA and could be incorporated in future therapeutic interventions.

  5. [Lymphocytic duodenosis: etiological study and clinical presentations].

    Science.gov (United States)

    Santolaria, Santos; Dominguez, Manuel; Alcedo, Javier; Abascal, Manuel; García-Prats, M Dolores; Marigil, Miguel; Vera, Jesus; Ferrer, Margarita; Montoro, Miguel

    2013-11-01

    Lymphocytic duodenosis (LD) is a characteristic lesion in the initial phases of celiac disease (CD) but can be associated with many other entities. The aim of this study was to evaluate the prevalence of distinct causes of LD and possible differences in clinical presentation according to etiology. A retrospective study was performed that included 194 patients diagnosed with LD (more than 25 intraepithelial lymphocytes per 100 epithelial cells). A preestablished strategy to evaluate the cause of the disease was followed that included celiac serology (antitransglutaminase antibodies), HLA-DQ2/DQ8 genotypes, diagnosis of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO). Diagnosis of CD was established on the basis of clinical and histological response to a gluten-free diet in patients with positive serology or compatible findings on HLA-DQ2 (at least one of the alleles) or -DQ8 (both alleles) study. The most frequent cause of LD was CD (39%), followed by SBBO (22%), H.pylori (14%), CD and SIBO (12%), and other causes (13%). Most of the patients (83%) had a compatible HLA-DQ2 or -DQ8 genotype. In these patients, the most frequent diagnosis was CD (46%), while in the absence of HLA-DQ2/DQ8, the most frequent diagnoses were SIBO (44%) and H. pylori (22%). CD was the most frequent diagnosis in patients referred for dyspepsia, diarrhea and anemia, while H. pylori was the most frequent diagnosis in patients with abdominal pain. The most common causes of LD in our environment are CD, followed by SIBO and H. pylori infection. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  6. Lymphocytes subsets in children with febrile convulsions.

    Science.gov (United States)

    Tuncer, Oğuz; Karaman, Sait; Caksen, Hüseyin; Oner, Ahmet Faik; Odabas, Dursun; Yilmaz, Cahide; Atas, Bülent

    2007-07-01

    In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p .05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.

  7. Multiple dysfunctions in developmental and activational stages of T lymphocytes, B lymphocytes and monocytes in ARC and AIDS patients.

    Science.gov (United States)

    Sei, Y; Tsang, P H; Petrella, R J; Bekesi, J G

    1987-11-01

    Peripheral blood leukocytes from ARC and AIDS patients were examined before and after phytohemagglutinin (PHA) stimulation by dual color flow cytometry and monoclonal antibodies which identify developmental and activational stages of T lymphocytes, B cells and monocytes. There was a persistent elevation in the total number of circulating Ia+ lymphocytes with progressive selection for B1+ Ia+ lymphocytes and T suppressor cells and a concurrent reduction in the antigen-presenting monocytes. Following PHA stimulation there was a marked decrease in all subsets of Ia+ lymphocytes and monocytes. These results indicate (a) multicellular dysfunctions in the immunosurveillance mechanisms in AIDS, and (b) that many functional subsets of circulating lymphocytes and monocytes were already activated and therefore poorly responsive to additional antigenic or mitogenic stimuli.

  8. Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

    2011-10-25

    N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

  9. Characterisation of [¹¹C]PR04.MZ in Papio anubis baboon: a selective high-affinity radioligand for quantitative imaging of the dopamine transporter.

    Science.gov (United States)

    Riss, Patrick J; Hooker, Jacob M; Shea, Colleen; Xu, Youwen; Carter, Pauline; Warner, Donald; Ferrari, Valentina; Kim, Sung-Won; Aigbirhio, Franklin I; Fowler, Joanna S; Roesch, Frank

    2012-01-01

    N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4'-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [(11)C]PR04.MZ ([(11)C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [(11)C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f(P)), plasma input functions and metabolic degradation of the radiotracer [(11)C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V(T)) and non-displaceable binding potentials (BP(ND)) for various brain regions and the blood were obtained from kinetic modelling. [(11)C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Pitch (F0) and formant profiles of human vowels and vowel-like baboon grunts: The role of vocalizer body size and voice-acoustic allometry

    Science.gov (United States)

    Rendall, Drew; Kollias, Sophie; Ney, Christina; Lloyd, Peter

    2005-02-01

    Key voice features-fundamental frequency (F0) and formant frequencies-can vary extensively between individuals. Much of the variation can be traced to differences in the size of the larynx and vocal-tract cavities, but whether these differences in turn simply reflect differences in speaker body size (i.e., neutral vocal allometry) remains unclear. Quantitative analyses were therefore undertaken to test the relationship between speaker body size and voice F0 and formant frequencies for human vowels. To test the taxonomic generality of the relationships, the same analyses were conducted on the vowel-like grunts of baboons, whose phylogenetic proximity to humans and similar vocal production biology and voice acoustic patterns recommend them for such comparative research. For adults of both species, males were larger than females and had lower mean voice F0 and formant frequencies. However, beyond this, F0 variation did not track body-size variation between the sexes in either species, nor within sexes in humans. In humans, formant variation correlated significantly with speaker height but only in males and not in females. Implications for general vocal allometry are discussed as are implications for speech origins theories, and challenges to them, related to laryngeal position and vocal tract length. .

  11. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  12. Fecal microbial diversity and putative function in captive western lowland gorillas (Gorilla gorilla gorilla), common chimpanzees (Pan troglodytes), Hamadryas baboons (Papio hamadryas) and binturongs (Arctictis binturong).

    Science.gov (United States)

    McKenney, Erin A; Ashwell, Melissa; Lambert, Joanna E; Fellner, Vivek

    2014-11-01

    Microbial populations in the gastrointestinal tract contribute to host health and nutrition. Although gut microbial ecology is well studied in livestock and domestic animals, little is known of the endogenous populations inhabiting primates or carnivora. We characterized microbial populations in fecal cultures from gorillas (Gorilla gorilla gorilla), common chimpanzees (Pan troglodytes), Hamadryas baboons (Papio hamadryas) and binturongs (Arctictis binturong) to compare the microbiomes associated with different gastrointestinal morphologies and different omnivorous feeding strategies. Each species was fed a distinct standardized diet for 2 weeks prior to fecal collection. All diets were formulated to reflect the species' feeding strategies in situ. Fresh fecal samples were pooled within species and used to inoculate in vitro batch cultures. Acetate, propionate, butyrate and valerate were measured after 24 h of incubation. Eubacterial DNA was extracted from individual fecal samples, pooled, and the cpn60 gene region was amplified and then sequenced to identify the major eubacterial constituents associated with each host species. Short chain fatty acids (P < 0.001) and methane (P < 0.001) were significantly different across species. Eubacterial profiles were consistent with fermentation data and suggest an increase in diversity with dietary fiber. © 2014 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  13. Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

    Science.gov (United States)

    Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Gilchrist, James J; Graham, Stephen M; Pensulo, Paul; Mwimaniwa, Grace; Banda, Meraby; Taylor, Terrie E; Molyneux, Elizabeth E; Drayson, Mark T; Ward, Steven A; Molyneux, Malcolm E; MacLennan, Calman A

    2015-11-18

    Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69(+) NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4(+) lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria. Copyright © 2016 Mandala et al.

  14. T- and B-lymphocyte chimerism in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Niblack, G.D.; Kateley, J.R.; Gengozian, N.

    1977-01-01

    Marmosets are natural blood chimeras, this condition resulting from the high frequency of fraternal twinning and the consistent development of placental vascular anastomoses between the two embryos. Identification of chimerism by sex-chromosome analysis of cultured blood lymphocytes provided a means of determining the proportion of chimerism among T and B lymphocytes. Peripheral blood lymphocytes were enriched for T or B cells by filtration through a nylon column (yields >95% T-cells) or inactivation of T lymphocytes by treatment with a goat anti-marmoset thymocyte antiserum in the presence of complement (yields >95% B cells). Mitogenic stimulation of these separated, enriched cell populations yielded metaphase plates which could be scored for percentage male and female cells. Tests on five different blood chimeras showed the T- and B-lymphocyte chimerism to be the same. Stimulation of blood lymphocytes with cells from another species of marmoset in a mixed lymphocyte culture test revealed the chimeric T-cell response (i.e., host and co-twin cells) to be similar to that obtained with a mitogenic lectin. The demonstration of equivalent T- and B-cell chimerism in these animals suggests derivation of these cells from a common stem cell pool and the response of both T-cell populations to an antigenic stimulus in proportions similar to their percentage chimerism suggests complete immunologic tolerance exists in this species for co-twin histocompatibility antigens.

  15. Evaluation of lymphocyte subgroups in children with subacute sclerosing panencephalitis.

    Science.gov (United States)

    Yilmaz, C; Yuca, S A; Yilmaz, N; Oner, A F; Caksen, H

    2009-01-01

    The aetiology of subacute sclerosing panencephalitis (SSPE) remains to be fully elucidated, although it follows infection with a hypermutant defective M-protein measles virus. This study analysed peripheral blood lymphocyte subgroups to determine their role in the pathophysiology of SSPE. It included 22 children with SSPE aged 2 - 15 years (patient group) and 22 age- and gender-matched healthy children (control group). In children or= 6 years old, there were no significant differences in the lymphocyte subgroups. In conclusion, these findings suggest that a low CD4(+) lymphocyte count might be responsible for SSPE in younger children.

  16. Influence of intravenously administered lidocaine on cerebral blood flow in a baboon model standardized under controlled general anaesthesia using single-photon emission tomography and technetium-99m hexamethylpropylene amine oxime

    Energy Technology Data Exchange (ETDEWEB)

    Dormehl, I.C. (AEC Inst. for Life Sciences, Pretoria Univ. (South Africa)); Lipp, M.D.W. (Klinik fuer Anaesthesiologie, Johannes Gutenberg Univ., Mainz (Germany)); Hugo, N. (AEC Inst. for Life Sciences, Pretoria Univ. (South Africa)); Daublaender, M. (Stadtkrankenhaus Landau, Abt. fuer Mund-, Kiefer- und Gesichtschirurgie (Germany)); Picard, J.A. (H.A. Grove Research Centre, Pretoria (South Africa))

    1993-11-01

    The baboon under general anaesthesia as a model to assess druginduced cerebral blood flow changes ([Delta] CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaestesia-related influencing factors, such as P[sub a]CO[sub 2] changes. The model sought in this study and described here allows control of P[sub a]CO[sub 2], in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functioal dependence of [Delta] CBF vs [Delta] P[sub a]CO[sub 2], using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to P[sub a]CO[sub 2] changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HMPAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between D CBF and the ensuing fall in P[sub a]CO[sub 2] deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate. (orig.)

  17. CD3 immunohistochemical staining in diagnosis of lymphocytic colitis

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Engel, Ulla; Holck, Susanne

    2016-01-01

    Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Traditionally, MC encompasses the 2 subgroups lymphocytic colitis (LC) and collagenous colitis, but recently, an additional subgroup, MC incomplete, has been introduced. Distinguishing between the subgroups relies exclusively...

