Improved Chemically Defined Basal Medium (CMRL-1969) for Primary Monkey Kidney and Human Diploid Cells 1

PubMed Central

Healy, G. M.; Teleki, S.; Seefried, A. V.; Walton, M. J.; Macmorine, H. G.

1971-01-01

An improved tissue culture basal medium, CMRL-1969, supplemented with serum, has been evaluated by measuring the growth responses of primary cultures of trypsin-dispersed monkey kidney cells (PMKC) and of an established culture of a human diploid cell strain (HDCS). Medium H597, an early modification of medium 199 which has been used successfully in the preparation of poliomyelitis vaccine for 15 years, was used for comparison. In addition, parallel testing was done with Basal Medium Eagle (BME) widely used for the growth of HDCS. The improvements in basal medium CMRL-1969 are attributed to changes in amino acid concentrations, in vitamin composition, and, in particular, to enhanced buffering capacity. The latter has been achieved by the use of free-base amino acids and by increasing the dibasic sodium phosphate. The new medium has already been used to advantage for the production of polioviruses in PMKC where equivalent titers were obtained from cultures initiated with 70% of the number of cells required with earlier media. The population-doubling time was reduced in this system. Also, with small inocula of HDCS, the time required to obtain maximum cell yield was shorter with CMRL-1969 than with BME. Both media were supplemented with 10% calf serum. Maximum cell yields after repeated subcultivation in the new basal medium were greatly increased and the stability of the strain, as shown by chromosomal analysis, was not affected. Basal medium CMRL-1969 can be prepared easily in liquid or powdered form. PMID:4322279

Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

PubMed

Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

2010-12-01

F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey.

PubMed

Henry, Scott P; Johnson, Mark; Zanardi, Thomas A; Fey, Robert; Auyeung, Diana; Lappin, Patrick B; Levin, Arthur A

2012-11-15

The primary target organ for uptake of systemically administered phosphorothioate oligonucleotides is the kidney cortex and the proximal tubular epithelium in particular. To determine the effect of oligonucleotide uptake on renal function, a detailed renal physiology study was performed in cynomolgus monkeys treated with 10-40 mg/kg/week ISIS 113715 for 4 weeks. The concentrations of oligonucleotide in the kidney cortex ranged from 1400 to 2600 μg/g. These concentrations were associated with histologic changes in proximal tubular epithelial cells that ranged from the appearance of cytoplasmic basophilic granules to atrophic and degenerative changes at higher concentrations. However, there were no renal functional abnormalities as determined by the typical measurements of blood urea nitrogen, serum creatinine, creatinine clearance, or urine specific gravity. Nor were there changes in glomerular filtration rate, or renal blood flow. Specific urinary markers of tubular epithelial cell damage, such as N-acetyl-glucosaminidase, and α-glutathione-s-transferase were not affected. Tubular function was further evaluated by monitoring the urinary excretion of amino acids, β(2)-microglobulin, or glucose. Renal function was challenged by administering a glucose load and by examining concentrating ability after a 4-h water deprivation. Neither challenge produced any evidence of change in renal function. The only change observed was a low incidence of increased urine protein/creatinine ratio in monkeys treated with ≥40 mg/kg/week which was rapidly reversible. Collectively, these data indicate that ISIS 113715-uptake by the proximal tubular epithelium has little or no effect on renal function at concentrations of 2600 μg/g. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Endogenous New World primate type C viruses isolated from owl monkey (Aotus trivirgatus) kidney cell line.

PubMed Central

Todaro, G J; Sherr, C J; Sen, A; King, N; Daniel, M D; Fleckenstein, B

1978-01-01

A type C virus (OMC-1) detected in a culture of owl monkey kidney cells resembled typical type C viruses morphologically, but was slightly larger than previously characterized mammalian type C viruses. OMC-1 can be transmitted to bat lung cells and cat embryo fibroblasts. The virions band at a density of 1.16 g/ml in isopycnic sucrose density gradients and contain reverse transcriptase and a 60-65S RNA genome composed of approximately 32S subunits. The reverse transcriptase is immunologically and biochemically distinct from the polymerases of othe retroviruses. Radioimmunoassays directed to the interspecies antigenic determinants of the major structure proteins of other type C viruses do not detect a related antigen in OMC-1. Nucleic acid hybridization experiments using labeled viral genomic RNA or proviral cDNA transcripts to normal cellular DNA of different species show that OMC-1 is an endogenous virus with multiple virogene copies (20-50 per haploid genome) present in normal owl monkey cells and is distinct from previously isolated type C and D viruses. Sequences related to the OMC-1 genome can be detected in other New World monkeys. Thus, similar to the Old World primates (e.g., baboons as a prototype), the New World monkeys contain endogenous type C viral genes that appear to have been transmitted in the primate germ line. Images PMID:76312

[The history of kidney transplantation].

PubMed

Hatzinger, M; Stastny, M; Grützmacher, P; Sohn, M

2016-10-01

The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.

Cisplatin-induced cytotoxicity in BSO-exposed renal proximal tubular epithelial cells: sex, age, and species.

PubMed

Lu, Yongke; Kawashima, Akira; Horii, Ikuo; Zhong, Laifu

2005-01-01

Cisplatin (CP)-induced kidney damage and effects of DL-buthionine-(S,R)-sulfoximine (BSO) on it are species- and age-different. It remains unclear whether CP-induced cytotoxicity in renal proximal tubular epithelial cells (RTEC), the main target cells of CP, is also species- and age-different; and whether CP-induced cytotoxicity varies with the difference in age and species, if any, is one of the questions. In the present study, the effects of BSO on CP-induced cytotoxicity in primary cultures of RTEC isolated from monkeys and different age and sex rats were studied. The RTEC were isolated from 3-week-old, 2-month-old, or 5-month-old rats, and 6-8 year-old monkeys. After subculturing, RTEC was inoculated into type I collagen-coated 96-well culture plates; after preincubation, 40 microM BSO was added, 16 hours later, varying concentrations of CP were added. At that time, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were performed to test cell viability. The concentrations of CP that inhibited 50% cell growth (IC50) of RTEC from rats and monkeys were 1.11 and 3.03 mM at 8 hours, and 0.51 and 1.24 mM at 24 hours, respectively. The BSO made the IC50s of RTEC from rats and monkeys lower, down to 0.07 and 0.48 mM at 8 hours, and 0.02 and 0.11 mM at 24 hours, respectively. The IC50s of RTEC from different sex and age rats were almost same. These results suggested that CP-induced cytotoxicity was concentration- and time-dependent, with species-dependent differences, rat RTEC were more susceptible to CP than monkey RTEC, rat RTEC were more dependent on glutathione (GSH) during the stress state were than monkey cells; CP-induced cytotoxicity was without sex- and age-dependent differences in rat RTEC.

Intra-Prostate Cancer Vaccine Inducer

DTIC Science & Technology

2006-02-01

analyzed by flowcytometry for Ii and MHC class II expression. The active constructs were used for the Ii suppression in the experiments planned in...care guidelines under an approved protocol. Cell lines and antibodies Green monkey kidney COS cells (#CRL-1650), cultured in RPMI-1640 medium with...AIDS vaccine protection in rhesus monkeys . J Virol 2004;78(14):7490-7. 12. Letvin NL, Montefiori DC, Yasutomi Y, et al. Potent, protective anti-HIV

The Monkey game: A computerized verbal working memory task for self-reliant administration in primary school children.

PubMed

Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Jolani, Shahab; Van Luit, Johannes E H

2016-06-01

In two studies, the psychometric properties of an online self-reliant verbal working memory task (the Monkey game) for primary school children (6-12 years of age) were examined. In Study 1, children (n = 5,203) from 31 primary schools participated. The participants completed computerized verbal and visual-spatial working memory tasks (i.e., the Monkey game and the Lion game) and a paper-and-pencil version of Raven's Standard Progressive Matrices. Reading comprehension and math achievement test scores were obtained from the schools. First, the internal consistency of the Monkey game was examined. Second, multilevel modeling was used to examine the effects of classroom membership. Multilevel multivariate regression analysis was used to examine the Monkey game's concurrent relationship with the Lion game and its predictive relationships with reading comprehension and math achievement. Also, age-related differences in performance were examined. In Study 2, the concurrent relationships between the Monkey game and two tester-led computerized working memory tasks were further examined (n = 140). Also, the 1- and 2-year stability of the Monkey game was investigated. The Monkey game showed excellent internal consistency, good concurrent relationships with the other working memory measures, and significant age differences in performance. Performance on the Monkey game was also predictive of subsequent reading comprehension and mathematics performance, even after controlling for individual differences in intelligence. Performance on the Monkey game was influenced by classroom membership. The Monkey game is a reliable and suitable instrument for the online computerized and self-reliant assessment of verbal working memory in primary school children.

Continuous exposure of animals to methylisobutylketone

NASA Technical Reports Server (NTRS)

Vernot, E. H.; Macewen, J. D.; Harris, E. S.

1971-01-01

Continuous exposure of dogs, monkeys, mice, and rats to MIBK for two weeks and all animals except mice for 90 days resulted in measurable adverse effects only in the case of rats. Rat kidney weights and kidney to body weight ratios were significantly elevated after exposure to 410 mg/cu m for two weeks, and kidney and liver organ weights and organ to body weight ratios were elevated after exposure to 820 mg/cu m for two weeks and to 410 mg/cu m for 90 days.

Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

PubMed

Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

2003-09-15

The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues.

Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro.

PubMed

Vierboom, Michel P M; Ossevoort, Miriam; Sick, Ella A; Haanstra, Krista; Jonker, Margreet

2003-01-01

The development of an in vitro assay predicting the chances of graft survival after treatment with immunoregulatory agents is a major topic in transplantation. Antibodies (Abs) interfering in the costimulatory pathway are promising candidates for the induction of tolerance. To evaluate these antibodies for clinical use studies non-human primates are the only feasible option due to species specificity of the antibodies. Peripheral blood mononuclear cells, isolated from a large panel of rhesus monkeys, were used in a unidirectional mixed lymphocyte reaction to evaluate the ability of antibodies blocking the costimulatory pathway, to affect both primary and secondary proliferative and cytolytic allospecific immune responses in vitro. These blocking antibodies were also used in protocols prolonging allograft survival in a life-supporting kidney allotransplant model in rhesus macaques. The ultimate aim is to establish a correlation between parameters obtained in vitro and the success of transplantation in vivo. The combination of anti-CD80 and anti-CD86 resulted in a complete abrogation of the primary alloresponse as measured in a proliferation assay. Adding anti-CD40 significantly reduced this inhibitory effect although the in vivo effects of this antibody have been shown to be beneficial. The secondary response was most prominently inhibited by the combination of anti-CD80/86. Paradoxically, anti-CD40 alone markedly inhibited the secondary proliferative response, but did not add to the inhibitory effect of the combination of anti-CD80/86. The cytolytic response was inhibited maximally only when CsA was added to the combination of anti-CD80/86. Treatment with monoclonal antibodies alone without immunosuppressive drugs was sufficient to maintain graft survival during the time of treatment in most animals. However, rejection was initiated as soon as the treatment ceased and no tolerance, resulting in long-term graft and patient survival, was established. The complete inhibition of primary alloresponses and the partial inhibition of secondary proliferative alloresponses correlate with prolonged graft survival during treatment, but have no predictive value for the success of tolerance induction for kidney allografts in rhesus monkeys.

Characterization of ovarian aging and reproductive senescence in vervet monkeys (Chlorocebus aethiops sabaeus).

PubMed

Atkins, Hannah M; Willson, Cynthia J; Silverstein, Marnie; Jorgensen, Matthew; Floyd, Edison; Kaplan, Jay R; Appt, Susan E

2014-02-01

Female vervet monkeys (Chlorocebus aethiops sabaeus) are used as an experimental model for chronic diseases relevant to women's health. However, reproductive senescence (menopause) has not yet been characterized for vervet monkeys. Here we describe the histologic, hormonal, and menstrual markers of reproductive senescence in vervet monkeys from the Wake Forest Vervet Research Colony. Ovaries from monkeys (age, 0 to 27 y) were serially sectioned (5 μm), stained, and photographed. In every 100th section, the numbers of primordial, primary, and secondary follicles were determined, and triplicate measurements were used to calculate mean numbers of follicles per ovary. Antimüllerian hormone (AMH), follicle stimulating hormone, and menstrual cycle length were measured in additional monkeys. Primordial follicles and AMH decreased significantly with age, and significant correlations between numbers of primordial and primary follicles and between numbers of primary and secondary follicles were noted. Histologic evaluation revealed that ovaries from 4 aged monkeys (older than 23 y) were senescent. One aged monkey transitioned to menopause, experiencing cycle irregularity over 4 y, eventual cessation of menses, and plasma AMH below the level of detection. Finally, with increasing age, the percentage of female vervets with offspring declined significantly. The present study provides insight into ovarian aging and reproductive senescence in vervet monkeys. Results highlight the importance of considering this nonhuman primate as a model to investigate the relationships between ovarian aging and chronic disease risk.

Cloning and sequencing of the cDNA species for mammalian dimeric dihydrodiol dehydrogenases.

PubMed Central

Arimitsu, E; Aoki, S; Ishikura, S; Nakanishi, K; Matsuura, K; Hara, A

1999-01-01

Cynomolgus and Japanese monkey kidneys, dog and pig livers and rabbit lens contain dimeric dihydrodiol dehydrogenase (EC 1.3.1.20) associated with high carbonyl reductase activity. Here we have isolated cDNA species for the dimeric enzymes by reverse transcriptase-PCR from human intestine in addition to the above five animal tissues. The amino acid sequences deduced from the monkey, pig and dog cDNA species perfectly matched the partial sequences of peptides digested from the respective enzymes of these animal tissues, and active recombinant proteins were expressed in a bacterial system from the monkey and human cDNA species. Northern blot analysis revealed the existence of a single 1.3 kb mRNA species for the enzyme in these animal tissues. The human enzyme shared 94%, 85%, 84% and 82% amino acid identity with the enzymes of the two monkey strains (their sequences were identical), the dog, the pig and the rabbit respectively. The sequences of the primate enzymes consisted of 335 amino acid residues and lacked one amino acid compared with the other animal enzymes. In contrast with previous reports that other types of dihydrodiol dehydrogenase, carbonyl reductases and enzymes with either activity belong to the aldo-keto reductase family or the short-chain dehydrogenase/reductase family, dimeric dihydrodiol dehydrogenase showed no sequence similarity with the members of the two protein families. The dimeric enzyme aligned with low degrees of identity (14-25%) with several prokaryotic proteins, in which 47 residues are strictly or highly conserved. Thus dimeric dihydrodiol dehydrogenase has a primary structure distinct from the previously known mammalian enzymes and is suggested to constitute a novel protein family with the prokaryotic proteins. PMID:10477285

COMPARISON OF EFFECTS OF DEUTERIUM OXIDE AND X-RAY IRRADIATION ON MULTIPLICATION OF POLIOVIRUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kritchevsky, D.; Manson, L.A.; Hartzell, R.W. Jr.

1963-01-01

An attenuated strain of poliomyelitis virus (CHAT) will not grow in monkey kidney cells at 40 un. Concent 85% C. When deuterium oxide (25 to 40%) is present in the medium, replication of CHAT virus will take place at 40 un. Concent 85% C. Since both deuterium oxide treatment and irradiation with x rays yield giant cells, the 2 treatments have been compared for their ability to support the growth of CHAT poliovirus at 40 un. Concent 85% C. At several levels of x irradiation, monkey kidney cells will not support the growth of CHAT virus at 40 un. Concentmore » 85% C. When D/sub 2/O is added to he medium of the x- irradiated cells at 40 un. Concent 85% C, replication of CHAT virus is observed. The effect is not due to cell size or number. (auth)« less

Molecular analyses of oral polio vaccine samples.

PubMed

Poinar, H; Kuch, M; Pääbo, S

2001-04-27

It has been suggested that the human immunodeficiency virus (HIV), and thus the acquired immunodeficiency syndrome (AIDS) it causes, was inadvertently introduced to humans by the use of an oral polio vaccine (OPV) during a vaccination campaign launched by the Wistar Institute, Philadelphia, PA, USA, in the Belgian Congo in 1958 and 1959. The "OPV/AIDS hypothesis" suggests that the OPV used in this campaign was produced in chimpanzee kidney epithelial cell cultures rather than in monkey kidney cell cultures, as stated by H. Koprowski and co-workers, who produced the OPV. If chimpanzee cells were indeed used, this would lend support to the OPV/AIDS hypothesis, since chimpanzees harbor a simian immunodeficiency virus, widely accepted to be the origin of HIV-1. We analyzed several early OPV pools and found no evidence for the presence of chimpanzee DNA; by contrast, monkey DNA is present.

The Aristotelian kidney.

PubMed

Marandola, P; Musitelli, S; Jallous, H; Speroni, A; de Bastiani, T

1994-01-01

Aristotle incorrectly observed the absence of the kidney in fish and birds and deduced that it was not essential for the existence of a living organism. This underlies his observations on structure and function of the kidney. From examination of rhesus monkeys he generalized that the right kidney is higher than the left. Aristotle did not consider that the renal pelvis is divided by a filter membrane into 2 chambers, and wrote that no blood reaches the renal pelvis. The theory of the 'filter kidney' cannot thus be attributed to Aristotle. The function of the kidney was described as being to separate the surplus liquid from the blood inside the renal meat (not in the renal pelvis) and to transform this liquid into what Aristotle called residuum, i.e. the urine. Aristotle also considered that the kidneys acted to anchor the blood vessels to the body. He only briefly considered renal pathology.

[Explantation method of isolating a persistent tick-borne encephalitis virus from the organs of infected monkeys].

PubMed

Levina, L S; Pogodina, V V

1981-01-01

The method of explantation was used to examine 63 organs from M. rhesus monkeys 92-783 days after intracerebral and subcutaneous inoculation with the Vasilchenko, Aina/1448 and 41/65 strains of tick-borne encephalitis virus. The optimal time for examination of the explants by tests of the hemagglutinating, cytopathogenic activity of the virus and its pathogenicity for mice was found to be the 15th day of cultivation. A comparative study of the properties of 3 isolates obtained from explants of the spleen, liver and subcortical cerebral ganglia 202 and 307 days after inoculation of monkeys was carried out. The isolates differed from the parental TBE virus strains by their capacity to form small plaques in PEKV cell cultures (pig embryo kidney cells in versen medium).

Pathobiological and Behavioral Effects of Lead Intoxication in the Infant Rhesus Monkey

PubMed Central

Allen, J. R.; McWey, P. J.; Suomi, S. J.

1974-01-01

When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5–9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers, they developed symptoms of lead intoxication within 6 weeks. Seizures, muscular tremors, and altered social interaction were the predominant changes. Visual impairment was also apparent in the more severely affected animals. In the animals showing obvious symptoms lead levels varied between 300 to 500 μg/100 ml of blood. Even in those animals having blood lead levels below 100 μg, hyperactivity and insomnia were observed. When the exposure to lead was eliminated, seizures subsided and visual impairment was reduced; however, the abnormal social interaction persisted. These animals also experienced a gradual decline in hematocrit and hemoglobin values during the period of examination. Liver and kidney biopsies obtained from these lead-exposed animals revealed characteristic intranuclear inclusions. When adolescent and adult monkeys were exposed to doses of lead acetate similar to those employed in the infant experiments, lead levels in excess of 200 μg/100 ml of blood were recorded. However, there were no obvious behavioral abnormalities observed. There were, however, numerous lead inclusion bodies in kidney biopsy specimens from these animals. These data suggest that, like man, the infant nonhuman primate is much more susceptible to lead intoxication than is the adult. The clinical and behavioral changes recorded in these infant rhesus monkeys suggest their use as an experimental model to evaluate lead intoxication. ImagesFIGURE 6. PMID:4208658

Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model.

PubMed

Moghadasali, Reza; Azarnia, Mahnaz; Hajinasrollah, Mostafa; Arghani, Hassan; Nassiri, Seyed Mahdi; Molazem, Mohammad; Vosough, Ahmad; Mohitmafi, Soroush; Najarasl, Mostafa; Ajdari, Zahra; Yazdi, Reza Salman; Bagheri, Mohsen; Ghanaati, Hossein; Rafiei, Behrooz; Gheisari, Yousof; Baharvand, Hossein; Aghdami, Nasser

2014-06-01

Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI. We chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology. Transplantation of 5 × 10(6) cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups. These data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Leaf Selection by Two Bornean Colobine Monkeys in Relation to Plant Chemistry and Abundance

PubMed Central

Matsuda, Ikki; Tuuga, Augustine; Bernard, Henry; Sugau, John; Hanya, Goro

2013-01-01

Focusing on the chemical basis of dietary selection while investigating the nutritional ecology of animals helps understand their feeding biology. It is also important to consider food abundance/biomass while studying the mechanism of animal food selection. We studied leaf selection in two Bornean folivorous primates in relation to plant chemistry and abundance: proboscis monkeys inhabiting a secondary riverine forest and red leaf monkeys inhabiting a primary forest. Both species tended to prefer leaves containing higher protein levels, although more abundant plant species were chosen within the preferred species, probably to maximise energy gain per unit time. However, the two species showed clear differences in their detailed feeding strategy. Red leaf monkeys strictly chose to consume young leaves to adapt to the poor nutritional environment of the primary forest, whereas proboscis monkeys were not highly selective because of the better quality of its common food in the riverine forest. PMID:23695180

Isolation and characterization of an equine rotavirus.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus, designated as the H-1 strain, was isolated from a diarrheic foal in primary African green monkey kidney cells and MA104 cells. This cell culture-adapted strain hemagglutinated erythrocytes of human group O, rhesus monkeys, guinea pigs, and sheep. It was found to be similar, if not identical, to porcine rotaviruses (strains OSU, EE, and A-580) by plaque reduction neutralization and hemagglutination inhibition tests, and, in addition, it was found to belong to subgroup 1. This equine rotavirus has an RNA electrophoretic migration pattern which was distinct from those of the three strains of porcine rotavirus. The serological relationship established by plaque reduction neutralization and hemagglutination inhibition tests between the equine (H-1) and porcine (OSU, EE, and A-580) rotaviruses is an example of a rotavirus of the same serotype being isolated from different species. The H-1 strain was distinct from four human rotavirus serotypes (Wa, DS-1, P, and St. Thomas 4) as well as from bovine rotavirus NCDV, simian rotavirus MMU18006, and canine rotavirus CU-1 by plaque reduction neutralization tests. This equine isolate (H-1) was found to be related antigenically to canine CU-1 and bovine NCDV rotaviruses in a one-way fashion by hemagglutination inhibition tests. Images PMID:6313746

Pharmacodynamics and subchronic toxicity in mice and monkeys of ISIS 388626, a second-generation antisense oligonucleotide that targets human sodium glucose cotransporter 2.

PubMed

Zanardi, Thomas A; Han, Su-Cheol; Jeong, Eun Ju; Rime, Soyub; Yu, Rosie Z; Chakravarty, Kaushik; Henry, Scott P

2012-11-01

ISIS 388626, a 2'-methoxyethyl (MOE)-modified antisense oligonucleotide (ASO) that targets human sodium glucose cotransporter 2 (SGLT2) mRNA, is in clinical trials for the management of diabetes. SGLT2 plays a pivotal role in renal glucose reabsorption, and inhibition of SGLT2 is anticipated to reduce hyperglycemia in diabetic subjects by increasing urinary glucose elimination. To selectively inhibit SGLT2 in the kidney, ISIS 388626 was designed as a "shortmer" ASO, consisting of only 12 nucleotides with two 2'-MOE-modified nucleotides at the termini. Mice and monkeys received up to 30 mg/kg/week ISIS 388626 via subcutaneous injection for 6 or 13 weeks. Dose-dependent decreases in renal SGLT2 mRNA expression were observed, which correlated with dose-related increases in glucosuria without concomitant hypoglycemia. There were no histologic changes in the kidney attributed to SGLT2 inhibition after 6 or 13 weeks of treatment. The remaining changes observed in these studies were typical of those produced in these species by the administration of oligonucleotides, correlated with high doses of ISIS 388626, and were unrelated to the inhibition of SGLT2 expression. The kidney contained the highest concentration of ISIS 388626, and dose-dependent basophilic granule accumulation in tubular epithelial cells of the kidney, which is evidence of oligonucleotide accumulation in these cells, was the only histologic change identified. No changes in kidney function were observed. These results revealed only readily reversible changes after the administration of ISIS 388626 and support the continued investigation of the safety and efficacy of ISIS 388626 in human trials.

Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash.

PubMed

Siegel, C; Johnston, S; Adair, S

1990-10-01

The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy.

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Occurrence of nonspecific reactions among stool specimens tested by the Abbott TestPack rotavirus enzyme immunoassay.

PubMed Central

Lipson, S M; Leonardi, G P; Salo, R J; Schutzbank, T E; Kaplan, M H

1990-01-01

Sixty-five stool specimens obtained from children suffering from gastroenteritis were tested for the presence of antigen to rotavirus by the Abbott TestPack Rotavirus (TestPack) enzyme immunoassay kit. The Kallestad Pathfinder enzyme immunoassay, polyacrylamide gel electrophoresis, immune electron microscopy, and virus isolation were utilized as reference assays. Fifty-four specimens were in accord by TestPack and Kallestad Pathfinder. Among 11 discordant specimens positive with TestPack but negative by Kallestad Pathfinder, rotavirus was not identified by polyacrylamide gel electrophoresis, immune electron microscopy, or isolation in primary African green monkey kidney cell cultures. TestPack displayed a performance specificity of 83%. The inordinately high number of stool specimens reported as false-positive by TestPack precludes the incorporation of this antigen detection kit into our routine regimen of diagnostic virologic testing. Images PMID:2166074

Serotypic characterization of rotaviruses derived from asymptomatic human neonatal infections.

PubMed Central

Hoshino, Y; Wyatt, R G; Flores, J; Midthun, K; Kapikian, A Z

1985-01-01

Nineteen rotavirus strains derived from asymptomatic neonates (seven from England, five from Australia, two from Venezuela, and five from Sweden) were successfully cultivated in primary African green monkey kidney cell cultures, serotyped by plaque reduction neutralization tests, subgrouped by indirect enzyme-linked immunosorbent assay, and electropherotyped by polyacrylamide gel electrophoresis. All 19 strains were shown to fall into one of the four known human serotypes; serotype 1 (all Venezuelan strains), serotype 2 (all Swedish strains), serotype 3 (all Australian strains), or serotype 4 (all English strains). Hyperimmune guinea pig serum raised against the Venezuelan strain (M37) neutralized not only serotype 1 (strain Wa) but also serotype 4 (strain St. Thomas no. 3) viruses to a similar degree. The English, Australian, and Venezuelan isolates were found to belong to subgroup 2, and the Swedish strains were subgroup 1 viruses. The potential importance of these rotaviruses obtained from neonates as possible vaccine candidates is discussed. Images PMID:2984247

9 CFR 113.55 - Detection of extraneous agents in Master Seed Virus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... MSV that is found unsatisfactory by any prescribed test. (a) At least a 1.0 ml aliquot per cell... monkey kidney) cell line; (2) Embryonic cells, neonatal cells, or a cell line of the species for which...) and (a)(2) of this section. Cell lines used shall have been found satisfactory when tested as...

Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney vero cells

USDA-ARS?s Scientific Manuscript database

Aflatoxin (AF)-producing fungi contaminate food and feed during preharvest, storage and processing periods. Once consumed, AF accumulates in tissues, causing illnesses in animals and humans. At least 20 different types of AFs have been identified, and of these, aflatoxin B1 (AFB1) is the most ubiqui...

Persistent Neuronal Firing in Primary Somatosensory Cortex in the Absence of Working Memory of Trial-Specific Features of the Sample Stimuli in a Haptic Working Memory Task

ERIC Educational Resources Information Center

Wang, Liping; Li, Xianchun; Hsiao, Steven S.; Bodner, Mark; Lenz, Fred; Zhou, Yong-Di

2012-01-01

Previous studies suggested that primary somatosensory (SI) neurons in well-trained monkeys participated in the haptic-haptic unimodal delayed matching-to-sample (DMS) task. In this study, 585 SI neurons were recorded in monkeys performing a task that was identical to that in the previous studies but without requiring discrimination and active…

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC-MS/MS.

PubMed

Pandey, Saurabh; Gautam, Nagsen; Kushwaha, Hari Narayan; Singh, Shio Kumar

2016-12-01

The pharmacokinetic profile of 99/411, a novel anti-malarial drug, was established in rats (12 mg/kg of body weight) and monkeys (20 mg/kg of body weight). Following oral administration, the presence of 99/411 was rapidly determined in rat plasma, tissues, urine, feces and monkey plasma using a validated LC-MS/MS method. The tissue distribution studies in rats indicated that the drug was partially distributed in all major tissues and plasma, and peak concentration levels were achieved within 0.5-4 h. Area under the curve in different rat tissues and plasma was found in order of blood > lung > intestine > heart > muscle > brain > kidney > spleen > liver. The total recoveries (within 86 h) of 99/411 were <0.0017% and <0.08% in urine and feces, respectively. The peak plasma concentration was 3499 ng/mL in rats after ~2 h of oral administration and 697-767 ng/mL in monkeys after ~6 h of oral administration. No plasma accumulation was observed in both male and female monkeys, even after multiple dosing. The preclinical pharmacokinetic profile and tissue distribution data are expected to assist in future clinical explorations of 99/411 as a promising anti-malarial agent. Copyright © 2016 John Wiley & Sons, Ltd.

Histopathology of Incidental Findings in Cynomolgus Monkeys (Macaca Fascicularis) Used in Toxicity Studies

PubMed Central

Sato, Junko; Doi, Takuya; Kanno, Takeshi; Wako, Yumi; Tsuchitani, Minoru; Narama, Isao

2012-01-01

The purpose of our publication is to widely communicate pictures of spontaneous findings occurring in cynomolgus monkeys. Focal lymphoplasmacytic infiltration is commonly seen in the general organs. The frequency and severity of these lesions may be influenced by the administration of drugs with an effect on the immune system. Lymphoplasmacytic infiltration in the lamina propria of the stomach is also frequently seen in cynomolgus monkeys, and it is caused mainly by a Helicobacter pylori infection. Various degrees of brown pigments are observed in various organs, and it is possible to distinguish the material of the pigments by its morphological features and site. A focal/segmental glomerular lesion is occasionally seen in a section of the kidney, and the minimal lesion has no influence on the urinalysis. We showed the common glomerular lesions in HE-stained sections, as well as in PAM- or PAS-stained sections, for understanding the details. Young and pubertal monkeys are usually used in toxicity studies; therefore, understanding various maturation stages of the genital system is important. In particular, the female genital system needs to be understood in the morphology, because their cyclic changes are different from other laboratory animals. Thus, we present the normal features of the cyclic changes of the female genital organs. Furthermore, we provide more information on spontaneous findings in cynomolgus monkeys for exact diagnoses in toxicity studies. PMID:22481861

Exogenous ACE2 Expression Allows Refractory Cell Lines To Support Severe Acute Respiratory Syndrome Coronavirus Replication

PubMed Central

Mossel, Eric C.; Huang, Cheng; Narayanan, Krishna; Makino, Shinji; Tesh, Robert B.; Peters, C. J.

2005-01-01

Of 30 cell lines and primary cells examined, productive severe acute respiratory syndrome coronavirus (Urbani strain) (SARS-CoV) infection after low-multiplicity inoculation was detected in only six: three African green monkey kidney epithelial cell lines (Vero, Vero E6, and MA104), a human colon epithelial line (CaCo-2), a porcine kidney epithelial line [PK(15)], and mink lung epithelial cells (Mv 1 Lu). SARS-CoV produced a lytic infection in Vero, Vero E6, and MA104 cells, but there was no visible cytopathic effect in Caco-2, Mv 1 Lu, or PK(15) cells. Multistep growth kinetics were identical in Vero E6 and MA104 cells, with maximum titer reached 24 h postinoculation (hpi). Virus titer was maximal 96 hpi in CaCo-2 cells, and virus was continually produced from infected CaCo-2 cells for at least 6 weeks after infection. CaCo-2 was the only human cell type of 13 tested that supported efficient SARS-CoV replication. Expression of the SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), resulted in SARS-CoV replication in all refractory cell lines examined. Titers achieved were variable and dependent upon the method of ACE2 expression. PMID:15731278

Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons

NASA Astrophysics Data System (ADS)

Cox, A. B.; Wood, D. H.; Lett, J. T.

Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey /1-3/, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (~2.6 cm) than the 32 MeV protons (~0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.

Renal evaluation of Aotus azarai infulatus by ultrasonography and serum chemistry profile.

PubMed

Lins, Fernanda Luiza de Miranda Lins e; Monteiro, Frederico Ozanan Barros; Takeshita, Rafaela Sayuri Cicalise; da Silva, Gilmara Abreu; Faturi, Cristian; Palha, Maria das Dores Correia; Monteiro, Maria Vivina Barros; Coutinho, Leandro Nassar; Kugelmeier, Tatiana; de Castro, Paulo Henrique Gomes

2012-05-01

This study aimed to characterize anatomical and biochemical properties of owl monkey kidneys in order to provide normal reference values. Sixty-nine Aotus azarai infulatus (45 males and 24 females) were divided into four different age groups (AG1: 3 months-1 year; AG2: 2-3 years; AG3: 4-6 years; and AG4: over 7 years old). The monkeys were evaluated with a serum chemistry profile, focusing on serum creatinine (SCr) and blood urea nitrogen (BUN) and with ultrasound. Mean body mass differed among the age groups. This significance was attributed to AG1 body mass being significantly lower than in AG2 and that in both AG2 and AG3 being significantly lower than in the two older age groups (AG3 and AG4). SCr and BUN concentrations differed significantly between the sexes and SCr level correlated positively with age. In contrast, renal measurements did not differ between males and females. Left and right renal volumes did not differ significantly within age groups, or among AG2, AG3, and AG4. Renal volumes in AG1, however, while not differing from those in AG2, did differ significantly from those in AG3 and AG4. In conclusion, this study provides ultrasonographic reference values for the morphology the kidneys in A. a. infulatus. Evidence is also provided that SCr and BUN levels in owl monkeys are influenced by the sex and age of the individual, factors that should be considered when interpreting test results. © 2012 Wiley Periodicals, Inc.

The PapG-adhesin at the tip of P-fimbriae provides Escherichia coli with a competitive edge in experimental bladder infections of cynomolgus monkeys

PubMed Central

1995-01-01

Human urinary tract infection is an infectious disease that depends on a series of host-microbial interactions. The bacteria first colonize the colon and then the periurethral/vaginal areas; they ascend to and infect first the bladder and then the kidneys. Expression of Escherichia coli P-fimbriae constitutes the strongest correlation to renal pathogenicity, but is also related to first-time cystitis in children. The role of P-fimbriae in the preceding steps in the infectious process is unknown. To examine this, we constructed, from a P-fimbriated E. coli strain with a class II G-adhesin preferentially binding to globoside, one isogenic mutant lacking the G-adhesin and another isogenic mutant in which we replaced the papG class II allele with a class III adhesin preferentially binding to the Forssman antigen. We report here the comparison of the adhesin knockout mutant (DS17-8) and the class-switch mutant (DS17-1) with the wild-type (DS17) for in vivo colonization of the gut, vagina, and bladder of cynomolgus monkeys. It was recently shown that the class II tip G-adhesin is a prerequisite for acute pyelonephritis to occur in the monkey model in the absence of other kidney-specific adhesins or obstruction of the urinary flow. Here we show that it is not required for bladder infection but gives a competitive advantage in mixed infections. In the vagina and colon, the G-adhesin gives no competitive advantage. PMID:7500014

Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

PubMed Central

Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

2017-01-01

Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity was 87.6%, and was eliminated in feces (49.8% of dose) and to a lesser extent in urine (20.6% of dose). Conclusion Together, the results indicate that APX001-related radioactivity is extensively distributed to major tissues (including tissues relevant to IFI) in both rats and monkeys and cleared primarily by biliary/fecal excretion. Disclosures R. Mansbach, Amplyx Pharmaceuticals Inc.: Consultant, Consulting fee; K. J. Shaw, Amplyx Pharmaceuticals Inc.: Employee, Salary; M. R. Hodges, Amplyx Pharmaceuticals: Employee, Salary; S. Coleman, Covance Laboratories: Employee, Salary; M. E. Fitzsimmons, Covance Laboratories: Employee, Salary

Continuous animal exposure to dichloromethane

NASA Technical Reports Server (NTRS)

Macewen, J. D.; Vernot, E. H.; Haun, C. C.