  18. Prognostic significance of serum immunoglobulin pareprotein in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨舒

    2012-01-01

    Objective To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia(CLL) ,and to explore its clinical associated laboratory features and prognostic implication. Methods Serum protein electrophoresis and immunofixation

  19. Lymphocyte apoptosis: role of uremia and permeability of dialysis membrane.

    Science.gov (United States)

    Soriano, Sagrario; Martín-Malo, Alejandro; Carracedo, Julia; Ramírez, Rafael; Rodríguez, Mariano; Aljama, Pedro

    2005-01-01

    Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used as controls. At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 +/- 6.9%) as compared with Non-D (7.2 +/- 2.8%; p dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.

  20. Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Guzman, Roberto E; Radi, Zaher A

    2007-02-01

    Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T-cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution.

  1. The nature of the refractive granules in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, N.P. Jr.; Hempelmann, L.H. [Los Alamos Scientific Lab., NM (United States)

    1949-04-19

    The number of refractive bodies in human lymphocytes increases in persons chronically exposed to low level doses of ionizing radiation. The observations of the optical properties, the histochemistry, and the method of formation of these bodies are described.

  2. Psychopatholgy, fundamental assumptions and CD-4 T lymphocyte ...

    African Journals Online (AJOL)

    in HIV-positive patients were associated with lower CD4 T-lymphocyte counts. Method: Self-rating .... depression) were excluded from participation. For comparison ... Examination (MMSE) and the HIV Dementia Scale (HDS). The. MMSE is the ...

  3. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-01-01

    Full Text Available

    Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles.

    Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  4. INFECTIOUS COMPLICATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    AnnaMaria Nosari

    2012-11-01

    Full Text Available Infectious complications have been known to be a major cause of morbidity and mortality in CLL patients who are predisposed to infections because of both the humoral immunodepression inherent to hematologic disease, which is related to stage and duration of CLL, and to further immunosuppression related to therapy. The majority of infections in CLL patients treated with alkilating agents is of bacterial origin. The immunodeficiency and natural infectious history of alkylator-resistant, corticosteroid-treated patients appears to have changed with the administration of purine analogs, which has been complicated by very severe and unusual infections and also more viral infections due to sustained reduction of CD4-positive T lymphocytes. The following introduction of monoclonal antibody therapies, in particular alemtuzumab, further increased the immunodepression, increasing also infections which appeared more often in patients with recurrent neutropenia due to chemotherapy cycles. Epidemiological data regarding fungal infections in lymphoproliferative disorders are scarce. Italian SEIFEM group in a retrospective multicentre study regarding CLL patients reported an incidence of mycoses 0.5%; however, chronic lymphoproliferative disorders emerged as second haematological underlying disease after acute leukemia in a French study on aspergillosis; in particular CLL with aspergillosis accounted for a third of these chronic lymphoproliferative diseases presenting mould infection.

  5. Leptomeningeal disease in chronic lymphocytic leukemia.

    Science.gov (United States)

    Lange, C P E; Brouwer, R E; Brooimans, R; Vecht, Ch J

    2007-12-01

    Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western hemisphere, with an annual incidence of 3:100000. Commonly patients are asymptomatic but not rarely disease progression occurs in the setting of lymphadenopathy and extensive leukemic burden. Leptomeningeal involvement in patients with CLL is infrequent, with presenting symptoms of headache (23%), acute or chronic changes in mental status (28%), cranial nerve abnormalities (54%) including optic neuropathy (28%), weakness of lower extremities (23%) and cerebellar signs (18%). In this report, we discuss a CLL patient with leptomeningeal involvement, who presented with neurological symptoms as the first clinical sign, and a diagnosis of leptomeningeal was made based on CSF cytology and flow cytometry. Treatment consisted of radiation therapy and intrathecal chemotherapy with arabinoside-cytosine and systemic chemotherapy. On the basis of this patient-report together with 37 other previously reported cases, the clinical characteristics together with treatment options and outcome of leptomeningeal involvement in CLL are reviewed. Our case together with data from the literature indicate that a timely diagnosis and intensive treatment of leptomeningeal disease of CLL may lead to longstanding and complete resolution of neurological symptoms.

  6. Sampling site matters when counting lymphocyte subpopulations.

    Directory of Open Access Journals (Sweden)

    Benson Ogunjimi

    Full Text Available Clinical and scientific work routinely relies on antecubital venipunctures for hematological, immunological or other analyses on blood. This study tested the hypothesis that antecubital veins can be considered to be a good proxy for other sampling sites. Using a hematocytometer and a flow cytometer, we analyzed the cell counts from samples coming from the radial artery, the dorsal hand veins and the antecubital veins from 18 volunteers. Most surprisingly, we identified the greatest difference not to exist between arterial and venous circulation, but between the distal (radial artery & dorsal hand veins and proximal (antecubital veins sampling sites. Naïve T cells had a higher cell count distally compared to proximally and the reverse was true for effector memory T cells. Despite these differences there were high correlations between the different sampling sites, which partially supports our initial hypothesis. Our findings are crucial for the future design and interpretation of immunological research, and for clinical practice. Furthermore, our results suggest a role for interval lymph nodes in the trafficking of lymphocytes.

  7. Richter Syndrome in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Vitale, Candida; Ferrajoli, Alessandra

    2016-02-01

    The term Richter syndrome (RS) indicates the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma. RS is a rare complication with an aggressive clinical course, bearing an unfavorable prognosis. In the majority of cases, CLL transforms into RS as diffuse large B cell lymphoma (DLBCL), and a clonal relation between the two processes can be found. However, clonally unrelated RS can occur and transformations to other histologies beside DLBCL have been described. Recent data have shed some light on genetic characteristics that can influence and drive the transformation from CLL to RS. This molecular information has not been translated yet into significant treatment advances, and currently the therapy regimens for RS continue to rely on intensive chemotherapy combinations followed by stem cell transplant in suitable candidates. Based on the rapid pace of discoveries in the field of hematological malignancies and on the recent revolution in the therapeutic landscape for CLL and B cell lymphomas, new therapeutic options for RS might be available in the upcoming years.

  8. Tumor infiltrating lymphocytes in ovarian cancer.

    Science.gov (United States)

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

  9. Isochromosome 17q in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Eyad Alhourani

    2015-01-01

    Full Text Available In chronic lymphocytic leukemia (CLL, presence of acquired cytogenetic abnormalities may help to estimate prognosis. However, deletion of TP53 gene, which is associated with an aggressive course of the disease and poor prognosis along with a lack of response to treatment, is one of the alterations which may escape cytogenetic diagnoses in CLL. Thus, other techniques have emerged such as interphase fluorescence in situ hybridization (iFISH. Deletion of TP53 may but must not go together with the formation of an isochromosome i(17q; surprisingly this subgroup of patients was not in the focus of CLL studies yet. This study was about if presence of i(17q could be indicative for a new subgroup in CLL with more adverse prognosis. As a result, TP53 deletion was detected in 18 out of 150 (12% here studied CLL cases. Six of those cases (~33% had the TP53 deletion accompanied by an i(17q. Interestingly, the cases with i(17q showed a tendency towards more associated chromosomal aberrations. These findings may be the bases for follow-up studies in CLL patients with TP53 deletion with and without i(17q; it may be suggested that the i(17q presents an even more adverse prognostic marker than TP53 deletion alone.

  10. Targeting CD20 in chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Nahas MR

    2015-03-01

    Full Text Available Myrna R Nahas, Jon E ArnasonBeth Israel Deaconess Medical Center, Boston, MA, USAAbstract: Chronic lymphocytic leukemia (CLL, the most common leukemia in adults, is standardly managed with chemotherapy in combination with the anti-CD20 antibody rituximab. In this review, we discuss the history, use, and evolution of rituximab in the treatment of CLL and explore the next generation CD20 antibodies ofatumumab and obinutuzumab with a focus on recent clinical trials. Increased understanding of the importance of B cell receptor (BCR signaling in CLL has resulted in the development of several drugs with significant clinical activity that are ideally suited for combination with CD20 therapy as is being currently explored. Moving forward, these developments have the potential to result in treatment regimens that do not include traditional chemotherapeutic agents, which is of particular importance in CLL given the late onset of diagnosis and potential frailty of the patients.Keywords: CLL, monoclonal antibody, rituximab, ofatumumab, obinutuzumab

  11. SUBTYPES OF B LYMPHOCYTES IN PATIENTS WITH AUTOIMMUNE HEMOCYTOPENIA

    Institute of Scientific and Technical Information of China (English)

    Li-min Xing; Hai-rong Jia; Juan Sun; Chong-li Yang; Zong-hong Shao; Rong Fu; Hong Liu; Jun Shi; Lie Bai; Mei-feng Tu; Hua-quan Wang; Zhen-zhu Cui

    2007-01-01

    Objective To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters.Methods Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed.Results The quantity of CD5+B lymphocytes of AIHA/Evans syndrome (34. 64% ± 19. 81% ) or IRP patients (35.81% ±16.83% ) was significantly higher than that of normal controls (12.00% ±1.97% , P<0. 05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P > 0. 05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r = - 0. 416, P< 0. 05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r = 1. 00, P<0. 05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r = 0. 761, P< 0. 05) and platelet-associated immunoglobulin M (r = 0. 925, P< 0. 05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b = - 0. 289, P< 0. 05), but had no correlation with colony forming unit-erythroid ( r = - 0. 205, P > 0. 05 ) or colony forming unit-granulocyte-macrophage colonies ( r = -0.214, P>0.05).Conclusions The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease

  12. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure

    Directory of Open Access Journals (Sweden)

    Erdal Durmus

    2015-01-01

    Full Text Available AbstractBackground:Neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up.Methods:This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization.Results:The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01. There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001. The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average.Conclusion:NLR and PLR were higher in HF patients than in age-sex matched controls. However, NLR and PLR were not sufficient to establish a diagnosis of HF. NLR can be used to predict mortality during the follow-up of HF patients.

  13. Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia.

    Science.gov (United States)

    Mohr, Audrey; Renaudineau, Yves; Bagacean, Cristina; Pers, Jacques-Olivier; Jamin, Christophe; Bordron, Anne

    2016-05-01

    Chronic lymphocytic leukemia (CLL) is characterized by an abnormal expansion of mature B cells in the bone marrow and their accumulation in blood and secondary lymphoid organs. Tumor CLL cells share expression of various surface molecules with many subsets of B cells and have several common characteristics with regulatory B cells (B regs). However, the identification of B regs and their role in CLL remain elusive. The aim of this review is to summarize recent works regarding the regulatory and phenotypic characteristic of B regs and their associated effects on the immune system. It is also meant to highlight their potential importance with regards to the immunotherapeutic response.

  14. Concanavalin A-induced activation of lymphocytic choriomeningitis virus memory lymphocytes into specifically cytotoxic T cells

    DEFF Research Database (Denmark)

    Marker, O; Thomsen, Allan Randrup; Andersen, G T

    1977-01-01

    When spleen cells, which have been primed to Lymphocytic Choriomeningitis (LCM) virus during a primary infection several months previously, are stimulated in vitro with Con A. highly specific secondary cytotoxic effector cells are generated. The degree of cytotoxicity revealed by such Con A......-stimulated cells is higher than that of non-incubated spleen cells harvested nine days following the primary infection, and the effect is totally inhibited by anti-theta serum plus complement treatment of the effector cells immediately before the cytotoxic test....

  15. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    OpenAIRE

    Cartwright, R. A.; Bernard, S.M.; Bird, C. C.; Darwin, C. M.; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-01-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, im...

  16. Genotoxicity of the herbicide butachlor in cultured human lymphocytes.

    Science.gov (United States)

    Sinha, S; Panneerselvam, N; Shanmugam, G

    1995-08-01

    Butachlor, a pre-emergence herbicide was investigated for its ability to induce sister chromatid exchanges (SCE) and chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Mitogen-stimulated lymphocytes were treated with three different concentrations (5, 10 and 20 micrograms/ml) of butachlor for 24, 48 and 72 h. Our results indicate a dose-dependent increase in the frequency of chromosomal aberrations at 24, 48 and 72 h of treatment with butachlor. No SCE was promoted by butachlor.

  17. Biophysical aspects of T lymphocyte activation at the immune synapse

    Directory of Open Access Journals (Sweden)

    Claire eHivroz

    2016-02-01

    Full Text Available T lymphocyte activation is a pivotal step of the adaptive immune response. It requires the recognition by T-cell receptors (TCR of peptides presented in the context of major histocompatibility complex molecules (pMHC present at the surface of antigen presenting cells (APCs. T lymphocyte activation also involves engagement of co-stimulatory receptors and adhesion molecules recognizing ligands on the APC. Integration of these different signals requires the formation of a specialized dynamic structure: the immune synapse. While the biochemical and molecular aspects of this cell-cell communication have been extensively studied, their mechanical features have only recently been addressed. Yet, the immune synapse is also the place of exchange of mechanical signals. Receptors engaged on the T lymphocyte surface are submitted to many tensile and traction forces. These forces are generated by various phenomena: membrane undulation/protrusion/retraction, cell mobility or spreading and dynamic remodeling of the actomyosin cytoskeleton inside the T lymphocyte. Moreover, the TCR can both induce force development, following triggering, and sense and convert forces into biochemical signals, as a bona fide mechanotransducer. Other co-stimulatory molecules such as LFA-1, engaged during immune synapse formation, also display these features. Moreover, T lymphocytes themselves are mechanosensitive, since substrate stiffness can modulate their response. In this review, we will summarize recent studies from a biophysical perspective to explain how mechanical cues can affect T lymphocyte activation. We will particularly discuss how forces are generated during immune synapse formation; how these forces affect various aspects of T lymphocyte biology; and what are the key features of T lymphocyte response to stiffness.

  18. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

    OpenAIRE

    Thomas Walcher; Peter Bernhardt; Dusica Vasic; Helga Bach; Renate Durst; Wolfgang Rottbauer; Daniel Walcher

    2010-01-01

    Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD...

  19. The lymphocyte transformation test in allergic contact dermatitis: New opportunities.

    Science.gov (United States)

    Popple, Amy; Williams, Jason; Maxwell, Gavin; Gellatly, Nichola; Dearman, Rebecca J; Kimber, Ian

    2016-01-01

    Allergic contact dermatitis (ACD) is driven by the activation and proliferation of allergen-specific memory T-lymphocytes and is currently diagnosed by patch testing with a selected panel of chemical allergens. The lymphocyte transformation test (LTT) can be used to monitor ex vivo T-lymphocyte responses to antigens, including contact allergens. The LTT is not viewed as being an alternative to patch testing, but it does seek to reflect experimentally skin sensitization to specific chemicals. The LTT is based on stimulation in vitro of antigen-driven T-lymphocyte proliferation. That is, exposure in culture of primed memory T-lymphocytes to the relevant antigen delivered in an appropriate configuration will provoke a secondary response that reflects the acquisition of skin sensitization. The technical aspects of this test and the utility of the approach for investigation of immune responses to contact allergens in humans are reviewed here, with particular emphasis on further development and refinement of the protocol. An important potential application is that it may provide a basis for characterizing those aspects of T-lymphocyte responses to contact allergens that have the greatest influence on skin sensitizing potency and this will be considered in some detail.

  20. Lymphocyte subset reference intervals in blood donors from northeastern Brazil

    Directory of Open Access Journals (Sweden)

    ALEX J.L. TORRES

    2015-06-01

    Full Text Available The reference intervals for leukocytes and lymphocytes currently used by most clinical laboratories present limitations as they are primarily derived from individuals of North American and European origin. The objective this study was to determine reference values for peripheral blood B lymphocytes, T lymphocyte subsets (CD4+, CD8+, naïve, memory, regulatory, TCRαβ and TCRγδ+ and NK cells from blood donors in Salvador-Bahia, Brazil. Results: The proportion of included male subjects was 73.7% and the median ages of males (34 and females (35 were found to be similar. Absolute counts total lymphocytes subsets to both gender was 1,956 (1,060-4,186 cells and relative values 34%. The T CD4+ and T CD8+ lymphocytes relative values was 51% (20-62 and 24% (9-28, respectively. The most statistically significant finding observed was a higher percentage of B lymphocytes (p=0.03 in females. Commonly cited subset reference intervals were found to be consistent with values in several populations from different geographic areas.

  1. Carbon nanotubes enhance cytotoxicity mediated by human lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Zhao Sun

    Full Text Available With the expansion of the potential applications of carbon nanotubes (CNT in biomedical fields, the toxicity and biocompatibility of CNT have become issues of growing concern. Since the immune system often mediates tissue damage during pathogenesis, it is important to explore whether CNT can trigger cytotoxicity through affecting the immune functions. In the current study, we evaluated the influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The results showed that while CNT at low concentrations (0.001 to 0.1 µg/ml did not cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated cytotoxicity against multiple human cell lines. In addition, CNT increased the secretion of IFN-γ and TNF-α by the lymphocytes. CNT also upregulated the NF-κB expression in lymphocytes, and the blockage of the NF-κB pathway reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results suggest that CNT at lower concentrations may prospectively initiate an indirect cytotoxicity through affecting the function of lymphocytes.

  2. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology

    Science.gov (United States)

    Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M.; Yin, Deling; Allan Mufson, R.; Zhou, Jian-nian

    2003-01-01

    Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immunosuppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis.

  3. Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review.

    Science.gov (United States)

    Jawad, Hadeel; McCarthy, Peter; O'Leary, Gerard; Heffron, Cynthia C

    2017-10-01

    Warthin tumor is the second most common salivary gland neoplasm. It occurs more commonly in males than in females. Malignant transformation in Warthin tumor is a rare but well-recognized phenomenon; however, the development or presentation of lymphoma in a Warthin tumor is rare. An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular lymph nodes. The histological diagnosis was malignant lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, present within the stroma of a Warthin tumor, and also present within the adjacent lymph node. This case is the third reported case describing a collision of Warthin tumor and chronic lymphocytic leukemia/small lymphocytic lymphoma. It also emphasizes the importance of careful examination of the lymphoid stroma of these tumors.

  4. MHC and non-MHC genes regulate elimination of lymphocytic choriomeningitis virus and antiviral cytotoxic T lymphocyte and delayed-type hypersensitivity mediating T lymphocyte activity in parallel

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Marker, O

    1989-01-01

    The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion, indicat......The course of systemic infection with lymphocytic choriomeningitis virus was studied in mouse strains differing in the MHC or non-MHC background. Virus clearance rates differed significantly between H-2 identical strains as well as between congenic strains differing in the H-2L subregion...

  5. Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes.

    Science.gov (United States)

    Zhelev, Zhivko; Ivanova, Donika; Bakalova, Rumiana; Aoki, Ichio; Higashi, Tatsuya

    2017-01-01

    The present study demonstrates specific sensitization of leukemia lymphocytes towards anticancer drugs using melatonin and clarifies the role of reactive oxygen species (ROS) for induction of apoptosis. The study covers four conventional and 11 new-generation anticancer drugs. Four parameters were analyzed simultaneously in leukemia and normal lymphocytes treated with drug, melatonin, or their combination: cell viability, induction of apoptosis, level of reactive oxygen species (ROS), and level of protein-carbonyl products. Almost all investigated combinations of melatonin with new-generation anticancer drugs were characterized by synergistic cytotoxicity towards leukemia lymphocytes, while the combinations with conventional drugs exhibited additive or antagonistic effects on cell viability. In leukemia lymphocytes, the additive cytotoxicity of doxorubicin plus melatonin was accompanied by low levels of ROS and protein-carbonyl products, as well as by suppression of apoptosis. In normal lymphocytes, none of the studied parameters changed significantly compared to cells treated with doxorubicin only. The combinations of everolimus plus melatonin and barasertib plus melatonin exhibited impressive synergistic cytotoxic effects on leukemia lymphocytes but did not affect the viability of normal lymphocytes. In leukemia cells, the synergistic cytotoxicity was accompanied by strong induction of apoptosis but a decrease of ROS to a level below that of the control. In normal lymphocytes, these combinations did not affect the level of ROS nor of protein-carbonyl products, and did not induce apoptosis. The data suggest that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects.

  6. Chronic lymphocytic leukemia/small lymphocytic lymphoma: another neoplasm related to the B-cell follicle?

    Science.gov (United States)

    Tandon, Bevan; Swerdlow, Steven H; Hasserjian, Robert P; Surti, Urvashi; Gibson, Sarah E

    2015-01-01

    Although there has been increased attention paid to the critical nature of nodal involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), the B-cell compartment it is most closely related to and its relationship to the follicle remain uncertain. A clinicopathologic investigation of 60 extramedullary biopsies of LEF1+ CLL/SLL, including 29 cases with perifollicular/follicular (PF/F) growth, was therefore performed. A subset of PF/F cases demonstrated inner mantle zone preservation or intra-mantle zone growth. All PF/F and 16/31 other cases contained CD21+ follicular dendritic cells. No cytogenetic, IGHV mutational or gene usage differences were seen between PF/F and diffuse cases. PF/F cases were more often kappa positive (p<0.03) and had fewer involved nodal sites (p=0.0004). These findings suggest that at least a subset of bona fide CLL/SLL is related to the follicle, most likely the outer mantle zone, and that at least a subset of the diffuse cases may represent "later" disease.

  7. Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma.