1972-01-01

Continuous exposures of dogs, monkeys, rats and mice to 5000 ppm and 1000 ppm of dichloromethane vapor (CH2Cl2) produced severe toxic effects on dogs, rats and mice. Dogs died after 3 weeks exposure to 1000 ppm and after 6 weeks exposure to 5000 ppm. Thirty percent of the mice also succumbed during four weeks exposure to 5000 ppm CH2Cl2. Although rats survived 14 weeks exposure to 5000 ppm, they experienced subnormal weight gains. Significant gross and histopathological hepatic lesions were noted in all 3 species at death or experimental termination in 14 weeks. In addition, rats showed abnormal kidney histopathology. Fat stains disclosed mild fatty increase in monkey livers after 14 weeks exposure to 1000 ppm CH2Cl2.

The examination of urine samples for pathogenic microbes by the luciferase assay for ATP. 1: The effect of the presence of fungi, fungal like bacteria and kidney cells in urine samples

NASA Technical Reports Server (NTRS)

Bush, V. N.

1973-01-01

A method for accurately determining urinary tract infections in man is introduced. The method is based on adenosine triphosphate (ATP) concentration in urine samples after removing nonbacterial ATP. Adenosine triphosphate concentration is measured from the bioluminescent reaction of luciferase when mixed with ATP. An examination was also made of the effectiveness of rupturing agents on monkey kidney cells Candia albicans, a Rhodotorula species, and a Streptomyces species in determining whether these cells could contribute ATP to the bacterial ATP value of a urine sample.

Studies on Typhus and Spotted Fever.

DTIC Science & Technology

1980-02-01

prowazekii-infected human somatic (fibroblast, endothelia)), but not chick, mouse or monkey , cells in culture: (a) intracellular antirickettsial action...that of the controls. No such effect on growth was apparent in CE cells, Nu E % o0 M Ŕ ZOO - .0 E 00 (1 CI - 4D W = .) C ~ o r- -!NBI Go !N 21501,,o o...human origin transformed or malignant cells, monkey primary or diploid and primary mouse embryo fibroblasts will permit expression of these effects to

A neural correlate of working memory in the monkey primary visual cortex.

PubMed

Supèr, H; Spekreijse, H; Lamme, V A

2001-07-06

The brain frequently needs to store information for short periods. In vision, this means that the perceptual correlate of a stimulus has to be maintained temporally once the stimulus has been removed from the visual scene. However, it is not known how the visual system transfers sensory information into a memory component. Here, we identify a neural correlate of working memory in the monkey primary visual cortex (V1). We propose that this component may link sensory activity with memory activity.

Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

PubMed

Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

2013-12-01

Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

Prevention of Influenza and other Respiratory Diseases

DTIC Science & Technology

1977-08-01

Virus isolation was attempted from throat washings collected in beef extract broth. These were stored at approximately -50 In a refrigerator at Lowry... throat cultures and blood specimens with individual Informed consent. Cooperation was remarkably good. Throat cultures were taken from...more rapidly in Rhesus monkey kidney tissue culture than did the A/Denver/77 strains. Viruses were isolated from 9 of 13 throat washings from

Two separable functional domains of simian virus 40 large T antigen: carboxyl-terminal region of simian virus 40 large T antigen is required for efficient capsid protein synthesis.

PubMed Central

Tornow, J; Polvino-Bodnar, M; Santangelo, G; Cole, C N

1985-01-01

The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T antigen lacks those residues known to be required for adenovirus helper function, and the block to productive infection by dlA2459 occurs at the same stage of infection as the block to productive adenovirus infection of CV-1 cells. These results suggest that the adenovirus helper function is required for productive infection by simian virus 40. Mutant dlA2459 was able to grow on the Vero and BSC-1 lines of African green monkey kidney cells. Additional mutants affecting the carboxyl-terminal portion of large T were prepared. Mutant inv2408 contains an inversion of the DNA between the BamHI and BclI sites (0.144 to 0.189 map units). This inversion causes transposition of the carboxyl-terminal 26 amino acids of large T antigen and the carboxyl-terminal 18 amino acids of VP1. This mutant was viable, even though the essential information absent from dlA2459 large T antigen has been transferred to the carboxyl terminus of VP1 of inv2408. The VP1 polypeptide carrying this carboxyl-terminal portion of large T could overcome the defect of dlA2459. This indicates that the carboxyl terminus of large T antigen is a separate and separable functional domain. Images PMID:2982029

Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo

We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retardingmore » ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.« less

Safety, Pharmacokinetic, and Efficacy Studies of Oral DB868 in a First Stage Vervet Monkey Model of Human African Trypanosomiasis

PubMed Central

Thuita, John K.; Wolf, Kristina K.; Murilla, Grace A.; Liu, Qiang; Mutuku, James N.; Chen, Yao; Bridges, Arlene S.; Mdachi, Raymond E.; Ismail, Mohamed A.; Ching, Shelley; Boykin, David W.; Hall, James Edwin; Tidwell, Richard R.; Paine, Mary F.; Brun, Reto; Wang, Michael Zhuo

2013-01-01

There are no oral drugs for human African trypanosomiasis (HAT, sleeping sickness). A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization, thus reducing healthcare costs of HAT. The development of oral medications is a key objective of the Consortium for Parasitic Drug Development (CPDD). In this study, we investigated the safety, pharmacokinetics, and efficacy of a new orally administered CPDD diamidine prodrug, 2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868; CPD-007-10), in the vervet monkey model of first stage HAT. DB868 was well tolerated at a dose up to 30 mg/kg/day for 10 days, a cumulative dose of 300 mg/kg. Mean plasma levels of biomarkers indicative of liver injury (alanine aminotransferase, aspartate aminotransferase) were not significantly altered by drug administration. In addition, no kidney-mediated alterations in creatinine and urea concentrations were detected. Pharmacokinetic analysis of plasma confirmed that DB868 was orally available and was converted to the active compound DB829 in both uninfected and infected monkeys. Treatment of infected monkeys with DB868 began 7 days post-infection. In the infected monkeys, DB829 attained a median Cmax (dosing regimen) that was 12-fold (3 mg/kg/day for 7 days), 15-fold (10 mg/kg/day for 7 days), and 31-fold (20 mg/kg/day for 5 days) greater than the IC50 (14 nmol/L) against T. b. rhodesiense STIB900. DB868 cured all infected monkeys, even at the lowest dose tested. In conclusion, oral DB868 cured monkeys with first stage HAT at a cumulative dose 14-fold lower than the maximum tolerated dose and should be considered a lead preclinical candidate in efforts to develop a safe, short course (5–7 days), oral regimen for first stage HAT. PMID:23755309

Fatal Angiostrongylus dujardini infection in callitrichid monkeys and suricates in an Italian zoological garden.

PubMed

Eleni, Claudia; Di Cesare, Angela; Cavicchio, Paolo; Tonnicchia, Maria Cristina; Meoli, Roberta; di Regalbono, Antonio Frangipane; Paoletti, Barbara; Pietrobelli, Mario; De Liberato, Claudio

2016-08-01

This paper reports four fatal cases of metastrongylid nematode Angiostrongylus dujardini infection observed in a Saguinus oedipus and a Callimico goeldii monkey and in two suricates (Suricata suricatta). All animals were kept in captivity in a zoo of central Italy. The two monkeys died with no premonitory signs, while the two-month-old suricates showed malaise, anorexia and tachypnea for a few days prior to death. Cardiomegaly and/or granulomatous pneumonia were the major anatomo-pathological findings. Inflammatory lesions were observed in the liver, heart and kidney of the suricates at histology. A. dujardini diagnosis was confirmed through both morphological identification of adult worms recovered at necropsy and molecular characterization of larvae in tissue samples. Callitrichidae and suricates are active predators and maintain their hunting behaviour in captivity and it is then likely that they were exposed to infection by preying on parasitized gastropods, intermediate hosts of A. dujardini, entering zoo enclosures from the surrounding environment. This is the first report of A. dujardini in Italy and in S. suricatta. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sex differences in rhesus monkey toy preferences parallel those of children

PubMed Central

Hassett, Janice M.; Siebert, Erin R.; Wallen, Kim

2008-01-01

Socialization processes, parents, or peers encouraging play with gender specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough and tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans. PMID:18452921

Nature of the refractive errors in rhesus monkeys (Macaca mulatta) with experimentally induced ametropias.

PubMed

Qiao-Grider, Ying; Hung, Li-Fang; Kee, Chea-Su; Ramamirtham, Ramkumar; Smith, Earl L

2010-08-23

We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. Copyright 2010 Elsevier Ltd. All rights reserved.

Nature of the Refractive Errors in Rhesus Monkeys (Macaca mulatta) with Experimentally Induced Ametropias

PubMed Central

Qiao-Grider, Ying; Hung, Li-Fang; Kee, Chea-su; Ramamirtham, Ramkumar; Smith, Earl L.

2010-01-01

We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. PMID:20600237

Various heterologous cells exhibit interferon induced transfer of viral resistance.

PubMed

Hughes, T K; Blalock, J E; Baron, S

1978-01-01

Previously it was shown that cocultivation of mouse L and human WISH or baby hamster kidney cells in the presence of mouse interferon resulted in decreased viral yield from both cell species. We now show that this phenomenon also occurs when rabbit kidney and human WISH cells, with their corresponding interferons, are cocultivated with human WISH and baby hamster kidney cells, respectively. This finding increases the number of donor cell types to three. The related finding that monkey VERO and chick embryo cells can be recipients of transferred resistance expands the number of heterologous recipient cell species capable of receiving transferred resistence to five. Not all cell types tested have been shown to function in this transfer system. The fact that VERO cells, which do not produce interferon, are capable of receiving transferred resistence is significant because it indicates that the mechanism of transfer does not involve production or interferon by the recipient cells.

Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys

PubMed Central

Pathiraja, Vimukthi; Villani, Vincenzo; Tasaki, Masayuki; Matar, Abraham J.; Duran-Struuck, Raimon; Yamada, Rei; Moran, Shannon G.; Clayman, Eric S.; Hanekamp, John; Shimizu, Akira; Sachs, David H.; Huang, Christene A.; Yamada, Kazuhiko

2016-01-01

We have previously reported that transplantation (Tx) of prevascularized donor islets as composite Islet-Kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cells (HSC) Tx in an attempt to induce tolerance in non-human primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IKTx. HSCTx was performed following mobilization and leukapheresis of the donors, and conditioning of the recipients with total body irradiation, T-cell depletion and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IKTx was performed either 20–22 (n=3) or 208 (n=1) days after HSCTx. All animals accepted IKs without rejection. All recipients required >20 U/day of insulin before IKTx to maintain less than 200mg/dl, whereas after IKTx 3 animals required minimal doses of insulin (1–3 U/day) and one animal was insulin-free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression. PMID:27376692

Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gozalo, Alfonso S.; Chavera, Alfonso; Montoya, Enrique J.

2008-02-01

The purpose of this study was to determine serum reference values for crea- tine kinase (CK), aspartate aminotransferase (AST), and lactate dehydroge- nase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease. Urine samples were also collected and semi-quantitative tests performed. There was no statistically significant difference between CK, AST, and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition, the CK/AST ratio revealed that 29% of the animals included in this study hadmore » values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries, and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman’s capsule, and peritubular space fibroplasia. These findings suggest that CK, AST, and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria, and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction.« less

Quantity Representation in Children and Rhesus Monkeys: Linear Versus Logarithmic Scales

ERIC Educational Resources Information Center

Beran, Michael J.; Johnson-Pynn, Julie S.; Ready, Christopher

2008-01-01

The performances of 4- and 5-year-olds and rhesus monkeys were compared using a computerized task for quantity assessment. Participants first learned two quantity anchor values and then responded to intermediate values by classifying them as similar to either the large anchor or the small anchor. Of primary interest was an assessment of where the…

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

PubMed

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

PubMed Central

Khachaturian, Mark Haig

2010-01-01

Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4–8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic). PMID:21243106

Prevention of renal scarring from pyelonephritis in nonhuman primates by vaccination with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate.

PubMed Central

Roberts, J A; Kaack, M B; Baskin, G; Svenson, S B

1993-01-01

Rhesus monkeys were vaccinated with a synthetic Escherichia coli serotype O8 oligosaccharide-protein conjugate. Using our experimental pyelonephritis monkey model, we tested whether such immunization was protective against the renal damage from inflammation following experimental infection with a P-fimbriated O-antigenically homologous E. coli strain. The vaccination did not significantly alter the duration of bacteriuria or interfere with the infection. However, the vaccine was efficient in renal protection, as vaccinated animals showed significantly less intratubular infiltration of neutrophils (P < 0.02) and the degree of renal scarring was also significantly less in these animals (P > 0.005) than in the control animals. Total kidney involvement in the vaccinated animals was 16.9%, compared with 32.5% in the control animals (P = 0.07). PMID:8225595

Internally-generated error signals in monkey frontal eye field during an inferred motion task

PubMed Central

Ferrera, Vincent P.; Barborica, Andrei

2010-01-01

An internal model for predictive saccades in frontal cortex was investigated by recording neurons in monkey frontal eye field during an inferred motion task. Monkeys were trained to make saccades to the extrapolated position of a small moving target that was rendered temporarily invisible and whose trajectory was altered. On roughly two-thirds of the trials, monkeys made multiple saccades while the target was invisible. Primary saccades were correlated with extrapolated target position. Secondary saccades significantly reduced residual errors resulting from imperfect accuracy of the first saccade. These observations suggest that the second saccade was corrective. As there was no visual feedback, corrective saccades could only be driven by an internally generated error signal. Neuronal activity in the frontal eye field was directionally tuned prior to both primary and secondary saccades. Separate subpopulations of cells encoded either saccade direction or direction error prior to the second saccade. These results suggest that FEF neurons encode the error after the first saccade, as well as the direction of the second saccade. Hence, FEF appears to contribute to detecting and correcting movement errors based on internally generated signals. PMID:20810882

Characterization, efficacy, pharmacokinetics, and biodistribution of 5kDa mPEG modified tetrameric canine uricase variant.

PubMed

Zhang, Chun; Fan, Kai; Luo, Hua; Ma, Xuefeng; Liu, Riyong; Yang, Li; Hu, Chunlan; Chen, Zhenmin; Min, Zhiqiang; Wei, Dongzhi

2012-07-01

PEGylated uricase is a promising anti-gout drug, but the only commercially marketed 10kDa mPEG modified porcine-like uricase (Pegloticase) can only be used for intravenous infusion. In this study, tetrameric canine uricase variant was modified by covalent conjugation of all accessible ɛ amino sites of lysine residues with a smaller 5kDa mPEG (mPEG-UHC). The average modification degree and PEGylation homogeneity were evaluated. Approximately 9.4 5 kDa mPEG chains were coupled to each monomeric uricase and the main conjugates contained 7-11 mPEG chains per subunit. mPEG-UHC showed significantly therapeutic or preventive effect on uric acid nephropathy and acute urate arthritis based on three different animal models. The clearance rate from an intravenous injection of mPEG-UHC varied significantly between species, at 2.61 mL/h/kg for rats and 0.21 mL/h/kg for monkeys. The long elimination half-life of mPEG-UHC in non-human primate (191.48 h, intravenous injection) indicated the long-term effects in humans. Moreover, the acceptable bioavailability of mPEG-UHC after subcutaneous administration in monkeys (94.21%) suggested that subcutaneous injection may be regarded as a candidate administration route in clinical trails. Non-specific tissue distribution was observed after administration of (125)I-labeled mPEG-UHC in rats, and elimination by the kidneys into the urine is the primary excretion route. Copyright © 2012 Elsevier B.V. All rights reserved.

Traditional Chinese medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques.

PubMed

Li, Maoqing; Fu, Linchun; Hu, Yinjie; Zhang, Miaomiao; He, Jinyang; Chen, Zhixi; Chen, Jinyan

2012-12-01

To investigate the traditional Chinese Medicine (TCM) etiology and pathogenesis of acquired immune deficiency syndrome (AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus (SIV) mac239. Thirty-five healthy Chinese rhesus macaques were divided into a model group (n = 30) and a control group (n = 5). The model was established by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lymphocyte subsets, plasma triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH) and cortisol (Cor) were tested periodically during the experiment. During the acute infection period of SIV, model monkeys temporarily showed clinical symptoms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3, T4, Cor, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed normal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of T3 and Cor. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3 appeared. The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the invasion of SIV virus, incubation of the virus, balance between virus and healthy "Qi", damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.

Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1

PubMed Central

Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

2015-01-01

The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement—there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

C-type lectins do not act as functional receptors for filovirus entry into cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuno, Keita; Nakayama, Eri; Noyori, Osamu

2010-12-03

Research highlights: {yields} Filovirus glycoprotein (GP) having a deficient receptor binding region were generated. {yields} Mutant GPs mediated virus entry less efficiently than wild-type GP. {yields} Mutant GPs bound to C-type lectins but not mediated entire steps of cellular entry. {yields} C-type lectins do not independently mediate filovirus entry into cells. {yields} Other molecule(s) are required for C-type lectin-mediated entry of filoviruses. -- Abstract: Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps ofmore » virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.« less

Functional near infrared spectroscopy for awake monkey to accelerate neurorehabilitation study

NASA Astrophysics Data System (ADS)

Kawaguchi, Hiroshi; Higo, Noriyuki; Kato, Junpei; Matsuda, Keiji; Yamada, Toru

2017-02-01

Functional near-infrared spectroscopy (fNIRS) is suitable for measuring brain functions during neurorehabilitation because of its portability and less motion restriction. However, it is not known whether neural reconstruction can be observed through changes in cerebral hemodynamics. In this study, we modified an fNIRS system for measuring the motor function of awake monkeys to study cerebral hemodynamics during neurorehabilitation. Computer simulation was performed to determine the optimal fNIRS source-detector interval for monkey motor cortex. Accurate digital phantoms were constructed based on anatomical magnetic resonance images. Light propagation based on the diffusion equation was numerically calculated using the finite element method. The source-detector pair was placed on the scalp above the primary motor cortex. Four different interval values (10, 15, 20, 25 mm) were examined. The results showed that the detected intensity decreased and the partial optical path length in gray matter increased with an increase in the source-detector interval. We found that 15 mm is the optimal interval for the fNIRS measurement of monkey motor cortex. The preliminary measurement was performed on a healthy female macaque monkey using fNIRS equipment and custom-made optodes and optode holder. The optodes were attached above bilateral primary motor cortices. Under the awaking condition, 10 to 20 trials of alternated single-sided hand movements for several seconds with intervals of 10 to 30 s were performed. Increases and decreases in oxy- and deoxyhemoglobin concentration were observed in a localized area in the hemisphere contralateral to the moved forelimb.

Can Tissue Cilia Lengths and Urine Cilia Proteins Be Markers of Kidney Diseases?

PubMed

Park, Kwon Moo

2018-05-01

The primary cilium is an organelle which consists of a microtubule in the core and a surrounding cilia membrane, and has long been recognized as a "vestigial organelle". However, new evidence demonstrates that the primary cilium has a notable effect on signal transduction in the cell and is associated with some genetic and non-genetic diseases. In the kidney, the primary cilium protrudes into the Bowman's space and the tubular lumen from the apical side of epithelial cells. The length of primary cilia is dynamically altered during the normal cell cycle, being shortened by retraction into the cell body at the entry of cell division and elongated at differentiation. Furthermore, the length of primary cilia is also dynamically changed in the cells, as a result and/or cause, during the progression of various kidney diseases including acute kidney injury and chronic kidney disease. Notably, recent data has demonstrated that the shortening of the primary cilium in the cell is associated with fragmentation, apart from retraction into the cell body, in the progression of diseases and that the fragmented primary cilia are released into the urine. This data reveals that the alteration of primary cilia length could be related to the progression of diseases. This review will consider if primary cilia length alteration is associated with the progression of kidney diseases and if the length of tissue primary cilia and the presence or increase of cilia proteins in the urine is indicative of kidney diseases.

Multi-scale recordings for neuroprosthetic control of finger movements.

PubMed

Baker, Justin; Bishop, William; Kellis, Spencer; Levy, Todd; House, Paul; Greger, Bradley

2009-01-01

We trained a rhesus monkey to perform individuated and combined finger flexions and extensions of the thumb, index, and middle finger. A Utah Electrode Array (UEA) was implanted into the hand region of the motor cortex contralateral to the monkey's trained hand. We also implanted a microwire electrocorticography grid (microECoG) epidurally so that it covered the UEA. The microECoG grid spanned the arm and hand regions of both the primary motor and somatosensory cortices. Previously this monkey had Implantable MyoElectric Sensors (IMES) surgically implanted into the finger muscles of the monkey's forearm. Action potentials (APs), local field potentials (LFPs), and microECoG signals were recorded from wired head-stage connectors for the UEA and microECoG grids, while EMG was recorded wirelessly. The monkey performed a finger flexion/extension task while neural and EMG data were acquired. We wrote an algorithm that uses the spike data from the UEA to perform a real-time decode of the monkey's finger movements. Also, analyses of the LFP and microECoG data indicate that these data show trial-averaged differences between different finger movements, indicating the data are potentially decodeable.

Isolation, propagation, and characterization of a second equine rotavirus serotype.

PubMed Central

Hoshino, Y; Wyatt, R G; Greenberg, H B; Kalica, A R; Flores, J; Kapikian, A Z

1983-01-01

A rotavirus designated strain H-2 was isolated in primary African green monkey kidney cells from a foal with diarrhea. This cell culture-adapted strain was found to be similar, if not identical, to simian rotavirus (strains MMU18006 and SA-11) and canine rotavirus (strain CU-1) and, in addition, demonstrated a one-way antigenic relationship with five human rotavirus strains (P, B, no. 14, no. 15, and YO) of the third human rotavirus serotype by the plaque reduction neutralization test. This is the fifth example of an animal rotavirus which shares serotypic specificity with a human rotavirus. The H-2 strain is distinct from the H-1 strain (Y. Hoshino et al., J. Clin. Microbiol., in press) of equine rotavirus not only in serotypic specificity by neutralization but also in subgroup specificity, hemagglutinating activity, and RNA electrophoretic migration pattern, thus establishing the existence of a second equine rotavirus serotype. This H-2 isolate is also distinct by neutralization from three other human rotavirus serotypes, 1 (Wa), 2 (DS-1), and 4 (St. Thomas no. 4), as well as bovine (NCDV), and porcine (OSU) rotaviruses. Images PMID:6309657

Behavioral Determinants of Cannabinoid Self-Administration in Old World Monkeys.

PubMed

John, William S; Martin, Thomas J; Nader, Michael A

2017-06-01

Reinforcing effects of Δ 9 -tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation. The effects of CP 55 940 (1.0-10 μg/kg, i.v.) and THC (3.0-300 μg/kg, i.v.) on food-maintained responding and body temperature were determined in these subjects prior to giving them access to self-administer each drug. Both drugs dose-dependently decreased food-maintained responding. CP 55 940 (0.001-3.0 μg/kg) functioned as a reinforcer in three monkeys, whereas THC (0.01-10 μg/kg) did not have reinforcing effects in any subject. CP 55 940 was least potent to decrease food-maintained responding in the monkeys in which CP 55 940 functioned as a reinforcer. Next, THC was administered daily to monkeys until tolerance developed to rate-decreasing effects. When THC SA was reexamined, it functioned as a reinforcer in three monkeys. In a group of cocaine-experienced male cynomolgus monkeys (N=4), THC SA was examined under a second-order schedule of reinforcement; THC functioned as reinforcer in two monkeys. These data suggest that SA of CBR agonists may be relatively independent of their rate-decreasing effects in Old World monkeys. Understanding individual differences in vulnerability to THC SA may lead to novel treatment strategies for marijuana abuse.

Metabolism and disposition of ABT-894, a novel α4β2 neuronal acetylcholine receptor agonist, in mice and monkeys.

PubMed

Liu, Hong; Fu, Wentao; Wetter, Jill; Xu, Hongyu; Guan, Zhiwen; Stuart, Patricia

2014-06-01

1.  Metabolism and disposition of ABT-894 was investigated in hepatocytes, in mice and monkeys receiving [(14)C]ABT-894. 2.  In hepatocytes, turnover rate of ABT-894 was slow in all species with more than 90% of parent remaining. M3 (carbamoyl glucuronide) and M6 (mono-oxidation) were detected across species. 3.  ABT-894 showed species-specific disposition profiles. ABT-894 was primarily eliminated by renal secretion in mice. Whereas, monkey mainly cleared ABT-894 metabolically. 4.  ABT-894 underwent two primary routes of metabolism in monkeys: N-carbamoyl glucuronidation to form M3 and oxidation product M1. M3 was the major metabolite in monkey excreta. M3 was observed in mice urine. Circulating levels of M3 in terms of M3/ABT-894 ratios were essentially absent in mice, but were high in monkeys. 5.  Understanding the species difference in the clearance mechanism is the key to the accurate projection of the human clearance and preclinical safety assessment. Lack of species difference in the metabolism of ABT-894 in hepatocytes certainly creates a challenge in predicting its metabolism and pharmacokinetics in human. Based on available metabolism and pharmacokinetic data of ABT-894 in human, monkey is the preferred species in predicting human clearance since it presents a similar clearance mechanism from that observed in human.

Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1.

PubMed

Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

2015-09-01

The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement-there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

DOE PAGES

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; ...

2014-11-19

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

Auditory and audio-vocal responses of single neurons in the monkey ventral premotor cortex.

PubMed

Hage, Steffen R

2018-03-20

Monkey vocalization is a complex behavioral pattern, which is flexibly used in audio-vocal communication. A recently proposed dual neural network model suggests that cognitive control might be involved in this behavior, originating from a frontal cortical network in the prefrontal cortex and mediated via projections from the rostral portion of the ventral premotor cortex (PMvr) and motor cortex to the primary vocal motor network in the brainstem. For the rapid adjustment of vocal output to external acoustic events, strong interconnections between vocal motor and auditory sites are needed, which are present at cortical and subcortical levels. However, the role of the PMvr in audio-vocal integration processes remains unclear. In the present study, single neurons in the PMvr were recorded in rhesus monkeys (Macaca mulatta) while volitionally producing vocalizations in a visual detection task or passively listening to monkey vocalizations. Ten percent of randomly selected neurons in the PMvr modulated their discharge rate in response to acoustic stimulation with species-specific calls. More than four-fifths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of the vocalization. Based on these audio-vocal interactions, the PMvr might be well positioned to mediate higher order auditory processing with cognitive control of the vocal motor output to the primary vocal motor network. Such audio-vocal integration processes in the premotor cortex might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2018 Elsevier B.V. All rights reserved.

CD105+-mesenchymal stem cells migrate into osteoarthritis joint: An animal model.

PubMed

Fernandez-Pernas, Pablo; Rodríguez-Lesende, Iván; de la Fuente, Alexandre; Mateos, Jesús; Fuentes, Isaac; De Toro, Javier; Blanco, Fco J; Arufe, M C

2017-01-01

Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model. CD105+-MSCs were injected twice into the OA monkeys with an interval of one week between them. The animals were euthanized one month after treatment. Immunohistochemistry analysis of different organs: spleen, heart, fat, liver, gut, pancreas, lung, skeletal muscle and kidney from the animals revealed that CD105+-MSCs migrated towards the injured knee joint. MSCs naive were found statistically significant increased in the injured knee in front of healthy one. CD105+-MSCs were negatives for CD68 and the area where CD105+-MSCs were found presented SDF-1 increased levels in front of healthy knee. We concluded that a characterized MSCs subset could be a safe alternative for cell therapy in clearly localized pathologies.

CD105+-mesenchymal stem cells migrate into osteoarthritis joint: An animal model

PubMed Central

Fernandez-Pernas, Pablo; Rodríguez-Lesende, Iván; de la Fuente, Alexandre; Mateos, Jesús; Fuentes, Isaac; De Toro, Javier; Blanco, Fco J.

2017-01-01

Mesenchymal stem cells are being the focus of connective tissue technology and regenerative medicine, presenting a good choice cell source for improving old and well recognized techniques of cartilage defect repair. For instance, the autologous chondrocyte transplantation using new concepts of regenerative medicine. The present study investigated the risk of xenogenicity of human synovial membrane-derived MSCs, injected into the monkeys using intravenous and intra-articular administration. The animal models used were adult monkeys Rhesus which had been injured into the left knee to create an Osteoarthritis (OA) animal model. CD105+-MSCs were injected twice into the OA monkeys with an interval of one week between them. The animals were euthanized one month after treatment. Immunohistochemistry analysis of different organs: spleen, heart, fat, liver, gut, pancreas, lung, skeletal muscle and kidney from the animals revealed that CD105+-MSCs migrated towards the injured knee joint. MSCs naive were found statistically significant increased in the injured knee in front of healthy one. CD105+-MSCs were negatives for CD68 and the area where CD105+-MSCs were found presented SDF-1 increased levels in front of healthy knee. We concluded that a characterized MSCs subset could be a safe alternative for cell therapy in clearly localized pathologies. PMID:29190645

Cashew Nut Positioning during Stone Tool Use by Wild Bearded Capuchin Monkeys (Sapajus libidinosus).

PubMed

Falótico, Tiago; Luncz, Lydia V; Svensson, Magdalena S; Haslam, Michael

2016-01-01

Wild capuchin monkeys (Sapajus libidinosus) at Serra da Capivara National Park, Brazil, regularly use stone tools to break open cashew nuts (Anacardium spp.). Here we examine 2 approaches used by the capuchins to position the kidney-shaped cashew nuts on an anvil before striking with a stone tool. Lateral positioning involves placing the nut on its flatter, more stable side, therefore requiring less attention from the monkey during placement. However, the less stable and never previously described arched position, in which the nut is balanced with its curved side uppermost, requires less force to crack the outer shell. We observed cashew nut cracking in a field experimental setting. Only 6 of 20 adults, of both sexes, were observed to deliberately place cashew nuts in an arched position, which may indicate that the technique requires time and experience to learn. We also found that use of the arched position with dry nuts, but not fresh, required, in 63% of the time, an initial processing to remove one of the cashew nut lobes, creating a more stable base for the arch. This relatively rare behaviour appears to have a complex ontogeny, but further studies are required to establish the extent to which social learning is involved. © 2017 S. Karger AG, Basel.

Visual habit formation in 3-month-old monkeys (Macaca mulatta): reversal of sex difference following neonatal manipulations of androgens.

PubMed

Hagger, C; Bachevalier, J

1991-10-25

The ability to perform on a concurrent visual discrimination task with 24-h intertrial intervals (24-h ITI task) develops a few weeks earlier in female than in male infant monkeys. To test whether this sex difference was related to the presence of perinatal androgens, plasma testosterone levels were reduced in male infant monkeys by neonatal orchiectomy and increased in neonatally ovariectomized female infant monkeys by treatment with either testosterone propionate (TP) or its reduced metabolite, dihydrotestosterone (DHT). At 3 months of age, the animals were tested on the 24-h ITI task and their performance compared with that of age-matched intact male and female monkeys. Orchiectomy which was followed by a slight but visible atrophy of the external genitalia, hastened performance of male infant monkeys to the level of intact infant females. Conversely, androgenization of ovariectomized female infant monkeys given DHT, which had only a slight virilizing effect on the external genitalia, showed the learning of these female infants to the rate of intact male infant monkeys. Curiously, although TP treatment in ovariectomized female infant monkeys was more effective than DHT in virilizing the external genitalia, it failed to slow the rate of learning. This dissociation between the effects of TP and DHT on external genital organs and learning abilities is discussed in terms of possible differences in dose-dependent, time-dependent, and receptor-binding mechanisms of the two androgens. The present study provides further evidence that early androgen secretions affect the organization not only of brain structures related to primary sexual characteristics but also of those related to learning abilities.

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

PubMed Central

Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A.; Zhao, Guoyan; Virgin, Herbert W.; Korber, Bette

2014-01-01

ABSTRACT Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCE Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. PMID:25410856

Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

PubMed

Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

2015-02-01

Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Monkey alcohol tissue research resource: banking tissues for alcohol research.

PubMed

Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

2014-07-01

An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better understand the disease processes associated with alcoholism. Copyright © 2014 by the Research Society on Alcoholism.

Quality indicators for the detection and management of chronic kidney disease in primary care in Canada derived from a modified Delphi panel approach.

PubMed

Tu, Karen; Bevan, Lindsay; Hunter, Katie; Rogers, Jess; Young, Jacqueline; Nesrallah, Gihad

2017-01-01

The detection and management of chronic kidney disease lies within primary care; however, performance measures applicable in the Canadian context are lacking. We sought to develop a set of primary care quality indicators for chronic kidney disease in the Canadian setting and to assess the current state of the disease's detection and management in primary care. We used a modified Delphi panel approach, involving 20 panel members from across Canada (10 family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1 pharmacist). Indicators identified from peer-reviewed and grey literature sources were subjected to 3 rounds of voting to develop a set of quality indicators for the detection and management of chronic kidney disease in the primary care setting. The final indicators were applied to primary care electronic medical records in the Electronic Medical Record Administrative data Linked Database (EMRALD) to assess the current state of primary care detection and management of chronic kidney disease in Ontario. Seventeen indicators made up the final list, with 1 under the category Prevalence, Incidence and Mortality; 4 under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis, 6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were female. Diagnosis and screening for chronic kidney disease were poorly performed. Only 27.1% of patients with stage 3 or higher disease had their diagnosis documented in their cumulative patient profile. Albumin-creatinine ratio testing was only performed for 16.3% of patients with a low estimated glomerular filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic kidney disease. Family physicians performed relatively better with the management of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease having an eGFR performed in the previous 18 months and 83.1% having a blood pressure recorded in the previous 9 months. We propose a set of measurable indicators to evaluate the quality of the management of chronic kidney disease in primary care. These indicators may be used to identify opportunities to improve current practice in Canada.

The connections of layer 4 subdivisions in the primary visual cortex (V1) of the owl monkey.

PubMed

Boyd, J D; Mavity-Hudson, J A; Casagrande, V A

2000-07-01

The primary visual cortex (V1) of primates receives signals from parallel lateral geniculate nucleus (LGN) channels. These signals are utilized by the laminar and compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V1 to synthesize new output pathways appropriate for the next steps of analysis. Within this framework, this study had two objectives: (i) to analyze the con- nections between primary input and output layers and compartments of V1; and (ii) to determine differences in connection patterns that might be related to species differences in physiological properties in an effort to link specific pathways to visual functions. In this study we examined the intrinsic interlaminar connections of V1 in the owl monkey, a nocturnal New World monkey, with a special emphasis on the projections from layer 4 to layer 3. Interlaminar connections were labeled via small iontophoretic or pressure injections of tracers [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera toxin subunit B conjugated to colloidal gold particles]. Our most significant finding was that layer 4 (4C of Brodmann) can be divided into three tiers based upon projections to the superficial layers. Specifically, we find that 4alpha (4Calpha), 4beta (4Cbeta) and 4ctr send primary projections to layers 3C (4B), 3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with Nissl staining supports a tripartite organization of layer 4. The cortical output layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any direct connections from layer 4 but receives heavy input from layers 3Balpha (3B) and 3C (4B). Some connectional differences also were observed between the subdivisions of layer 3 and the infragranular layers. No consistent differences in connections were observed that distinguished CO blobs from interblobs or that could be correlated with differences in visual lifestyle (nocturnal versus diurnal) when compared with connectional data in other primates. Re-examination of data from previous studies in squirrel and macaque monkeys suggests that the tripartite organization of layer 4 and the unique projection pattern of layer 4ctr are not restricted to owl monkeys, but are common to a number of primate species.

Neurogenic regulation of renal tubular sodium reabsorption.

PubMed

DiBona, G F

1977-08-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies have demonstrated adrenergic nerve terminals in direct contact with basement membranes of mammalian (rat, dog, and monkey) renal tubular epithelial cells. Low-level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Antinatriuresis was prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Rat kidney micropuncture studies have localized a site of enhanced tubular sodium reabsorption to the proximal tubule. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney on renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. The possible effects of anesthesia and uncertainties about the completeness of surgical renal denervation and other tubular segmental sites of action are critically analyzed. The clinical implications of this mechanism in pathologic conditions of sodium and water retention are discussed and and a prospectus for future work is presented.

Ames Research Center life sciences payload - Overview of results of a spaceflight of 24 rats and 2 monkeys

NASA Technical Reports Server (NTRS)

Callahan, P. X.; Schatte, C.; Grindeland, R. E.; Bowman, G.; Lencki, W. A.

1985-01-01

Engineering and biological data gathered with the research animal holding facilities (RAHFs) used on the Spacelab 3 mission are summarized. The animals totaled 24 rats and two squirrel monkeys. The RAHFs included biotelemetry, cameras and environmental monitoring equipment. The primary mission goal was engineering evaluation of the RAHFs and ancillary equipment. Tightly-fitted seals were found to be a necessity for keeping waste and food particles from contaminating the Spacelab equipment. All the rats returned with little muscle tone and suppressed immune systems. The monkeys displayed highly individual responses to spaceflight. Both species exhibited reduced abilities to maintain meticulously clean furs in weightlessness. Details of several physiological changes detected during post-flight autopsies are provided.

Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

PubMed

Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

2015-07-01

The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Comparison of functional recovery of manual dexterity after unilateral spinal cord lesion or motor cortex lesion in adult macaque monkeys.

PubMed

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F; Mir, Anis; Schwab, Martin E; Belhaj-Saif, Abderraouf; Rouiller, Eric M

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns ("true" recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex.

Comparison of Functional Recovery of Manual Dexterity after Unilateral Spinal Cord Lesion or Motor Cortex Lesion in Adult Macaque Monkeys

PubMed Central

Hoogewoud, Florence; Hamadjida, Adjia; Wyss, Alexander F.; Mir, Anis; Schwab, Martin E.; Belhaj-Saif, Abderraouf; Rouiller, Eric M.

2013-01-01

In relation to mechanisms involved in functional recovery of manual dexterity from cervical cord injury or from motor cortical injury, our goal was to determine whether the movements that characterize post-lesion functional recovery are comparable to original movement patterns or do monkeys adopt distinct strategies to compensate the deficits depending on the type of lesion? To this aim, data derived from earlier studies, using a skilled finger task (the modified Brinkman board from which pellets are retrieved from vertical or horizontal slots), in spinal cord and motor cortex injured monkeys were analyzed and compared. Twelve adult macaque monkeys were subjected to a hemi-section of the cervical cord (n = 6) or to a unilateral excitotoxic lesion of the hand representation in the primary motor cortex (n = 6). In addition, in each subgroup, one half of monkeys (n = 3) were treated for 30 days with a function blocking antibody against the neurite growth inhibitory protein Nogo-A, while the other half (n = 3) represented control animals. The motor deficits, and the extent and time course of functional recovery were assessed. For some of the parameters investigated (wrist angle for horizontal slots and movement types distribution for vertical slots after cervical injury; movement types distribution for horizontal slots after motor cortex lesion), post-lesion restoration of the original movement patterns (“true” recovery) led to a quantitatively better functional recovery. In the motor cortex lesion groups, pharmacological reversible inactivation experiments showed that the peri-lesion territory of the primary motor cortex or re-arranged, spared domain of the lesion zone, played a major role in the functional recovery, together with the ipsilesional intact premotor cortex. PMID:23885254

Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys.

PubMed

Fregosi, Michela; Contestabile, Alessandro; Hamadjida, Adjia; Rouiller, Eric M

2017-06-01

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Internal state of monkey primary visual cortex (V1) predicts figure-ground perception.

PubMed

Supèr, Hans; van der Togt, Chris; Spekreijse, Henk; Lamme, Victor A F

2003-04-15

When stimulus information enters the visual cortex, it is rapidly processed for identification. However, sometimes the processing of the stimulus is inadequate and the subject fails to notice the stimulus. Human psychophysical studies show that this occurs during states of inattention or absent-mindedness. At a neurophysiological level, it remains unclear what these states are. To study the role of cortical state in perception, we analyzed neural activity in the monkey primary visual cortex before the appearance of a stimulus. We show that, before the appearance of a reported stimulus, neural activity was stronger and more correlated than for a not-reported stimulus. This indicates that the strength of neural activity and the functional connectivity between neurons in the primary visual cortex participate in the perceptual processing of stimulus information. Thus, to detect a stimulus, the visual cortex needs to be in an appropriate state.

Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys.

PubMed

Neuringer, Martha; Sandstrom, Marita M; Johnson, Elizabeth J; Snodderly, D Max

2004-09-01

The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD. Copyright Association for Research in Vision and Ophthalmology

Chronic Kidney Disease in Kidney Stone Formers

PubMed Central

Krambeck, Amy E.; Lieske, John C.

2011-01-01

Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

Laminar and regional distribution of galanin binding sites in cat and monkey visual cortex determined by in vitro receptor autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosier, A.M.; Vandesande, F.; Orban, G.A.

1991-03-08

The distribution of galanin (GAL) binding sites in the visual cortex of cat and monkey was determined by autoradiographic visualization of ({sup 125}I)-GAL binding to tissue sections. Binding conditions were optimized and, as a result, the binding was saturable and specific. In cat visual cortex, GAL binding sites were concentrated in layers I, IVc, V, and VI. Areas 17, 18, and 19 exhibited a similar distribution pattern. In monkey primary visual cortex, the highest density of GAL binding sites was observed in layers II/III, lower IVc, and upper V. Layers IVA and VI contained moderate numbers of GAL binding sites,more » while layer I and the remaining parts of layer IV displayed the lowest density. In monkey secondary visual cortex, GAL binding sites were mainly concentrated in layers V-VI. Layer IV exhibited a moderate density, while the supragranular layers contained the lowest proportion of GAL binding sites. In both cat and monkey, we found little difference between regions subserving central and those subserving peripheral vision. Similarities in the distribution of GAL and acetylcholine binding sites are discussed.« less

Postnatal change in sulcal length asymmetry in cerebrum of cynomolgus monkeys (Macaca fascicularis).

PubMed

Sakamoto, Kazuhito; Sawada, Kazuhiko; Fukunishi, Katsuhiro; Noritaka, Imai; Sakata-Haga, Hiromi; Yoshihiro, Fukui

2014-02-01

The purpose of this study was to determine the timing of the onset of adult-type sulcal length asymmetry during postnatal development of the male cynomolgus monkey cerebrum. The monkey brain has already reached adult size by 3 months of age, although the body weight only represents 1/8 of the adult body weight by that time. The fronto-occipital length and the cerebral width also reached adult levels by that postnatal age with no left/right bias. Consistently, lengths of the major primary sulci reached adult levels by 3 months of age, and then decreased slightly in sexually mature monkeys (4-6.5 years of age). Asymmetry quotient analysis showed that sulcal length asymmetry patterns gradually changed during postnatal development. The male adult pattern of sulcal length asymmetry was acquired after 24 months of age. In particular, age-dependent rightward lateralization of the arcuate sulcal length was revealed during cerebral maturation by three-way ANOVA. The results suggest that the regional difference in cerebral maturation from adolescence to young adulthood modifies the sulcal morphology with characteristic asymmetric patterns in male cynomolgus monkeys. Copyright © 2013 Wiley Periodicals, Inc.

Protein phosphorylations in poliovirus infected cells.

PubMed

James, L A; Tershak, D R

1981-01-01

In vivo phosphorylation of proteins that are associated with polysomes of poliovirus-infected VERO (African green monkey kidney) and HeLa (Henrietta Lacks) cells differed from phosphorylations observed with uninfected cells that were fed fresh medium. With both types of cells infection stimulated phosphorylation of proteins with molecular weights of 40 000-41 000, 39 000, 34 000, 32 000, and 24 000. Similarities of phosphorylations in VERO and HeLa cells suggest that they are a specific consequence of infection and might serve a regulatory function during protein synthesis.

Hormesis and the salk polio vaccine.

PubMed

Calabrese, Edward J

2012-01-01

The production of the Salk vaccine polio virus by monkey kidney cells was generated using the synthetic tissue culture medium, Mixture 199. In this paper's retrospective assessment of this process, it was discovered that Mixture 199 was modified by the addition of ethanol to optimize animal cell survival based on experimentation that revealed a hormetic-like biphasic response relationship. This hormesis-based optimization procedure was then applied to all uses of Mixture 199 and modifications of it, including its application to the Salk polio vaccine during preliminary testing and in its subsequent major societal treatment programs.

A prospective field evaluation of an enzyme immunoassay: Detection of eastern equine encephalomyelitis virus antigen in pools of Culiseta melanura

USGS Publications Warehouse

Scott, T.W.; Olson, J.G.; Lewis, T.E.; Carpenter, J.W.; Lorenz, L.H.; Lembeck, L.A.; Joseph, S.R.; Pagac, B.B.

1987-01-01

A prospective field study was conducted to determine the sensitivity and specificity of an enzyme immunoassay (EIA) compared to virus isolation in cell culture for the detection of eastern equine encephalomyelitis (EEE) virus in naturally infected mosquitoes. A total of 10,811 adult female Culiseta melanura were collected in light traps during 1985 from four locations in Maryland. Eastern equine encephalomyelitis virus was isolated from 5 of 495 mosquito pools in African green monkey kidney and baby hamster kidney cell cultures. All five virus-infected pools were detected by the EIA, and all 490 uninfected pools were correctly scored as not containing virus. The EIA did not produce false positive or false negative results. Results support the assertion of previous researchers that the antigen detection EIA is a rapid, sensitive, specific, and simple alternative to traditional bioassays for the detection of EEE virus in mosquitoes.

IgA antibasement membrane nephritis with pulmonary hemorrhage.

PubMed

Border, W A; Baehler, R W; Bhathena, D; Glassock, R J

1979-07-01

Goodpasture's syndrome has characteristically been described as being mediated by IgG antibodies. We have recently seen a 55-year-old man who developed renal failure and hemoptysis; a renal biopsy showed linear deposits of IgA and C3 involving glomerular and tubular basement membrane. Serologic tests for detecting (IgG) antiglomerular basement membrane antibodies were negative. Elution studies of kidney and lung showed the presence of an IgA antibasement membrane antibody only. The patient's serum contained IgA, but not IgG, antibodies reactive with glomerular and tubular basement membrane of normal human kidney and alveolar basement membrane of normal human lung. Attempts to transfer disease with the patient's IgA antibody to a monkey and to Lewis and Brown-Norway rats were unsuccessful. Immunoglobulin A antibasement membrane antibody must be considered in the design of immunoserologic procedures for the diagnosis of Goodpasture's syndrome.

Possibilities of vaccine manufacture in human diploid cell strains with a serum replacement factor.

PubMed

Candal, F J; George, V G; Ades, E W

1991-07-01

Cell lines MDCK (canine kidney), BGM (Buffalo green monkey kidney) and human embryonic lung fibroblast will support viral growth efficiently in medium without serum. Both MRC-5 and WI-38 cell strains have been approved by the Food and Drug Administration for manufacturing viral vaccines against cytomegalovirus and varicella-zoster virus. In this study we examine these two cell lines and viruses for their ability to grow in medium containing a serum replacement. The serum substitute used is LPSR-1 (low protein serum replacement). Using LPSR-1 in defined medium, we demonstrate multipassage cell growth and viral cultivation and replication equivalent to those obtained in medium containing fetal bovine serum (FBS). Viral growth after complete elimination of FBS varies and depends on cell line and virus. Serum substitutes can eliminate FBS in the viral growth phase of vaccine production and reduce costs.

Comparison of antibody responses and virus shedding following administration of trivalent oral poliomyelitis vaccines prepared either in monkey or human diploid cell substrates.

PubMed Central

Freestone, D. S.; Kelly, A.; Ferris, R.; Simmons, R. L.; Bowker, C.; Letley, E.; Bye, C.

1980-01-01

Nineteen (22.9%) of 83 sera collected before vaccination from adult volunteers aged 21-64 years were without neutralizing antibody to poliomyelitis at levels of 0.15 i.u./ml for types I and II and 0.1 i.u./ml for type III. Some correlations were found between the history of previous vaccination and the presence of antibody but these were not well defined. Vaccination with a single dose of trivalent oral polio vaccine elicited fourfold or greater antibody responses to one or more poliomyelitis types in 53 (63.9%) volunteers, the percentage antibody resposnes being inversely related to the titre of antibody present before vaccination. Types I, II or III poliomyelitis virus were recovered from 76.8% of faecal samples collected 1 week after vaccination. The percentage recovery progressively declined thereafter until virus was recovered from 10.5% of samples collected 6 weeks after vaccination. Type for type, the titres and percentages of antibody responses and virus shedding in faeces were similar following trivalent oral poliomyelitis vaccines whether prepared in monkey or human diploid cell substrates. Some change in reproductive capacity temperature (r.c.t./40) marker was found in faecal isolates from volunteers vaccinated with monkey kidney and human diploid grown vaccines but no change in 'd' marker was found. PMID:6243327

The uncertain response in humans and animals

NASA Technical Reports Server (NTRS)

Smith, J. D.; Shields, W. E.; Schull, J.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

1997-01-01

There has been no comparative psychological study of uncertainty processes. Accordingly, the present experiments asked whether animals, like humans, escape adaptively when they are uncertain. Human and animal observers were given two primary responses in a visual discrimination task, and the opportunity to escape from some trials into easier ones. In one psychophysical task (using a threshold paradigm), humans escaped selectively the difficult trials that left them uncertain of the stimulus. Two rhesus monkeys (Macaca mulatta) also showed this pattern. In a second psychophysical task (using the method of constant stimuli), some humans showed this pattern but one escaped infrequently and nonoptimally. Monkeys showed equivalent individual differences. The data suggest that escapes by humans and monkeys are interesting cognitive analogs and may reflect controlled decisional processes prompted by the perceptual ambiguity at threshold.

Memory monitoring by animals and humans

NASA Technical Reports Server (NTRS)

Smith, J. D.; Shields, W. E.; Allendoerfer, K. R.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

1998-01-01

The authors asked whether animals and humans would use similarly an uncertain response to escape indeterminate memories. Monkeys and humans performed serial probe recognition tasks that produced differential memory difficulty across serial positions (e.g., primacy and recency effects). Participants were given an escape option that let them avoid any trials they wished and receive a hint to the trial's answer. Across species, across tasks, and even across conspecifics with sharper or duller memories, monkeys and humans used the escape option selectively when more indeterminate memory traces were probed. Their pattern of escaping always mirrored the pattern of their primary memory performance across serial positions. Signal-detection analyses confirm the similarity of the animals' and humans' performances. Optimality analyses assess their efficiency. Several aspects of monkeys' performance suggest the cognitive sophistication of their decisions to escape.

Intrinsic-Signal Optical Imaging Reveals Cryptic Ocular Dominance Columns in Primary Visual Cortex of New World Owl Monkeys

PubMed Central

Kaskan, Peter M.; Lu, Haidong D.; Dillenburger, Barbara C.; Roe, Anna W.; Kaas, Jon H.

2007-01-01

A significant concept in neuroscience is that sensory areas of the neocortex have evolved the remarkable ability to represent a number of stimulus features within the confines of a global map of the sensory periphery. Modularity, the term often used to describe the inhomogeneous nature of the neocortex, is without a doubt an important organizational principle of early sensory areas, such as the primary visual cortex (V1). Ocular dominance columns, one type of module in V1, are found in many primate species as well as in carnivores. Yet, their variable presence in some New World monkey species and complete absence in other species has been enigmatic. Here, we demonstrate that optical imaging reveals the presence of ocular dominance columns in the superficial layers of V1 of owl monkeys (Aotus trivirgatus), even though the geniculate inputs related to each eye are highly overlapping in layer 4. The ocular dominance columns in owl monkeys revealed by optical imaging are circular in appearance. The distance between left eye centers and right eye centers is approximately 650 μm. We find no relationship between ocular dominance centers and other modular organizational features such as orientation pinwheels or the centers of the cytochrome oxidase blobs. These results are significant because they suggest that functional columns may exist in the absence of obvious differences in the distributions of activating inputs and ocular dominance columns may be more widely distributed across mammalian taxa than commonly suggested. PMID:18974855

Cloning and Expression of cDNA for Rat Heme Oxygenase

NASA Astrophysics Data System (ADS)

Shibahara, Shigeki; Muller, Rita; Taguchi, Hayao; Yoshida, Tadashi

1985-12-01

Two cDNA clones for rat heme oxygenase have been isolated from a rat spleen cDNA library in λ gt11 by immunological screening using a specific polyclonal antibody. One of these clones has an insert of 1530 nucleotides that contains the entire protein-coding region. To confirm that the isolated cDNA encodes heme oxygenase, we transfected monkey kidney cells (COS-7) with the cDNA carried in a simian virus 40 vector. The heme oxygenase was highly expressed in endoplasmic reticulum of transfected cells. The nucleotide sequence of the cloned cDNA was determined and the primary structure of heme oxygenase was deduced. Heme oxygenase is composed of 289 amino acids and has one hydrophobic segment at its carboxyl terminus, which is probably important for the insertion of heme oxygenase into endoplasmic reticulum. The cloned cDNA was used to analyze the induction of heme oxygenase in rat liver by treatment with CoCl2 or with hemin. RNA blot analysis showed that both CoCl2 and hemin increased the amount of hybridizable mRNA, suggesting that these substances may act at the transcriptional level to increase the amount of heme oxygenase.

Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: Systematic review.

PubMed

Moretti, Milena; Lava, Sebastiano A G; Zgraggen, Lorenzo; Simonetti, Giacomo D; Kottanattu, Lisa; Bianchetti, Mario G; Milani, Gregorio P

2017-06-01

Textbooks and reviews do not mention the association of symptomatic primary Epstein-Barr virus infectious mononucleosis with acute kidney injury in subjects without immunodeficiency or autoimmunity. Stimulated by our experience with two cases, we performed a review of the literature. The literature documents 38 cases (26 male and 12 female individuals ranging in age from 0.3 to 51, median 18 years) of symptomatic primary Epstein-Barr virus infectious mononucleosis complicated by acute kidney injury: 27 acute interstitial nephritides, 1 jaundice-associated nephropathy, 7 myositides and 3 hemolytic uremic syndromes. Acute kidney injury requiring renal replacement therapy was observed in 18 (47%) cases. Acute kidney injury did not resolve in one patient with acute interstitial nephritis. Two patients died because of systemic complications. The remaining 35 cases fully recovered. In individuals with acute symptomatic Epstein-Barr virus infectious mononucleosis, a relevant kidney injury is rare but the outcome potentially fatal. It results from interstitial nephritis, myositis-associated acute kidney injury, hemolytic uremic syndrome or jaundice-associated nephropathy. Copyright © 2017 Elsevier B.V. All rights reserved.

Linear Stimulus-Invariant Processing and Spectrotemporal Reverse Correlation in Primary Auditory Cortex

DTIC Science & Technology

2003-01-01

stability. The ectosylvian gyrus, which includes the primary auditory cortex, was exposed by craniotomy and the dura was reflected. The contralateral... awake monkey. Journal Revista de Acustica, 33:84–87985–06–8. Victor, J. and Knight, B. (1979). Nonlinear analysis with an arbitrary stimulus ensemble

Oblique effect in visual area 2 of macaque monkeys

PubMed Central

Shen, Guofu; Tao, Xiaofeng; Zhang, Bin; Smith, Earl L.; Chino, Yuzo M.

2014-01-01

The neural basis of an oblique effect, a reduced visual sensitivity for obliquely oriented stimuli, has been a matter of considerable debate. We have analyzed the orientation tuning of a relatively large number of neurons in the primary visual cortex (V1) and visual area 2 (V2) of anesthetized and paralyzed macaque monkeys. Neurons in V2 but not V1 of macaque monkeys showed clear oblique effects. This orientation anisotropy in V2 was more robust for those neurons that preferred higher spatial frequencies. We also determined whether V1 and V2 neurons exhibit a similar orientation anisotropy soon after birth. The oblique effect was absent in V1 of 4- and 8-week-old infant monkeys, but their V2 neurons showed a significant oblique effect. This orientation anisotropy in infant V2 was milder than that in adults. The results suggest that the oblique effect emerges in V2 based on the pattern of the connections that are established before birth and enhanced by the prolonged experience-dependent modifications of the neural circuitry in V2. PMID:24511142

Hormesis and the Salk Polio Vaccine

PubMed Central

Calabrese, Edward J.

2011-01-01

The production of the Salk vaccine polio virus by monkey kidney cells was generated using the synthetic tissue culture medium, Mixture 199. In this paper’s retrospective assessment of this process, it was discovered that Mixture 199 was modified by the addition of ethanol to optimize animal cell survival based on experimentation that revealed a hormetic-like biphasic response relationship. This hormesis-based optimization procedure was then applied to all uses of Mixture 199 and modifications of it, including its application to the Salk polio vaccine during preliminary testing and in its subsequent major societal treatment programs. PMID:22423232

Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

DTIC Science & Technology

1989-01-01

Reticuloendothelium Acute leukemia 32.7 M Electron 1.6 15.0 Subcutis (Leg) Fibrosarcoma 40.5 M Proton 55 8.0 Brain Glioblastoma 42.9 M Electron 1.6 15.0...Subcutis (Leg) Fibrosarcoma 54.3 M Proton 55 6.0 Subcutis (Leg) Fibrosarcoma 54.5 M Proton 55 6.0 Brain Glioblastoma 54.8 M Electron 1.6 15.0 Kidney...55 4.0 Brain Glioblastoma 93.5 F Proton 55 6.0 Brain Glioblastoma 99.7 M Proton Mixed 12.0 Subcutis (Leg) Fibrosarcoma 108.1 M Proton 55 6.0 Mucosa

Radiation enhanced reactivation of herpes simplex virus: effect of caffeine.

PubMed

Hellman, K B; Lytle, C D; Bockstahler, L E

1976-09-01

Ultaviolet enhanced (Weigle) reactivation of UV-irradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cell monolayers was decreased by caffeine. X-ray enhanced reactivation of UV-irradiated virus in X-irradiated monolayers (X-ray reactivation) and UV- or X-ray-inactivated capacity of the cells to support unirradiated virus plaque formation were unaffected by caffeine. The results suggest that a caffeine-sensitive process is necessary for the expression of Weigle reactivation for herpes virus. Since cafeine did not significantly affect X-ray reactivation, different mechanisms may be responsible for the expression of Weigle reactivation and X-ray reactivation.

Cloning of nascent monkey DNA synthesized early in the cell cycle.

PubMed

Kaufmann, G; Zannis-Hadjopoulos, M; Martin, R G

1985-04-01

To study the structure and complexity of animal cell replication origins, we have isolated and cloned nascent DNA from the onset of S phase as follows: African green monkey kidney cells arrested in G1 phase were serum stimulated in the presence of the DNA replication inhibitor aphidicolin. After 18 h, the drug was removed, and DNA synthesis was allowed to proceed in vivo for 1 min. Nuclei were then prepared, and DNA synthesis was briefly continued in the presence of Hg-dCTP. The mercury-labeled nascent DNA was purified in double-stranded form by extrusion (M. Zannis-Hadjopoulos, M. Perisco, and R. G. Martin, Cell 27:155-163, 1981) followed by sulfhydryl-agarose affinity chromatography. Purified nascent DNA (ca. 500 to 2,000 base pairs) was treated with mung bean nuclease to remove single-stranded ends and inserted into the NruI site of plasmid pBR322. The cloned fragments were examined for their time of replication by hybridization to cellular DNA fractions synthesized at various intervals of the S phase. Among five clones examined, four hybridized preferentially with early replicating fractions.

Development of a new live attenuated mumps virus vaccine in human diploid cells.

PubMed

Sassani, A; Mirchamsy, H; Shafyi, A; Ahourai, P; Razavi, J; Gholami, M R; Mohammadi, A; Ezzi, A; Rahmani, M; Fateh, G

1991-07-01

A new live attenuated mumps vaccine was developed in human diploid cells. The S-12 virus was isolated from a 10-year-old girl showing typical symptoms of mumps infection, the diagnosis was confirmed by a pediatrician. The virus was isolated in green monkey kidney cells, without passage in chick embryo cavity or chick embryo fibroblasts. Attenuation of the wild virus was performed by serial passages in human diploid cells (MRC-5). The attenuated virus was characterized by identity tests, as well as by a reduction in plaque size, as marker tests. The virus was free from adventitious agents and safe for laboratory animals as well as for monkeys. The reactogenicity and immunogenicity of the S-12 virus for man was investigated by administration of a monovalent vaccine to 20 seronegative adult male volunteers and 30 children aged 1 to 5 years without history of mumps infection or vaccination. Seroconversion was obtained in 95% of the vaccinees. The new vaccine has the advantage of not requiring specific pathogen-free eggs, and being free from avian proteins and therefore can be used in sensitized patients.

Altered figure-ground perception in monkeys with an extra-striate lesion.

PubMed

Supèr, Hans; Lamme, Victor A F

2007-11-05

The visual system binds and segments the elements of an image into coherent objects and their surroundings. Recent findings demonstrate that primary visual cortex is involved in this process of figure-ground organization. In the primary visual cortex the late part of a neural response to a stimulus correlates with figure-ground segregation and perception. Such a late onset indicates an involvement of feedback projections from higher visual areas. To investigate the possible role of feedback in figure-ground perception we removed dorsal extra-striate areas of the monkey visual cortex. The findings show that figure-ground perception is reduced when the figure is presented in the lesioned hemifield and perception is normal when the figure appeared in the intact hemifield. In conclusion, our observations show the importance for recurrent processing in visual perception.

Comparison of Object Recognition Behavior in Human and Monkey

PubMed Central

Rajalingham, Rishi; Schmidt, Kailyn

2015-01-01

Although the rhesus monkey is used widely as an animal model of human visual processing, it is not known whether invariant visual object recognition behavior is quantitatively comparable across monkeys and humans. To address this question, we systematically compared the core object recognition behavior of two monkeys with that of human subjects. To test true object recognition behavior (rather than image matching), we generated several thousand naturalistic synthetic images of 24 basic-level objects with high variation in viewing parameters and image background. Monkeys were trained to perform binary object recognition tasks on a match-to-sample paradigm. Data from 605 human subjects performing the same tasks on Mechanical Turk were aggregated to characterize “pooled human” object recognition behavior, as well as 33 separate Mechanical Turk subjects to characterize individual human subject behavior. Our results show that monkeys learn each new object in a few days, after which they not only match mean human performance but show a pattern of object confusion that is highly correlated with pooled human confusion patterns and is statistically indistinguishable from individual human subjects. Importantly, this shared human and monkey pattern of 3D object confusion is not shared with low-level visual representations (pixels, V1+; models of the retina and primary visual cortex) but is shared with a state-of-the-art computer vision feature representation. Together, these results are consistent with the hypothesis that rhesus monkeys and humans share a common neural shape representation that directly supports object perception. SIGNIFICANCE STATEMENT To date, several mammalian species have shown promise as animal models for studying the neural mechanisms underlying high-level visual processing in humans. In light of this diversity, making tight comparisons between nonhuman and human primates is particularly critical in determining the best use of nonhuman primates to further the goal of the field of translating knowledge gained from animal models to humans. To the best of our knowledge, this study is the first systematic attempt at comparing a high-level visual behavior of humans and macaque monkeys. PMID:26338324

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were asmore » capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.« less

Monkey's health service: an evaluation of the implementation of resources designed to support the learning of primary school-aged children in England about healthy lifestyles and NHS services.

PubMed

Medforth, Nicholas; Timpson, Hannah; Greenop, Daz; Lavin, Rachel

2015-01-01

The National Health Service Institute for Innovation and Improvement was established to help the NHS to improve healthcare by rapidly developing and disseminating knowledge and evidence about new ways of working. One example is the Emergency and Urgent Care Pathway for Children and Young People which focused on providing high quality and safe healthcare for children and young people requiring urgent or emergency treatment for the most common illnesses and injuries. Monkey's Guide to Healthy Living and NHS Services was developed to increase awareness of acute health services in primary school-aged children. This free resource was posted to every primary school in England. A process and impact evaluation was undertaken to explore how the resource was being utilized during 2013-2014. A small number of in-depth case studies were developed involving classroom-based observations and teacher interviews along with a much larger online survey which was emailed to all primary schools in England. On the whole, the resource was viewed as useful, engaging, and informative; with children, teachers, and other professionals particularly valuing the monkey puppet, video clips, and teacher resources. The National Evaluation highlighted that most respondents integrated the materials into the curriculum, used them as a one-off lesson, or developed their own innovative and strategic approaches to make the best use of the resources; almost two-thirds of schools who responded to the survey felt the resources led to pupils knowing about the available NHS services and healthy lifestyles; over half felt pupils were now more informed about the most appropriate services to use.

Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature.

PubMed

Sun, Ke; You, Qihan; Zhao, Ming; Yao, Hongtian; Xiang, Hua; Wang, Lijun

2013-01-01

Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney.

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

PubMed

Oura, T; Hotta, K; Lei, J; Markmann, J; Rosales, I; Dehnadi, A; Kawai, K; Ndishabandi, D; Smith, R-N; Cosimi, A B; Kawai, T

2017-03-01

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Biodistribution and Radiation Dosimetry of the Integrin Marker 64Cu-BaBaSar-RGD2 Determined from Whole-Body PET/CT in a Non-Human Primate

NASA Astrophysics Data System (ADS)

Liu, Shuanglong; Vorobyova, Ivetta; Park, Ryan; Conti, Peter S.

2017-10-01

Introduction: 64Cu-BaBaSar-RGD2 is a positron emission radiotracer taken up by integrin αvβ3, which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of 64Cu-BaBaSar-RGD2 in a non-human primate with positron emission tomography and to estimate the absorbed doses in major organs for human. Materials and methods: Whole-body PET imaging was done in a Siemens Biograph scanner in a male macaque monkey. After an i.v. injection of 13.1–19.7 MBq/kg of 64Cu-BaBaSar-RGD2, whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstruction of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (VOI) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and residence time of each organ was calculated by integration of the time-activity curves. Human absorbed doses were estimated using the standard human model in OLINDA/EXM software. Results: Injection of 64Cu-BaBaSar-RGD2 was well tolerated in the macaque monkey, with no serious tracer-related adverse events observed. 64Cu-BaBaSar-RGD2 was cleared rapidly from the blood pool, with a 12.1-min biological half-time. Increased 64Cu-BaBaSar-RGD2 uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID%) values at 1 h after injection approximately 35.50 ± 6.47 and 36.89 ± 5.48, respectively. The calculated effective dose was 15.30 ± 2.21 µSv/MBq, and the kidneys had the highest absorbed dose at 108.43 ± 16.41 µGy/MBq using the non-voiding model. For an injected activity of 925 MBq 64Cu for human, the effective dose would be 14.2 ± 2.1 mSv. Discussion: Due to the limitation of the monkey number, we evaluated 64Cu-BaBaSar-RGD2 in the same monkey of three imaging sessions. Measured absorbed doses and effective doses of 64Cu-BaBaSar-RGD2 are comparable to other reported RGD-derived radiopharmaceuticals labeled with 64Cu and 18F. Therefore, 64Cu-BaBaSar-RGD2 can be safely injected into humans for studying integrin αvβ3 expression non-invasively.

Rhesus monkeys (Macaca mulatta), video tasks, and implications for stimulus-response spatial contiguity

NASA Technical Reports Server (NTRS)

Rumbaugh, Duane M.; Richardson, W. Kirk; Washburn, David A.; Hopkins, William D.; Savage-Rumbaugh, E. Sue

1989-01-01

Recent reports support the argument that the efficiency of primate learning is compromised to the degree that there is spatial discontiguity between discriminands and the locus of response. Experiments are reported here in which two rhesus monkeys easily mastered precise control of a joystick to respond to a variety of computer-generated targets despite the fact that the joystick was located 9 to 18 cm from the video screen. It is argued that stimulus-response contiguity is a significant parameter of learning only to the degree that the monkey visually attends to the directional movements of its hand in order to displace discriminands. If attention is focused on the effects of the hand's movement rather than on the hand itself, stimulus-response contiguity is no longer a primary parameter of learning. The implications of these results for mirror-guided studies are discussed.

Molecular epidemiology of measles virus infection in Shanghai in 2000-2012: the first appearance of genotype D8.

PubMed

Li, Shuhua; Qian, Xiaohua; Yuan, Zhengan; Sun, Xiaodong; Li, Chongshan; Tang, Xian; Yang, Yanji; Gong, Xiangzhen; Cao, Guangwen

2014-01-01

The purpose of this study was to identify measles virus in Shanghai in 2012 and study the genotype trend of measles virus epidemic strains during 2000-2012. Nose and throat swab specimens were collected from 34 suspected measles cases in Shanghai. Measles virus was isolated using Vero-SLAM cells (African green monkey kidney cells/lymphoid signal activating factor-transfected African green monkey kidney cells). The 450 bp of C terminus of the N gene and the entire hemagglutinin gene sequence was amplified using RT-PCR. Phylogenetic analysis was performed by comparing the seven measles strains in Shanghai with the reference strains for H1a, H1b and D8 genotypes, as well as the Chinese measles virus vaccine strain. Seven measles viruses strains were isolated from the 34 throat swap specimens. Six strains were genotype H1a, which is the predominant strain in China and one strain was genotype D8, which is the first imported strain since 2000. All these seven strains maintained most of the glycosylation sites except subtype H1a, which lost one glycosylation site. Since 2000, measles virus strains in Shanghai are consistent with measles virus from other provinces in China with H1a being the predominant genotype. This study is also the first report of genotype D8 strain in Shanghai. All strains maintained their glycosylation sites except H1a that lost one glycosylation site. These strains could still be neutralized by the Chinese measles vaccine. We suggest that Shanghai Center for Disease Control laboratories should strengthen their approaches to monitor measles cases to prevent further spread of imported strains. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Residual attention guidance in blindsight monkeys watching complex natural scenes.