    Science.gov (United States)

    Nasr, Samih H; Shanafelt, Tait D; Hanson, Curtis A; Fidler, Mary E; Cornell, Lynn D; Sethi, Sanjeev; Chaffee, Kari G; Morris, Joseph; Leung, Nelson

    2015-06-01

    Granulomatous interstitial nephritis (GIN) is an uncommon pathologic lesion encountered in 0.5% to 5.9% of renal biopsies. Drugs, sarcoidosis, and infections are responsible for most cases of GIN. Malignancy is not an established cause of GIN. Here, we report a series of 5 patients with GIN secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients were mostly elderly white males with an established history of CLL/SLL who presented with severe renal impairment (median peak serum creatinine, 7.3 mg/dL), leukocyturia, and mild proteinuria. One had nephromegaly. In 2 patients, the development and relapse of renal insufficiency closely paralleled the level of lymphocytosis. Kidney biopsy in all patients showed GIN concomitant with CLL/SLL leukemic interstitial infiltration. Granulomas were nonnecrotizing and epithelioid and were associated with giant cells. One biopsy showed granulomatous arteritis. One patient had a granulomatous reaction in lymph nodes and skin. Steroids with/without CLL/SLL-directed chemotherapy led to partial improvement of kidney function in all patients except 1 who had advanced cortical scarring on biopsy. In conclusion, we report an association between CLL/SLL and GIN. Patients typically present with severe renal failure due to both GIN and leukemic interstitial infiltration, which tends to respond to steroids with/without CLL/SLL-directed chemotherapy. The pathogenesis of GIN in this clinical setting is unknown but may represent a local hypersensitivity reaction to the CLL/SLL tumor cells.

  8. Baclofen effects on alcohol seeking, self-administration and extinction of seeking responses in a within-session design in baboons.

    Science.gov (United States)

    Duke, Angela N; Kaminski, Barbara J; Weerts, Elise M

    2014-01-01

    Baclofen, a gamma-aminobutyric acidB receptor agonist, is currently under investigation as a potential treatment to prevent relapse to drinking in alcohol-dependent persons. In the current study, two groups of baboons were trained under a chained schedule of reinforcement (CSR), with three linked components, which were each correlated with different response requirements and cues. Fulfilling the requirement in the second link initiated the third link where either alcohol (n = 4) or a preferred non-alcoholic beverage (Tang, n = 5) was available for self-administration; failure to complete the response requirement in Link 2 ended the session (no access to alcohol or Tang). Seeking responses in Link 2 were used as indices of the motivational processes thought to be involved in relapse. The effects of baclofen (0.1-2.4 mg/kg) were examined under conditions with alcohol or Tang access and under extinction. Under the CSR, baclofen (1.8 and 2.4 mg/kg) significantly decreased (P baclofen (2.4 mg/kg) reduced Tang self-administration and consumption. Under within-session extinction conditions, baclofen (1.8 and 2.4 mg/kg) facilitated extinction of responding for both alcohol and Tang, particularly during the first 10 minutes of extinction. Baclofen may be effective in reducing craving and alcohol drinking, although the facilitation of extinction and suppression of both alcohol and Tang self-administration by baclofen suggests these effects may be related to a more general suppression of consummatory and conditioned behaviors.

  9. Early endothelial damage detected by circulating particles in baboons fed a diet high in simple carbohydrates in conjunction with saturated or unsaturated fat.

    Science.gov (United States)

    Shi, Qiang; Hodara, Vida; Meng, Qinghe; Voruganti, V Saroja; Rice, Karen; Michalek, Joel E; Comuzzie, Anthony G; VandeBerg, John L

    2014-01-01

    Studies have shown that high-fat diets cause blood vessel damage, however, assessing pathological effects accurately and efficiently is difficult. In this study, we measured particle levels of static endothelium (CD31+ and CD105+) and activated endothelium (CD62E+, CD54+ and CD106+) in plasma. We determined individual responses to two dietary regimens in two groups of baboons. One group (n = 10), was fed a diet high in simple carbohydrates and saturated fats (the HSF diet) and the other (n = 8) received a diet high in simple carbohydrates and unsaturated fats (the HUF diet). Plasma samples were collected at 0, 3, and 7 weeks. The percentages of CD31+ and CD62E+ particles were elevated at 3 weeks in animals fed either diet, but these elevations were statistically significant only in animals fed the HUF diet. Surprisingly, both percentages and counts of CD31+ particles were significantly lower at week 7 compared to week 0 and 3 in the HSF group. The median absolute counts of CD105+ particles were progressively elevated over time in the HSF group with a significant increase from week 0 to 7; the pattern was somewhat different for the HUF group with significant increase from week 3 to 7. The counts of CD54+ particles exhibited wide variation in both groups during the dietary challenge, while the median counts of CD106+ particles were significantly lower at week 3 than at week 0 and week 7. Endothelial particles exhibited time-dependent changes, suggesting they were behaving as quantifiable surrogates for the early detection of vascular damage caused by dietary factors.

  10. Distinct Physiologic and Inflammatory Responses Elicited in Baboons after Challenge with Shiga Toxin Type 1 or 2 from Enterohemorrhagic Escherichia coli▿

    Science.gov (United States)

    Stearns-Kurosawa, D. J.; Collins, Valta; Freeman, Scott; Tesh, Vernon L.; Kurosawa, Shinichiro

    2010-01-01

    Shiga toxin-producing Escherichia coli is a principal source of regional outbreaks of bloody diarrhea and hemolytic-uremic syndrome in the United States and worldwide. Primary bacterial virulence factors are Shiga toxin types 1 and 2 (Stx1 and Stx2), and we performed parallel analyses of the pathophysiologies elicited by the toxins in nonhuman primate models to identify shared and unique consequences of the toxemias. After a single intravenous challenge with purified Stx1 or Stx2, baboons (Papio) developed thrombocytopenia, anemia, and acute renal failure with loss of glomerular function, in a dose-dependent manner. Differences in the timing and magnitude of physiologic responses were observed between the toxins. The animals were more sensitive to Stx2, with mortality at lower doses, but Stx2-induced renal injury and mortality were delayed 2 to 3 days compared to those after Stx1 challenge. Multiplex analyses of plasma inflammatory cytokines revealed similarities (macrophage chemoattractant protein 1 [MCP-1] and tumor necrosis factor alpha [TNF-α]) and differences (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) elicited by the toxins with respect to the mediator induced and timing of the responses. Neither toxin induced detectable levels of plasma TNF-α. To our knowledge, this is the first time that the in vivo consequences of the toxins have been compared in a parallel and reproducible manner in nonhuman primates, and the data show similarities to patient observations. The availability of experimental nonhuman primate models for Stx toxemias provides a reproducible platform for testing antitoxin compounds and immunotherapeutics with outcome criteria that have clinical meaning. PMID:20308301

  11. Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues.

    Science.gov (United States)

    Guo, Chunming; Li, Cun; Myatt, Leslie; Nathanielsz, Peter W; Sun, Kang

    2013-04-01

    Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings' susceptibility to metabolic syndrome.

  12. Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells.

    Science.gov (United States)

    Stroncek, David F; Lee, Daniel W; Ren, Jiaqiang; Sabatino, Marianna; Highfill, Steven; Khuu, Hanh; Shah, Nirali N; Kaplan, Rosandra N; Fry, Terry J; Mackall, Crystal L

    2017-03-16

    Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes.

  13. Prognostic impact of lymphocytes in soft tissue sarcomas.

    Directory of Open Access Journals (Sweden)

    Sveinung W Sorbye

    Full Text Available PURPOSE: The purpose of this study was to clarify the prognostic significance of lymphocyte infiltration in soft tissue sarcomas (STS. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of tumor infiltrating lymphocytes is controversial as the immune system has conflicting roles during cancer development. EXPERIMENTAL DESIGN: Tissue microarrays from 249 patients with STS were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+, CD20+ and CD45+ lymphocytes in tumors. RESULTS: In univariate analyses, increased numbers of CD4+ (P = 0.008 and CD20+ (P = 0.006 lymphocytes in tumor correlated significantly with an improved disease-specific survival (DSS in patients with wide resection margins (n = 108. In patients with non-wide resection margins (n = 141 increased numbers of CD3+ (P = 0.028 lymphocytes in tumor correlated significantly with shorter DSS. In multivariate analyses, a high number of CD20+ lymphocytes (HR = 5.5, CI 95%  = 1.6-18.6, P = 0.006 in the tumor was an independent positive prognostic factor for DSS in patients with wide resections margins. CONCLUSIONS: High density of CD20+ lymphocytes in STS with wide resection margins is an independent positive prognostic indicator for these patients. Further research is needed to define if CD20+ cells can modify tumors in a way that reduces disease progression and metastatic potential.

  14. Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

    Science.gov (United States)

    Dardick, I; Caldwell, D R; Moher, D; Jabi, M

    1988-08-01

    Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even

  15. No-carrier-added (NCA) N-(3-( sup 18 F)fluoropropyl)-N-norbuprenorphine and N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine -synthesis, anatomical distribution in mice and rats, and tomographic studies in a baboon

    Energy Technology Data Exchange (ETDEWEB)

    Lanqin Bai; Renrui Teng; Chyngyann Shiue; Wolf, A.P.; Dewey, S.L. (Brookhaven National Lab., Upton, NY (USA)); Holland, M.J.; Simon, E.J. (New York Univ., NY (USA). Medical Center)

    1990-01-01

    N-(3-Fluoropropyl)-N-norbuprenorphine (3a) and N-(3-fluoropropyl)-N-nordiprenorphine (4a) were synthesized by N-alkylation of norbuprenorphine (1) and nordiprenorphine (2) with 1-bromo-3-fluoropropane. The corresponding no-carrier-added (NCA) N-(3-({sup 18}F)fluoropropyl)-N-norbuprenorphine (3b) and N-(3-({sup 18}F)fluoropropyl)-N-nordiprenorphine (4b) were synthesized by N-alkylation of 1 and 2 with NCA 1-({sup 18}F)fluoro-3-iodopropane. In vitro studies indicate that in the absence of sodium chloride, compounds 3a, 4a, N-propyl-N-norbuprenorphine (5), buprenorphine and diprenorphine are reasonably comparable in binding affinity for opioid receptors. In the presence of 100 mM sodium chloride, however, compounds 3a, 4a and 5, are clearly less potent than buprenorphine and diprenorphine. The anatomical distribution study of compound 3b in mice shows radioactivity accumulating in bone. Rat studies of both compounds 3b and 4b indicate the specific distribution of these two radioligands within certain cortical and subcortical regions of rat brain. However, the absolute uptake of compound 4b in rat brain was only half that of compound 3b. PET studies of 3b in a baboon revealed specific binding of compound 3b in striatum and cerebellum. At 1 h after injection, ratios of specific/non-specific binding of 3b in striatum and cerebellum of a baboon were 1.9 and 1.7 respectively. (author).