PubMed

Yoshida, Masatoshi; Itti, Laurent; Berg, David J; Ikeda, Takuro; Kato, Rikako; Takaura, Kana; White, Brian J; Munoz, Douglas P; Isa, Tadashi

2012-08-07

Patients with damage to primary visual cortex (V1) demonstrate residual performance on laboratory visual tasks despite denial of conscious seeing (blindsight) [1]. After a period of recovery, which suggests a role for plasticity [2], visual sensitivity higher than chance is observed in humans and monkeys for simple luminance-defined stimuli, grating stimuli, moving gratings, and other stimuli [3-7]. Some residual cognitive processes including bottom-up attention and spatial memory have also been demonstrated [8-10]. To date, little is known about blindsight with natural stimuli and spontaneous visual behavior. In particular, is orienting attention toward salient stimuli during free viewing still possible? We used a computational saliency map model to analyze spontaneous eye movements of monkeys with blindsight from unilateral ablation of V1. Despite general deficits in gaze allocation, monkeys were significantly attracted to salient stimuli. The contribution of orientation features to salience was nearly abolished, whereas contributions of motion, intensity, and color features were preserved. Control experiments employing laboratory stimuli confirmed the free-viewing finding that lesioned monkeys retained color sensitivity. Our results show that attention guidance over complex natural scenes is preserved in the absence of V1, thereby directly challenging theories and models that crucially depend on V1 to compute the low-level visual features that guide attention. Copyright © 2012 Elsevier Ltd. All rights reserved.

Postnatal Development of Intrinsic Horizontal Axons in Macaque Inferior Temporal and Primary Visual Cortices.

PubMed

Wang, Quanxin; Tanigawa, Hisashi; Fujita, Ichiro

2017-04-01

Two distinct areas along the ventral visual stream of monkeys, the primary visual (V1) and inferior temporal (TE) cortices, exhibit different projection patterns of intrinsic horizontal axons with patchy terminal fields in adult animals. The differences between the patches in these 2 areas may reflect differences in cortical representation and processing of visual information. We studied the postnatal development of patches by injecting an anterograde tracer into TE and V1 in monkeys of various ages. At 1 week of age, labeled patches with distribution patterns reminiscent of those in adults were already present in both areas. The labeling intensity of patches decayed exponentially with projection distance in monkeys of all ages in both areas, but this trend was far less evident in TE. The number and extent of patches gradually decreased with age in V1, but not in TE. In V1, axonal and bouton densities increased postnatally only in patches with short projection distances, whereas in TE this density change occurred in patches with various projection distances. Thus, patches with area-specific distribution patterns are formed early in life, and area-specific postnatal developmental processes shape the connectivity of patches into adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spatial processing in the auditory cortex of the macaque monkey

NASA Astrophysics Data System (ADS)

Recanzone, Gregg H.

2000-10-01

The patterns of cortico-cortical and cortico-thalamic connections of auditory cortical areas in the rhesus monkey have led to the hypothesis that acoustic information is processed in series and in parallel in the primate auditory cortex. Recent physiological experiments in the behaving monkey indicate that the response properties of neurons in different cortical areas are both functionally distinct from each other, which is indicative of parallel processing, and functionally similar to each other, which is indicative of serial processing. Thus, auditory cortical processing may be similar to the serial and parallel "what" and "where" processing by the primate visual cortex. If "where" information is serially processed in the primate auditory cortex, neurons in cortical areas along this pathway should have progressively better spatial tuning properties. This prediction is supported by recent experiments that have shown that neurons in the caudomedial field have better spatial tuning properties than neurons in the primary auditory cortex. Neurons in the caudomedial field are also better than primary auditory cortex neurons at predicting the sound localization ability across different stimulus frequencies and bandwidths in both azimuth and elevation. These data support the hypothesis that the primate auditory cortex processes acoustic information in a serial and parallel manner and suggest that this may be a general cortical mechanism for sensory perception.

Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.

PubMed

George, Sunil K; Abolbashari, Mehran; Jackson, John D; Aboushwareb, Tamer; Atala, Anthony; Yoo, James J

2016-01-01

Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).

Validation of DTI Tractography-Based Measures of Primary Motor Area Connectivity in the Squirrel Monkey Brain

PubMed Central

Gao, Yurui; Choe, Ann S.; Stepniewska, Iwona; Li, Xia; Avison, Malcolm J.; Anderson, Adam W.

2013-01-01

Diffusion tensor imaging (DTI) tractography provides noninvasive measures of structural cortico-cortical connectivity of the brain. However, the agreement between DTI-tractography-based measures and histological ‘ground truth’ has not been quantified. In this study, we reconstructed the 3D density distribution maps (DDM) of fibers labeled with an anatomical tracer, biotinylated dextran amine (BDA), as well as DTI tractography-derived streamlines connecting the primary motor (M1) cortex to other cortical regions in the squirrel monkey brain. We evaluated the agreement in M1-cortical connectivity between the fibers labeled in the brain tissue and DTI streamlines on a regional and voxel-by-voxel basis. We found that DTI tractography is capable of providing inter-regional connectivity comparable to the neuroanatomical connectivity, but is less reliable measuring voxel-to-voxel variations within regions. PMID:24098365

Neuronal responses in visual area V2 (V2) of macaque monkeys with strabismic amblyopia.

PubMed

Bi, H; Zhang, B; Tao, X; Harwerth, R S; Smith, E L; Chino, Y M

2011-09-01

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia.

Neuronal Responses in Visual Area V2 (V2) of Macaque Monkeys with Strabismic Amblyopia

PubMed Central

Bi, H.; Zhang, B.; Tao, X.; Harwerth, R. S.; Smith, E. L.

2011-01-01

Amblyopia, a developmental disorder of spatial vision, is thought to result from a cascade of cortical deficits over several processing stages beginning at the primary visual cortex (V1). However, beyond V1, little is known about how cortical development limits the visual performance of amblyopic primates. We quantitatively analyzed the monocular and binocular responses of V1 and V2 neurons in a group of strabismic monkeys exhibiting varying depths of amblyopia. Unlike in V1, the relative effectiveness of the affected eye to drive V2 neurons was drastically reduced in the amblyopic monkeys. The spatial resolution and the orientation bias of V2, but not V1, neurons were subnormal for the affected eyes. Binocular suppression was robust in both cortical areas, and the magnitude of suppression in individual monkeys was correlated with the depth of their amblyopia. These results suggest that the reduced functional connections beyond V1 and the subnormal spatial filter properties of V2 neurons might have substantially limited the sensitivity of the amblyopic eyes and that interocular suppression was likely to have played a key role in the observed alterations of V2 responses and the emergence of amblyopia. PMID:21263036

Tetanus antibody titers and duration of immunity to clinical tetanus infections in free-ranging rhesus monkeys (Macaca mulatta).

PubMed

Kessler, Matthew J; Berard, John D; Rawlins, Richard G; Bercovitch, Fred B; Gerald, Melissa S; Laudenslager, Mark L; Gonzalez-Martinez, Janis

2006-07-01

Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2-year-old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two-dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long-term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long-term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great. (c) 2005 Wiley-Liss, Inc.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

Embedding of Cortical Representations by the Superficial Patch System

PubMed Central

Da Costa, Nuno M. A.; Girardin, Cyrille C.; Naaman, Shmuel; Omer, David B.; Ruesch, Elisha; Grinvald, Amiram; Douglas, Rodney J.

2011-01-01

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system—Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15–24. or daisy architecture—Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419–451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response–like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954–956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical input. PMID:21383233

Recombination Between Guanidine-resistant and Dextran Sulfate-resistant Mutants of Type 1 Poliovirus

PubMed Central

Sergiescu, Dina; Aubert-Combiescu, Andrei; Crainic, Radu

1969-01-01

Mixed infection of monkey kidney cells with two mutants of the LSc2ab strain of poliovirus, one resistant to guanidine and the other resistant to both dextran sulfate and 2-(α-hydroxybenzyl)-benzimidazole (HBB), yielded progeny in which the number of guardexr particles exceeded by a factor of 7 to 10 the expected number of similar particles occurring through spontaneous mutation; recombination would explain the fairly high excess of doubly mutant particles that was obtained. Scoring of HBB resistance in 50 guardexr clones suggested that, during recombination, resistance to dextran sulfate is not associated with HBB resistance. Images PMID:4305674

Species difference in the mechanism of nonlinear pharmacokinetics of E2074, a novel sodium channel inhibitor, in rats, dogs, and monkeys.

PubMed

Nagaya, Yoko; Takenaka, Osamu; Kusano, Kazutomi; Yoshimura, Tsutomu

2013-05-01

New chemical entities often exhibit nonlinear pharmacokinetics (PK) profiles in experimental animals. However, the number of studies that have focused on species differences in nonlinear PK is very limited; thus, the aim of this study was to clarify the mechanism of the nonlinear PK of E2074 (2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl)oxy]-8-azabicyclo[3.2.1]oct-8-yl}propyl]-4,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one), a novel sodium channel inhibitor, in rats, dogs, and monkeys. Nonlinear PK profiles with more than dose-proportional increases of Cmax and area under the plasma concentration curve were observed in all species after oral administration. The Michaelis-Menten constant (Km) values of hepatic microsomal metabolism were 7.23 and 0.41 μM in rats and dogs in vitro, respectively, which were lower than the unbound maximum plasma concentrations after oral administration in vivo, indicating that the nonlinear PK in rats and dogs was attributable to the saturation of hepatic metabolism. However, we do not believe that the saturation of hepatic metabolism was the mechanism of nonlinearity in monkeys because of the high Km value (42.44 μM) observed in liver microsomes. Intestinal metabolism was observed in monkey intestinal microsomes but not in rats and dogs, and the nonlinear PK in monkeys was diminished by inhibition of intestinal metabolism with a concomitant oral dose of ketoconazole. These results suggest that saturation of the intestinal metabolism is the potential mechanism of nonlinearity in monkeys. P-glycoprotein was not involved in the nonlinear PK profiles in any species. In conclusion, the mechanism of the nonlinear PK of E2074 is species dependent, with the saturation of hepatic metabolism in rats and dogs and that of intestinal metabolism in monkeys being the primary cause.

Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections.

PubMed

Fura, Aberra; Khanna, Ashish; Vyas, Viral; Koplowitz, Barry; Chang, Shu-Ying; Caporuscio, Christian; Boulton, David W; Christopher, Lisa J; Chadwick, Kristina D; Hamann, Lawrence G; Humphreys, W Griffith; Kirby, Mark

2009-06-01

Saxagliptin is a potent, selective, reversible dipeptidyl peptidase 4 (DPP4) inhibitor specifically designed for extended inhibition of the DPP4 enzyme and is currently under development for the treatment of type-2 diabetes. The pharmacokinetics of saxagliptin were evaluated in rats, dogs, and monkeys and used to predict its human pharmacokinetics. Saxagliptin was rapidly absorbed and had good bioavailability (50-75%) in the species tested. The plasma clearance of saxagliptin was higher in rats (115 ml/min/kg) than in dogs (9.3 ml/min/kg) and monkeys (14.5 ml/min/kg) and was predicted to be low to moderate in humans. The plasma elimination half-life was between 2.1 and 4.4 h in rats, dogs, and monkeys, and both metabolism and renal excretion contributed to the overall elimination. The primary metabolic clearance pathway involved the formation of a significant circulating, pharmacologically active hydroxylated metabolite, M2. The volume of distribution values observed in rats, dogs, and monkeys (1.3-5.2 l/kg) and predicted for humans (2.7 l/kg) were greater than those for total body water, indicating extravascular distribution. The in vitro serum protein binding was low (< or =30%) in rats, dogs, monkeys, and humans. After intra-arterial administration of saxagliptin to Sprague-Dawley and Zucker diabetic fatty rats, higher levels of saxagliptin and M2 were observed in the intestine (a proposed major site of drug action) relative to that in plasma. Saxagliptin has prolonged pharmacodynamic properties relative to its plasma pharmacokinetic profile, presumably due to additional contributions from M2, distribution of saxagliptin and M2 to the intestinal tissue, and prolonged dissociation of both saxagliptin and M2 from DPP4.

Kidney transplantation after previous liver transplantation: analysis of the organ procurement transplant network database.

PubMed

Gonwa, Thomas A; McBride, Maureen A; Mai, Martin L; Wadei, Hani M

2011-07-15

Patients after liver transplant have a high incidence of chronic kidney disease and end-stage renal disease (ESRD). We investigated kidney transplantation after liver transplantation using the Organ Procurement Transplant Network database. The Organ Procurement Transplant Network database was queried for patients who received kidney transplantation after previous liver transplantation. These patients were compared with patients who received primary kidney transplantation alone during the same time period. Between 1997 and 2008, 157,086 primary kidney transplants were performed. Of these, 680 deceased donor kidney transplants and 410 living donor kidney transplants were performed in previous recipients of liver transplants. The number of kidney after liver transplants performed each year has increased from 37 per year to 124 per year in 2008. The time from liver transplant to kidney transplant increased from 8.2 to 9.0 years for living donor transplants and from 5.4 to 9.6 years for deceased donor. The 1, 3, and 5 year actuarial graft survival in both living donor kidney after liver transplant and deceased donor kidney after liver transplant are less than the kidney transplant alone patients. However, the death-censored graft survivals are equal. The patient survival is also less but is similar to what would be expected in liver transplant recipients who did not have ESRD. In 2008, kidney after liver transplantation represented 0.9% of the total kidney alone transplants performed in the United States. Kidney transplantation is an appropriate therapy for selected patients who develop ESRD after liver transplantation.

Preclinical pharmacokinetics of the novel PI3K inhibitor GDC-0941 and prediction of its pharmacokinetics and efficacy in human.

PubMed

Salphati, Laurent; Pang, Jodie; Plise, Emile G; Chou, Bilin; Halladay, Jason S; Olivero, Alan G; Rudewicz, Patrick J; Tian, Qingping; Wong, Susan; Zhang, Xiaolin

2011-12-01

The phosphatidylinositol 3-kinase (PI3K) pathway is a major determinant of cell cycling and proliferation. Its deregulation is associated with the development of many cancers. GDC-0941, a potent and selective inhibitor of PI3K, was characterised preclinically in in vitro and in vivo studies. Plasma protein binding was extensive, with free fraction less than 7%, and blood-to-plasma ratio ranged from 0.6 to 1.2 among the species tested. GDC-0941 human hepatic clearance was predicted to be moderate by liver microsomal incubations. GDC-0941 had high permeability in Madin-Darby canine kidney cells. The clearance of GDC-0941 was high in mouse (63.7 mL/min/kg), rat (49.3 mL/min/kg) and cynomolgus monkey (58.6 mL/min/kg), and moderate in dog (11.9 mL/min/kg). The volume of distribution ranged from 2.52 L/kg in rat to 2.94 L/kg in monkey. Oral bioavailability ranged from 18.6% in monkey to 77.9% in mouse. Predicted human clearance and volume of distribution using allometry were 6 mL/min/kg and 2.9 L/kg, respectively. The human efficacious doses were predicted based on results from preclinical pharmacokinetic studies and xenograft models. GDC-0941 preclinical characterisation and predictions of its properties in human supported its progression towards clinical development. GDC-0941 is currently in phase II clinical trials.

Complex of simian virus 40 large-T antigen and host 53,000-molecular-weight protein in monkey cells.

PubMed Central

Harlow, E; Pim, D C; Crawford, L V

1981-01-01

Mouse cells transformed by simian virus 40 (SV40) have been shown to contain a complex of the virus-coded large-T antigen with a host 53,000-molecular-weight (53K) protein. Initial attempts to detect a similar complex in lytically infected cells were unsuccessful, and it therefore seemed that the complex might be peculiar to transformed or abortively transformed nonpermissive cells. Immunoprecipitation of [32P]phosphate-labeled extracts of SV40-infected CV-1 African green monkey kidney cells with antibodies specific for large-T or the 53K protein revealed that the large-T-53K protein complex was formed during lytic infections. Only a minor fraction of the large-T present was associated with 53K protein, and large-T and the 53K host protein cosedimented during centrifugation through sucrose gradients. We used monospecific sera and monoclonal antibodies to study the rate of synthesis and phosphorylation of the 53K protein during lytic infections. Infection of CV-1 cells with SV40 increased the rate of synthesis of the 53K protein fivefold over that in mock-infected cells. At the same time, the rate of phosphorylation of the 53K protein increased more than 30-fold compared with control cultures. Monkey cells transformed by UV-irradiated SV40 (Gluzman et al., J. Virol. 22:256-266, 1977) also contained the large-T-53K protein complex. The formation of the complex is therefore not a peculiarity of SV40-transformed rodent cells but is a common feature of SV40 infections. Images PMID:6163871

Cervical carotid and circle of willis arterial anatomy of macaque monkeys: a comparative anatomy study.

PubMed

Kumar, Nishant; Lee, John J; Perlmutter, Joel S; Derdeyn, Colin P

2009-07-01

Macaque monkeys are used in many research applications, including cerebrovascular investigations. However, detailed catalogs of the relevant vascular anatomy are scarce. We present our experience with macaque vessel patterns as determined by digital subtraction angiography of 34 different monkeys. We retrospectively analyzed digital subtraction angiograms obtained during experimental internal carotid artery (ICA) catheterization and subsequent injection of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine. Results were catalogued according to vascular distribution and variants observed. Macaque monkeys have a bovine aortic arch. The carotid vessels generally bifurcate, but are occasionally observed to divide into three vessels. The external carotid gives rise primarily to two trunks: an occipital branch and a common vessel that subsequently gives off the lingual, facial, and superior thyroid arteries. The internal maxillary artery may be present as a terminal branch of the external carotid or as a branch of the occipital artery. The ICA is similar in course to that of the human. The anterior circle of Willis was intact in all monkeys in our study. Its primary difference from that of the human is the union of the bilateral anterior cerebral arteries as a single (azygous) median vessel. Macaque cervical carotid and circle of Willis arterial anatomy differs from humans in a couple of specific patterns. Knowledge of these differences and similarities between human and macaque anatomy is important in developing endovascular macaque models of human diseases, such as ischemic stroke.

Predictive cues for auditory stream formation in humans and monkeys.

PubMed

Aggelopoulos, Nikolaos C; Deike, Susann; Selezneva, Elena; Scheich, Henning; Brechmann, André; Brosch, Michael

2017-12-18

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60-140 ms post-stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cervical Carotid and Circle of Willis Arterial Anatomy of Macaque Monkeys: A Comparative Anatomy Study

PubMed Central

Kumar, Nishant; Lee, John J.; Perlmutter, Joel S.; Derdeyn, Colin P.

2009-01-01

Macaque monkeys are used in many research applications, including cerebrovascular investigations. However, detailed catalogs of the relevant vascular anatomy are scarce. We present our experience with macaque vessel patterns as determined by digital subtraction angiography of 34 different monkeys. METHODS AND MATERIALS: We retrospectively analyzed digital subtraction angiograms obtained during experimental internal carotid artery catheterization and subsequent injection of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). Results were catalogued according to vascular distribution and variants observed. RESULTS: Macaque monkeys have a bovine aortic arch. The carotid vessels generally bifurcate, but are occasionally observed to divide into three vessels. The external carotid gives rise primarily to two trunks: an occipital branch and a common vessel that subsequently gives off the lingual, facial, and superior thyroid arteries. The internal maxillary artery may be present as a terminal branch of the external carotid or as a branch of the occipital artery. The internal carotid artery is similar in course to that of the human. The anterior circle of Willis was intact in all monkeys in our study. Its primary difference from that of the human is the union of the bilateral anterior cerebral arteries as a single (azygous) median vessel. CONCLUSIONS: Macaque cervical carotid and circle of Willis arterial anatomy differs from humans in a couple of specific patterns. Knowledge of these differences and similarities between human and macaque anatomy is important in developing endovascular macaque models of human diseases, such as ischemic stroke. PMID:19434671

A MEG investigation of somatosensory processing in the rhesus monkey

PubMed Central

Wilson, Tony W.; Godwin, Dwayne W.; Czoty, Paul W.; Nader, Michael A.; Kraft, Robert A.; Buchheimer, Nancy C.; Daunais, James B.

2009-01-01

The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole-head MEG instrumentation to record neuromagnetic responses in adult rhesus monkeys. Nonhuman primate models of human disease provide the closest phylogenetic link to humans. The present, non-invasive imaging study could promote exciting links between invasive animal studies and non-invasive human studies, allowing experimentally induced deficits and pharmacological treatments to be interpreted in light of resulting brain network interactions. PMID:19306931

Spontaneous and Drug-induced Arteritis/Polyarteritis in the Göttingen Minipig-Review.

PubMed

Dincer, Zuhal; Piccicuto, Virginie; Walker, Ursula Junker; Mahl, Andreas; McKeag, Sean

2018-02-01

Arteritis/polyarteritis occurs spontaneously in many species used in preclinical toxicology studies. In Göttingen minipigs, arteritis/polyarteritis is an occasionally observed background change. In the minipig, this finding differs in frequency and nature from age-related polyarteritis nodosa in rats or monkeys, and Beagle pain syndrome in dogs. In minipigs, it can be present in a single small- or medium-sized artery of an organ or a few organs and is most commonly recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. The etiology is unknown although it has been considered in minipigs as well as in rats, dogs, and monkeys to be possibly immune mediated. This background change is important with respect to its nature and distribution in the minipig in order to distinguish it from drug-induced vascular changes, which might occur in similar locations and have similar morphologic features. This review summarizes the morphology, incidence, and predilection sites of arteritis as a spontaneously occurring background change and as a drug-induced vasculopathy in the minipig, and also describes the main aspects to consider when evaluating vascular changes in Göttingen minipig toxicity studies and their human relevance.

Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

PubMed Central

Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

2009-01-01

In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

PubMed

Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

2004-06-01

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Transplantation outcomes in primary hyperoxaluria.

PubMed

Bergstralh, E J; Monico, C G; Lieske, J C; Herges, R M; Langman, C B; Hoppe, B; Milliner, D S

2010-11-01

Optimal transplantation strategies are uncertain in primary hyperoxaluria (PH) due to potential for recurrent oxalosis. Outcomes of different transplantation approaches were compared using life-table methods to determine kidney graft survival among 203 patients in the International Primary Hyperoxaluria Registry. From 1976-2009, 84 kidney alone (K) and combined kidney and liver (K + L) transplants were performed in 58 patients. Among 58 first kidney transplants (32 K, 26 K + L), 1-, 3- and 5-year kidney graft survival was 82%, 68% and 49%. Renal graft loss occurred in 26 first transplants due to oxalosis in ten, chronic allograft nephropathy in six, rejection in five and other causes in five. Delay in PH diagnosis until after transplant favored early graft loss (p = 0.07). K + L had better kidney graft outcomes than K with death-censored graft survival 95% versus 56% at 3 years (p = 0.011). Among 29 year 2000-09 first transplants (24 K + L), 84% were functioning at 3 years compared to 55% of earlier transplants (p = 0.05). At 6.8 years after transplantation, 46 of 58 patients are living (43 with functioning grafts). Outcomes of transplantation in PH have improved over time, with recent K + L transplantation highly successful. Recurrent oxalosis accounted for a minority of kidney graft losses. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Left Lateral Sectionectomy of the Native Liver and Combined Living-Related Liver–Kidney Transplantation for Primary Hyperoxaluria Type 1

PubMed Central

Chen, Guo-Yong; Wei, Si-Dong; Zou, Zhong-Wu; Tang, Gao-Feng; Sun, Jian-Jun; Zhou, Shao-Tang

2015-01-01

Abstract Primary hyperoxaluria type I (PH1), the most severe form of primary hyperoxalurias, is a liver disease of the metabolic defect in glyoxylate detoxification that can be corrected by liver transplantation. A 21-year-old man presented to our center after 4 months of regular hemodialysis for kidney failure caused by nephrolithiasis. A diagnosis of PH1 was confirmed by mutations of the AGXT gene. Left lateral sectionectomy of the native liver was performed; and auxiliary partial orthotopic liver transplantation (APOLT) and kidney transplantation were carried out synchronously using a living donor. After transplantation, the patient's plasma oxalate and creatinine levels substantially decreased and the patient recovered well with good dual grafts function. APOLT and kidney transplantation can compensate the liver deficient in liver enzyme production and aid the renal elimination of oxalate, thus serving as an effective treatment option for patients with PH1. In conclusion, left lateral sectionectomy of the native liver and combined living-related liver–kidney transplantation can be a surgical option for PH1. PMID:26252291

Attitudes to kidney donation among primary care patients in rural Crete, Greece.

PubMed

Symvoulakis, Emmanouil K; Komninos, Ioannis D; Antonakis, Nikos; Morgan, Myfanwy; Alegakis, Athanasios; Tsafantakis, Emmanouil; Chatziarsenis, Marios; Philalithis, Anastas; Jones, Roger

2009-02-10

In Greece, there is limited research on issues related to organ donation, and the low rate of registration as donors requires explanation. This study reports the findings of a survey of knowledge and attitudes to kidney donation among primary care patients in rural Crete, Greece. Two rural primary care settings in the island of Crete, Anogia Health Centre and Vrachasi Practice, were involved in a questionnaire survey. This was conducted among primary care patients (aged 18 years and over) with routine appointments, to assess their knowledge and attitudes to kidney donation. General practitioners (GPs) recruited patients and questionnaires were completed following the patients' medical consultation. Pearson's chi square tests were used and crude odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in order to investigate into the possible associations between the respondents' knowledge, attitudes and specific concerns in relation to their socio-demographic features. Logistic regression analyses were used to examine differences by geographical location. The 224 (92.5%) of the 242 primary care attenders who were approached agreed to participate. Only 2.2% (5/224) of the respondents carried a donor card. Most participants (84.4%, 189/224) did not feel well informed about registering as a kidney donor. More than half of the respondents (54.3%, 121/223) were unwilling to register as a kidney donor and donate kidneys for transplant after death. Over a third of respondents (35.4%, 79/223) were not confident that medical teams would try as hard as possible to save the life of a person who has agreed to donate organs. People with a higher level of education were more likely to be willing to register as kidney donors [(OR: 3.3; 95% CI: 1.8-6.0), p < 0.001)] and to be less worried about their kidneys being removed after death [(OR: 0.3; 95% CI: 0.1-0.5), p < 0.001)] than those having a lower level of education. Lack of knowledge and information regarding organ donation and negative attitudes related to registration as donors were the main findings of this study. Efforts should be based on targeting the attitudes to organ donation of individuals and population groups.

Enterotoxins of Staphylococci

DTIC Science & Technology

1988-01-01

staphylococcal enterotoxin B in monkeys. Appl . Microbial. 16:187-192. Huang, I.-Y. and Bergdoll. M. S. (1970). The primary structure of staphylococcal enterotoxin...EPIDEMIOLOGY 132 III. PRODUCTION AND ISOLATION 132 A. Production 132 B. Purification 134 C. Purity 135 IV. STRUCTURE AND FUNCTION 138 A. Basic Structure 138 B...Primary Structure and Active Site 138 C. Modification Studies 142 D. Conformation 143 V. DETECTION METHODS 146 VI. SYNTHESIS 148 A. Cloning of

V1 mechanisms underlying chromatic contrast detection

PubMed Central

Hass, Charles A.

2013-01-01

To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1

PubMed Central

Dagnino, Bruno; Gariel-Mathis, Marie-Alice

2014-01-01

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. PMID:25392172

Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1.

PubMed

Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Roelfsema, Pieter R

2015-02-01

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. Copyright © 2015 the American Physiological Society.

Association between Organ Procurement Organization Social Network Centrality and Kidney Discard and Transplant Outcomes1

PubMed Central

Butala, Neel M.; King, Marissa D.; Reitsma, William; Formica, Richard N.; Abt, Peter L.; Reese, Peter P.; Parikh, Chirag R.

2015-01-01

Background Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes. Methods We identified 106,160 deceased-donor kidneys recovered for transplant from 2000–2010 in SRTR. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping. Results An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (OR:1.021, CI:1.006, 1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes. Conclusions Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs. PMID:26102610

Correspondence of presaccadic activity in the monkey primary visual cortex with saccadic eye movements

PubMed Central

Supèr, Hans; van der Togt, Chris; Spekreijse, Henk; Lamme, Victor A. F.

2004-01-01

We continuously scan the visual world via rapid or saccadic eye movements. Such eye movements are guided by visual information, and thus the oculomotor structures that determine when and where to look need visual information to control the eye movements. To know whether visual areas contain activity that may contribute to the control of eye movements, we recorded neural responses in the visual cortex of monkeys engaged in a delayed figure-ground detection task and analyzed the activity during the period of oculomotor preparation. We show that ≈100 ms before the onset of visually and memory-guided saccades neural activity in V1 becomes stronger where the strongest presaccadic responses are found at the location of the saccade target. In addition, in memory-guided saccades the strength of presaccadic activity shows a correlation with the onset of the saccade. These findings indicate that the primary visual cortex contains saccade-related responses and participates in visually guided oculomotor behavior. PMID:14970334

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

PubMed Central

Umeda, Tatsuya; Seki, Kazuhiko; Sato, Masa-aki; Nishimura, Yukio; Kawato, Mitsuo; Isa, Tadashi

2012-01-01

Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR) algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates. PMID:23112841

A Brain-Machine Interface Instructed by Direct Intracortical Microstimulation

PubMed Central

O'Doherty, Joseph E.; Lebedev, Mikhail A.; Hanson, Timothy L.; Fitzsimmons, Nathan A.; Nicolelis, Miguel A. L.

2009-01-01

Brain–machine interfaces (BMIs) establish direct communication between the brain and artificial actuators. As such, they hold considerable promise for restoring mobility and communication in patients suffering from severe body paralysis. To achieve this end, future BMIs must also provide a means for delivering sensory signals from the actuators back to the brain. Prosthetic sensation is needed so that neuroprostheses can be better perceived and controlled. Here we show that a direct intracortical input can be added to a BMI to instruct rhesus monkeys in choosing the direction of reaching movements generated by the BMI. Somatosensory instructions were provided to two monkeys operating the BMI using either: (a) vibrotactile stimulation of the monkey's hands or (b) multi-channel intracortical microstimulation (ICMS) delivered to the primary somatosensory cortex (S1) in one monkey and posterior parietal cortex (PP) in the other. Stimulus delivery was contingent on the position of the computer cursor: the monkey placed it in the center of the screen to receive machine–brain recursive input. After 2 weeks of training, the same level of proficiency in utilizing somatosensory information was achieved with ICMS of S1 as with the stimulus delivered to the hand skin. ICMS of PP was not effective. These results indicate that direct, bi-directional communication between the brain and neuroprosthetic devices can be achieved through the combination of chronic multi-electrode recording and microstimulation of S1. We propose that in the future, bidirectional BMIs incorporating ICMS may become an effective paradigm for sensorizing neuroprosthetic devices. PMID:19750199

Opportunities for improving management of advanced chronic kidney disease.

PubMed

Patwardhan, Meenal B; Matchar, David B; Samsa, Gregory P; Haley, William E

2008-01-01

Evidence suggests that management of advanced chronic kidney disease affects patient outcomes. To identify clinical areas that demand attention from a quality improvement perspective, we sought to examine the extent of conformance to an advanced chronic kidney disease guideline in a range of practices. A total of 237 patient medical records were abstracted from 4 primary care providers and 4 nephrology private practices across the country. In the practices studied, management of advanced chronic kidney disease patients was suboptimal for patients managed by primary care providers as well as those managed by nephrologists (overall conformance 27% and 42%, respectively), specifically for anemia, bone disease, and timing for renal replacement therapy. The current exercise (in conjunction with a literature search and focused and individual interviews with providers and patients) offered valuable information that was used to develop a toolkit for optimizing management of advanced chronic kidney disease.

Methanol exposure does not produce oxidatively damaged DNA in lung, liver or kidney of adult mice, rabbits or primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCallum, Gordon P.; Siu, Michelle; Sweeting, J. Nicole

2011-01-15

In vitro and in vivo genotoxicity tests indicate methanol (MeOH) is not mutagenic, but carcinogenic potential has been claimed in one controversial long-term rodent cancer bioassay that has not been replicated. To determine whether MeOH could indirectly damage DNA via reactive oxygen species (ROS)-mediated mechanisms, we treated male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys with MeOH (2.0 g/kg ip) and 6 h later assessed oxidative damage to DNA, measured as 8-oxo-2'-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8-oxodG in lung, liver or kidney of any species. Chronic treatment of CD-1 micemore » with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. These results were corroborated in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, which accumulated 8-oxodG in lung, kidney and liver with age, but exhibited no increase following MeOH, despite a 2-fold increase in renal 8-oxodG in Ogg1 KO mice following treatment with a ROS-initiating positive control, the renal carcinogen potassium bromate (KBrO{sub 3}; 100 mg/kg ip). These observations suggest that MeOH exposure does not promote the accumulation of oxidatively damaged DNA in lung, kidney or liver, and that environmental exposure to MeOH is unlikely to initiate carcinogenesis in these organs by DNA oxidation.« less

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects.

PubMed

Verdelli, C; Corbetta, S

2017-01-01

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed. © 2017 European Society of Endocrinology.

Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus)

PubMed Central

Freeman, Sara M.; Walum, Hasse; Inoue, Kiyoshi; Smith, Aaron L.; Goodman, Mark M.; Bales, Karen L.; Young, Larry J.

2014-01-01

The coppery titi monkey (Callicebus cupreus) is a socially monogamous New World primate that has been studied in the field and the laboratory to investigate the behavioral neuroendocrinology of primate pair bonding and parental care. Arginine vasopressin has been shown to influence male titi monkey pair-bonding behavior, and studies are currently underway to examine the effects of oxytocin on titi monkey behavior and physiology. Here, we use receptor autoradiography to identify the distribution of arginine vasopressin 1a (AVPR1a) and oxytocin receptors (OXTR) in hemispheres of titi monkey brain (n=5). AVPR1a are diffuse and widespread throughout the brain, but the OXTR distribution is much more limited, with the densest binding being in the hippocampal formation (dentate gyrus, CA1 field) and the presubiculum (layers I and III). Moderate OXTR binding was detected in the nucleus basalis of Meynert, pulvinar, superior colliculus, layer 4C of primary visual cortex, periaqueductal gray, pontine gray, nucleus prepositus, and spinal trigeminal nucleus. OXTR mRNA overlapped with OXTR radioligand binding, confirming that the radioligand was detecting OXTR protein. AVPR1a binding is present throughout the cortex, especially in cingulate, insular, and occipital cortices, as well as in the caudate, putamen, nucleus accumbens, central amygdala, endopiriform nucleus, hippocampus (CA4 field), globus pallidus, lateral geniculate nucleus, infundibulum, habenula, periaqueductal gray, substantia nigra, olivary nucleus, hypoglossal nucleus, and cerebellum. Furthermore, we show that, in titi monkey brain, the OXTR antagonist ALS-II-69 is highly selective for OXTR and that the AVPR1a antagonist SR49059 is highly selective for AVPR1a. Based on these results and the fact that both ALS-II-69 and SR49059 are non-peptide, small-molecule antagonists that should be capable of crossing the blood brain barrier, these two compounds emerge as excellent candidates for the pharmacological manipulation of OXTR and AVPR1a in future behavioral experiments in titi monkeys and other primate species. PMID:24814726

Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.

PubMed

Yu, Rosie Z; Kim, Tae-Won; Hong, An; Watanabe, Tanya A; Gaus, Hans J; Geary, Richard S

2007-03-01

The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. Plasma pharmacokinetics following parental administration was similar across species, exhibiting a rapid distribution phase with t(1/2alpha) of several hours and a prolonged elimination phase with t(1/2beta) of days. The prolonged elimination phase represents equilibrium between tissues and circulating drug due to slow elimination from tissues. Absorption was nearly complete following s.c. injection, with bioavailability ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species as a function of body weight alone, and this correlation was improved when corrected for plasma protein binding. In all of the animal models studied, the highest tissue concentrations of ISIS 301012 were observed in kidney and liver. Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS 301012 is highly bound to plasma proteins, probably preventing rapid removal by renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5-mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012 exceeded their respective protein binding capacity. Thus, urinary excretion increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway of this compound, as demonstrated by 32% of dose recovered in total excreta by 14 days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is predictable from the pharmacokinetics measured in animals. The pharmacokinetic properties of ISIS 301012 provide guidance for clinical development and support infrequent dose administration.

Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients: Primary Results from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

PubMed Central

Bostom, Andrew G.; Carpenter, Myra A.; Kusek, John W.; Levey, Andrew S.; Hunsicker, Lawrence; Pfeffer, Marc A.; Selhub, Jacob; Jacques, Paul F.; Cole, Edward; Gravens-Mueller, Lisa; House, Andrew A.; Kew, Clifton; McKenney, Joyce L.; Pacheco-Silva, Alvaro; Pesavento, Todd; Pirsch, John; Smith, Stephen; Solomon, Scott; Weir, Matthew

2015-01-01

Background Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. Methods and Results In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Conclusions Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. PMID:21482964

Attitudes to kidney donation among primary care patients in rural Crete, Greece

PubMed Central

Symvoulakis, Emmanouil K; Komninos, Ioannis D; Antonakis, Nikos; Morgan, Myfanwy; Alegakis, Athanasios; Tsafantakis, Emmanouil; Chatziarsenis, Marios; Philalithis, Anastas; Jones, Roger

2009-01-01

Background In Greece, there is limited research on issues related to organ donation, and the low rate of registration as donors requires explanation. This study reports the findings of a survey of knowledge and attitudes to kidney donation among primary care patients in rural Crete, Greece. Methods Two rural primary care settings in the island of Crete, Anogia Health Centre and Vrachasi Practice, were involved in a questionnaire survey. This was conducted among primary care patients (aged 18 years and over) with routine appointments, to assess their knowledge and attitudes to kidney donation. General practitioners (GPs) recruited patients and questionnaires were completed following the patients' medical consultation. Pearson's chi square tests were used and crude odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in order to investigate into the possible associations between the respondents' knowledge, attitudes and specific concerns in relation to their socio-demographic features. Logistic regression analyses were used to examine differences by geographical location. Results The 224 (92.5%) of the 242 primary care attenders who were approached agreed to participate. Only 2.2% (5/224) of the respondents carried a donor card. Most participants (84.4%, 189/224) did not feel well informed about registering as a kidney donor. More than half of the respondents (54.3%, 121/223) were unwilling to register as a kidney donor and donate kidneys for transplant after death. Over a third of respondents (35.4%, 79/223) were not confident that medical teams would try as hard as possible to save the life of a person who has agreed to donate organs. People with a higher level of education were more likely to be willing to register as kidney donors [(OR: 3.3; 95% CI: 1.8–6.0), p < 0.001)] and to be less worried about their kidneys being removed after death [(OR: 0.3; 95% CI: 0.1–0.5), p < 0.001)] than those having a lower level of education. Conclusion Lack of knowledge and information regarding organ donation and negative attitudes related to registration as donors were the main findings of this study. Efforts should be based on targeting the attitudes to organ donation of individuals and population groups. PMID:19208215

Detailed kinetics of EBV-specific CD4+ and CD8+ T cells during primary EBV infection in a kidney transplant patient.

PubMed

Piriou, Erwan R W A N; van Dort, Karel; Weel, Jan F L; Bemelman, Frederike J; Gamadia, Laila E; van Oers, Marinus H J; van Baarle, Debbie

2006-04-01

The etiology of infectious mononucleosis is poorly understood and usually detected many weeks after infection. Here, we present a unique case of primary symptomatic EBV infection after kidney transplantation, in whom we analyzed both EBV-specific CD4+ and CD8+ T cells in detail from the moment of infection up to latency. We show that EBV-specific T-cell responses in peripheral blood during primary EBV infection after kidney transplantation peaked early after the appearance of viral load, but well before onset of IM symptoms, suggesting that IM in this case is not caused by high numbers of CD8+ T cells per se but may be caused by lack of homing to lymph nodes or tonsils.

Pharmacokinetics and Magnetic Resonance Imaging of Biodegradable Macromolecular Blood-Pool Contrast Agent PG-Gd in Non-Human Primates: A Pilot Study

PubMed Central

Tian, Mei; Wen, Xiaoxia; Jackson, Edward F.; Ng, Chaan; Uthamanthil, Rajesh; Liang, Dong; Gelovani, Juri G.; Li, Chun

2012-01-01

The purpose of this study was to evaluate poly(L-glutamic acid)-benzyl-DTPA-Gd (PG-Gd), a new biodegradable macromolecular magnetic resonance imaging contrast agent, for its pharmacokinetics and MRI enhancement in nonhuman primates. Studies were performed in rhesus monkeys at intravenous doses of 0.01, 0.02, and 0.08 mmol Gd/kg. T1-weighted MR images were acquired at 1.5T using fast spoiled gradient recalled echo and fast spin echo imaging protocols. The small-molecule contrast agent Magnevist was used as a control. PG-Gd in the monkey showed a bi-exponential disposition. The initial blood concentrations within 2 hours of PG-Gd administration were much higher than for those of Magnevist. The high blood concentration of PG-Gd was consistent with the MR imaging data, which showed prolonged circulation of PG-Gd in the blood pool. Enhancement of blood vessels and organs with a high blood perfusion (heart, liver, and kidney) was clearly visualized at 2 hours after contrast injection at the three doses used. A greater than proportional increase of the area under the blood concentration-time curve was observed when the administered single dose was increased from 0.01 mmol/kg to 0.08 mmol/kg. By 2 days after PG-Gd injection, the contrast agent was mostly cleared from all major organs, including kidney. The mean residence time was 15 hours at the 0.08 mmol/kg dose. A similar pharmacokinetic profile was observed in mice, with a mean residence time of 5.4 hours and a volume of distribution at steady-state of 85.5 mL/kg, indicating that the drug was mainly distributed in the blood compartment. Based on this pilot study, further investigations on potential systemic toxicity of PG-Gd in both rodents and large animals are needed before testing this agent in humans. PMID:21861289

Do females pay attention to secondary sexual coloration in vervet monkeys ( Chlorocebus aethiops)?

NASA Astrophysics Data System (ADS)

Gerald, Melissa S.; Ayala, James; Ruíz-Lambides, Angelina; Waitt, Corri; Weiss, Alexander

2010-01-01

Several primate species show sexual dichromatism with males displaying conspicuous coloration of the pelage or skin. Studies of scrotal coloration in male vervet monkeys ( Chlorocebus aethiops) suggest that it is an important intrasexual signal, with relatively dark, colourful males dominating paler males. To date, no studies have examined the influence of male colour on intersexual social interactions in vervet monkeys. The primary goal of the present study was to evaluate whether female vervet monkeys attend to male coloration. We experimentally introduced females, housed with either “pale” or “dark” males, to stimulus males whose scrota were pale, dark, or pale but painted to look dark. Overall, during introductions, females did not differ in time spent directing affiliative behaviour toward pale, dark, and painted males; however, females, permanently housed with dark males, spent significantly more time directing affiliative behaviour toward pale than painted males. When the stimulus male was pale, affiliative exchanges between males and females were longer than when the stimulus male was painted. Home male colour was not related to female-initiated aggression. Home male colour was also not related to male-initiated aggression, although painted stimulus males were more likely to initiate aggression than pale stimulus males. These findings lead us to conclude that females pay attention to male coloration, but do not bias their interactions toward males solely on the basis of natural male coloration.

Do females pay attention to secondary sexual coloration in vervet monkeys (Chlorocebus aethiops)?

PubMed

Gerald, Melissa S; Ayala, James; Ruíz-Lambides, Angelina; Waitt, Corri; Weiss, Alexander

2010-01-01

Several primate species show sexual dichromatism with males displaying conspicuous coloration of the pelage or skin. Studies of scrotal coloration in male vervet monkeys (Chlorocebus aethiops) suggest that it is an important intrasexual signal, with relatively dark, colourful males dominating paler males. To date, no studies have examined the influence of male colour on intersexual social interactions in vervet monkeys. The primary goal of the present study was to evaluate whether female vervet monkeys attend to male coloration. We experimentally introduced females, housed with either "pale" or "dark" males, to stimulus males whose scrota were pale, dark, or pale but painted to look dark. Overall, during introductions, females did not differ in time spent directing affiliative behaviour toward pale, dark, and painted males; however, females, permanently housed with dark males, spent significantly more time directing affiliative behaviour toward pale than painted males. When the stimulus male was pale, affiliative exchanges between males and females were longer than when the stimulus male was painted. Home male colour was not related to female-initiated aggression. Home male colour was also not related to male-initiated aggression, although painted stimulus males were more likely to initiate aggression than pale stimulus males. These findings lead us to conclude that females pay attention to male coloration, but do not bias their interactions toward males solely on the basis of natural male coloration.

Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

PubMed

Clarke, D O; Hilbish, K G; Waters, D G; Newcomb, D L; Chellman, G J

2015-12-01

The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

Mitigation of septic shock in mice and rhesus monkeys by human chorionic gonadotrophin-related oligopeptides

PubMed Central

Khan, N A; Vierboom, M P M; van Holten – Neelen, C; Breedveld, E; Zuiderwijk-Sick, E; Khan, A; Kondova, I; Braskamp, G; Savelkoul, H F J; Dik, W A; ‘t Hart, B A; Benner, R

2010-01-01

The marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta- and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans. PMID:20345979

Quality of chronic kidney disease management in primary care: a retrospective study.

PubMed

Van Gelder, Vincent A; Scherpbier-De Haan, Nynke D; De Grauw, Wim J C; Vervoort, Gerald M M; Van Weel, Chris; Biermans, Marion C J; Braspenning, Jozé C C; Wetzels, Jack F M

2016-01-01

Early detection and appropriate management of chronic kidney disease (CKD) in primary care are essential to reduce morbidity and mortality. To assess the quality of care (QoC) of CKD in primary healthcare in relation to patient and practice characteristics in order to tailor improvement strategies. Retrospective study using data between 2008 and 2011 from 47 general practices (207 469 patients of whom 162 562 were adults). CKD management of patients under the care of their general practitioner (GP) was qualified using indicators derived from the Dutch interdisciplinary CKD guideline for primary care and nephrology and included (1) monitoring of renal function, albuminuria, blood pressure, and glucose, (2) monitoring of metabolic parameters, and alongside the guideline: (3) recognition of CKD. The outcome indicator was (4) achieving blood pressure targets. Multilevel logistic regression analysis was applied to identify associated patient and practice characteristics. Kidney function or albuminuria data were available for 59 728 adult patients; 9288 patients had CKD, of whom 8794 were under GP care. Monitoring of disease progression was complete in 42% of CKD patients, monitoring of metabolic parameters in 2%, and blood pressure target was reached in 43.1%. GPs documented CKD in 31.4% of CKD patients. High QoC was strongly associated with diabetes, and to a lesser extent with hypertension and male sex. Room for improvement was found in all aspects of CKD management. As QoC was higher in patients who received structured diabetes care, future CKD care may profit from more structured primary care management, e.g. according to the chronic care model. Quality of care for chronic kidney disease patients in primary care can be improved. In comparison with guideline advice, adequate monitoring of disease progression was observed in 42%, of metabolic parameters in 2%, correct recognition of impaired renal function in 31%, and reaching blood pressure targets in 43% of chronic kidney disease patients. Quality of care was higher in patients with diabetes. Chronic kidney disease management may be improved by developing strategies similar to diabetes care.

Centrosome Defects, Genetic Instability and Breast Cancer Progression

DTIC Science & Technology

2005-08-01

and is associated with cell cycle progression. Primary cilia loss is thought to be the cause of polycystic kidney disease, a condition in which kidney...polycyctin2 which is also implicated in polycystic kidney disease (Pazour, Baker et al. 2002; Pazour anrd Rosenbaum 2002; Pazour, San Agustin et al. 2002...1941-51. Pazour, G. J. (2004). "Intraflagellar transport and cilia-dependent renal disease: the ciliary hypothesis of polycystic kidney disease." J

Wild monkeys flake stone tools.

PubMed

Proffitt, Tomos; Luncz, Lydia V; Falótico, Tiago; Ottoni, Eduardo B; de la Torre, Ignacio; Haslam, Michael

2016-11-03

Our understanding of the emergence of technology shapes how we view the origins of humanity. Sharp-edged stone flakes, struck from larger cores, are the primary evidence for the earliest stone technology. Here we show that wild bearded capuchin monkeys (Sapajus libidinosus) in Brazil deliberately break stones, unintentionally producing recurrent, conchoidally fractured, sharp-edged flakes and cores that have the characteristics and morphology of intentionally produced hominin tools. The production of archaeologically visible cores and flakes is therefore no longer unique to the human lineage, providing a comparative perspective on the emergence of lithic technology. This discovery adds an additional dimension to interpretations of the human Palaeolithic record, the possible function of early stone tools, and the cognitive requirements for the emergence of stone flaking.

Endothelial sirtuin 1 inactivation enhances capillary rarefaction and fibrosis following kidney injury through Notch activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kida, Yujiro; Zullo, Joseph A.; Renal Research Institute, Department of Physiology, New York Medical College, Valhalla, NY

Peritubular capillary (PTC) rarefaction along with tissue fibrosis is a hallmark of chronic kidney disease (CKD). However, molecular mechanisms of PTC loss have been poorly understood. Previous studies have demonstrated that functional loss of endothelial sirtuin 1 (SIRT1) impairs angiogenesis during development and tissue damage. Here, we found that endothelial SIRT1 dysfunction causes activation of endothelial Notch1 signaling, which leads to PTC rarefaction and fibrosis following kidney injury. In mice lacking functional SIRT1 in the endothelium (Sirt1 mutant), kidney injury enhanced apoptosis and senescence of PTC endothelial cells with impaired endothelial proliferation and expanded myofibroblast population and collagen deposition. Comparedmore » to wild-type kidneys, Sirt1 mutant kidneys up-regulated expression of Delta-like 4 (DLL4, a potent Notch1 ligand), Hey1 and Hes1 (Notch target genes), and Notch intracellular domain-1 (NICD1, active form of Notch1) in microvascular endothelial cells (MVECs) post-injury. Sirt1 mutant primary kidney MVECs reduced motility and vascular assembly and enhanced senescence compared to wild-type kidney MVECs. This difference in the phenotype was negated with Notch inhibition. Concurrent stimulation of DLL4 and transforming growth factor (TGF)-β1 increased trans-differentiation of primary kidney pericytes into myofibroblast more than TGF-β1 treatment alone. Collectively, these results indicate that endothelial SIRT1 counteracts PTC rarefaction by repression of Notch1 signaling and antagonizes fibrosis via suppression of endothelial DLL4 expression. - Highlights: • SIRT1 represses Notch1 signaling in capillary endothelial cells in the kidney. • Endothelial SIRT1 is depleted in the kidney following injury. • Activation of endothelial Notch impairs angiogenesis in the kidney. • Increased expression of endothelial DLL4 enhances renal fibrosis.« less

Evolutionary Origin of OwlRep, a Megasatellite DNA Associated with Adaptation of Owl Monkeys to Nocturnal Lifestyle

PubMed Central

Nishihara, Hidenori; Stanyon, Roscoe; Kusumi, Junko; Hirai, Hirohisa

2018-01-01

Abstract Rod cells of many nocturnal mammals have a “non-standard” nuclear architecture, which is called the inverted nuclear architecture. Heterochromatin localizes to the central region of the nucleus. This leads to an efficient light transmission to the outer segments of photoreceptors. Rod cells of diurnal mammals have the conventional nuclear architecture. Owl monkeys (genus Aotus) are the only taxon of simian primates that has a nocturnal or cathemeral lifestyle, and this adaptation is widely thought to be secondary. Their rod cells were shown to exhibit an intermediate chromatin distribution: a spherical heterochromatin block was found in the central region of the nucleus although it was less complete than that of typical nocturnal mammals. We recently demonstrated that the primary DNA component of this heterochromatin block was OwlRep, a megasatellite DNA consisting of 187-bp-long repeat units. However, the origin of OwlRep was not known. Here we show that OwlRep was derived from HSAT6, a simple repeat sequence found in the centromere regions of human chromosomes. HSAT6 occurs widely in primates, suggesting that it was already present in the last common ancestor of extant primates. Notably, Strepsirrhini and Tarsiformes apparently carry a single HSAT6 copy, whereas many species of Simiiformes contain multiple copies. Comparison of nucleotide sequences of these copies revealed the entire process of the OwlRep formation. HSAT6, with or without flanking sequences, was segmentally duplicated in New World monkeys. Then, in the owl monkey linage after its divergence from other New World monkeys, a copy of HSAT6 was tandemly amplified, eventually forming a megasatellite DNA. PMID:29294004

CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

PubMed

Kang, Yu; Zheng, Bo; Shen, Bin; Chen, Yongchang; Wang, Lei; Wang, Jianying; Niu, Yuyu; Cui, Yiqiang; Zhou, Jiankui; Wang, Hong; Guo, Xuejiang; Hu, Bian; Zhou, Qi; Sha, Jiahao; Ji, Weizhi; Huang, Xingxu

2015-12-20

Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal. We previously reported successful clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome targeting in cynomolgus monkeys. Here, we describe a male fetal monkey in which targeted genome editing using CRISPR/Cas9 produced Dax1-null mutations in most somatic tissues and in the gonads. This DAX1-deficient monkey displayed defects in adrenal gland development and abnormal testis architecture with small cords, expanded blood vessels and extensive fibrosis. Sertoli cell formation was not affected. This phenotype strongly resembles findings in human patients with AHC-HH caused by mutations in DAX1. We further detected upregulation of Wnt/β-catenin-VEGF signaling in the fetal Dax1-deficient testis, suggesting abnormal activation of signaling pathways in the absence of DAX1 as one mechanism of AHC-HH. Our study reveals novel insight into the role of DAX1 in HH and provides proof-of-principle for the generation of monkey models of human disease via CRISPR/Cas9-mediated gene targeting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Establishment of a rhesus monkey model of chronic temporal lobe epilepsy using repetitive unilateral intra-amygdala kainic acid injections.

PubMed

Chi, Yajie; Wu, Bolin; Guan, Jianwei; Xiao, Kuntai; Lu, Ziming; Li, Xiao; Xu, Yuting; Xue, Shan; Xu, Qiang; Rao, Junhua; Guo, Yanwu

2017-09-01

Temporal lobe epilepsy (TLE) is a common type of acquired epilepsy refractory to medical treatment. As such, establishing animal models of this disease is critical to developing new and effective treatment modalities. Because of their small head size, rodents are not suitable for comprehensive electroencephalography (EEG) evaluation via scalp or subdural electrodes. Therefore, a larger primate model that closely recapitulates signs of TLE is needed; here we describe a rhesus monkey model resembling chronic TLE. Eight monkeys were divided into two groups: kainic acid (KA) group (n=6) and saline control group (n=2). Intra-amygdala KA injections were performed biweekly via an Ommaya device until obvious epileptiform discharges were recorded. Video-EEG recording was conducted intermittently throughout the experiment using both scalp and subdural electrodes. Brains were then analyzed for Nissl and glial fibrillary acid protein (GFAP) immunostaining. After 2-4 injections of KA (approximately 1.2-2.4mg, 0.12-0.24mg/kg), interictal epileptiform discharges (IEDs) were recorded in all KA-treated animals. Spontaneous recurrent seizures (SRSs) accompanied by symptoms mimicking temporal lobe absence (undetectable without EEG recording), but few mild motor signs, were recorded in 66.7% (four of six) KA-treated animals. Both IEDs and seizures indicated a primary epileptic zone in the right temporal region and contralateral discharges were later detected. Segmental pyramidal cell loss and gliosis were detected in the brain of a KA-treated monkey. Through a modified protocol of unilateral repetitive intra-amygdala KA injections, a rhesus monkey model with similar behavioral and brain electrical features as TLE was developed. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous Assessment of Transporter-Mediated Drug-Drug Interactions Using a Probe Drug Cocktail in Cynomolgus Monkey.

PubMed

Kosa, Rachel E; Lazzaro, Sarah; Bi, Yi-An; Tierney, Brendan; Gates, Dana; Modi, Sweta; Costales, Chester; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena V

2018-06-07

We aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion transporting polypeptide (OATP)1B, breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and organic anion transporter (OAT)3. Pharmacokinetics of substrate cocktail consisting of pitavastatin (OATP1B substrate), rosuvastatin (OATP1B/BCRP/OAT3), sulfasalazine (BCRP) and talinolol (P-gp) were obtained in cynomolgus monkey - alone or in combination with transporter inhibitors. Single dose rifampicin (30 mg/kg) significantly (p<0.01) increased the plasma exposure of all four drugs, with a marked effect on pitavastatin and rosuvastatin (AUC ratio ~21-39). Elacridar, BCRP/P-gp inhibitor, increased the AUC of sulfasalazine, talinolol, as well as rosuvastatin and pitavastatin. An OAT1/3 inhibitor (probenecid) significantly (p<0.05) impacted the renal clearance of rosuvastatin (~8-fold). In vitro, rifampicin (10μM) inhibited uptake of pitavastatin, rosuvastatin and sulfasalazine by monkey and human primary hepatocytes. Transport studies using membrane vesicles suggested that all probe substrates, except talinolol, are transported by cynoBCRP; while talinolol is a cynoP-gp substrate. Elacridar and rifampicin inhibited both cynoBCRP and cynoP-gp in vitro, indicating potential for in vivo intestinal efflux inhibition. In conclusion, a probe substrate cocktail was validated to simultaneously evaluate perpetrator impact on multiple clinically relevant transporters using the cynomolgus monkey. The results support the use of the cynomolgus monkey as a model that could enable drug-drug interaction risk assessment, before advancing a new molecular entity into clinical development, as well as providing mechanistic insights on transporter-mediated interactions. The American Society for Pharmacology and Experimental Therapeutics.

Identification of Novel Kaposi's Sarcoma-Associated Herpesvirus Orf50 Transcripts: Discovery of New RTA Isoforms with Variable Transactivation Potential

PubMed Central

Wakeman, Brian S.; Izumiya, Yoshihiro

2016-01-01

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma and multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50. RTA is a known transactivator of multiple viral genes, allowing it to control the switch between latency and virus replication. We report here the identification of six alternatively spliced Orf50 transcripts that are generated from four distinct promoters. These newly identified promoters are shown to be transcriptionally active in 293T (embryonic kidney), Vero (African-green monkey kidney epithelial), 3T12 (mouse fibroblast), and RAW 264.7 (mouse macrophage) cell lines. Notably, the newly identified Orf50 transcripts are predicted to encode four different isoforms of the RTA which differ by 6 to 10 residues at the amino terminus of the protein. We show the global viral transactivation potential of all four RTA isoforms and demonstrate that all isoforms can transcriptionally activate an array of KSHV promoters to various levels. The pattern of transcriptional activation appears to support a transcriptional interference model within the Orf50 region, where silencing of previously expressed isoforms by transcription initiation from upstream Orf50 promoters has the potential to modulate the pattern of viral gene activation. IMPORTANCE Gammaherpesviruses are associated with the development of lymphomas and lymphoproliferative diseases, as well as several other types of cancer. The human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is tightly associated with the development of Kaposi's sarcoma and multicentric Castleman's disease, as well as a rare form of B cell lymphoma (primary effusion lymphoma) primarily observed in HIV-infected individuals. RTA is an essential viral gene product involved in the initiation of gammaherpesvirus replication and is conserved among all known gammaherpesviruses. We show here for KSHV that transcription of the gene encoding RTA is complex and leads to the expression of several isoforms of RTA with distinct functions. This observed complexity in KSHV RTA expression and function likely plays a critical role in the regulation of downstream viral and cellular gene expression, leading to the efficient production of mature virions. PMID:27795414

Differential expression of liver and kidney proteins in a mouse model for primary hyperoxaluria type I.

PubMed

Hernández-Fernaud, Juan R; Salido, Eduardo

2010-11-01

Mutations in the alanine-glyoxylate aminotransferase gene (AGXT) are responsible for primary hyperoxaluria type I, a rare disease characterized by excessive hepatic oxalate production that leads to renal failure. A deeper understanding of the changes in the metabolic pathways secondary to the lack of AGXT expression is needed in order to explore substrate depletion as a therapeutic strategy to limit oxalate production in primary hyperoxaluria type I. We have developed an Agxt knockout (AgxtKO) mouse that reproduces some key features of primary hyperoxaluria type I. To improve our understanding of the metabolic adjustments subsequent to AGXT deficiency, we performed a proteomic analysis of the changes in expression levels of various subcellular fractions of liver and kidney metabolism linked to the lack of AGXT. In this article, we report specific changes in the liver and kidney proteome of AgxtKO mice that point to significant variations in gluconeogenesis, glycolysis and fatty acid pathways. Journal compilation © 2010 FEBS. No claim to original German government works.

Biophysical characterization and structural determination of the potent cytotoxic Psathyrella asperospora lectin.

PubMed

Ribeiro, João P; Ali Abol Hassan, Mohamed; Rouf, Razina; Tiralongo, Evelin; May, Tom W; Day, Christopher J; Imberty, Anne; Tiralongo, Joe; Varrot, Annabelle

2017-05-01

A lectin with strong cytotoxic effect on human colon cancer HT29 and monkey kidney VERO cells was recently identified from the Australian indigenous mushroom Psathyrella asperospora and named PAL. We herein present its biochemical and structural analysis using a multidisciplinary approach. Glycan arrays revealed binding preference towards N-acetylglucosamine (GlcNAc) and, to a lesser extent, towards sialic acid (Neu5Ac). Submicromolar and millimolar affinity was measured by surface plasmon resonance for GlcNAc and NeuAc, respectively. The structure of PAL was resolved by X-ray crystallography, elucidating both the protein's amino acid sequence as well as the molecular basis rationalizing its binding specificity. Proteins 2017; 85:969-975. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A RADIOBIOLOGICAL ANALOGY BETWEEN MEASLES VIRUS AND TEMPERATE PHAGES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackerman, P.H.; Black, F.L.

1961-02-01

Measles virus was found to be more resistant to ultraviolet (uv) than to ionizing radiations. The capacity of monkey kidney cells to grow unirradiated measles virus or measles virus irradiated with gamma rays was not affected appreciably by uv irradiation of the cells. However, the capacity of cells to grow uv irradiated virus was reduced by uv irradiation of the cells. In contrast, uv irradiation of cells did not affect their capacity to grow uv- treated polio virus. These effects of radiation on the measles virus system are analogous to effects on the phage P22 system and are compatible withmore » the hypothesis of cellular repair of damaged virus previously suggested for the temperate phage. (auth)« less

Current practice in Latin America of flexible ureterorenoscopy with laser for treating kidney stones.

PubMed

Manzo, B O; Bertacchi, M; Lozada, E; Rasguido, A; Aleman, E; Cabrera, M; Rodríguez, A; Manzo, G; Sánchez, H; Blasco, J

2016-05-01

The use of flexible ureterorenoscopy for treating kidney stones has increased in recent years, with considerable worldwide variation in the surgical technique and indications. To determine the current practice, technique variations, use and indications of flexible ureterorenoscopy for treating kidney stones in Latin American. We sent (by email and web link) an anonymous questionnaire with 30 questions on flexible ureterorenoscopy for treating kidney stones to Latin American urologists from January 2015 to July 2015. We collected the responses through the Survey Monkey system. A total of 283 urologists in 15 Latin American countries participated (response rate, 10.8%); 254 answered the questionnaire completely; 52.8% were urologists from Mexico and 11% were from Argentina; 11.8% of the responders stated that they performed >100 cases per year; 15.2% considered ureterorenoscopy as the treatment of choice for stones >2cm, and 19.6% performed ureterorenoscopy in single stages for calculi measuring >2.5cm. Some 78.4% use fluoroscopy, 69.1% use a ureteral sheath in all cases, 55.8% place double-J catheters at the end of surgery, 37.3% considered a stone-free state to be 0 fragments, and 41.2% use plain radiography to assess the stone-free condition. Most participating urologists consider flexible ureterorenoscopy as the first-choice treatment for stones <2cm; a small percentage of these urologists perform >100 ureterorenoscopies per year. More than half of the urologists routinely used fluoroscopy and ureteral access sheath; the most common method for determining the stone-free state is plain abdominal radiography. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Flexible Ureterorenoscopy for Treatment of Kidney Stones: Establishment as Primary Standard Therapy in a Tertiary Stone Center.

PubMed

Ising, Stephan; Labenski, Heike; Baltes, Stefan; Khaffaf, Aso; Thomas, Christian; Wiesner, Christoph

2015-01-01

To analyze the primary stone free rate (pSFR) of flexible ureterorenoscopy (fURS) in the treatment of renal stones and to identify clinical predictors for the primary freedom from renal stones. Two hundred and seventy five patients, who underwent fURS for kidney stones were analyzed. Index stone size was 6 mm. The stone was located in the lower calyx in 48%. Ureteral access sheath was used in 97%. Operation time was 35 min and primary stone clearance was 83%. pSFR increased from 74% in 2012 to 83% in 2013 and 90% in 2014 (p = 0.001). Preoperative stenting, index stone size, cumulative stone size, lithotripsy, ureteral access sheath and operation time were significantly correlated with the pSFR by univariate analysis. Multivariate regression analysis showed index stone size, cumulative stone size, ureteral access sheath and operation time as independent parameters for pSFR. fURS for kidney stones is safe with a high pSFR. Clinical parameters for pSFR are stone size, use of ureteral access sheath and operation time. In future, the effective use of fURS for the removal of kidney stones needs to be checked by prospective randomized trials. © 2015 S. Karger AG, Basel.

Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

PubMed

Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

2016-01-01

We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance.

Task-Relevant Information Modulates Primary Motor Cortex Activity Before Movement Onset.

PubMed

Calderon, Cristian B; Van Opstal, Filip; Peigneux, Philippe; Verguts, Tom; Gevers, Wim

2018-01-01

Monkey neurophysiology research supports the affordance competition hypothesis (ACH) proposing that cognitive information useful for action selection is integrated in sensorimotor areas. In this view, action selection would emerge from the simultaneous representation of competing action plans, in parallel biased by relevant task factors. This biased competition would take place up to primary motor cortex (M1). Although ACH is plausible in environments affording choices between actions, its relevance for human decision making is less clear. To address this issue, we designed an functional magnetic resonance imaging (fMRI) experiment modeled after monkey neurophysiology studies in which human participants processed cues conveying predictive information about upcoming button presses. Our results demonstrate that, as predicted by the ACH, predictive information (i.e., the relevant task factor) biases activity of primary motor regions. Specifically, first, activity before movement onset in contralateral M1 increases as the competition is biased in favor of a specific button press relative to activity in ipsilateral M1. Second, motor regions were more tightly coupled with fronto-parietal regions when competition between potential actions was high, again suggesting that motor regions are also part of the biased competition network. Our findings support the idea that action planning dynamics as proposed in the ACH are valid both in human and non-human primates.

Complex pitch perception mechanisms are shared by humans and a New World monkey.

PubMed

Song, Xindong; Osmanski, Michael S; Guo, Yueqi; Wang, Xiaoqin

2016-01-19

The perception of the pitch of harmonic complex sounds is a crucial function of human audition, especially in music and speech processing. Whether the underlying mechanisms of pitch perception are unique to humans, however, is unknown. Based on estimates of frequency resolution at the level of the auditory periphery, psychoacoustic studies in humans have revealed several primary features of central pitch mechanisms. It has been shown that (i) pitch strength of a harmonic tone is dominated by resolved harmonics; (ii) pitch of resolved harmonics is sensitive to the quality of spectral harmonicity; and (iii) pitch of unresolved harmonics is sensitive to the salience of temporal envelope cues. Here we show, for a standard musical tuning fundamental frequency of 440 Hz, that the common marmoset (Callithrix jacchus), a New World monkey with a hearing range similar to that of humans, exhibits all of the primary features of central pitch mechanisms demonstrated in humans. Thus, marmosets and humans may share similar pitch perception mechanisms, suggesting that these mechanisms may have emerged early in primate evolution.

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys.

PubMed

Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Fanales-Belasio, Emanuele; Moretti, Sonia; Sernicola, Leonardo; Cara, Andrea; Negri, Donatella R M; Buttò, Stefano; Fiorelli, Valeria; Tripiciano, Antonella; Scoglio, Arianna; Caputo, Antonella; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Ciccozzi, Massimo; Heeney, Jonathan; Titti, Fausto; Cafaro, Aurelio; Ensoli, Barbara

2004-09-03

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

The stimulus-evoked population response in visual cortex of awake monkey is a propagating wave

PubMed Central

Muller, Lyle; Reynaud, Alexandre; Chavane, Frédéric; Destexhe, Alain

2014-01-01

Propagating waves occur in many excitable media and were recently found in neural systems from retina to neocortex. While propagating waves are clearly present under anaesthesia, whether they also appear during awake and conscious states remains unclear. One possibility is that these waves are systematically missed in trial-averaged data, due to variability. Here we present a method for detecting propagating waves in noisy multichannel recordings. Applying this method to single-trial voltage-sensitive dye imaging data, we show that the stimulus-evoked population response in primary visual cortex of the awake monkey propagates as a travelling wave, with consistent dynamics across trials. A network model suggests that this reliability is the hallmark of the horizontal fibre network of superficial cortical layers. Propagating waves with similar properties occur independently in secondary visual cortex, but maintain precise phase relations with the waves in primary visual cortex. These results show that, in response to a visual stimulus, propagating waves are systematically evoked in several visual areas, generating a consistent spatiotemporal frame for further neuronal interactions. PMID:24770473

Loss of Neurofilament Labeling in the Primary Visual Cortex of Monocularly Deprived Monkeys

PubMed Central

Duffy, Kevin R.; Livingstone, Margaret S.

2009-01-01

Visual experience during early life is important for the development of neural organizations that support visual function. Closing one eye (monocular deprivation) during this sensitive period can cause a reorganization of neural connections within the visual system that leaves the deprived eye functionally disconnected. We have assessed the pattern of neurofilament labeling in monocularly deprived macaque monkeys to examine the possibility that a cytoskeleton change contributes to deprivation-induced reorganization of neural connections within the primary visual cortex (V-1). Monocular deprivation for three months starting around the time of birth caused a significant loss of neurofilament labeling within deprived-eye ocular dominance columns. Three months of monocular deprivation initiated in adulthood did not produce a loss of neurofilament labeling. The evidence that neurofilament loss was found only when deprivation occurred during the sensitive period supports the notion that the loss permits restructuring of deprived-eye neural connections within the visual system. These results provide evidence that, in addition to reorganization of LGN inputs, the intrinsic circuitry of V-1 neurons is altered when monocular deprivation occurs early in development. PMID:15563721

Primary Cilia Are Not Calcium-Responsive Mechanosensors

PubMed Central

Delling, M.; Indzhykulian, A. A.; Liu, X.; Liu, Y.; Xie, T.; Corey, D. P.; Clapham, D. E.