  16. Apoptosis of matured T lymphocytes induced by mouse sertoli cells in cocultures in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Yang; LIN Zi-hao; ZHU Xiao-hai; LIU Shan-rong

    2001-01-01

    Objective: To study whether mouse sertoli cells can induce the apoptosis of matured T lymphocytes in cocultures in vitro. Methods: With TUNEL, DNA electrophoresis, eleetro-mierography and flow cytometry, we examined the apoptosis and its rates of mouse matured T lymphocytes in control group (T lymphocytes only), group A (T lymphocytes + culture medium of sertoli cells), group B (T lymphocytes + sertoli cells). Results: Under electro-micrography, chromatin condensation, karyopyknosis, karyorhexis and apoptotic body were observed in some T lymphocytes in 3 groups; some nucleuses were stained dark blue with TUNEL; a typical DNA ladder was found with DNA electrophoresis. The apoptotic rates of T lymphocytes in group A and B were significantly higher than that in control group (P<0.01). The apoptotic rate of T lymphocytes in group B was significantly higher than that in group A (P<0.01). Conclusion: In coculture condition in vitro,mouse sertoli cells can induce the apoptosis of matured T lymphocytes.

  17. Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Prusek, W. (Szpital Wojewodzki, Wroclaw (Poland)); Astaldi, G. (The Blood Research Foundation Centre, Tortona (Italy))

    1979-01-01

    The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than the viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so-called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity.

  18. Cytotoxic T lymphocytes specific for the simian immunodeficiency virus.

    Science.gov (United States)

    Letvin, N L; Schmitz, J E; Jordan, H L; Seth, A; Hirsch, V M; Reimann, K A; Kuroda, M J

    1999-08-01

    A non-human primate model for acquired immunodeficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, was used to explore the role of the AIDS virus-specific cytotoxic T-lymphocyte (CTL) response in disease pathogenesis. This CTL response was measured using the major histocompatibility complex (MHC) class I/peptide tetramer technology. Large numbers of tetramer-binding CD8+ T lymphocytes were demonstrable not only in the peripheral blood, but in lymph nodes and even in semen of chronically SIV-infected monkeys. The central role of these effector T lymphocytes in containing SIV spread during primary infection was demonstrated by showing that early SIV clearance during primary infection correlated with the emergence of the tetramer binding CD8+ T lymphocytes and that in vivo depletion of CD8+ lymphocytes eliminated the ability of the infected monkeys to contain SIV replication. These observations suggest that an effective AIDS vaccine should elicit a potent virus-specific CTL response. In fact, a live, recombinant SIV vaccine constructed using the attenuated pox virus vector modified vaccinia Ankara (MVA) elicited a high-frequency CTL response, comparable in magnitude to that elicited by SIV infection itself. This suggests that vaccine modalities such as MVA may prove useful in creating an effective human immunodeficiency virus (HIV) vaccine. These studies also indicate the power of both the SIV/macaque model and MHC class I/peptide tetramers for assessing AIDS vaccine strategies.

  19. Antibody production in early life supported by maternal lymphocyte factors.

    Science.gov (United States)

    Shimamura, Michio; Huang, Yi-Ying; Goji, Hiroshi

    2003-01-20

    To examine the influence of maternal lymphocyte factors on the immune responses in offspring in early life, antibody production in neonates born to either normal or lymphocyte-deficient mothers was analyzed. Recombination activating gene (Rag)-2(+/-) mouse neonates born to Rag-2(+/+), Rag-2(+/-)or Rag-2(-/-)mothers were injected with goat anti-mouse IgD antiserum, and IgE and IgG(1) production was evaluated. The levels of IgE and IgG(1) were higher in the pups born to Rag-2(+/+)and Rag-2(+/-) dams than to lymphocyte-deficient Rag-2(-/-) dams. The enhanced antibody production in the former compared with the latter neonates was also found following immunization with ovalbumin or TNP-Ficoll. Thus, the presence of maternal lymphocyte factors was suggested in neonates that augmented antigen-specific antibody production in both T cell-dependent and -independent pathways. A reduction in antibody production was observed in normal neonates when they were foster-nursed by Rag-2(-/-) mothers. Thus, the maternal lymphocyte factors enhancing the immune responses in newborns were shown to be present in breast-milk.

  20. T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Kaur Manminder

    2012-03-01

    Full Text Available Abstract Background There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD patients. The clinical benefits of corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes play a role in this corticosteroid insensitivity. Objectives To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls. Methods Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS, smokers (S and COPD patients were stimulated with phytohaemagglutinin (PHA & phorbol myristate acetate (PMA, +/- dexamethasone. Supernatants were assayed for interleukin (IL-2 and interferon (IFNγ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ expression. Results The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (p p Conclusions IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.

  1. T-lymphocyte and B-lymphocyte dichotomy in anuran amphibians: III. Assessment and identification of inducible killer T-lymphocytes (IKTL) and spontaneous killer T-lymphocytes (SKTL).

    Science.gov (United States)

    Klempau, A E; Cooper, E L

    1984-01-01

    We have established the existence of alloreactive inducible killer (IK) T-lymphocytes in Rana pipiens by injecting immunogenic concentrations of allogeneic frog erythrocytes (RBC). Assessment of specific IK activity was determined microscopically, observing effector-target conjugate formation, and spectrophotometrically as released hemoglobin (Hb) from lysed targets (RBC). The presence of spontaneous killer (SK) T-lymphocyte activity was also determined using unimmunized frogs and similar assay conditions. Assays using rabbit anti-frog Thy-1.1 antiserum inhibition, but not E-rosetted T-lymphocyte depletion, confirmed the T-lymphocyte category of both effector cell populations in Rana pipiens. For IK activity, we determined the 1) best priming doses, 2) best effector cell source (peripheral blood), 3) best priming route (intraperitoneal), 4) kinetics of immunity development, and 5) kinetics of lysis. Kinetics of lysis and organ distribution for spontaneous killer cells were also determined. Our results may assist 1) in establishing the evolutionary origin of cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells, and 2) in predicting where the capacity of immuno-surveillance against modified-self appeared in phylogeny. The implications are important for understanding origins of mechanisms of resistance against neoplastic conditions.

  2. Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

    Directory of Open Access Journals (Sweden)

    Thomas Walcher

    2010-01-01

    Full Text Available Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0±0.1 fold increase in cell migration (P<.01; n=7. Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2±0.1 fold induction at 0.1 µmol/L ivabradine (P<.01 compared to SDF-1-treated cells, n=7. The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC. Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect.

  3. Rituximab for the treatment of patients with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    M Gentile

    2010-03-01

    Full Text Available M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20 enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy

  4. NEUTROPHIL/LYMPHOCYTE RATIO AND PLATELET/LYMPHOCYTE RATIO IN PATIENTS WITH NSCLC

    Science.gov (United States)

    Cukic, Vesna

    2016-01-01

    Objective: to compare neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in patients with NSCLC (Non- Small- Cell Lung Cancer): with and without metastases at the time of diagnosis to find out if there is the importance of these cell ratios in the assessment of severity NSCLC. Material and Methods: this is the retrospective analysis of NRL and PRL in patients with NSCLC at the time of the diagnosis of disease before any anti tumor treatment (chemotherapy, radiotherapy, surgery). 57 of patients with NSCLC treated in the first three months of 2016. year were chosen at random regardless of sex and age. We examined full blood count cells (FBC), calculated NLR and PLR in every patient and compared obtained values in patients with and patients without metastases. Results: In 57 patients with NSCLC there were 15 males with metastases, 28 without metastases, and 8 females with metastases, 6 without metastases. Since there was no regularity in the distribution of obtained values of NLR and PLR we made the Mann-Whitney U test. Mean values are presented with a median and interquartile percentiles. There was no significant difference in NLR between patients without and with metastases (p = 0.614; p = NS) as well as in PLR (p=0,068; p=NS). Conclusion: There must be a link between the immune status of the organism and lung cancer development. Immune cells have become of interest in recent years and much work has been done to study their role in the genesis of cancer but it did not give satisfactory results. Further clinical studies on large number of patients and further laboratory examination of the role of immune cells in cancer development and suppression are required. PMID:27999489

  5. Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis.

    Science.gov (United States)

    Bootello, A; Fernandez-Cruz, E; Escartin, P; Blanco, M F; Gosalvez, M; Segovia De Arana, J M

    1976-01-01

    Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens. PMID:1277585

  6. Resistance to Dasatinib in primary chronic lymphocytic leukemia lymphocytes involves AMPK-mediated energetic re-programming.

    Science.gov (United States)

    Martinez Marignac, Veronica L; Smith, Sarah; Toban, Nader; Bazile, Miguel; Aloyz, Raquel

    2013-12-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in the western world. Although promising new therapies for this incurable disease are being tested in clinical trials, the therapeutic relevance of metabolic rewiring in chronic lymphocytic leukemia (CLL) is poorly understood. The aim of this study was to identify targetable metabolic differences in primary CLL lymphocytes by the use of Dasatinib. Dasatinib is a multi-tyrosine kinase inhibitor used to treat chronic myelogenous leukemia (CML) and is being tested in clinical trials for several cancers including CLL. This drug has been shown to be beneficial to CML patients suffering from diabetes by reducing their glucose plasma levels. In keeping with this previous observation, we report that Dasatinib induced glucose use while reducing lactate production, suggesting that this tyrosine kinase inhibitor decreases aerobic glycolysis and shifts glucose use in primary CLL lymphocytes. Our results suggest that primary CLL lymphocytes (independently of traditional prognostic factors) can be stratified in two subsets by their sensitivity to Dasatinib in vitro. Increased glucose use induced by Dasatinib or by inhibition of mitochondrial respiration was not sufficient to sustain survival and ATP levels in CLL samples sensitive to Dasatinib. The two subsets of primary CLL lymphocytes are characterized as well by a differential dependency on mitochondrial respiration and the use of anabolic or catabolic processes to cope with induced metabolic/energetic stress. Differential metabolic reprogramming between subsets is supported by the contrasting effect on the survival of Dasatinib treated CLL lymphocytes with pharmacological inhibition of two master metabolic regulators (mTorc1 and AMPK) as well as induced autophagy. Alternative metabolic organization between subsets is further supported by the differential basal expression (freshly purified lymphocytes) of active AMPK, regulators of glucose metabolism and

  7. D-ribose inhibits DNA repair synthesis in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Zunica, G.; Marini, M.; Brunelli, M.A.; Chiricolo, M.; Franceschi, C.

    1986-07-31

    D-ribose is cytotoxic for quiescent human lymphocytes and severely inhibits their PHA-induced proliferation at concentrations (25-50 mM) at which other simple sugars are ineffective. In order to explain these effects, DNA repair synthesis was evaluated in PHA-stimulated human lymphocytes treated with hydroxyurea and irradiated. D-ribose, in contrast to other reducing sugars, did not induce repair synthesis and therefore did not apparently damage DNA in a direct way, although it markedly inhibited gamma ray-induced repair. Taking into account that lymphocytes must rejoin physiologically-formed DNA strand breaks in order to enter the cell cycle, we suggest that D-ribose exerts its cytotoxic activity by interfering with metabolic pathways critical for the repair of DNA breaks.