2016-01-01

Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium1. This Ca2+- Responsive MechanoSensor (CaRMS) hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers2,3. Here, we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. First, we developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator (GECI) in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca2+ influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signaling. PMID:27007841

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse

PubMed Central

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F.; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2018-01-01

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time– and bile-acid-concentration–dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. PMID:27000539

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

PubMed

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2016-08-05

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

Primary Hyperparathyroidism

MedlinePlus

... blood calcium (above a certain level) • Impaired kidney function Non-surgical treatment: checkups and medicines For some patients without signs or symptoms, doctors recommend regular checkups instead of surgery. ... to check kidney function, and checks of bone density. A doctor may ...

Transplantation and the primary care physician.

PubMed

McGill, Rita L; Ko, Tina Y

2011-11-01

Increasing appreciation of the survival benefits of kidney transplantation, compared with chronic dialysis, has resulted in more patients with kidney disease being referred and receiving organs. The evolving disparity between a rapidly increasing pool of candidates and a smaller pool of available donors has created new issues for the physicians who care for kidney patients and their potential living donors. This article outlines current efforts to address the growing number of patients who await transplantation, including relaxation of traditional donation criteria, maximization of living donation, and donation schemas that permit incompatible donor-recipient pairs to participate through paired donation and transplantation chains. New ethical issues faced by donors and recipients are discussed. Surgical advances that reduce the morbidity of donors are also described, as is the role of the primary physician in medical issues of both donors and recipients. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Breast cancer metastatic to the kidney with renal vein involvement.

PubMed

Nasu, Hatsuko; Miura, Katsutoshi; Baba, Megumi; Nagata, Masao; Yoshida, Masayuki; Ogura, Hiroyuki; Takehara, Yasuo; Sakahara, Harumi

2015-02-01

The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

PubMed Central

Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

2014-01-01

The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

A perchlorate sensitive iodide transporter in frogs

PubMed Central

Carr, Deborah L.; Carr, James A.; Willis, Ray E.; Pressley, Thomas A.

2008-01-01

Nucleotide sequence comparisons have identified a gene product in the genome database of African clawed frogs (Xenopus laevis) as a probable member of the solute carrier family of membrane transporters. To confirm its identity as a putative iodide transporter, we examined the function of this sequence after heterologous expression in mammalian cells. A green monkey kidney cell line transfected with the Xenopus nucleotide sequence had significantly greater 125I uptake than sham-transfected control cells. The uptake in carrier-transfected cells was significantly inhibited in the presence of perchlorate, a competitive inhibitor of mammalian Na+/iodide symporter. Tissue distributions of the sequence were also consistent with a role in iodide uptake. The mRNA encoding the carrier was found to be expressed in the thyroid gland, stomach, and kidney of tadpoles from X. laevis, as well as the bullfrog Rana catesbeiana. The ovaries of adult X. laevis also were found to express the carrier. Phylogenetic analysis suggested that the putative X. laevis iodide transporter is orthologous to vertebrate Na+-dependent iodide symporters. We conclude that the amphibian sequence encodes a protein that is indeed a functional Na+/iodide symporter in Xenopus laevis, as well as Rana catesbeiana. PMID:18275962

Size-dependent cellular uptake mechanism and cytotoxicity toward calcium oxalate on Vero cells

NASA Astrophysics Data System (ADS)

Sun, Xin-Yuan; Gan, Qiong-Zhi; Ouyang, Jian-Ming

2017-02-01

Urinary crystals with various sizes are present in healthy individuals and patients with kidney stone; however, the cellular uptake mechanism of calcium oxalate of various sizes has not been elucidated. This study aims to compare the internalization of nano-/micron-sized (50 nm, 100 nm, and 1 μm) calcium oxalate monohydrate (COM) and dihydrate (COD) crystals in African green monkey renal epithelial (Vero) cells. The internalization and adhesion of COM and COD crystals to Vero cells were enhanced with decreasing crystal size. Cell death rate was positively related to the amount of adhered and internalized crystals and exhibited higher correlation with internalization than that with adhesion. Vero cells mainly internalized nano-sized COM and COD crystals through clathrin-mediated pathways as well as micron-sized crystals through macropinocytosis. The internalized COM and COD crystals were distributed in the lysosomes and destroyed lysosomal integrity to some extent. The results of this study indicated that the size of crystal affected cellular uptake mechanism, and may provide an enlightenment for finding potential inhibitors of crystal uptake, thereby decreasing cell injury and the occurrence of kidney stones.

Repeated serum creatinine measurement in primary care: Not all patients have chronic renal failure.

PubMed

Gentille Lorente, Delicia; Gentille Lorente, Jorge; Salvadó Usach, Teresa

2015-01-01

To assess the prevalence of kidney failure in patients from a primary care centre in a basic healthcare district with laboratory availability allowing serum creatinine measurements. An observational descriptive cross-sectional study. A basic healthcare district serving 23,807 people aged ≥ 18 years. Prevalence of kidney failure among 17,240 patients having at least one laboratory measurement available was 8.5% (mean age 77.6 ± 12.05 years). In 33.2% of such patients an occult kidney failure was found (98.8% were women). Prevalence of chronic kidney failure among 10,011 patients having at least 2 laboratory measurements available (≥ 3 months apart) was 5.5% with mean age being 80.1 ± 10.0 years (most severely affected patients were those aged 75 to 84); 59.7% were men and 76.3% of cases were in stage 3. An occult kidney failure was found in 5.3% of patients with women being 86.2% of them (a glomerular filtration rate<60 ml/min was estimated for plasma creatinine levels of 0.9 mg/dl or higher). Comparison of present findings to those previously reported demonstrates the need for further studies on the prevalence of overall (chronic and acute) kidney failure in Spain in order to estimate the real scope of the disease. Primary care physicians play a critical role in disease detection, therapy, control and recording (in medical records). MDRD equation is useful and practical to estimate glomerular filtration rate. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease.

PubMed

Chen, Yumay; Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Juang, Charity; Riley, Daniel J

2014-07-17

Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron.

Dietary flexibility of Bale monkeys (Chlorocebus djamdjamensis) in southern Ethiopia: effects of habitat degradation and life in fragments.

PubMed

Mekonnen, Addisu; Fashing, Peter J; Bekele, Afework; Hernandez-Aguilar, R Adriana; Rueness, Eli K; Stenseth, Nils Chr

2018-02-06

Understanding the effects of habitat modification on the feeding strategies of threatened species is essential to designing effective conservation management plans. Bale monkeys (Chlorocebus djamdjamensis) are endemic to the rapidly shrinking montane forests of the southern Ethiopian Highlands. Most populations inhabit continuous bamboo forest subsisting largely on the young leaves and shoots of a single species of bamboo. Because of habitat disturbance in recent decades, however, there are now also several dozen small populations inhabiting isolated forest fragments where bamboo has been degraded. During 12-months, we assessed Bale monkey responses to habitat degradation by comparing habitat composition, phenological patterns, and feeding ecology in a largely undisturbed continuous forest (Continuous groups A and B) and in two fragments (Patchy and Hilltop groups). We found that habitat quality and food availability were much lower in fragments than in continuous forest. In response to the relative scarcity of bamboo in fragments, Bale monkeys spent significantly less time feeding on the young leaves and shoots of bamboo and significantly more time feeding on non-bamboo young leaves, fruits, seeds, stems, petioles, and insects in fragments than in continuous forest. Groups in fragments also broadened their diets to incorporate many more plant species (Patchy: ≥ 47 and Hilltop: ≥ 35 species)-including several forbs, graminoids and cultivated crops-than groups in continuous forest (Continuous A: 12 and Continuous B: 8 species). Nevertheless, bamboo was still the top food species for Patchy group (30% of diet) as well as for both continuous forest groups (mean = 81%). However, in Hilltop group, for which bamboo was especially scarce, Bothriochloa radicans (Poaceae), a grass, was the top dietary species (15% of diet) and bamboo ranked 10th (2%). We demonstrate that Bale monkeys are more dietarily flexible than previously thought and able to cope with some degradation of their primary bamboo forest habitat. However, crop raiding and other terrestrial foraging habits more common among fragment groups may place them at greater risk of hunting by humans. Thus, longitudinal monitoring is necessary to evaluate the long-term viability of Bale monkey populations in fragmented habitats.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

PubMed Central

Dorman, David C; Struve, Melanie F; Gross, Elizabeth A; Wong, Brian A; Howroyd, Paul C

2005-01-01

Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (≤0.3 mg Mn/m3) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology. PMID:16242036

Decoding Lower Limb Muscle Activity and Kinematics from Cortical Neural Spike Trains during Monkey Performing Stand and Squat Movements

PubMed Central

Ma, Xuan; Ma, Chaolin; Huang, Jian; Zhang, Peng; Xu, Jiang; He, Jiping

2017-01-01

Extensive literatures have shown approaches for decoding upper limb kinematics or muscle activity using multichannel cortical spike recordings toward brain machine interface (BMI) applications. However, similar topics regarding lower limb remain relatively scarce. We previously reported a system for training monkeys to perform visually guided stand and squat tasks. The current study, as a follow-up extension, investigates whether lower limb kinematics and muscle activity characterized by electromyography (EMG) signals during monkey performing stand/squat movements can be accurately decoded from neural spike trains in primary motor cortex (M1). Two monkeys were used in this study. Subdermal intramuscular EMG electrodes were implanted to 8 right leg/thigh muscles. With ample data collected from neurons from a large brain area, we performed a spike triggered average (SpTA) analysis and got a series of density contours which revealed the spatial distributions of different muscle-innervating neurons corresponding to each given muscle. Based on the guidance of these results, we identified the locations optimal for chronic electrode implantation and subsequently carried on chronic neural data recordings. A recursive Bayesian estimation framework was proposed for decoding EMG signals together with kinematics from M1 spike trains. Two specific algorithms were implemented: a standard Kalman filter and an unscented Kalman filter. For the latter one, an artificial neural network was incorporated to deal with the nonlinearity in neural tuning. High correlation coefficient and signal to noise ratio between the predicted and the actual data were achieved for both EMG signals and kinematics on both monkeys. Higher decoding accuracy and faster convergence rate could be achieved with the unscented Kalman filter. These results demonstrate that lower limb EMG signals and kinematics during monkey stand/squat can be accurately decoded from a group of M1 neurons with the proposed algorithms. Our findings provide new insights for extending current BMI design concepts and techniques on upper limbs to lower limb circumstances. Brain controlled exoskeleton, prostheses or neuromuscular electrical stimulators for lower limbs are expected to be developed, which enables the subject to manipulate complex biomechatronic devices with mind in more harmonized manner. PMID:28223914

Auditory cortex of bats and primates: managing species-specific calls for social communication

PubMed Central

Kanwal, Jagmeet S.; Rauschecker, Josef P.

2014-01-01

Individuals of many animal species communicate with each other using sounds or “calls” that are made up of basic acoustic patterns and their combinations. We are interested in questions about the processing of communication calls and their representation within the mammalian auditory cortex. Our studies compare in particular two species for which a large body of data has accumulated: the mustached bat and the rhesus monkey. We conclude that the brains of both species share a number of functional and organizational principles, which differ only in the extent to which and how they are implemented. For instance, neurons in both species use “combination-sensitivity” (nonlinear spectral and temporal integration of stimulus components) as a basic mechanism to enable exquisite sensitivity to and selectivity for particular call types. Whereas combination-sensitivity is already found abundantly at the primary auditory cortical and also at subcortical levels in bats, it becomes prevalent only at the level of the lateral belt in the secondary auditory cortex of monkeys. A parallel-hierarchical framework for processing complex sounds up to the level of the auditory cortex in bats and an organization into parallel-hierarchical, cortico-cortical auditory processing streams in monkeys is another common principle. Response specialization of neurons seems to be more pronounced in bats than in monkeys, whereas a functional specialization into “what” and “where” streams in the cerebral cortex is more pronounced in monkeys than in bats. These differences, in part, are due to the increased number and larger size of auditory areas in the parietal and frontal cortex in primates. Accordingly, the computational prowess of neural networks and the functional hierarchy resulting in specializations is established early and accelerated across brain regions in bats. The principles proposed here for the neural “management” of species-specific calls in bats and primates can be tested by studying the details of call processing in additional species. Also, computational modeling in conjunction with coordinated studies in bats and monkeys can help to clarify the fundamental question of perceptual invariance (or “constancy”) in call recognition, which has obvious relevance for understanding speech perception and its disorders in humans. PMID:17485400

Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death—A Dutch Cohort Study

PubMed Central

Peters-Sengers, Hessel; Homan van der Heide, Jaap J.; Heemskerk, Martin B. A.; ten Berge, Ineke J. M.; Ultee, Fred C. W.; Idu, Mirza M.; Betjes, Michiel G. H.; van Zuilen, Arjan D.; Christiaans, Maarten H. L.; Hilbrands, Luuk H.; de Vries, Aiko P. J.; Nurmohamed, Azam S.; Berger, Stefan P.; Bemelman, Frederike J.

2017-01-01

Background Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. Methods We used the Dutch Organ Transplantation Registry to include recipients (≥18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). Results Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m2 and cDCD, 45.8 (24.1) mL/min/m2; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m2 and cDCD, 47.7 (21.7) mL/min/m2; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. Conclusions We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction. PMID:27257998

Pancreas retransplantation: a second chance for diabetic patients?

PubMed

Buron, Fanny; Thaunat, Olivier; Demuylder-Mischler, Sandrine; Badet, Lionel; Brunet, Maria; Ber, Charles-Eric; Thivolet, Charles; Martin, Xavier; Berney, Thierry; Morelon, Emmanuel

2013-01-27

If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.

Preclinical Evaluation of an Anti-Nectin-4 ImmunoPET Reagent in Tumor-Bearing Mice and Biodistribution Studies in Cynomolgus Monkeys.

PubMed

Campbell, Dean O; Noda, Akihiro; Verlinsky, Alla; Snyder, Josh; Fujita, Yuji; Murakami, Yoshihiro; Fushiki, Hiroshi; Miyoshi, Sosuke; Lacayo, Sergio; Cabral, Edward; Yang, Peng; Stover, David R; Joseph, Ingrid B J K

2016-10-01

Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models. The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated. A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues. [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

Motor Variability Arises from a Slow Random Walk in Neural State

PubMed Central

Chaisanguanthum, Kris S.; Shen, Helen H.

2014-01-01

Even well practiced movements cannot be repeated without variability. This variability is thought to reflect “noise” in movement preparation or execution. However, we show that, for both professional baseball pitchers and macaque monkeys making reaching movements, motor variability can be decomposed into two statistical components, a slowly drifting mean and fast trial-by-trial fluctuations about the mean. The preparatory activity of dorsal premotor cortex/primary motor cortex neurons in monkey exhibits similar statistics. Although the neural and behavioral drifts appear to be correlated, neural activity does not account for trial-by-trial fluctuations in movement, which must arise elsewhere, likely downstream. The statistics of this drift are well modeled by a double-exponential autocorrelation function, with time constants similar across the neural and behavioral drifts in two monkeys, as well as the drifts observed in baseball pitching. These time constants can be explained by an error-corrective learning processes and agree with learning rates measured directly in previous experiments. Together, these results suggest that the central contributions to movement variability are not simply trial-by-trial fluctuations but are rather the result of longer-timescale processes that may arise from motor learning. PMID:25186752

Short poly-glutamine repeat in the androgen receptor in New World monkeys.

PubMed

Hiramatsu, Chihiro; Paukner, Annika; Kuroshima, Hika; Fujita, Kazuo; Suomi, Stephen J; Inoue-Murayama, Miho

2017-12-01

The androgen receptor mediates various physiological and developmental functions and is highly conserved in mammals. Although great intraspecific length polymorphisms in poly glutamine (poly-Q) and poly glycine (poly-G) regions of the androgen receptor in humans, apes and several Old World monkeys have been reported, little is known about the characteristics of these regions in New World monkeys. In this study, we surveyed 17 species of New World monkeys and found length polymorphisms in these regions in three species (common squirrel monkeys, tufted capuchin monkeys and owl monkeys). We found that the poly-Q region in New World monkeys is relatively shorter than that in catarrhines (humans, apes and Old World monkeys). In addition, we observed that codon usage for poly-G region in New World monkeys is unique among primates. These results suggest that the length of polymorphic regions in androgen receptor genes have evolved uniquely in New World monkeys.

Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.

PubMed

Parikh, Chirag R; Puthumana, Jeremy; Shlipak, Michael G; Koyner, Jay L; Thiessen-Philbrook, Heather; McArthur, Eric; Kerr, Kathleen; Kavsak, Peter; Whitlock, Richard P; Garg, Amit X; Coca, Steven G

2017-12-01

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes. Copyright © 2017 by the American Society of Nephrology.

Primary Ewing's Sarcoma/Primitive Neuroectodermal Tumor of Kidney with Caval Involvement in a Pregnant Woman.

PubMed

Ding, Yinghui; Huang, Zhenlin; Ding, Yafei; Jia, Zhankui; Gu, Chaohui; Xue, Rui; Yang, Jinjian

2016-01-01

In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible. © 2016 S. Karger AG, Basel.

Chromatin Structure and the Cell Cycle

PubMed Central

Pederson, Thoru

1972-01-01

Pancreatic DNase I is used to probe the structure of chromatin isolated from synchronized HeLa cells. The degree to which DNA in chromatin is protected from DNase attack varies during the G1, S, and G2 phases of the cell cycle. In addition, the DNase sensitivity of chromatin from contact-inhibited African green monkey kidney cells differs from that of actively dividing, subconfluent cultures. These cell cycle-dependent chromatin changes were observed consistently at all enzyme concentrations (5000-fold range) and incubation times (15 min-2 hr) tested. The results indicate that the degree of complexing between DNA and chromosomal proteins changes during interphase, and they suggest that the chromosome coiling cycle of visible mitosis may extend in more subtle form over the entire cell cycle. PMID:4626402

EFFECTS OF HEAVY WATER ON POLIOVIRUS MULTIPLICATION: RESULTS AND SPECULATIONS ON MECHANISM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kritchevsky, D.; Carp, R.I.; Koprowski, H.

1961-07-15

The CHAT strain of type I polio virus was grown on monkey kidney cell monolayers maintained in normal growth medium, in deuterium oxide, and irradiated by 300 r of x radiation. Duplicate cultures were kept at 35 and 40 deg C. Preliminary observations indicated the effect of deuterium oxide on plague size is more pronounced than that of x rays. Different plaque ratios were obtained for virus grown in deuterium oxide at 37 and 40 deg C. Mechanisms by which deuterium oxide influenced virus growth appeared to involve the extent of randomization of the virus structure and to be manifestmore » either by altering the stability of the hydrogen bonding in the molecule or by affecting the transition temperature of the helix-random coil transformation. (C.H.)« less

Rotavirus infection in wild marsupials (Didelphis marsupialis) of the Amazon region.

PubMed

Linhares, A C; Pereira, J D; Nakauth, C M; Gabbay, Y B

1986-01-01

Rotavirus was detected by enzyme-linked immunosorbent assay in faecal specimens collected from two (1.35%) of 148 marsupials trapped in the Amazon jungle environment. The positive samples were both from the "common opossum", Didelphis marsupialis. No infections were found in the stools of 198 animals belonging to other mammalian species: the latter included small rodents, chiropterans and primates. Electron microscopic examination of one (MA 5928) rotavirus-positive specimen showed a large number of empty particles. However, both rotavirus strains grew when inoculated in MA 104 cells (foetal Rhesus monkey kidney cells) producing clear cytopathogenic effect; indirect immunofluorescence technique of these cells showed a typical granular cytoplasmic fluorescence. The electrophoretic profile of strain MA 5928 showed a high grade of homology with that of SA 11, but also showed minor differences.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Establishment of immortal swine kidney epithelial cells.

PubMed

Kwak, Sungwook; Jung, Ji-Eun; Jin, Xun; Kim, Sun-Myung; Kim, Tae-Kyung; Lee, Joong-Seob; Lee, Soo-Yeon; Pian, Xumin; You, Seungkwon; Kim, Hyunggee; Choi, Yun-Jaie

2006-01-01

Using normal swine kidney epithelial (SKE) cells that were shown to be senescent at passages 12 to 14, we have established one lifespan-extended cell line and two lifespan-extended cell lines by exogenous introduction of the human catalytic subunit of telomerase (hTERT) and simian virus 40 large T-antigen (SV40LT), all of which maintain epithelial morphology and express cytokeratin, a marker of epithelial cells. SV40LT- and hTERT-transduced immortal cell lines appeared to be smaller and exhibited more uniform morphology relative to primary and spontaneously immortalized SKE cells. We determined the in vitro lifespan of primary SKE cells using a standard 3T6 protocol. There were two steps of the proliferation barrier at 12 and 20, in which a majority of primary SKE cells appeared enlarged, flattened, vacuolated, and ss-galactosidase-positive, all phenotypical characteristics of senescent cells. Lifespan-extended SKE cells were eventually established from most of the cellular foci, which is indicative of spontaneous cellular conversion at passage 23. Beyond passage 25, the rate of population doubling of the established cells gradually increased. At passage 30, immortal cell lines grew faster than primary counterpart cells in 10% FBS-DMEM culture conditions, and only SV40LT-transduced immortal cells grew faster than primary and other SKE immortal cells in 0.5% FBS-DMEM. These lifespan-extended SKE cell lines failed to grow in an anchorage-independent manner in soft-agar dishes. Hence, three immortalized swine kidney epithelial cells that are not transformed would be valuable biological tools for virus propagation and basic kidney epithelial cell research.

Risk of Acute Kidney Injury After Intravenous Contrast Media Administration.

PubMed

Hinson, Jeremiah S; Ehmann, Michael R; Fine, Derek M; Fishman, Elliot K; Toerper, Matthew F; Rothman, Richard E; Klein, Eili Y

2017-05-01

The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. In the largest well-controlled study of acute kidney injury following contrast administration in the ED to date, intravenous contrast was not associated with an increased frequency of acute kidney injury. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Click train encoding in primary and non-primary auditory cortex of anesthetized macaque monkeys.

PubMed

Oshurkova, E; Scheich, H; Brosch, M

2008-06-02

We studied encoding of temporally modulated sounds in 28 multiunits in the primary auditory cortical field (AI) and in 35 multiunits in the secondary auditory cortical field (caudomedial auditory cortical field, CM) by presenting periodic click trains with click rates between 1 and 300 Hz lasting for 2-4 s. We found that all multiunits increased or decreased their firing rate during the steady state portion of the click train and that all except two multiunits synchronized their firing to individual clicks in the train. Rate increases and synchronized responses were most prevalent and strongest at low click rates, as expressed by best modulation frequency, limiting frequency, percentage of responsive multiunits, and average rate response and vector strength. Synchronized responses occurred up to 100 Hz; rate response occurred up to 300 Hz. Both auditory fields responded similarly to low click rates but differed at click rates above approximately 12 Hz at which more multiunits in AI than in CM exhibited synchronized responses and increased rate responses and more multiunits in CM exhibited decreased rate responses. These findings suggest that the auditory cortex of macaque monkeys encodes temporally modulated sounds similar to the auditory cortex of other mammals. Together with other observations presented in this and other reports, our findings also suggest that AI and CM have largely overlapping sensitivities for acoustic stimulus features but encode these features differently.

Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a randomized controlled trial.

PubMed

Diamantidis, Clarissa J; Bosworth, Hayden B; Oakes, Megan M; Davenport, Clemontina A; Pendergast, Jane F; Patel, Sejal; Moaddeb, Jivan; Barnhart, Huiman X; Merrill, Peter D; Baloch, Khaula; Crowley, Matthew J; Patel, Uptal D

2018-06-01

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m 2 , mean eGFR was 80.7 ml/min/1.73 m 2 , and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided. NCT01829256. Copyright © 2018 Elsevier Inc. All rights reserved.

Identification of a novel AGXT gene mutation in primary hyperoxaluria after kidney transplantation failure.

PubMed

M'dimegh, Saoussen; Omezzine, Asma; Hamida-Rebai, Mériam Ben; Aquaviva-Bourdain, Cécile; M'barek, Ibtihel; Sahtout, Wissal; Zellama, Dorsaf; Souche, Geneviéve; Achour, Abdellatif; Abroug, Saoussen; Bouslama, Ali

2016-11-01

Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine-glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. The aim of this study was to determine the molecular etiology of kidney transplant loss in a young Tunisian individual. We present a young man with end-stage renal disease who received a kidney allograft and experienced early graft failure. There were no improvement in kidney function; he required hemodialysis and graft biopsy revealed calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Genetic study in the AGXT gene by PCR direct sequencing identified three missense changes in heterozygote state: the p. Gly190Arg mutation next to two other novels not previously described. The classification of the deleterious effect of the missense changes was developed using the summered results of four different mutation assessment algorithms, SIFT, PolyPhen, Mutation Taster, and Align-GVGD. This system classified the changes as polymorphism in one and as mutation in other. The patient was compound heterozygous mutations. Structural analysis showed that the novel mutation, p.Pro28Ser mutation, affects near the dimerization interface of AGT and positioned on binding site instead of the inhibitor, amino-oxyacetic acid (AOA). With the novel AGXT mutation, the mutational spectrum of this gene continues to broaden in our population. The diagnosis of PH1 was not recognized until after renal transplant with fatal consequences, which led us to confirm the importance of screening before planning for kidney transplantation in population with a relatively high frequency of AGXT mutation carriers. Copyright © 2016 Elsevier B.V. All rights reserved.

Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korber, Bette

2009-01-01

Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virusmore » for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.« less

Representation of the visual field in the primary visual area of the marmoset monkey: magnification factors, point-image size, and proportionality to retinal ganglion cell density.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Rosa, Marcello G P

2013-04-01

The primary visual area (V1) forms a systematic map of the visual field, in which adjacent cell clusters represent adjacent points of visual space. A precise quantification of this map is key to understanding the anatomical relationships between neurons located in different stations of the visual pathway, as well as the neural bases of visual performance in different regions of the visual field. We used computational methods to quantify the visual topography of V1 in the marmoset (Callithrix jacchus), a small diurnal monkey. The receptive fields of neurons throughout V1 were mapped in two anesthetized animals using electrophysiological recordings. Following histological reconstruction, precise 3D reconstructions of the V1 surface and recording sites were generated. We found that the areal magnification factor (M(A) ) decreases with eccentricity following a function that has the same slope as that observed in larger diurnal primates, including macaque, squirrel, and capuchin monkeys, and humans. However, there was no systematic relationship between M(A) and polar angle. Despite individual variation in the shape of V1, the relationship between M(A) and eccentricity was preserved across cases. Comparison between V1 and the retinal ganglion cell density demonstrated preferential magnification of central space in the cortex. The size of the cortical compartment activated by a punctiform stimulus decreased from the foveal representation towards the peripheral representation. Nonetheless, the relationship between the receptive field sizes of V1 cells and the density of ganglion cells suggested that each V1 cell receives information from a similar number of retinal neurons, throughout the visual field. Copyright © 2012 Wiley Periodicals, Inc.

Functional analysis of aldehyde oxidase using expressed chimeric enzyme between monkey and rat.

PubMed

Itoh, Kunio; Asakawa, Tasuku; Hoshino, Kouichi; Adachi, Mayuko; Fukiya, Kensuke; Watanabe, Nobuaki; Tanaka, Yorihisa

2009-01-01

Aldehyde oxidase (AO) is a homodimer with a subunit molecular mass of approximately 150 kDa. Each subunit consists of about 20 kDa 2Fe-2S cluster domain storing reducing equivalents, about 40 kDa flavine adenine dinucleotide (FAD) domain and about 85 kDa molybdenum cofactor (MoCo) domain containing a substrate binding site. In order to clarify the properties of each domain, especially substrate binding domain, chimeric cDNAs were constructed by mutual exchange of 2Fe-2S/FAD and MoCo domains between monkey and rat. Chimeric monkey/rat AO was referred to one with monkey type 2Fe-2S/FAD domains and a rat type MoCo domain. Rat/monkey AO was vice versa. AO-catalyzed 2-oxidation activities of (S)-RS-8359 were measured using the expressed enzyme in Escherichia coli. Substrate inhibition was seen in rat AO and chimeric monkey/rat AO, but not in monkey AO and chimeric rat/monkey AO, suggesting that the phenomenon might be dependent on the natures of MoCo domain of rat. A biphasic Eadie-Hofstee profile was observed in monkey AO and chimeric rat/monkey AO, but not rat AO and chimeric monkey/rat AO, indicating that the biphasic profile might be related to the properties of MoCo domain of monkey. Two-fold greater V(max) values were observed in monkey AO than in chimeric rat/monkey AO, and in chimeric monkey/rat AO than in rat AO, suggesting that monkey has the more effective electron transfer system than rat. Thus, the use of chimeric enzymes revealed that 2Fe-2S/FAD and MoCo domains affect the velocity and the quantitative profiles of AO-catalyzed (S)-RS-8359 2-oxidation, respectively.

The susceptibility of rhesus monkeys to motion sickness

NASA Technical Reports Server (NTRS)

Corcoran, Meryl L.; Daunton, Nancy G.; Fox, Robert A.

1990-01-01

The susceptibility of rhesus monkeys to motion sickness was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150 deg/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion test, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness.

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

PubMed Central

Armour, Eric A.; Carson, Robert P.

2012-01-01

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

PubMed

Armour, Eric A; Carson, Robert P; Ess, Kevin C

2012-08-15

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

Characteristics of renal papillae in kidney stone formers.

PubMed

Marien, Tracy P; Miller, Nicole L

2016-12-01

The mechanism of kidney stone formation is not well understood. In order to better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones. A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini's duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed. The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini's duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini's duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects. Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes. Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.

Fine Structure of Changes Produced in Cultured Cells Sampled at Specified Intervals During a Single Growth Cycle of Polio Virus

PubMed Central

Kallman, Frances; Williams, Robley C.; Dulbecco, Renato; Vogt, Marguerite

1958-01-01

Primary suspended cultures of rhesus monkey kidney cells were infected with poliomyelitis virus, type 1 (Brunhilde strain). The release of virus from these cells over a one-step growth curve was correlated with their change in fine structure, as seen in the electron microscope. Most of the cells were infected nearly simultaneously, and morphological changes developed in the cells were sufficiently synchronous to be classified into three stages. The earliest change (stage I) became visible at a time when virus release into the culture fluid begins, some 3 hours after adsorption. Accentuation of the abnormal characteristics soon occurs, at 4 to 7 hours after adsorption, and results in stage II. Stage III represents the appearance of cells after their rate of virus release had passed its maximum, and probably the abnormal morphology of these cells reflects non-specific physiological damage. There seems to be consistency between the previously described cellular changes as seen under the light microscope and the finer scale changes reported here. Cytoplasmic bodies, called U bodies, were seen in large number at the time when the virus release was the most rapid (stage II). While these bodies are not of proper size to be considered polio virus, they seem to be specifically related to the infection. No evidence was found for the presence of particles that could even be presumptively identified with those of polio virus. PMID:13549502

Nephrology comanagement and the quality of antibiotic prescribing in primary care for patients with chronic kidney disease: a retrospective cross-sectional study.

PubMed

Zhu, Justin X G; Nash, Danielle M; McArthur, Eric; Farag, Alexandra; Garg, Amit X; Jain, Arsh K

2018-04-12

In primary care, patients with chronic kidney disease (CKD) are frequently prescribed excessive doses of antibiotics relative to their kidney function. We examined whether nephrology comanagement is associated with improved prescribing in primary care. In a retrospective propensity score-matched cross-sectional study, we studied the appropriateness of antibiotic prescriptions by primary care physicians to Ontarians ≥66 years of age with CKD Stages 4 and 5 (estimated glomerular filtration rate <30 mL/min/1.73 m2 not receiving dialysis) from 1 April 2003 to 31 March 2014. Comanagement was defined as having at least one outpatient visit with a nephrologist within the year prior to antibiotic prescription date. We compared the rate of appropriately dosed antibiotics in primary care between 3937 patients who were comanaged by a nephrologist and 3937 patients who were not. Only 1184 (30%) of 3937 noncomanaged patients had appropriately dosed antibiotic prescriptions prescribed by a primary care physician. Nephrology comanagement was associated with an increased likelihood that an appropriately dosed prescription was prescribed by a primary care physician; however, the magnitude of the effect was modest [1342/3937 (34%); odds ratio 1.20 (95% confidence interval 1.09-1.32); P < 0.001]. The majority of antibiotics prescribed by primary care physicians are inappropriately dosed in CKD patients, whether or not a nephrologist is comanaging the patient. Nephrologists have an opportunity to increase awareness of appropriate dosing of medications in primary care through the patients they comanage.

Habitat selection of black-and-white snub-nosed monkeys (Rhinopithecus bieti) in Tibet: implications for species conservation.

PubMed

Xiang, Zuo-Fu; Huo, Sheng; Xiao, Wen

2011-04-01

As anthropogenic habitat changes are often considered a threat to natural ecosystems and wildlife, a sound understanding of the effects of habitat alteration on endangered species is crucial when designing management strategies or performing conservation activities. Black-and-white snub-nosed monkeys (Rhinopithecus bieti) are categorized as endangered on the IUCN Red List and are endemic to the trans-Himalayas in China. At present, there are only 15 groups and 2,500 individuals remaining in the wild, and they are facing intense habitat degradation with selective logging for house building and firewood. Habitat deterioration through wood extraction is occurring at Xiaochangdu, Tibet, where one stable group of R. bieti lives in a marginal habitat in the northernmost part of the species' distribution. To understand the species' response to selective logging in an extremely marginal habitat, data on habitat preference and diet composition of a group of R. bieti were collected at Xiaochangdu from 2003 to 2005. The monkeys used different habitats nonrandomly during the year. The selection index for secondary conifer forest (SC), where selective logging has occurred, was the highest of all habitat types (>1), suggesting that the groups strongly preferred SC. The monkeys fed more on buds/leaves, more on flowers/fruit/seeds, and less on lichen in SC than in primary conifer forest (PC). Dietary diversity was significantly higher in SC than in PC. These results indicate that over the short term, low-intensity disturbances may result in increased foliage diversity that enable groups of R. bieti to survive in this marginal habitat. © 2010 Wiley-Liss, Inc.

Effect of vaccination schedule on immune response of Macaca mulatta to cell culture-grown Rocky Mountain spotted fever vaccine.

PubMed Central

Sammons, L S; Kenyon, R H; Pedersen, C E

1976-01-01

The effect of vaccination schedule on the immune response of Macaca mulatta to formalin-inactivated chicken embryo cell culture (CEC)-grown Rickettsia rickettsii vaccine was studied. Schedules consisted of inoculation on day 1 only, on days 1 and 15, on days 1 and 30, on days 1, 8, and 15, or on days 1, 15, and 45. Humoral antibody measured by microagglutination and indirect immunofluorescence and resistance to challenge with 10(4) plaque-forming units of yolk sac-grown R. rickettsii were assessed. Seroconversion was noted in all monkeys after the first dose of vaccine. A second dose administered 8 or 15 days after the primary infection, or a third given 7 or 30 days after the second, produced no long-term effect on antibody titer. Only monkeys given two doses of vaccine at a 30-day interval showed an increase in antibody titer during the period before challenge. Vaccination with one, two, or three doses of CEC vaccine prevented development of rash and rickettsemia after challenge. The two-dose schedules appeared to induce the highest degree of resistance to challenge, as indicated by unaltered hematological parameters and body temperature in monkeys. The one- and three-dose schedules were somewhat less effective, in that some challenged monkeys within each group displayed febrile and leukocyte responses associated with Rocky Mountain spotted fever infection. Our data suggest that administration of two doses of CEC vaccine at 15- or 30-day intervals is the immunization schedule of choice. PMID:823173

Rhythm sensitivity in macaque monkeys

PubMed Central

Selezneva, Elena; Deike, Susann; Knyazeva, Stanislava; Scheich, Henning; Brechmann, André; Brosch, Michael

2013-01-01

This study provides evidence that monkeys are rhythm sensitive. We composed isochronous tone sequences consisting of repeating triplets of two short tones and one long tone which humans perceive as repeating triplets of two weak and one strong beat. This regular sequence was compared to an irregular sequence with the same number of randomly arranged short and long tones with no such beat structure. To search for indication of rhythm sensitivity we employed an oddball paradigm in which occasional duration deviants were introduced in the sequences. In a pilot study on humans we showed that subjects more easily detected these deviants when they occurred in a regular sequence. In the monkeys we searched for spontaneous behaviors the animals executed concomitant with the deviants. We found that monkeys more frequently exhibited changes of gaze and facial expressions to the deviants when they occurred in the regular sequence compared to the irregular sequence. In addition we recorded neuronal firing and local field potentials from 175 sites of the primary auditory cortex during sequence presentation. We found that both types of neuronal signals differentiated regular from irregular sequences. Both signals were stronger in regular sequences and occurred after the onset of the long tones, i.e., at the position of the strong beat. Local field potential responses were also significantly larger for the durational deviants in regular sequences, yet in a later time window. We speculate that these temporal pattern-selective mechanisms with a focus on strong beats and their deviants underlie the perception of rhythm in the chosen sequences. PMID:24046732

Primary and Secondary Vestibular Connections in the Brain Stem and Cerebellum: An Axoplasmic Transport Study in the Monkey and Cat

DTIC Science & Technology

1983-08-25

Edinger-Westphal nucleus in the cat, Brain Research, 141 (1978) 153-159. Lorente de No, R., Etudes sur le cerveau posterieur. Ill, Sur 1 es connexions...extra-cerebelleuses des fascicules afferents au cerveau , et sur la fontion de cet organe, Trav. Lab. Rech. Biol. Univ. Madrid, 22 (1924) 51-65

"Silent" kidney stones in "asymptomatic" primary hyperparathyroidism-a comparison of multidetector computed tomography and ultrasound.

PubMed

Selberherr, Andreas; Hörmann, Marcus; Prager, Gerhard; Riss, Philipp; Scheuba, Christian; Niederle, Bruno

2017-03-01

The purpose of this study was to demonstrate the high number of kidney stones in primary hyperparathyroidism (PHPT) and the low number of in fact "asymptomatic" patients. Forty patients with PHPT (28 female, 12 male; median age 58 (range 33-80) years; interquartile range 17 years [51-68]) without known symptoms of kidney stones prospectively underwent multidetector computed tomography (MDCT) and ultrasound (US) examinations of the urinary tract prior to parathyroid surgery. Images were evaluated for the presence and absence of stones, as well as for the number of stones and sizes in the long axis. The MDCT and US examinations were interpreted by two experienced radiologists who were blinded to all clinical and biochemical data. Statistical analysis was performed using the Wilcoxon signed-rank test. US revealed a total of 4 kidney stones in 4 (10 %) of 40 patients (median size 6.5 mm, interquartile range 11.5 mm). MDCT showed a total of 41 stones (median size was 3 mm, interquartile range 2.25 mm) in 15 (38 %) of 40 patients. The number of kidney stones detected with MDCT was significantly higher compared to US (p = 0.00124). MDCT is a highly sensitive method for the detection of "silent" kidney stones in patients with PHPT. By widely applying this method, the number of asymptomatic courses of PHPT may be substantially reduced. MDCT should be used primarily to detect kidney stones in PHPT and to exclude asymptomatic PHPT.

APOL1 risk variants, race, and progression of chronic kidney disease.

PubMed

Parsa, Afshin; Kao, W H Linda; Xie, Dawei; Astor, Brad C; Li, Man; Hsu, Chi-yuan; Feldman, Harold I; Parekh, Rulan S; Kusek, John W; Greene, Tom H; Fink, Jeffrey C; Anderson, Amanda H; Choi, Michael J; Wright, Jackson T; Lash, James P; Freedman, Barry I; Ojo, Akinlolu; Winkler, Cheryl A; Raj, Dominic S; Kopp, Jeffrey B; He, Jiang; Jensvold, Nancy G; Tao, Kaixiang; Lipkowitz, Michael S; Appel, Lawrence J

2013-12-05

Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease

PubMed Central

Parsa, Afshin; Kao, W.H. Linda; Xie, Dawei; Astor, Brad C.; Li, Man; Hsu, Chi-yuan; Feldman, Harold I.; Parekh, Rulan S.; Kusek, John W.; Greene, Tom H.; Fink, Jeffrey C.; Anderson, Amanda H.; Choi, Michael J.; Wright, Jackson T.; Lash, James P.; Freedman, Barry I.; Ojo, Akinlolu; Winkler, Cheryl A.; Raj, Dominic S.; Kopp, Jeffrey B.; He, Jiang; Jensvold, Nancy G.; Tao, Kaixiang; Lipkowitz, Michael S.; Appel, Lawrence J.

2014-01-01

BACKGROUND Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.) PMID:24206458

Urinary markers of renal damage in hypertensive children diagnosed with ambulatory blood pressure monitoring.

PubMed

Girişgen, İlknur; Sönmez, Ferah; Yenisey, Ciğdem; Kurt-Omurlu, İmran

2014-01-01

Primary hypertension is the most important risk factor for chronic kidney disease in adulthood. However, the role of hypertension in kidney damage in childhood is not known exactly. The aim of this study was to evaluate the ambulatory blood pressure measurements of healthy children diagnosed as hypertensive with routine office blood pressure monitoring and to investigate the effects of primary hypertension on the kidney. Fifty-six patients who had blood pressure higher than 90th percentile during their well-child follow-up and 27 healthy children with normal blood pressure were included in the study. Twenty-four hour blood pressure measurements were recorded for all the patients. Microalbumin and N-acetyl-β-D-glucosaminidase (NAG) levels in the 24-hour urine were determined in the study groups. According to the results of ambulatory blood pressure measurements, 52% of the patients were diagnosed as white coat hypertension. The patients and the white coat hypertensive group had higher levels of urinary NAG than the control group. No significant difference was found in the levels of urinary microalbumin excretion between the primary hypertension and control groups. It was thought that ambulatory blood pressure measurement was necessary for the true diagnosis of hypertension in children, and further, that primary and white coat hypertension had effects on kidney damage in childhood. It is suggested that urine NAG excretion might be used as an early sign of hypertension-induced renal damage.

Preventing Acute Kidney Injury: a qualitative study exploring 'sick day rules' implementation in primary care.

PubMed

Morris, Rebecca L; Ashcroft, Darren; Phipps, Denham; Bower, Peter; O'Donoghue, Donal; Roderick, Paul; Harding, Sarah; Lewington, Andrew; Blakeman, Thomas

2016-07-22

In response to growing demand for urgent care services there is a need to implement more effective strategies in primary care to support patients with complex care needs. Improving primary care management of kidney health through the implementation of 'sick day rules' (i.e. temporary cessation of medicines) to prevent Acute Kidney Injury (AKI) has the potential to address a major patient safety issue and reduce unplanned hospital admissions. The aim of this study is to examine processes that may enable or constrain the implementation of 'sick day rules' for AKI prevention into routine care delivery in primary care. Forty semi-structured interviews were conducted with patients with stage 3 chronic kidney disease and purposefully sampled, general practitioners, practice nurses and community pharmacists who either had, or had not, implemented a 'sick day rule'. Normalisation Process Theory was used as a framework for data collection and analysis. Participants tended to express initial enthusiasm for sick day rules to prevent AKI, which fitted with the delivery of comprehensive care. However, interest tended to diminish with consideration of factors influencing their implementation. These included engagement within and across services; consistency of clinical message; and resources available for implementation. Participants identified that supporting patients with multiple conditions, particularly with chronic heart failure, made tailoring initiatives complex. Implementation of AKI initiatives into routine practice requires appropriate resourcing as well as training support for both patients and clinicians tailored at a local level to support system redesign.

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study.

PubMed

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-04-01

Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. To explore processes underpinning the implementation of CKD management in primary care. Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity.

[Kidney function and liver transplantation].

PubMed

Gámán, György; Gelley, Fanni; Gerlei, Zsuzsa; Dabasi, Eszter; Görög, Dénes; Fehérvári, Imre; Kóbori, László; Lengyel, Gabriella; Zádori, Gergely; Fazakas, János; Doros, Attila; Sárváry, Enikő; Nemes, Balázs

2013-06-30

In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. Retrospective data analysis was performed after primary liver transplantations (n = 319). impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). Selection of personalized immunosuppressive medication has a positive effect on renal function.

Phylogenetic analysis of HERV-K LTR-like elements in primates: presence in some new world monkeys and evidence of recent parallel evolution in these species and in homo sapiens.

PubMed

Kim, H S; Wadekar, R V; Takenaka, O; Hyun, B H; Crow, T J

1999-01-01

Solitary long terminal repeats (LTRs) of the human endogenous retroviruses K family (HERV-K) have been found to be coexpressed with sequences of closely located genes. We identified forty-three HERV-K LTR-like elements in primates (African great apes, two Old World monkeys, and two New World monkeys) and analyzed them along with human-specific HERV-K LTRs. We report detection of HERV-K LTR-like elements from New World monkeys, as represented by the squirrel monkey and the night monkey, for the first time. Analysis revealed a high degree of sequence homology with human-specific HERV-K LTRs. A phylogenetic tree obtained by the neighbor-joining method revealed that five sequence (SMS-1, 2, 5, 6, 7) from the squirrel monkey and three sequences (NM6-4, 5, 9) from the night monkey are more closely related to human-specific HERV-K LTRs than they are to those of apes (the chimpanzee and gorilla) and Old World monkeys (the African green monkey and rhesus monkey). The findings are consistent with the concept the HERV-K LTR-like elements have proliferated independently and recently in the genome of primates, and that such proliferation has been more recent in Homo sapiens and in these representatives of New World monkeys than in some Old World monkeys.

Nonidentity of Some Simian Virus 40-induced Enzymes with Tumor Antigen

PubMed Central

Kit, Saul; Melnick, Joseph L.; Anken, Milton; Dubbs, Del Rose; de Torres, R. A.; Kitahara, Tsunehiro

1967-01-01

The complement-fixing tumor (T) antigen induced by simian virus 40 (SV40) has been prepared from SV40-infected cell cultures, from infected cell cultures treated at the time of infection with 1-β-d-arabinofuranosylcytosine (ara-C), and from SV40-transformed cells. Upon partial purification, the T antigen exhibited the following properties: it was tightly adsorbed by calcium phosphate gel, it was precipitated by acetic acid at pH 5 or by ammonium sulfate at about 20 to 32% saturation, and it had a molecular weight greater than 250,000, as estimated by Sephadex G-200 gel chromatography. In contrast, deoxycytidylate (dCMP) deaminase, thymidylate (dTMP) kinase, and thymidine (dT) kinase were less strongly bound to calcium phosphate and were not precipitated at pH 5; these enzymes also had much lower molecular weights than the T antigen, as did dihydrofolic (FH2) reductase. Furthermore, higher ammonium sulfate concentrations were required to precipitate dCMP deaminase, dTMP kinase, and FH2 reductase activities than to precipitate the T antigen. Another difference was that the T antigen was not stabilized, but dCMP deaminase, dTMP kinase, and dT kinase, were stabilized, respectively, by dCTP, dTMP, and dT or dTTP. Deoxyribonucleic acid (DNA) polymerase activity resembled the T antigen in adsorption to calcium phosphate, in precipitation by ammonium sulfate or at pH 5, and in the rate of inactivation when incubated at 38 C. However, the polymerase activity could be partly separated from the T antigen by Sephadex G-200 gel chromatography. The cell fraction containing partially purified T antigen also contained a soluble complement-fixing antigen (presumably a subunit of the viral capsid) which reacted with hyperimmune monkey sera. The latter antigen was present in very low titers or absent from cell extracts prepared from SV40-infected monkey kidney cell cultures which had been treated with ara-C at the time of infection, or from SV40-transformed mouse kidney (mKS) or hamster tumor (H-50) cells. The T antigen, however, was present in usual amounts in SV40-transformed cells or ara-C treated, infected cells. PMID:4316227

Canine distemper virus isolated from a monkey efficiently replicates on Vero cells expressing non-human primate SLAM receptors but not human SLAM receptor.

PubMed

Feng, Na; Liu, Yuxiu; Wang, Jianzhong; Xu, Weiwei; Li, Tiansong; Wang, Tiecheng; Wang, Lei; Yu, Yicong; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Gao, Yuwei; Hu, Guixue; Xia, Xianzhu

2016-08-02

In 2008, an outbreak of canine distemper virus (CDV) infection in monkeys was reported in China. We isolated CDV strain (subsequently named Monkey-BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM receptors from dog, monkey and human origin, and analyzed the H gene of Monkey-BJ01-DV with other strains. The Monkey-BJ01-DV isolate replicated to the highest titer on Vero cells expressing dog-origin SLAM (10(5.2±0.2) TCID50/ml) and monkey-origin SLAM (10(5.4±0.1) TCID50/ml), but achieved markedly lower titers on human-origin SLAM cells (10(3.3±0.3) TCID50/ml). Phylogenetic analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related to other CDV strains obtained during recent CDV epidemics among species of the Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV, Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V, Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other animals at the same period. Our results suggested that the monkey origin-CDV-H protein could possess specific substitutions to adapt to the new host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect and replicate in host cells, but further adaptation may be required for efficient replication in host cells expressing the human SLAM receptor.

Recovery of Renibacterium salmoninarum from naturally infected salmonine stocks in Michigan using a modified culture protocol

USGS Publications Warehouse

Faisal, M.; Eissa, A.E.; Starliper, C.E.

2010-01-01

Renibacterium salmoninarum, the causative agent of bacterial kidney disease (BKD), is a fastidious and slow-growing bacterium that is extremely difficult to grow in vitro. Herein, we describe a modified primary culture protocol that encompasses a modified bacteriological culture medium and a tissue processing procedure. In order to facilitate the release of R. salmoninarum from granulomatous tissues, kidneys of infected fish were homogenized in a high speed stomacher. The kidney disease medium (KDM2), routinely used for primary culture of R. salmoninarum was modified by the addition of antibiotics and metabolites. When a relatively large inoculum of diluted kidney homogenate was streak-plate inoculated onto the modified KDM2, colonial growth of R. salmoninarum was achieved within 5-7. days, compared to the standard of two weeks or more. The modified procedure was then used to determine the prevalence of R. salmoninarum among representative captive and feral salmonid stocks in Michigan. Prevalence and clinical manifestations varied among species, strains of fish, and locations; however, R. salmoninarum isolates were biochemically homogenous. The improved primary culture procedure described in this study enabled selective and quick isolation of R. salmoninarum. Also, the isolates retrieved in this study constitute a unique biological resource for future studies of R. salmoninarum in the Laurentian Great Lakes. ?? 2009 University of Cairo.

Molecular Cloning of Pituitary Glycoprotein α-Subunit and Follicle Stimulating Hormone and Chorionic Gonadotropin β-Subunits from New World Squirrel Monkey and Owl Monkey

PubMed Central

Scammell, Jonathan G.; Funkhouser, Jane D.; Moyer, Felricia S.; Gibson, Susan V.; Willis, Donna L.

2008-01-01

The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone α-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature β subunits of follicle stimulating hormone (FSHβ) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHβ. New World primate glycoprotein hormone α-polypeptides and FSHβ subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the β-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the β-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGβ are 143 and 144 amino acids in length and 77% homologous with human CGβ. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGβ, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGβs. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG. PMID:17897645

Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey.

PubMed

Scammell, Jonathan G; Funkhouser, Jane D; Moyer, Felricia S; Gibson, Susan V; Willis, Donna L

2008-02-01

The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone alpha-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature beta subunits of follicle stimulating hormone (FSHbeta) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHbeta. New World primate glycoprotein hormone alpha-polypeptides and FSHbeta subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the beta-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the beta-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGbeta are 143 and 144 amino acids in length and 77% homologous with human CGbeta. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGbeta, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGbetas. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG.

Late diagnosis of primary hyperoxaluria after failed kidney transplantation.

PubMed

Spasovski, Goce; Beck, Bodo B; Blau, Nenad; Hoppe, Bernd; Tasic, Velibor

2010-09-01

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive inborn error of the glyoxylate metabolism that is based on absence, deficiency or mislocalization of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase. Hyperoxaluria leads to recurrent formation of calculi and/or nephrocalcinosis and often early end-stage renal disease (ESRD) accompanied by systemic calcium oxalate crystal deposition. In this report, we describe an adult female patient with only one stone passage before development of ESRD. With unknown diagnosis of PH, the patient received an isolated kidney graft and developed an early onset of graft failure. Although initially presumed as an acute rejection, the biopsy revealed calcium oxalate crystals, which then raised a suspicion of primary hyperoxaluria. The diagnosis was later confirmed by hyperoxaluria, elevated plasma oxalate levels and mutation of the AGXT gene, showing the patient to be compound heterozygous for the c.33_34InsC and c.508G > A mutations. Plasma oxalate levels did not decrease after high-dose pyridoxine treatment. Based on this case report, we would recommend in all patients even with a minor history of nephrolithiasis but progression to chronic renal failure to exclude primary hyperoxaluria before isolated kidney transplantation is considered.

Alkaline Phosphatase for the Prevention of Intestinal and Renal Injury in a Rat Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

DTIC Science & Technology

2017-09-01

primary outcome), physiologic, and biomarker evidence of intestinal and kidney injury in this model with administration of escalating doses of bovine...these techniques is necessary for surgical repair, the associated ischemia-reperfusion injury to the intestines and kidneys can lead to substantial...prevention of intestinal and kidney injury after pediatric cardiopulmonary bypass with deep hypothermic circulatory arrest. In this model, we place 5-10kg

Sustained Pyridoxine Response in Primary Hyperoxaluria Type 1 Recipients of Kidney Alone Transplant

PubMed Central

Lorenz, Elizabeth C; Lieske, John C; Seide, Barbara M; Meek, Alicia M; Olson, Julie B; Bergstralh, Eric J; Milliner, Dawn S

2015-01-01

Combined kidney liver transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant. We examined the efficacy of pyridoxine therapy following kidney alone transplant in five patients homozygous for G170R transplanted between 9/1999 and 7/2013. All patients were maintained on pyridoxine post-transplant. Median age at transplant was 39 years (range 33–67 years). Median follow-up post-transplant was 8.5 years (range 0.2–13.9 years). At the end of follow-up, 4 grafts were functioning. One graft failed 13.9 years post-transplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, post-transplant urine oxalate levels were < 0.5 mmol/24 hr the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following kidney alone transplant. Therefore, pyridoxine combined with kidney alone transplantation should be considered for PH1 patients with a homozygous G170R mutation. PMID:24797341

Seroepidemiological survey of pathogenic Yersinia in breeding squirrel monkeys in Japan.

PubMed

Iwata, Taketoshi; Une, Yumi; Lee, Ken-ichi; Nakamura, Shin-ichi; Taniguchi, Takahide; Hayashidani, Hideki

2010-08-01

To investigate the prevalence of antibodies to pathogenic Yersinia in breeding squirrel monkeys, the serum samples of 252 squirrel monkeys from 9 zoological gardens in Japan were tested by ELISA using plasmid-encoded Yersinia outer membrane protein (Yops) as the antigen. The cutoff value was calculated by using the serum samples of the squirrel monkeys from Suriname, where no prevalence of pathogenic Yersinia have been reported. According to the cutoff value, 164 of 252 (65.1%) squirrel monkeys were considered positive against pathogenic Yersinia. These positive monkeys belonged to 8 of the 9 zoological gardens, and the percentage of the seropositive monkeys ranged from 22.2 to 89.4%. Furthermore, in one zoological garden, the positive rate of the squirrel monkeys which were over 1 year old (95.7%) was significantly higher than those which were under 1 year old (23.3%). These results suggested that pathogenic Yersinia is highly prevalent among breeding monkeys in Japan.

Kidney versus Islet Allograft Survival after Induction of Mixed Chimerism with Combined Donor Bone Marrow Transplantation

PubMed Central

Oura, Tetsu; Ko, Dicken S.C.; Boskovic, Svjetlan; O'Neil, John J.; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R. Neal; Cosimi, A. B.; Kawai, Tatsuo

2016-01-01

Background We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC-mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. Methods A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that includes low dose total body and thymic irradiation, horse ATG (Atgam), six doses of anti-CD154 monoclonal antibody (mAb) and a one month course of cyclosporine (CyA) (Islet-A). In Islet-B, anti-CD8 mAb was administered in place of CyA. In Islet-C, two recipients were treated with Islet-B but without Atgam. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and bone marrow transplantation (Kidney-A) following the same conditioning regimen used in Islet-A. Results The majority of Kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned Islet/BM recipients (Islet-A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to calcineurin inhibitor (CNI) toxicity, three recipients were treated with anti-CD8 mAb in place of CNI. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet-C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Conclusion Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CNI-free regimen that includes anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more durable mixed chimerism may be necessary for induction of islet allograft tolerance. PMID:26337731

Primary Monophasic Synovial Sarcoma of the Kidney: A Case Report and Review of Literature

PubMed Central

Lopes, Henrique; Pereira, Caio A.D.; Zucca, Luís E.R.; Serrano, Sérgio V.; Silva, Sandra R.M.; Camparoto, Marjori L.; Cárcano, Flavio M.

2013-01-01

Primary synovial sarcoma (SS) of the kidney is a rare neoplasm and its presenting features are similar to other common renal tumors, making early diagnosis difficult. To date, few cases have been reported in the literature. Primary renal SSs can exist in either a monophasic or a biphasic pattern, the former being more common and tending to have a better prognosis than the biphasic variant. Herein we describe a case of primary renal SS that was diagnosed based on histopathology and immunohistochemistry after radical nephrectomy. Fusion gene product analysis was also done by FISH and RT-PCR. Patient follow-up and literature review are presented, focused on systemic therapy. We highlight that these tumors should be correctly diagnosed as clinical results and specific treatment are distinct from primary epithelial renal cell carcinoma. Adjuvant chemotherapy should be tailored for each patient in the management of disease, although its role still remains unclear. PMID:24137053

Culture of prostate epithelial cells of the rhesus monkey on extracellular matrix substrate: influence of steroids and insulin-like growth factors.

PubMed

Udayakumar, T S; Jeyaraj, D A; Rajalakshmi, M; Sharma, R S

1999-09-01

Rhesus monkey prostate epithelial cells from the cranial lobe were isolated and cultured in flasks coated either with collagen IV or laminin. The effects of stromal cell medium, androgens and growth factors on cell number, thymidine incorporation and secretory activity were assessed. The results indicate that dihydrotestosterone (DHT) and androstenedione have stimulatory influences on cell proliferation and secretion in coated flasks. DHT was more effective in increasing cell number but the induction of secretory activity was similar with both steroids. The combination of IGF-I and -II resulted in inducing better cell proliferation and secretory activity than the individual IGFs but, of the two IGFs, IGF-I was more effective than IGF-II. DHT with IGFs was more potent in inducing proliferation, differentiation and secretion than androstenedione. Even in the absence of steroids or growth factors, colony formation and confluence occurred in coated flasks but cell differentiation and secretion only to a limited extent. In conclusion, we were able to establish an in vitro primary culture of prostate epithelial cells from rhesus monkey using extracellular matrix proteins, steroids and growth factors as additional supplements. This culture system may be useful to study prostate cell physiology and to identify drugs that can inhibit cell proliferation.

Disposition and metabolism of [14C]lemborexant, a novel dual orexin receptor antagonist, in rats and monkeys.

PubMed

Ueno, Takashi; Ishida, Tomomi; Kusano, Kazutomi

2018-05-28

1. The disposition and metabolism of lemborexant, a novel dual orexin receptor antagonist currently under development as a therapeutic agent for insomnia disorder, were evaluated after a single oral administration of [ 14 C]lemborexant in Sprague-Dawley rats (10 mg/kg) and cynomolgus monkeys (3 mg/kg). 2. In both species, [ 14 C]lemborexant was rapidly absorbed: radioactivity concentration in blood peaked at 0.83-1.8 h, and decreased with elimination half-life of 110 h. The radioactivity administered was excreted primarily into faeces, with relatively little excreted into urine. 3. Lemborexant was not detected in bile, urine, or faeces, indicating that lemborexant administered orally was completely absorbed from the gastrointestinal tract and that the main elimination pathway was metabolism in both species. 4. In rats, lemborexant was found to be minor in plasma (≤5.2% of total radioactivity), and M9 (hydroxylated form) was the major circulating metabolite. In monkeys, the major circulating components were lemborexant, M4 (N-oxide metabolite), M13 (di-oxidised form), M14 (di-oxidised form), and M16 (glucuronide of mono-oxidised form). 5. In both species, lemborexant was metabolised to various metabolites by multiple pathways, the primary of which was oxidation of the dimethylpyrimidine or fluorophenyl moiety.

Las Islas de los Changos (the Monkey Islands): the economic impact of ecotourism in the region of Los Tuxtlas, Veracruz, Mexico.

PubMed

Serio-Silva, Juan Carlos

2006-05-01

This study evaluates the popularity and economic impact of Las Islas de los Changos (the Monkey Islands) as an ecotourism site on Lake Catemaco in the Los Tuxtlas region of Veracruz, Mexico. Two small island colonies of exotic primates, stumptail macaques (Macaca arctoides), have proved to be highly beneficial for the local economy as the main attraction for tourists in this region. From July 1991 to June 1992, data were collected on the number of tourists who took boat trips to visit the primates, and the amount of money spent on tours to the islands. The data suggest that at least 28,470 passengers visit these primate troops annually and spend approximately 88,970 U.S. dollars (USD). Follow-up questionnaires during July 1997 to June 2000 to hotelkeepers and tourist boat operators identified the Monkey Islands as the primary destination for tourists to this region. A comparison of the net income obtained by local ecotourism operators with wages earned through other types of employment in the Los Tuxtlas region, such as working in natural reserves, agriculture, or renting grazing land for cattle, show the relative importance of Las Islas de Los Changos in sustaining the local economy. 2005 Wiley-Liss, Inc.

Identification of Novel Kaposi's Sarcoma-Associated Herpesvirus Orf50 Transcripts: Discovery of New RTA Isoforms with Variable Transactivation Potential.

PubMed

Wakeman, Brian S; Izumiya, Yoshihiro; Speck, Samuel H

2017-01-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that has been associated with primary effusion lymphoma and multicentric Castleman's disease, as well as its namesake Kaposi's sarcoma. As a gammaherpesvirus, KSHV is able to acutely replicate, enter latency, and reactivate from this latent state. A key protein involved in both acute replication and reactivation from latency is the replication and transcriptional activator (RTA) encoded by the gene Orf50 RTA is a known transactivator of multiple viral genes, allowing it to control the switch between latency and virus replication. We report here the identification of six alternatively spliced Orf50 transcripts that are generated from four distinct promoters. These newly identified promoters are shown to be transcriptionally active in 293T (embryonic kidney), Vero (African-green monkey kidney epithelial), 3T12 (mouse fibroblast), and RAW 264.7 (mouse macrophage) cell lines. Notably, the newly identified Orf50 transcripts are predicted to encode four different isoforms of the RTA which differ by 6 to 10 residues at the amino terminus of the protein. We show the global viral transactivation potential of all four RTA isoforms and demonstrate that all isoforms can transcriptionally activate an array of KSHV promoters to various levels. The pattern of transcriptional activation appears to support a transcriptional interference model within the Orf50 region, where silencing of previously expressed isoforms by transcription initiation from upstream Orf50 promoters has the potential to modulate the pattern of viral gene activation. Gammaherpesviruses are associated with the development of lymphomas and lymphoproliferative diseases, as well as several other types of cancer. The human gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is tightly associated with the development of Kaposi's sarcoma and multicentric Castleman's disease, as well as a rare form of B cell lymphoma (primary effusion lymphoma) primarily observed in HIV-infected individuals. RTA is an essential viral gene product involved in the initiation of gammaherpesvirus replication and is conserved among all known gammaherpesviruses. We show here for KSHV that transcription of the gene encoding RTA is complex and leads to the expression of several isoforms of RTA with distinct functions. This observed complexity in KSHV RTA expression and function likely plays a critical role in the regulation of downstream viral and cellular gene expression, leading to the efficient production of mature virions. Copyright © 2016 American Society for Microbiology.

Comprehensive transcriptional map of primate brain development

PubMed Central

Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bennett, Jeffrey L.; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Haynor, David R.; Hejazinia, Nika; Hoerder-Suabedissen, Anna; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Gibbs, Richard A.; Rogers, Jeffrey; Hohmann, John G.; Hawrylycz, Michael J.; Hevner, Robert F.; Molnár, Zoltán; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Amaral, David G.; Bernard, Amy; Lein, Ed S.

2017-01-01

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny. PMID:27409810

A geometric analysis of semicircular canals and induced activity in their peripheral afferents in the rhesus monkey

NASA Technical Reports Server (NTRS)

Reisine, H.; Simpson, J. I.; Henn, V.

1988-01-01

Experiments were carried out to determine anatomically the planes of the semicircular canals of two juvenile rhesus monkeys, using plastic casts of the semicircular canals, and the anatomical measurements were related to the directional coding of neural signals transmitted by primary afferents innervating the same simicircular canals. In the experiments, animals were prepared for monitoring the eye position by the implantation of silver-silver chloride electrodes into the bony orbit. Following the recording of semicircular canal afferent activity, the animals were sacrificed; plastic casting resin was injected into the bony canals; and, when the temporal bone was demineralized and removed, the coordinates of points spaced along the circumference of the canal casts were measured. A comparison of the sensitivity vectors determined in these experiments and the anatomical measures showed that the average difference between a sensitivity vector and its respective normal vector was 6.3 deg.

Interspecies differences in metabolism of arsenic by cultured primary hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drobna, Zuzana; Walton, Felecia S.; Harmon, Anne W.

2010-05-15

Biomethylation is the major pathway for the metabolism of inorganic arsenic (iAs) in many mammalian species, including the human. However, significant interspecies differences have been reported in the rate of in vivo metabolism of iAs and in yields of iAs metabolites found in urine. Liver is considered the primary site for the methylation of iAs and arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in this pathway. Thus, the As3mt-catalyzed methylation of iAs in the liver determines in part the rate and the pattern of iAs metabolism in various species. We examined kinetics and concentration-response patterns for iAsmore » methylation by cultured primary hepatocytes derived from human, rat, mice, dog, rabbit, and rhesus monkey. Hepatocytes were exposed to [{sup 73}As]arsenite (iAs{sup III}; 0.3, 0.9, 3.0, 9.0 or 30 nmol As/mg protein) for 24 h and radiolabeled metabolites were analyzed in cells and culture media. Hepatocytes from all six species methylated iAs{sup III} to methylarsenic (MAs) and dimethylarsenic (DMAs). Notably, dog, rat and monkey hepatocytes were considerably more efficient methylators of iAs{sup III} than mouse, rabbit or human hepatocytes. The low efficiency of mouse, rabbit and human hepatocytes to methylate iAs{sup III} was associated with inhibition of DMAs production by moderate concentrations of iAs{sup III} and with retention of iAs and MAs in cells. No significant correlations were found between the rate of iAs methylation and the thioredoxin reductase activity or glutathione concentration, two factors that modulate the activity of recombinant As3mt. No associations between the rates of iAs methylation and As3mt protein structures were found for the six species examined. Immunoblot analyses indicate that the superior arsenic methylation capacities of dog, rat and monkey hepatocytes examined in this study may be associated with a higher As3mt expression. However, factors other than As3mt expression may also contribute to the interspecies differences in the hepatocyte capacity to methylate iAs.« less

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds

PubMed Central

Madani, Navid; Princiotto, Amy M.; Easterhoff, David; Bradley, Todd; Luo, Kan; Williams, Wilton B.; Liao, Hua-Xin; Moody, M. Anthony; Phad, Ganesh E.; Vázquez Bernat, Néstor; Melillo, Bruno; Santra, Sampa; Smith, Amos B.; Karlsson Hedestam, Gunilla B.; Haynes, Barton

2016-01-01

ABSTRACT The human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recognize conserved Env epitopes are thought to be an important component of a protective immune response. However, to date, HIV-1 Env immunogens that elicit broadly neutralizing antibodies have not been identified, creating hurdles for vaccine development. Small-molecule CD4-mimetic compounds engage the CD4-binding pocket on the gp120 exterior Env and induce Env conformations that are highly sensitive to neutralization by antibodies, including antibodies directed against the conserved Env region that interacts with CCR5/CXCR4. Here, we show that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within 6 months by several Env vaccine candidates, including gp120 monomers. Monoclonal antibodies directed against the gp120 V2 and V3 variable regions were isolated from the immunized monkeys and humans; these monoclonal antibodies neutralized a primary HIV-1 only when the virus was sensitized by a CD4-mimetic compound. Thus, in addition to their direct antiviral effect, CD4-mimetic compounds dramatically enhance the HIV-1-neutralizing activity of antibodies that can be elicited with currently available immunogens. Used as components of microbicides, the CD4-mimetic compounds might increase the protective efficacy of HIV-1 vaccines. IMPORTANCE Preventing HIV-1 transmission is a high priority for global health. Eliciting antibodies that can neutralize transmitted strains of HIV-1 is difficult, creating problems for the development of an effective vaccine. We found that small-molecule CD4-mimetic compounds sensitize HIV-1 to antibodies that can be elicited in vaccinated humans and monkeys. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus-sensitizing microbicide is combined with a vaccine. PMID:26962221

Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

PubMed

Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

2012-12-15

Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation. Copyright © 2012 Elsevier Inc. All rights reserved.

Transformation of Mouse Macrophages by Simian Virus 40

PubMed Central

Stone, Lawrence B.; Takemoto, Kenneth K.

1970-01-01

Studies were undertaken to prove that simian virus 40 (SV40) can transform the mouse macrophage, a cell type naturally restricted from deoxyribonucleic acid (DNA) replication. Balb/C macrophages infected with SV40 demonstrated T-antigen production and induced DNA synthesis simultaneously. In the absence of apparent division, these cells remained T antigen-positive for at least 45 days. SV40 could be rescued from nondividing, unaltered macrophages during the T antigen-producing period. Proliferating transformants appeared at an average of 66 days post-SV40 infection. Established cell lines were T antigen-positive and were negative for infectious virus, but yielded SV40 after fusion with African green monkey kidney cells. Their identity as transformed macrophages was substantiated by evaluation of cellular morphology, phagocytosis, acid phosphatase, β1c synthesis, and aminoacridine incorporation. Images PMID:4320698

Information processing occurs via critical avalanches in a model of the primary visual cortex

NASA Astrophysics Data System (ADS)

Bortolotto, G. S.; Girardi-Schappo, M.; Gonsalves, J. J.; Pinto, L. T.; Tragtenberg, M. H. R.