  8. Antigen-specific lymphocyte transformation in patients with recent yersiniosis.

    Science.gov (United States)

    Vuento, R

    1983-04-01

    Lymphocyte transformation in patients with recent yersiniosis was studied. A micromethod using washed blood cells and Yersinia enterocolitica antigen was employed. The washed blood cells were incubated in the presence of various dilutions of heat-treated whole bacteria; these proved as antigen superior to gentamicin- or formalin-treated bacteria. Patients with recent yersiniosis had a significantly higher response against Yersinia antigen as compared to 20 healthy controls, who had either no response or a low response. No difference could be observed in responses against PPD or streptokinase-streptodornase, or in the mitogen responses between these two groups. A marked cross-reaction was observed between Yersinia and Escherichia coli antigen. The results show that patients with recent yersiniosis develop lymphocyte transformation response against Yersinia. Lymphocyte transformation test can be used in the study of host responses against infecting Yersinia in patients with different clinical pictures of yersiniosis.

  9. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions...... is an indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  10. Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

    Science.gov (United States)

    Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.

    2006-10-01

    Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

  11. Serotonin Transporter Clustering in Blood Lymphocytes of Reeler Mice

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Baltanas

    2010-01-01

    Full Text Available Serotonin transporter clustering is an important feature for regulation of this transporter activity. We used immunocytochemistry to analyze alterations in serotonin transporter clustering in blood lymphocytes of reeler mice. Serotonin transporter immunolabelling is observed mostly as a patchy staining in lymphocytes membranes. Comparison of the number and size of serotonin transporter clusters in wild-type mice, heterozygous reeler mice, and homozygous reeler mice showed an increase in the number and size of clusters in heterozygous reeler mice, but only an increase in clusters size in homozygous reeler mice. Reelin is down-regulated in the brain of schizophrenia, autism, and mood disorders, and is also expressed in blood plasma. There is the possibility therefore that alterations in serotonin transporter clustering in blood lymphocytes associated with a decrease in reelin expression may be operative in some cardiovascular or immune system alterations showing comorbidity with these mental disorders.

  12. Human lymphocyte sub-populations and K cells.

    Science.gov (United States)

    Sandilands, G; Gray, K; Cooney, A; Froebel, K; Anderson, J R

    1976-01-01

    Peripheral blood lymphocytes from 19 normal subjects were examined for surface Ig (SIg) and capacity to form rosettes with normal and neuraminidase-treated sheep erythrocytes and with chicken erythrocytes sensitised with IgG antibody. Information on the relationship between the presence of SIg and capacity to form rosettes was obtained by combined tests and depletion experiments. By these means, a population of lymphocytes with Fc receptors, but lacking SIg (mean 14.6%) was defined and shown to correlate closely with cytotoxic activity for antibody-sensitised target cells. Indirect evidence was also obtained that these lymphocytes, which are regarded as the major population of antibody-dependent cytotoxic cells, are capable of forming rosettes with normal and neuraminidase-treated sheep erythrocytes. The nature of these cells is briefly discussed.

  13. Cytotoxicity and genotoxicity of gliotoxin on human lymphocytes in vitro

    Directory of Open Access Journals (Sweden)

    Mohammed Adel Nouri

    2015-07-01

    Full Text Available The cytotoxic effects on human lymphocytes of two gliotoxin samples (one pure sample produced in the laboratory for this study, and one sample purchased from a standard source were assessed at four different concentrations (25, 50, 100 and 200 ng/ml using the methylthiazol tetrazolium (MTT bioassay. The results showed that growth was inhibited by 21, 39.10, 61.99 and 87.45% for each of the four concentrations of the pure sample, respectively, and by 17.89, 34.92, 58.34 and 85.22% respectively, in the case of the standard purchased sample. Deoxyribonucleic acid (DNA was extracted from the lymphocytes and analysed by electrophoresis on a 1% agarose gel. Gliotoxin appeared to have the ability to degrade or damage the DNA. The present study showed that both the growth inhibition and DNA damage experienced by the human lymphocytes increased linearly with increasing concentrations of toxin.

  14. Key role of mitochondria in apoptosis of lymphocytes.

    Science.gov (United States)

    Boichuk, S V; Minnebaev, M M; Mustafin, I G

    2001-12-01

    Changes in the mitochondrial potential, expression of phosphatidylserine, parameters of direct and lateral light scattering, and DNA fragmentation during spontaneous and induced apoptosis in peripheral blood lymphocytes were studied by flow cytofluorometry. Dexamethasone and Ca2+ ionophore A23187 served as inductors of apoptosis. A decrease in the mitochondrial potential is an early sign of spontaneous and induced apoptosis. Phosphatidylserine expression on the outer plasma membrane occurred later and inversely depended on the mitochondrial potential. Our results indicate that the involvement of mitochondria in spontaneous and induced apoptosis accompanied by a decrease in the mitochondrial potential is an early and key event of programmed lymphocyte death. The decrease in the mitochondrial potential of lymphocytes induced degradation of their nuclei (DNA fragmentation) and promoted elimination of apoptotic cells (phosphatidylserine expression).

  15. Herpesvirus sylvilagus infects both B and T lymphocytes in vivo.

    Science.gov (United States)

    Kramp, W J; Medveczky, P; Mulder, C; Hinze, H C; Sullivan, J L

    1985-01-01

    Herpesvirus sylvilagus infection of cottontail rabbits (Sylvilagus floridanus) was studied as a model of herpesvirus-induced lymphoproliferative disorders. Leukocytosis, splenomegaly, proliferation of T cells and virus production by lymphocytes characterized this infectious mononucleosis-like disease. Approximately two copies of circular herpesvirus sylvilagus genomes per cell were detected in spleen cells at 2 weeks postinfection, and circular genomes could still be observed after 4 months. Circular viral genomes were found in both B and T lymphocytes. Small amounts of linear viral DNA (0.1 to 0.3 copies per cell) were also detected in both B and T cells. These results indicated that the virus did not replicate in the majority of lymphocytes in vivo. Herpesvirus sylvilagus infection in cottontail rabbits could be useful as a model for studying the complex virus-host relationships of lymphotropic herpesviruses and perhaps as an animal model for Epstein-Barr virus infection in humans. Images PMID:2993667

  16. Kinetics of circulating B lymphocytes in human myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Boccadoro, M.; Gavarotti, P.; Fossati, G.; Massaia, M.; Pileri, A.; Durie, B.G.

    1983-04-01

    The tritiated thymidine labeling index (LI%) of peripheral B lymphocytes was studied in eight myeloma patients using simultaneous immunofluorescence and autoradiography. The LI% values were low (0.3%-5.1%), but significantly increased as compared to normal controls. In addition, there was excellent correlation between the LI% values and myeloma disease activity: lowest LI% values were observed in remission patients and the highest at the time of relapse. Simultaneous LI% evaluation of bone marrow myeloma cells in five patients gave concordant results, indicating the same kinetic behavior in both these compartments, particularly in the relapse phase. These data indicate both that circulating B lymphocytes include the neoplastic clone and that these B lymphocytes and bone marrow myeloma cells have similar kinetics.

  17. MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

    Directory of Open Access Journals (Sweden)

    S. V. Khaidukov

    2009-01-01

    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  18. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  19. Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

    Science.gov (United States)

    Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata Jr, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves

    2015-02-01

    To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

  20. Chronic lymphocytic leukaemia: case control epidemiological study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Bernard, S M; Bird, C C; Darwin, C M; O'Brien, C; Richards, I D; Roberts, B; McKinney, P A

    1987-07-01

    This is the second report of a large case control study of lymphoma/leukaemia occurring in Yorkshire during 1979-84, and deals with chronic lymphocytic leukaemia presenting either in its haematological (CLL) or more solid lymphomatous (malignant lymphoma-lymphocytic or MLL) forms. In all, 330 cases and 561 controls were interviewed. The results support the concept that CLL/MLL is a condition of multiple aetiologies with evidence for genetic predisposition through an excess of family cases, immune perturbation demonstrated by excessive previous skin diseases and phenylbutazone use, and viral involvement shown by links with infectious diseases and multiple sclerosis.

  1. Effects of cobalt and chromium ions on lymphocyte migration.

    Science.gov (United States)

    Baskey, Stephen J; Lehoux, Eric A; Catelas, Isabelle

    2017-04-01

    A T cell-mediated hypersensitivity reaction has been reported in some patients with CoCrMo-based implants. However, the role of cobalt and chromium ions in this reaction remains unclear. The objective of the present study was to analyze the effects of Co(2+) and Cr(3+) in culture medium, as well as the effects of culture supernatants of macrophages exposed to Co(2+) or Cr(3+) , on the migration of lymphocytes. The release of cytokines/chemokines by macrophages exposed to Co(2+) and Cr(3+) was also analyzed. The migration of murine lymphocytes was quantified using the Boyden chamber assay and flow cytometry, while cytokine/chemokine release by J774A.1 macrophages was measured by ELISA. Results showed an ion concentration-dependent increase in TNF-α and MIP-1α release and a decrease in MCP-1 and RANTES release. Migration analysis showed that the presence of Co(2+) (8 ppm) and Cr(3+) (100 ppm) in culture medium increased the migration of T lymphocytes, while it had little or no effect on the migration of B lymphocytes, suggesting that Co(2+) and Cr(3+) can stimulate the migration of T but not B lymphocytes. Levels of T lymphocyte migration in culture medium containing Co(2+) or Cr(3+) were not statistically different from those in culture supernatants of macrophages exposed to Co(2+) or Cr(3+) , suggesting that the effects of the ions and chemokines were not additive, possibly because of ion interference with the chemokines and/or their cognate receptors. Overall, results suggest that Co(2+) and Cr(3+) are capable of stimulating the migration of T (but not B) lymphocytes in the absence of cytokines/chemokines, and could thereby contribute to the accumulation of more T than B lymphocytes in periprosthetic tissues of some patients with CoCrMo-based implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:916-924, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. Polycyclic’ Aromatic Hydrocarbon Induced Intracellular Signaling and Lymphocyte Apoptosis

    DEFF Research Database (Denmark)

    Schneider, Alexander M.

    of this research indicate that the AhR is controlled by the cell progression through the cell cycle. This may imply differential cellular sensitivity to the toxins, and a role for the AhR in cell growth/differentiation. Previous PAH inununotoxicity research did not adequately address effects on immature...... lymphocytes. Our experiments on preB lymphocytes supported by stromal cells suggest that apoptosis is one of the mechanisms for PAH immunosuppression. It could be either due to direct effect of the PAH on the B cells, via stromal cell signaling. Ubiquitous PAH-like toxin, fluoranthene, was tested for it...

  3. Life and death of lymphocytes: a role in immunesenescence

    Directory of Open Access Journals (Sweden)

    Agrawal Sudhanshu

    2005-08-01

    Full Text Available Abstract Human aging is associated with progressive decline in immune functions, increased frequency of infections. Among immune functions, a decline in T cell functions during aging predominates. In this review, we will discuss the molecular signaling in two major pathways of apoptosis, namely death receptor pathway and mitochondrial pathway, and their alterations in both T and B lymphocytes in human aging with a special emphasis on naïve and different memory subsets of CD8+ T cells. We will also discuss a possible role of lymphocyte apoptosis in immune senescence.

  4. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

    DEFF Research Database (Denmark)

    Tenzer, Stefan; Wee, Edmund; Burgevin, Anne

    2009-01-01

    Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated ......Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group...

  5. Effect of oral proguanil on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    In vitro studies have indicated that the antifolates pyrimethamine [4, 6] and cycloguanil (the active metabolite of proguanil) suppress the proliferation of stimulated human lymphocytes; proguanil has no effect [2]. During the early growth phase of the cells, 14C-thymidine (14C-TdR) incorporation...... on human lymphocytes, the present study was undertaken. Little information is available about the serum levels of proguanil and cycloguanil following ingestion of prophylactic doses [8]. Therefore, the serum concentrations of proguanil and cycloguanil were estimated, to allow comparison with previous...

  6. Lymphocyte fluorescent profiles (LFP): a possible screening technique in neoplasia.

    Science.gov (United States)

    Love, L A; Metcalf, N F; Metcalf, W K; Sharp, J G

    1979-05-01

    A technique involving fluorescent protein staining and microfluorometry has been developed for measuring the lymphocyte fluorescent profile (LFP) of peripheral blood lymphocytes. In contrast to normal humans who display a regular bell-shaped curve, the profile from patients with cancer is irregular, showing a bimodal distribution of fluorescence, with a significant population of cells fluorescing at a higher relative intensity. It is suggested that this elevation in protein concentration is due to an immune response to the presence of a neoplasm, and thus this technique may prove to be a useful indicator of malignancy.

  7. Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1996-05-01

    Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded as other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.

  8. Chronic lymphocytic-leukemia with pleomorphic lymphocytes (cll-pleo) - a comparative-study with typical cll.

    Science.gov (United States)

    Batata, A; Shen, B; Batata, S

    1994-05-01

    Cell suspensions from the peripheral brood of 21 cases of chronic lymphocytic leukemia with pleomorphic lymphocytes (CLL-pleo) and 155 cases of typical CLL were analyzed to define the phenotype of the former and compare it with the phenotype of the latter. CLL-pleo was characterized by weak fluorescence intensity of surface immunoglobulin (mean channel number on flow cytometry <200), positive mouse rosettes and CD5, and negative CD22 and tartrate resistant acid phosphatase. Comparison of the positive rates of the markers and of the mean percentages of marker-expressing cells showed no statistical difference between CLL-pleo and typical CLL. CLL-pleo constitutes a morphological variant of typical CLL bearing the same membrane phenotype as typical CLL, although the mean absolute lymphocyte count in CLL-pleo was significantly higher than that of typical CLL.

  9. Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

    DEFF Research Database (Denmark)

    Ellingsen, A R; Sørensen, F B; Larsen, Jytte Overgaard

    2001-01-01

    Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin...

  10. Population Pharmacokinetics of Ofatumumab in Patients With Chronic Lymphocytic Leukemia, Follicular Lymphoma, and Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Struemper, Herbert; Sale, Mark; Patel, Bela R;

    2014-01-01

    Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma...

  11. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice.

    Science.gov (United States)

    Charlton, B; Zhang, M D; Slattery, R M

    2001-12-01

    Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

  12. Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

    Science.gov (United States)

    A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

  13. The imbalance of helper T lymphocytes and cytotoxic T lymphocytes in acute renal transplantation rejection

    Institute of Scientific and Technical Information of China (English)

    YAN JIANG; ZHI QIN TANG; LIN PENG; YU LIANG WANG; ZHI PING WANG

    2007-01-01

    To investigate the imbalance state of helper T lymphocytes (Th) and cytotoxic T lymphocytes (Tc) and the roles of Th1/Th2/Th3 and Tc1/Tc2 cells in renal transplantation rejection, the percentages of these cells in peripheral blood of 24 cases of renal transplantation recipients with acute rejection and the dynamic changes of the CD4/CD8 ratio were determined by flow cytometry analysis,while 30 cases of healthy individuals were set up as controls. In these healthy controls, the percentages of the Th1, Th2 and Th3 cells were (10.45±8.15)%, (5.05±4.15)% and (3.90±3.21)%,and those of Tc1 and Tc2 cells were (9.83±7.03)% and (4.51±2.17)%, respectively. However,the percentages of Th1 and Tc1 cells in peripheral blood of the stable recipients after transplantation were (7.29±5.62)% and (7.04±5.15)%, showing definite reduction, while those of Th2, Th3and Tc2 cells showed significant increase, (6.34±5.67)%, (4.94±4.14) % and ( 6.86 ±4.42) %, respectively. In case of recipients with acute rejection, the percentages of Th1 and Tc1 cells appeared to be (18.55±13.21)% and (15.84±11.72)%, also showing significant increase, but those of Th2,Th3 and Tc2 cells appeared to be reduced, (4.19±3.62)%, (3.02±2.83)% and (3.88±1.63) %, respectively. Significant differences could be detected among these three groups (P <0.05). The CD4/CD8 ratio in cases with acute rejection was higher than those of stable recipients (2.24±0.59 vs 1.95±0.45), but that of the stable recipients and healthy controls (1.98±0.31 )showed no any significant difference. From the above observation, it is evident that imbalance between Th1, Th2 and Th3 with Te1 and Tc2 cells may exist after renal transplantation and probably, the immune imbalance may be induced through the secretion of cytokines INF-γ by Th1 or Te1 cells , I1-4 by Th2 and Tc2 cells and TGF-β by Th3.

  14. The peripheral blood compartment in patients with Graves' disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes

    Science.gov (United States)

    Van der Weerd, K; Van Hagen, P M; Schrijver, B; Kwekkeboom, D J; De Herder, W W; Ten Broek, M R J; Postema, P T E; Van Dongen, J J M; Staal, F J T; Dik, W A

    2013-01-01

    Graves' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)+ and CD25+] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38highCD27−, P < 0·03) and pre-naive mature (CD38lowCD27−IgD+CD5+, P < 0·04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5+, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5+ B lymphocytes within the peripheral blood. The increase in CD5+ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5+ B lymphocytes. PMID:23901889

  15. Lymphocyte subsets in healthy Malawians: implications for immunologic assessment of HIV infection in Africa.

    Science.gov (United States)

    Mandala, Wilson L; MacLennan, Jenny M; Gondwe, Esther N; Ward, Steven A; Molyneux, Malcolm E; MacLennan, Calman A

    2010-01-01

    CD4(+)T lymphocyte measurements are the most important indicator of mortality in HIV-infected individuals in resource-limited settings. There is currently a lack of comprehensive immunophenotyping data from African populations to guide the immunologic assessment of HIV infection. To quantify variation in absolute and relative lymphocyte subsets with age in healthy Malawians. Lymphocyte subsets in peripheral blood of 539 healthy HIV-uninfected Malawians stratified by age were enumerated by flow cytometry. B and T-lymphocyte and T-lymphocyte subset absolute concentrations peaked in early childhood then decreased to adult levels, whereas lymphocyte subset proportions demonstrated much less variation with age. Adult lymphocyte subsets were similar to those in developed countries. In contrast, high B-lymphocyte and CD8(+)T-lymphocyte levels among children under 2 years, relative to those in developed countries, resulted in low CD4(+)T-lymphocyte percentages that varied little between 0 and 5 years (35% to 39%). The CD4(+)T-lymphocyte percentages in 35% of healthy children under 1 year and 18% of children age 1 to 3 years were below the World Health Organization threshold defining immunodeficiency in HIV-infected children in resource-limited settings. Thirteen percent of healthy children under 18 months old had a CD4:CD8T-lymphocyte ratio <1.0, which is commonly associated with HIV infection. All immunologic parameters except absolute natural killer lymphocyte concentration varied significantly with age, and percentage and overall absolute CD4(+)T-lymphocyte counts were higher in females than males. Although lymphocyte subsets in Malawian adults are similar to those from developed countries, CD4(+)T-lymphocyte percentages in young children are comparatively low. These findings need to be considered when assessing the severity of HIV-related immunodeficiency in African children under 3 years. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by

  16. Subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carcinoma: a case report

    OpenAIRE

    Choi Young Sik; Han You Jin; Yeo Go Eun; Kwon Su Kyoung; Kim Bu Kyung; Park Yo-Han; Kim Sung Won; Chun Bong Kwon; Kong Eun Hee; Kim Jeong Hoon

    2013-01-01

    Abstract Introduction Subacute lymphocytic thyroiditis is anautoimmune thyroid disease presenting with transient thyrotoxicosis as well as transient hypothyroidism. Several factors have been thought to be the initiating event in subacute lymphocytic thyroiditis. However, subacute lymphocytic thyroiditis that develops after thyroid lobectomy has not yet been reported in the literature. We report a case of subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carc...

  17. Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

    Energy Technology Data Exchange (ETDEWEB)

    Harris, G. (Kennedy Inst. of Rheumatology, London (UK). Div. of Experimental Pathology); Cramp, W.A.; Edwards, J.C.; George, A.M.; Sabovljev, S.A.; Hart, L.; Hughes, G.R.V. (Hammersmith Hospital, London (UK)); Denman, A.M. (Northwich Park Hospital, Harrow (UK)); Yatvin, M.B. (Wisconsin Clinical Cancer Center, Madison (USA))

    1985-06-01

    The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

  18. Langerhans cells and subsets of lymphocytes in the nasal mucosa

    DEFF Research Database (Denmark)

    Hellquist-Dahl, B; Olsen, K E; Irander, K;

    1991-01-01

    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...

  19. Increased circulating apoptotic lymphocytes in children with Down syndrome

    NARCIS (Netherlands)

    Gemen, E.F.A.; Verstegen, R.H.J.; Leuvenink, J.; Vries, E. de

    2012-01-01

    Down syndrome (DS) resembles immunodeficiency with increased infections, auto-immune diseases, and hematological malignancies. Until now, immunological studies in DS mainly focused on T-lymphocytes. We recently described a profound B-lymphocytopenia in children with DS. This could be caused by incre

  20. FUNCTIONAL AORTIC STIFFNESS:ROLE OF CD4+ T LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    Beenish A. Majeed

    2015-08-01

    Full Text Available The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1-/- mice and additionally characterized the component of vascular stiffness due to vasoconstriction versus vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young’s modulus in C57BL/6J mice by 3-fold but caused no change in the RAG 1-/- mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1-/- mice. In order to account for the hydraulic versus material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity decreased from 3- to 2-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  1. Association of lymphocytic colitis and lactase deficiency in pediatric population.

    Science.gov (United States)

    Sun, Jihong; Lin, Jingmei; Parashette, Kalayan; Zhang, Jianjun; Fan, Rong

    2015-02-01

    Characterized by colonic mucosa intraepithelial lymphocytosis, lymphocytic colitis is primarily an entity presented in the middle-aged to elderly patient population. Very few large series of lymphocytic colitis of childhood occurrence are available in the medical literature. Ten cases each of lymphocytic colitis and of colonic lymphocytosis of other diagnosis, all with duodenal disaccharidases analysis data, were collected from the files of our institution. The electronic medical records were reviewed and multiple variables were analyzed. The ten patients with lymphocytic colitis presented with diarrhea. Of these, three had abdominal pain. The age range was 2-18 years. Nearly all patients were Caucasian (90%) and 70% were female. Endoscopically, most had normal appearing colonic mucosa. Significant past medical history, family medical history and associated comorbidities included celiac disease, Down syndrome, juvenile arthritis and other autoimmune diseases. Interestingly, the most revealing observation was that the majority of cases (80%) were associated with lactase deficiency and, for the most part, gastrointestinal symptoms improved simply by treatment with Lactaid or avoidance of dairy products. This association is statistically significant. Our clinicopathological study indicates that the typical pediatric patient is a female Caucasian. A large of portion of the patients had associated lactase deficiency and improved on Lactaid supplement alone.

  2. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker

    2012-01-01

    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...

  3. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors

    DEFF Research Database (Denmark)

    Xochelli, Aliki; Baliakas, Panagiotis; Kavakiotis, Ioannis

    2017-01-01

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether...

  4. IAN family critically regulates survival and development of T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Takeshi Nitta

    2006-04-01

    Full Text Available The IAN (immune-associated nucleotide-binding protein family is a family of functionally uncharacterized GTP-binding proteins expressed in vertebrate immune cells and in plant cells during antibacterial responses. Here we show that all eight IAN family genes encoded in a single cluster of mouse genome are predominantly expressed in lymphocytes, and that the expression of IAN1, IAN4, and IAN5 is significantly elevated upon thymic selection of T lymphocytes. Gain-of-function experiments show that the premature overexpression of IAN1 kills immature thymocytes, whereas short hairpin RNA-mediated loss-of-function studies show that IAN4 supports positive selection. The knockdown of IAN5 perturbs the optimal generation of CD4/CD8 double-positive thymocytes and reduces the survival of mature T lymphocytes. We also show evidence suggesting that IAN4 and IAN5 are associated with anti-apoptotic proteins Bcl-2 and Bcl-xL, whereas IAN1 is associated with pro-apoptotic Bax. Thus, the IAN family is a novel family of T cell-receptor-responsive proteins that critically regulate thymic development and survival of T lymphocytes and that potentially exert regulatory functions through the association with Bcl-2 family proteins.

  5. Iron Deficiency Impairs Intra-Hepatic Lymphocyte Mediated Immune Response.

    Directory of Open Access Journals (Sweden)

    Eliano Bonaccorsi-Riani

    Full Text Available Hepatic expression of iron homeostasis genes and serum iron parameters predict the success of immunosuppression withdrawal following clinical liver transplantation, a phenomenon known as spontaneous operational tolerance. In experimental animal models, spontaneous liver allograft tolerance is established through a process that requires intra-hepatic lymphocyte activation and deletion. Our aim was to determine if changes in systemic iron status regulate intra-hepatic lymphocyte responses. We used a murine model of lymphocyte-mediated acute liver inflammation induced by Concanavalin A (ConA injection employing mice fed with an iron-deficient (IrDef or an iron-balanced diet (IrRepl. While the mild iron deficiency induced by the IrDef diet did not significantly modify the steady state immune cell repertoire and systemic cytokine levels, it significantly dampened inflammatory liver damage after ConA challenge. These findings were associated with a marked decrease in T cell and NKT cell activation following ConA injection in IrDef mice. The decreased liver injury observed in IrDef mice was independent from changes in the gut microflora, and was replicated employing an iron specific chelator that did not modify intra-hepatic hepcidin secretion. Furthermore, low-dose iron chelation markedly impaired the activation of isolated T cells in vitro. All together, these results suggest that small changes in iron homeostasis can have a major effect in the regulation of intra-hepatic lymphocyte mediated responses.

  6. Signaling lymphocyte activating molecule (SLAM) expression in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Piskin, A Kevser; Akpinar, Pinar; Muftuoglu, Sevda; Anlar, Banu

    2007-08-01

    Signaling lymphocyte activating molecule (SLAM) is a receptor for measles virus which also has immunomodulatory activity. We analyzed SLAM expression in mononuclear cells (MNC) of patients with SSPE (n=7) and control subjects (n=7) from the same population. Native 10% PAGE analysis in cell and brain tissue extracts followed by Western blotting using monoclonal anti-human SLAM showed four types of bands. Differences in the type and amount of SLAM expression were observed between SSPE and control cases. Lymphocytes of SSPE patients showed two types of SLAM bands in comparison to only one in control lymphocytes. Stimulation of cells with lipopolysaccharide (80 u/ml) and concanavalin A (1 microg/ml) in vitro led to the appearance of a second isoform in both groups. Brain homogenates of SSPE patients (n=2) displayed all four types of SLAM isoforms at significantly higher levels than those of control brains (n=2). Our results show native PAGE enables the detection of all SLAM isotypes. The expression of SLAM is increased in lymphocytes, monocytes, and brain tissues of SSPE patients.

  7. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Science.gov (United States)

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y; Gryaznov, Sergei M; Johnston, James B; Lees-Miller, Susan P; Assouline, Sarit E; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  8. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Directory of Open Access Journals (Sweden)

    May Shawi

    Full Text Available We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR, can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1 if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2 the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  9. Paraneoplastic pemphigus as the initial presentation of chronic lymphocytic leukemia

    NARCIS (Netherlands)

    van Mook, WNKA; Fickers, MMF; Theunissen, PHMH; vander Kley, JAMJ; Duijvestijn, JA; Pas, HH; Flikweert, DC

    2001-01-01

    The case history of a 61-year-old male patient is described, who presented with severe stomatitis, conjunctivitis and leukocytosis. The diagnosis chronic lymphocytic leukemia (CLL) stage A (0) was made, for which no treatment was necessary. Progression of stomatitis and conjunctivitis and erythosqua

  10. Effects of a Simulated Tennis Match on Lymphocyte Subset Measurements

    Science.gov (United States)

    Schafer, Mark; Kell, Holly; Navalta, James; Tibana, Ramires; Lyons, Scott; Arnett, Scott

    2014-01-01

    Tennis is an activity requiring both endurance and anaerobic components, which could have immunosuppressive effects postexercise. Purpose: The purpose of this investigation was to determine the effect of a simulated tennis match on apoptotic and migratory markers on lymphocyte subsets. Method: Male high school (n = 5) and college (n = 3) tennis…

  11. Invasive aspergillosis related to ibrutinib therapy for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Benjamin Arthurs, MD

    2017-01-01

    Full Text Available We report a case of invasive pulmonary aspergillosis in a patient taking ibrutinib, a Bruton's tyrosine kinase inhibitor used to treat refractory chronic lymphocytic leukemia. We hypothesize that ibrutinib promoted this infection by suppressing innate immune responses against Aspergillus. Clinicians should be aware of potential Aspergillus infections in patients treated with this drug.

  12. Role of Circulating Lymphocytes in Patients with Sepsis

    Directory of Open Access Journals (Sweden)

    Raul de Pablo

    2014-01-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome due to infection. The incidence rate is estimated to be up to 19 million cases worldwide per year and the number of cases is rising. Infection triggers a complex and prolonged host response, in which both the innate and adaptive immune response are involved. The disturbance of immune system cells plays a key role in the induction of abnormal levels of immunoregulatory molecules. Furthermore, the involvement of effector immune system cells also impairs the host response to the infective agents and tissue damage. Recently, postmortem studies of patients who died of sepsis have provided important insights into why septic patients die and showed an extensive depletion of CD4 and CD8 lymphocytes and they found that circulating blood cells showed similar findings. Thus, the knowledge of the characterization of circulating lymphocyte abnormalities is relevant for the understanding of the sepsis pathophysiology. In addition, monitoring the immune response in sepsis, including circulating lymphocyte subsets count, appears to be potential biomarker for predicting the clinical outcome of the patient. This paper analyzes the lymphocyte involvement and dysfunction found in patients with sepsis and new opportunities to prevent sepsis and guide therapeutic intervention have been revealed.

  13. Increased circulating apoptotic lymphocytes in children with Down syndrome

    NARCIS (Netherlands)

    Gemen, E.F.A.; Verstegen, R.H.J.; Leuvenink, J.; Vries, E. de

    2012-01-01

    Down syndrome (DS) resembles immunodeficiency with increased infections, auto-immune diseases, and hematological malignancies. Until now, immunological studies in DS mainly focused on T-lymphocytes. We recently described a profound B-lymphocytopenia in children with DS. This could be caused by

  14. The expanding role of bendamustine in chronic lymphocytic leukemia

    OpenAIRE

    Nair KS; Ujjani C

    2015-01-01

    Kruti Sheth Nair, Chaitra Ujjani Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC, USA Abstract: As the most prevalent form of adult leukemia, chronic lymphocytic leukemia (CLL) affects thousands of patients each year. Given the indolent nature of the disease, symptomatic patients frequently experience multiple relapses throughout their clinical course. Better therapeutic options are needed, particularly for the elderly population that characterize...

  15. Growing B Lymphocytes in a Three-Dimensional Culture System

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

    A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing

  16. Automated Scoring and Analysis of Micronucleated Human Lymphocytes.

    Science.gov (United States)

    Callisen, Hannes Heinrich

    Physical and chemical mutagens and carcinogens in our environment produce chromosome abberations in the circulating peripheral blood lymphocytes. The abberations, in turn, give rise to micronuclei when the lymphocytes proliferate in culture. In order to improve the micronucleus assay as a method for screening human populations for chromosome damage, I have (1) developed a high-resolution optical low-light-level micrometry expert system (HOLMES) to digitize and process microscope images of micronuclei in human peripheral blood lymphocytes, (2) defined a protocol of image processing techniques to objectively and uniquely identify and score micronuclei, and (3) analysed digital images of lymphocytes in order to study methods for (a) verifying the identification of suspect micronuclei, (b) classifying proliferating and non-proliferating lymphocytes, and (c) understanding the mechanisms of micronuclei formation and micronuclei fate during cell division. For the purpose of scoring micronuclei, HOLMES promises to (a) improve counting statistics since a greater number of cells can be scored without operator/microscopist fatigue, (b) provide for a more objective and consistent criterion for the identification of micronuclei than the human observer, and (c) yield quantitative information on nuclear and micronuclear characteristics useful in better understanding the micronucleus life cycle. My results on computer aided identification of micronuclei on microscope slides are gratifying. They demonstrate that automation of the micronucleus assay is feasible. Manual verification of HOLMES' results show correct extraction of micronuclei from the scene for 70% of the digitized images and correct identification of the micronuclei for 90% of the extracted objects. Moreover, quantitative analysis on digitized images of lymphocytes using HOLMES has revealed several exciting results: (a) micronuclear DNA content may be estimated from simple area measurements, (b) micronuclei seem to

  17. File list: ALL.Bld.20.AllAg.T-Lymphocytes [Chip-atlas[Archive

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