2016-01-01

We study a new biologically motivated model for the Macaque monkey primary visual cortex which presents power-law avalanches after a visual stimulus. The signal propagates through all the layers of the model via avalanches that depend on network structure and synaptic parameter. We identify four different avalanche profiles as a function of the excitatory postsynaptic potential. The avalanches follow a size-duration scaling relation and present critical exponents that match experiments. The structure of the network gives rise to a regime of two characteristic spatial scales, one of which vanishes in the thermodynamic limit.

Should We Formulate an Incentivized Model Facilitating Kidney Donation from Living Donors? A Focus on Turkey's Current System.

PubMed

Avci, Ercan

2018-04-23

Kidney transplantation is a lifesaving medical treatment. However, very high demand for kidneys with low kidney donation causes a black market that exploits patients' desperation and donors' vulnerability. The current kidney donation programs fail to produce promising results to avoid illegal and unethical kidney trafficking and commercialism. Even though the primary goal of kidney donation is to increase the number of deceased organ donations, in some countries, like Turkey, due to religious or cultural concerns, it is impossible to supply adequate deceased kidney donations. In this view, the aim of this paper is to examine kidney trafficking in the scope of Turkey's current organ donation system and propose a new model, named the Incentivized Kidney Donation Model (IKDM), to increase kidney donation from living donors. The model encompasses the following benefits offered to kidney donors; lifetime health insurance, exemptions from copayments/contribution shares, priority when receiving an organ, priority when finding a job, income tax exemptions for salaried employees, and free or discounted public utilities. This normative model has the potential to promote donors' altruistic acts as well as the solidarity and loyalty among members of a society without violating ethical values and internationally accepted principles. © 2018 John Wiley & Sons Ltd.

Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colcher, D.; Teramoto, Y.A.; Schlom, J.

1977-12-01

A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observedmore » with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species.« less

SV40 host-substituted variants: a new look at the monkey DNA inserts and recombinant junctions.

PubMed

Singer, Maxine; Winocour, Ernest

2011-04-10

The available monkey genomic data banks were examined in order to determine the chromosomal locations of the host DNA inserts in 8 host-substituted SV40 variant DNAs. Five of the 8 variants contained more than one linked monkey DNA insert per tandem repeat unit and in all cases but one, the 19 monkey DNA inserts in the 8 variants mapped to different locations in the monkey genome. The 50 parental DNAs (32 monkey and 18 SV40 DNA segments) which spanned the crossover and flanking regions that participated in monkey/monkey and monkey/SV40 recombinations were characterized by substantial levels of microhomology of up to 8 nucleotides in length; the parental DNAs also exhibited direct and inverted repeats at or adjacent to the crossover sequences. We discuss how the host-substituted SV40 variants arose and the nature of the recombination mechanisms involved. Copyright © 2011 Elsevier Inc. All rights reserved.

Low blood cell counts in wild Japanese monkeys after the Fukushima Daiichi nuclear disaster.

PubMed

Ochiai, Kazuhiko; Hayama, Shin-ichi; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Uno, Taiki; Kato, Takuya; Konno, Fumiharu; Kawamoto, Yoshi; Tsuchida, Shuichi; Omi, Toshinori

2014-07-24

In April 2012 we carried out a 1-year hematological study on a population of wild Japanese monkeys inhabiting the forest area of Fukushima City. This area is located 70 km from the Fukushima Daiichi Nuclear Power Plant (NPP), which released a large amount of radioactive material into the environment following the Great East Japan Earthquake of 2011. For comparison, we examined monkeys inhabiting the Shimokita Peninsula in Aomori Prefecture, located approximately 400 km from the NPP. Total muscle cesium concentration in Fukushima monkeys was in the range of 78-1778 Bq/kg, whereas the level of cesium was below the detection limit in all Shimokita monkeys. Compared with Shimokita monkeys, Fukushima monkeys had significantly low white and red blood cell counts, hemoglobin, and hematocrit, and the white blood cell count in immature monkeys showed a significant negative correlation with muscle cesium concentration. These results suggest that the exposure to some form of radioactive material contributed to hematological changes in Fukushima monkeys.

Low blood cell counts in wild Japanese monkeys after the Fukushima Daiichi nuclear disaster

PubMed Central

Ochiai, Kazuhiko; Hayama, Shin-ichi; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Uno, Taiki; Kato, Takuya; Konno, Fumiharu; Kawamoto, Yoshi; Tsuchida, Shuichi; Omi, Toshinori

2014-01-01

In April 2012 we carried out a 1-year hematological study on a population of wild Japanese monkeys inhabiting the forest area of Fukushima City. This area is located 70 km from the Fukushima Daiichi Nuclear Power Plant (NPP), which released a large amount of radioactive material into the environment following the Great East Japan Earthquake of 2011. For comparison, we examined monkeys inhabiting the Shimokita Peninsula in Aomori Prefecture, located approximately 400 km from the NPP. Total muscle cesium concentration in Fukushima monkeys was in the range of 78–1778 Bq/kg, whereas the level of cesium was below the detection limit in all Shimokita monkeys. Compared with Shimokita monkeys, Fukushima monkeys had significantly low white and red blood cell counts, hemoglobin, and hematocrit, and the white blood cell count in immature monkeys showed a significant negative correlation with muscle cesium concentration. These results suggest that the exposure to some form of radioactive material contributed to hematological changes in Fukushima monkeys. PMID:25060710

The pattern of the arterial supply of the pancreas in anthropoid apes, catarrhine monkeys and platyrrhine monkeys.

PubMed

Shawuti, Alimujiang; Miyaki, Takayoshi; Saito, Toshiyuki; Itoh, Masahiro

2009-11-01

To get the full understanding of the arterial distribution to the pancreas, the analysis of the distribution of the variety of monkey species would be helpful. In this study, we studied the layout of the pancreatic artery in anthropoids (1 gorilla, 3 chimpanzees and 2 white-handed gibbons), in catarrhine monkeys (1 hamadryas baboon, 2 anubid baboons, 10 savannah monkeys) and in platyrrhine monkeys (6 squirrel monkeys). The pancreas of the monkeys was supplied by the arteries originating from the celiac trunk and/or superior mesenteric artery. There were three patterns in the arterial distribution; (1) the celiac artery supplied the major area of the pancreas. (2) the superior mesenteric artery supplied the major area of the pancreas. (3) the celiac artery supplied the whole pancreas. The pattern of the arterial distribution to the monkey pancreas had a wide variety. The result would be helpful for the elucidation of the development of the vascular distribution in the pancreas.

Basics of kidney biopsy: A nephrologist's perspective

PubMed Central

Agarwal, S. K.; Sethi, S.; Dinda, A. K.

2013-01-01

The introduction of the kidney biopsy is one of the major events in the history of nephrology. Primary indications of kidney biopsy are glomerular hematuria/proteinuria with or without renal dysfunction and unexplained renal failure. Kidney biopsy is usually performed in prone position but in certain situations, supine and lateral positions may be required. Biopsy needles have changed with times from Vim–Silverman needle to Tru-cut needle to spring-loaded automatic gun. The procedure has also changed from blind bedside kidney biopsy to ultrasound marking to real-time ultrasound guidance to rarely computerized tomography guidance and laparoscopic and open biopsy. In very specific situations, transjugular kidney biopsy may be required. Most of the centers do kidney biopsy on short 1-day admission, whereas some take it as an outdoor procedure. For critical interpretation of kidney biopsy, adequate sample and clinical information are mandatory. Tissue needs to be stained with multiple stains for delineation of various components of kidney tissue. Many consider that electron microscopy (EM) is a must for all kidney biopsies, but facilities for EM are limited even in big centers. Sophisticated tests such as immunohistochemistry and in-situ hybridization are useful adjuncts for definitive diagnosis in certain situations. PMID:23960337

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

PubMed Central

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-01-01

Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

Evaluation of a mentorship program to support chronic kidney disease care.

PubMed

Pang, Jocelyn; Grill, Allan; Bhatt, Monisha; Woodward, Graham L; Brimble, Scott

2016-08-01

Primary care providers (PCPs) are ideally situated to detect and manage patients with chronic kidney disease (CKD), but they could use more support from nephrologists to accomplish this. To improve early detection and management of CKD in primary care, and improve referrals to nephrologists through education and greater partnership between nephrologists and PCPs. Nephrologists provided mentorship to PCPs in Ontario through a collaborative relationship. Nephrologists provided PCPs with educational orientation sessions and need-based advice on patient cases. Primary care providers with more than 5 years of experience were more likely to use the program. Primary care providers expressed high satisfaction with the program and reported that it was effective in supporting routine CKD screening efforts, management of early CKD, appropriate referrals, and building a collaborative relationship with nephrologists. Copyright© the College of Family Physicians of Canada.

Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model▿ †

PubMed Central

Lin, Philana Ling; Rodgers, Mark; Smith, Le'kneitah; Bigbee, Matthew; Myers, Amy; Bigbee, Carolyn; Chiosea, Ion; Capuano, Saverio V.; Fuhrman, Carl; Klein, Edwin; Flynn, JoAnne L.

2009-01-01

We previously described that low-dose Mycobacterium tuberculosis infection in cynomolgus macaques results in a spectrum of disease similar to that of human infection: primary disease, latent infection, and reactivation tuberculosis (S. V. Capuano III, D. A. Croix, S. Pawar, A. Zinovik, A. Myers, P. L. Lin, S. Bissel, C. Fuhrman, E. Klein, and J. L. Flynn, Infect. Immun. 71:5831-5844, 2003). This is the only established model of latent infection, and it provides a unique opportunity to understand host and pathogen differences across of range of disease states. Here, we provide a more extensive and detailed characterization of the gross pathology, microscopic histopathology, and immunologic characteristics of monkeys in each clinical disease category. The data underscore the similarities between human and nonhuman primate M. tuberculosis infection. Furthermore, we describe novel methods of quantifying gross pathology and bacterial burden that distinguish between active disease and latent infection, and we extend the usefulness of this model for comparative studies. Early in infection, an abnormal chest X ray, M. tuberculosis growth by gastric aspirate, and increased mycobacterium-specific gamma interferon (IFN-γ) in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells were associated with the development of active disease. At necropsy, disease was quantified with respect to pathology and bacterial numbers. Microscopically, a spectrum of granuloma types are seen and differ with disease type. At necropsy, monkeys with active disease had more lung T cells and more IFN-γ from PBMC, BAL, and mediastinal lymph nodes than monkeys with latent infection. Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis. PMID:19620341

A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (saimiri sciureus) based on diffusion tensor imaging

NASA Astrophysics Data System (ADS)

Gao, Yurui; Parvathaneni, Prasanna; Schilling, Kurt G.; Wang, Feng; Stepniewska, Iwona; Xu, Zhoubing; Choe, Ann S.; Ding, Zhaohua; Gore, John C.; Chen, Li min; Landman, Bennett A.; Anderson, Adam W.

2016-03-01

Modern magnetic resonance imaging (MRI) brain atlases are high quality 3-D volumes with specific structures labeled in the volume. Atlases are essential in providing a common space for interpretation of results across studies, for anatomical education, and providing quantitative image-based navigation. Extensive work has been devoted to atlas construction for humans, macaque, and several non-primate species (e.g., rat). One notable gap in the literature is the common squirrel monkey - for which the primary published atlases date from the 1960's. The common squirrel monkey has been used extensively as surrogate for humans in biomedical studies, given its anatomical neuro-system similarities and practical considerations. This work describes the continued development of a multi-modal MRI atlas for the common squirrel monkey, for which a structural imaging space and gray matter parcels have been previously constructed. This study adds white matter tracts to the atlas. The new atlas includes 49 white matter (WM) tracts, defined using diffusion tensor imaging (DTI) in three animals and combines these data to define the anatomical locations of these tracks in a standardized coordinate system compatible with previous development. An anatomist reviewed the resulting tracts and the inter-animal reproducibility (i.e., the Dice index of each WM parcel across animals in common space) was assessed. The Dice indices range from 0.05 to 0.80 due to differences of local registration quality and the variation of WM tract position across individuals. However, the combined WM labels from the 3 animals represent the general locations of WM parcels, adding basic connectivity information to the atlas.

Dorsal premotor cortex: neural correlates of reach target decisions based on a color-location matching rule and conflicting sensory evidence

PubMed Central

Coallier, Émilie; Michelet, Thomas

2015-01-01

We recorded single-neuron activity in dorsal premotor (PMd) and primary motor cortex (M1) of two monkeys in a reach-target selection task. The monkeys chose between two color-coded potential targets by determining which target's color matched the predominant color of a multicolored checkerboard-like Decision Cue (DC). Different DCs contained differing numbers of colored squares matching each target. The DCs provided evidence about the correct target ranging from unambiguous (one color only) to very ambiguous and conflicting (nearly equal number of squares of each color). Differences in choice behavior (reach response times and success rates as a function of DC ambiguity) of the monkeys suggested that each applied a different strategy for using the target-choice evidence in the DCs. Nevertheless, the appearance of the DCs evoked a transient coactivation of PMd neurons preferring both potential targets in both monkeys. Reach response time depended both on how long it took activity to increase in neurons that preferred the chosen target and on how long it took to suppress the activity of neurons that preferred the rejected target, in both correct-choice and error-choice trials. These results indicate that PMd neurons in this task are not activated exclusively by a signal proportional to the net color bias of the DCs. They are instead initially modulated by the conflicting evidence supporting both response choices; final target selection may result from a competition between representations of the alternative choices. The results also indicate a temporal overlap between action selection and action initiation processes in PMd and M1. PMID:25787952

Influence of experimental history on nicotine self-administration in squirrel monkeys.

PubMed

Desai, Rajeev I; Sullivan, Katherine A; Kohut, Stephen J; Bergman, Jack

2016-06-01

Methods for establishing robust long-term self-administration of intravenous (i.v.) nicotine, the primary psychoactive agent in tobacco, are not well-established in laboratory animals. Here, we examine the use of a fading procedure to establish robust and consistent i.v. nicotine self-administration under second-order schedule conditions in squirrel monkeys. First, self-administration behavior was developed in two groups of male squirrel monkeys using a second-order fixed-interval 5-min schedule with fixed-ratio 5 units (FI 5-min (FR5: S)). Comparable performances were maintained by i.v. cocaine (0.032 mg/kg/injection (inj); group A, n = 3) and the combination of food delivery (20-30 % condensed milk) and 0.01 mg/kg/inj i.v. nicotine (group B, n = 3). Subsequently, the concentration of condensed milk was gradually reduced to zero in the second group and self-administration behavior was maintained by i.v. nicotine alone. Next, self-administration of a range of doses of i.v. nicotine (0.001-0.032 mg/kg/inj) and, in additional experiments, the minor tobacco alkaloid anatabine (0.01-0.18 mg/kg/inj) was studied in both groups. Results show that nicotine and anatabine had reinforcing effects in both groups. However, optimal doses of nicotine and anatabine maintained significantly higher rates of i.v. self-administration behavior in subjects trained with the fading procedure than in subjects provided with a history of cocaine-maintained responding. These results illustrate conditions under which robust i.v. nicotine self-administration can be established in squirrel monkeys and the influence of prior experimental history in the expression of reinforcing effects of nicotine and anatabine.

A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (Saimiri sciureus) based on diffusion tensor imaging

PubMed Central

Gao, Yurui; Parvathaneni, Prasanna; Schilling, Kurt G.; Wang, Feng; Stepniewska, Iwona; Xu, Zhoubing; Choe, Ann S.; Ding, Zhaohua; Gore, John C.; Chen, Li Min; Landman, Bennett A.; Anderson, Adam W.

2016-01-01

Modern magnetic resonance imaging (MRI) brain atlases are high quality 3-D volumes with specific structures labeled in the volume. Atlases are essential in providing a common space for interpretation of results across studies, for anatomical education, and providing quantitative image-based navigation. Extensive work has been devoted to atlas construction for humans, macaque, and several non-primate species (e.g., rat). One notable gap in the literature is the common squirrel monkey – for which the primary published atlases date from the 1960’s. The common squirrel monkey has been used extensively as surrogate for humans in biomedical studies, given its anatomical neuro-system similarities and practical considerations. This work describes the continued development of a multi-modal MRI atlas for the common squirrel monkey, for which a structural imaging space and gray matter parcels have been previously constructed. This study adds white matter tracts to the atlas. The new atlas includes 49 white matter (WM) tracts, defined using diffusion tensor imaging (DTI) in three animals and combines these data to define the anatomical locations of these tracks in a standardized coordinate system compatible with previous development. An anatomist reviewed the resulting tracts and the inter-animal reproducibility (i.e., the Dice index of each WM parcel across animals in common space) was assessed. The Dice indices range from 0.05 to 0.80 due to differences of local registration quality and the variation of WM tract position across individuals. However, the combined WM labels from the 3 animals represent the general locations of WM parcels, adding basic connectivity information to the atlas. PMID:27064328

Neural effects of MDMA as determined by functional magnetic resonance imaging and magnetic resonance spectroscopy in awake marmoset monkeys.

PubMed

Meyer, Jerrold S; Brevard, Matthew E; Piper, Brian J; Ali, Syed F; Ferris, Craig F

2006-08-01

We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of a recreational dose (1 mg/kg p.o.) of 3,4-methylenedioxymethamphetamine (MDMA) on regional brain activity in awake, restrained marmoset monkeys. In a second study, magnetic resonance spectroscopy (MRS) and postmortem measurements of serotonin transporter (SERT) binding and serotonin (5-HT) concentrations were used to determine the neurotoxic effects of low (4 x 1 mg/kg p.o.) and high (4 x 10 mg/kg i.m.) doses of MDMA. Several brain areas were significantly activated by the low oral dose of MDMA, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit composed of the dorsal thalamus, sensory motor cortex, and basal ganglia. MDMA activated the primary visual cortex under baseline conditions and also enhanced the visual cortical response to photic stimulation. The onset of brain activation correlated well with the rise in plasma MDMA concentrations measured in separate monkeys given the same drug treatment. In the second study, the ratio of N-acetylaspartate (NAA; a putative neuronal marker) to creatine was significantly reduced in the hypothalamus following either MDMA treatment regimen, suggesting a particular vulnerability of this structure to MDMA-induced damage. Monkeys given the high-dose regimen also showed prolonged hyperthermia and reductions in 5-HT and SERT in a number of brain areas. These results are the first to identify the pattern of MDMA-induced brain activation in a nonhuman primate model, and they further suggest that even recreational doses of MDMA may have adverse consequences as indicated by the reduced hypothalamic NAA/creatine ratio.

A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (Saimiri sciureus) based on diffusion tensor imaging.

PubMed

Gao, Yurui; Parvathaneni, Prasanna; Schilling, Kurt G; Wang, Feng; Stepniewska, Iwona; Xu, Zhoubing; Choe, Ann S; Ding, Zhaohua; Gore, John C; Chen, Li Min; Landman, Bennett A; Anderson, Adam W

2016-02-27

Modern magnetic resonance imaging (MRI) brain atlases are high quality 3-D volumes with specific structures labeled in the volume. Atlases are essential in providing a common space for interpretation of results across studies, for anatomical education, and providing quantitative image-based navigation. Extensive work has been devoted to atlas construction for humans, macaque, and several non-primate species (e.g., rat). One notable gap in the literature is the common squirrel monkey - for which the primary published atlases date from the 1960's. The common squirrel monkey has been used extensively as surrogate for humans in biomedical studies, given its anatomical neuro-system similarities and practical considerations. This work describes the continued development of a multi-modal MRI atlas for the common squirrel monkey, for which a structural imaging space and gray matter parcels have been previously constructed. This study adds white matter tracts to the atlas. The new atlas includes 49 white matter (WM) tracts, defined using diffusion tensor imaging (DTI) in three animals and combines these data to define the anatomical locations of these tracks in a standardized coordinate system compatible with previous development. An anatomist reviewed the resulting tracts and the inter-animal reproducibility (i.e., the Dice index of each WM parcel across animals in common space) was assessed. The Dice indices range from 0.05 to 0.80 due to differences of local registration quality and the variation of WM tract position across individuals. However, the combined WM labels from the 3 animals represent the general locations of WM parcels, adding basic connectivity information to the atlas.

Cortical and subcortical connections of V1 and V2 in early postnatal macaque monkeys.

PubMed

Baldwin, Mary K L; Kaskan, Peter M; Zhang, Bin; Chino, Yuzo M; Kaas, Jon H

2012-02-15

Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age. Copyright © 2011 Wiley-Liss, Inc.

Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage

PubMed Central

Kiland, Julie A.; Gabelt, B’Ann T.; Tezel, Gülgün; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 ± 6.0%; P ≤ .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm’s canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies. PMID:20126491

Context cue-dependent saccadic adaptation in rhesus macaques cannot be elicited using color

PubMed Central

Smalianchuk, Ivan; Khanna, Sanjeev B.; Smith, Matthew A.; Gandhi, Neeraj J.

2015-01-01

When the head does not move, rapid movements of the eyes called saccades are used to redirect the line of sight. Saccades are defined by a series of metrical and kinematic (evolution of a movement as a function of time) relationships. For example, the amplitude of a saccade made from one visual target to another is roughly 90% of the distance between the initial fixation point (T0) and the peripheral target (T1). However, this stereotypical relationship between saccade amplitude and initial retinal error (T1-T0) may be altered, either increased or decreased, by surreptitiously displacing a visual target during an ongoing saccade. This form of motor learning (called saccadic adaptation) has been described in both humans and monkeys. Recent experiments in humans and monkeys have suggested that internal (proprioceptive) and external (target shape, color, and/or motion) cues may be used to produce context-dependent adaptation. We tested the hypothesis that an external contextual cue (target color) could be used to evoke differential gain (actual saccade/initial retinal error) states in rhesus monkeys. We did not observe differential gain states correlated with target color regardless of whether targets were displaced along the same vector as the primary saccade or perpendicular to it. Furthermore, this observation held true regardless of whether adaptation trials using various colors and intrasaccade target displacements were randomly intermixed or presented in short or long blocks of trials. These results are consistent with hypotheses that state that color cannot be used as a contextual cue and are interpreted in light of previous studies of saccadic adaptation in both humans and monkeys. PMID:25995353

Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected Donors to Noninfected Recipients: An Open-Label Nonrandomized Trial.

PubMed

Durand, Christine M; Bowring, Mary G; Brown, Diane M; Chattergoon, Michael A; Massaccesi, Guido; Bair, Nichole; Wesson, Russell; Reyad, Ashraf; Naqvi, Fizza F; Ostrander, Darin; Sugarman, Jeremy; Segev, Dorry L; Sulkowski, Mark; Desai, Niraj M

2018-04-17

Given the high mortality rate for patients with end-stage kidney disease receiving dialysis and the efficacy and safety of hepatitis C virus (HCV) treatments, discarded kidneys from HCV-infected donors may be a neglected public health resource. To determine the tolerability and feasibility of using direct-acting antivirals (DAAs) as prophylaxis before and after kidney transplantation from HCV-infected donors to non-HCV-infected recipients (that is, HCV D+/R- transplantation). Open-label nonrandomized trial. (ClinicalTrials.gov: NCT02781649). Single center. 10 HCV D+/R- kidney transplant candidates older than 50 years with no available living donors. Transplantation of kidneys from deceased donors aged 13 to 50 years with positive HCV RNA and HCV antibody test results. All recipients received a dose of grazoprevir (GZR), 100 mg, and elbasvir (EBR), 50 mg, immediately before transplantation. Recipients of kidneys from donors with genotype 1 infection continued receiving GZR-EBR for 12 weeks after transplantation; those receiving organs from donors with genotype 2 or 3 infection had sofosbuvir, 400 mg, added to GZR-EBR for 12 weeks of triple therapy. The primary safety outcome was the incidence of adverse events related to GZR-EBR treatment. The primary efficacy outcome was the proportion of recipients with an HCV RNA level below the lower limit of quantification 12 weeks after prophylaxis. Among 10 HCV D+/R- transplant recipients, no treatment-related adverse events occurred, and HCV RNA was not detected in any recipient 12 weeks after treatment. Nonrandomized study design and a small number of patients. Pre- and posttransplantation HCV treatment was safe and prevented chronic HCV infection in HCV D+/R- kidney transplant recipients. If confirmed in larger studies, this strategy should markedly expand organ options and reduce mortality for kidney transplant candidates without HCV infection. Merck Sharp & Dohme.

What interests them in the pictures?--differences in eye-tracking between rhesus monkeys and humans.

PubMed

Hu, Ying-Zhou; Jiang, Hui-Hui; Liu, Ci-Rong; Wang, Jian-Hong; Yu, Cheng-Yang; Carlson, Synnöve; Yang, Shang-Chuan; Saarinen, Veli-Matti; Rizak, Joshua D; Tian, Xiao-Guang; Tan, Hen; Chen, Zhu-Yue; Ma, Yuan-Ye; Hu, Xin-Tian

2013-10-01

Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a picture. In the current study, three sets of pictures containing monkeys, humans or both were presented to rhesus monkeys and humans. The eye movements on these pictures by the two species were recorded using a Tobii eye-tracking system. We found that monkeys paid more attention to the head and body in pictures containing monkeys, whereas both monkeys and humans paid more attention to the head in pictures containing humans. The humans always concentrated on the eyes and head in all the pictures, indicating the social role of facial cues in society. Although humans paid more attention to the hands than monkeys, both monkeys and humans were interested in the hands and what was being done with them in the pictures. This may suggest the importance and necessity of hands for survival. Finally, monkeys scored lower in eye-tracking when fixating on the pictures, as if they were less interested in looking at the screen than humans. The locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys.

PubMed

Czoty, P W; Gould, R W; Gage, H D; Nader, M A

2017-09-01

Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus.

PubMed

Joshi, Anand C; Das, Vallabh E

2013-10-01

Previously, we showed that neurons in the supraoculomotor area (SOA), known to encode vergence angle in normal monkeys, encode the horizontal eye misalignment in strabismic monkeys. The SOA receives afferent projections from the caudal fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the cerebellum. The objectives of the present study were to investigate the potential roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye alignment in strabismic monkeys. We used unilateral injections of the GABAA agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic monkey S1 with ≈ 4° of exotropia; 5 injections in esotropic monkey S2 with ≈ 34° of esotropia) and the PIN (3 injections in monkey S1). cFN inactivation induced horizontal saccade dysmetria in all experiments (mean 39% increase in ipsilesional saccade gain and 26% decrease in contralesional gain). Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN inactivation induced a divergent change in eye alignment in both monkeys, with exotropia increasing by an average of 9.8° in monkey S1 and esotropia decreasing by an average of 11.2° in monkey S2 (P < 0.001). Unilateral PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward saccades by 13% and also induced a convergent change in eye alignment, reducing exotropia by an average of 2.7° (P < 0.001). We conclude that cFN/PIN influences on conjugate eye movements in strabismic monkeys are similar to those postulated in normal monkeys and cFN/PIN play important and complementary roles in maintaining the steady-state misalignment in strabismus.

Kidneys at Higher Risk of Discard: Expanding the Role of Dual Kidney Transplantation

PubMed Central

Tanriover, B.; Mohan, S.; Cohen, D. J.; Radhakrishnan, J.; Nickolas, T. L.; Stone, P. W.; Tsapepas, D. S.; Crew, R. J.; Dube, G. K.; Sandoval, P. R.; Samstein, B.; Dogan, E.; Gaston, R. S.; Tanriover, J. N.; Ratner, L. E.; Hardy, M. A.

2014-01-01

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) >85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80–90% and >90%). Kidneys with KDPI >90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74–2.29) compared to ones with KDPI <80%. DKTs of KDPI >90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62–0.89) and better patient survival (HR = 0.79, 95% CI 0.64–0.98) compared to single ECD kidneys with KDPI >90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile. PMID:24472195

Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney

PubMed Central

Chertow, Glenn M.; Hebbar, Sudarshan; Vaziri, Nosratola D.; Ward, Keith W.; Meyer, Colin J.

2012-01-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2–related factor 2 (Nrf2)–mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl–induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl–induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets. PMID:22859857

Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.

PubMed

Reisman, Scott A; Chertow, Glenn M; Hebbar, Sudarshan; Vaziri, Nosratola D; Ward, Keith W; Meyer, Colin J

2012-10-01

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.

Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.

PubMed

Ezzelarab, M B; Zahorchak, A F; Lu, L; Morelli, A E; Chalasani, G; Demetris, A J; Lakkis, F G; Wijkstrom, M; Murase, N; Humar, A; Shapiro, R; Cooper, D K C; Thomson, A W

2013-08-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5-10 × 10(6) /kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on Day -2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n = 6) and 113.5 days (p < 0.05) in DCreg-treated animals (n = 6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95(+) T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further preclinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

PubMed Central

Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

2014-01-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (p< 0.05) in DCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. PMID:23758811

Haematuria as an uncommon initial presenting symptom of metastatic squamous cell carcinoma (SCC) to kidney

PubMed Central

Kawsar, Hameem I; Spiro, Timothy P; Daw, Hamed A

2011-01-01

A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney. PMID:22688475

SOME EVIDENCE OF PSYCHIC BLINDNESS IN MONKEYS WITH FOCAL-HEAD IRRADIATION OF THE TEMPORAL LOBES

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDowell, A.A.; Brown, W.L.

1963-12-01

This study was conducted to compare the effects of various extra-cage social stimuli on the free-cage behavior of normal monkeys and of monkeys with previous focal-head irradiation. Four control and four focal-head irradiated monkeys with nearly identical training histories were used, the latter being the survivors of a focal-head irradiation study conducted 41/2 yr earlier. They had received 3000 r x radiation to an area of the head containing the inferior parietal lobule and posterior aspect of the temporal lobe, and repeated 30 days later Each group was systematically observed under each of four socialstimulus conditions with the order ofmore » condition presentation counterbalanced within each group over a 4-day period. The four social-stimulus conditions included: absence of social stimulus, an adult male monkey, an adult female monkey at menses, and an adult female monkey at estimated time of ovulation. The socialstimulus conditions showed no effect on the nondirected activities of the normal monkeys, but produced a marked decrease in the nondirected activities of the focal-head irradiated monkeys, with the least number of such activities being manifest in the presence of the adult female monkey at ovulation. Under conditions of social stimulation the normal monkeys showed a marked decrease in total directed activities of the non-social-stimulus condition, while the focal-head irradiated monkeys showed a marked increase, the effect in each instance being greatest in the presence of the female at ovulation. The directed activities, toward the cage as an object, of the controls decreasrd and those of the experimental subjects increased. The controls were more than twice as responsive to the female at estimated time of ovulation as to the other two social stimuli, while the experimental monkeys were equally responsive to each of the three social stimuli. The data suggest the presence of psychic blindness in the monkeys previously exposed to focal-head irradiation of the temporal lobes. (BBB)« less

Trends in serum creatinine testing in Oxfordshire, UK, 1993-2013: a population-based cohort study.

PubMed

Oke, Jason; Shine, Brian; McFadden, Emily; Stevens, Richard; Lasserson, Daniel; Perera, Rafael

2015-12-16

To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time. Retrospective study of all serum creatinine, urine albumin and urine creatinine tests. Primary and secondary care in Oxfordshire from 1993 to 2013. Unselected population of 1,220,447 people. The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored. Creatinine requests from primary care increased steadily from 1997 and exceeded 220,000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m(2)) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3-5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year. There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Early adaptation to altered gravitational environments in the squirrel monkey

NASA Technical Reports Server (NTRS)

Fuller, C. A.

1985-01-01

The feeding behavior of two squirrel monkeys flown in Spacelab 3 is compared to that of six monkeys exposed to 1.5 G through centrifugation. The monkeys in the centrifugation study were housed unrestrained in cages, maintained at 25 C + or - 1 C, exposed to a 12:12 light/dark cycle, and had unrestrained access to food and water. The Spacelab monkeys were maintained at 26 C, exposed to a 12:12 light/dark cycle and had unlimited food and water. It is observed that the centrifuge rats displayed a change in feeding behavior for 4 days prior to resuming a normal pattern; one Spacelab monkey exhibited a 6 day depression before recover to control levels, and the feeding pattern of the second monkey was not influenced by the environment. It is noted that the effect of an altered dynamic environment is variable on the feeding behavior of individual monkeys.

Embryotrophic factor-3 from human oviductal cells affects the messenger RNA expression of mouse blastocyst.

PubMed

Lee, Y L; Lee, K F; Xu, J S; Kwok, K L; Luk, J M; Lee, W M; Yeung, W S B

2003-02-01

Our previous results showed that embryotrophic factor-3 (ETF-3) from human oviductal cells increased the size and hatching rate of mouse blastocysts in vitro. The present study investigated the production of ETF-3 by an immortalized human oviductal cell line (OE-E6/E7) and the effects of ETF-3 on the mRNA expression of mouse embryos. The ETF-3 was purified from primary oviductal cell conditioned media using sequential liquid chromatographic systems, and antiserum against ETF-3 was raised. The ETF-3-supplemented Chatot-Ziomek-Bavister medium was used to culture Day 1 MF1 x BALB/c mouse embryos for 4 days. The ETF-3 treatment significantly enhanced the mouse embryo blastulation and hatching rate. The antiserum, at concentrations of 0.03-3%, abolished the embryotrophic effect of ETF-3. Positive ETF-3 immunoreactivity was detected in the primary oviductal cells, OE-E6/E7, and blastocysts derived from ETF-3 treatment. Vero cells (African Green Monkey kidney cell line), fibroblasts, and embryos cultured in control medium did not possess ETF-3 immunoreactivity. The mRNA expression patterns of the treated embryos were studied at the blastocyst stage by mRNA differential display reverse transcription-polymerase chain reaction (DDRT-PCR). The DDRT-PCR showed that some of the mRNAs were differentially expressed after ETF-3 treatment. Twelve of the differentially expressed mRNAs that had high homology with cDNA sequences in the GenBank were selected for further characterization. The differential expression of seven of these mRNAs (ezrin, heat shock 70-kDa protein, cytochrome c oxidase subunit VIIa-L precursor, proteinase-activated receptor 2, eukaryotic translation initiation factor 2beta, cullin 1, and proliferating cell nuclear antigen) was confirmed by semiquantitative RT-PCR. In conclusion, immortalized oviductal cells produce ETF-3, which influences mRNA expression of mouse blastocyst.

Increasing the supply of kidneys for transplantation by making living donors the preferred source of donor kidneys.

PubMed

Testa, Giuliano; Siegler, Mark

2014-12-01

At the present time, increasing the use of living donors offers the best solution to the organ shortage problem. The clinical questions raised when the first living donor kidney transplant was performed, involving donor risk, informed consent, donor protection, and organ quality, have been largely answered. We strongly encourage a wider utilization of living donation and recommend that living donation, rather than deceased donation, become the first choice for kidney transplantation. We believe that it is ethically sound to have living kidney donation as the primary source for organs when the mortality and morbidity risks to the donor are known and kept extremely low, when the donor is properly informed and protected from coercion, and when accepted national and local guidelines for living donation are followed.

Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

NASA Technical Reports Server (NTRS)

Sato, N.; Kiuchi, K.; Shen, Y. T.; Vatner, S. F.; Vatner, D. E.

1995-01-01

To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

EXPERIMENTS ON THE TRANSMISSION OF SCARLET FEVER TO THE LOWER MONKEYS

PubMed Central

Draper, George; Hanford, John M.

1913-01-01

1. The reported successful transfer of scarlet fever to both higher and lower monkeys is not definitely established. 2. In the course of the experiments here reported, the infectious agent can be assumed to have been carried over to the monkeys. The failure to cause infection probably proceeds from the insusceptibility of the monkeys employed, or to the manner of introducing the agent. 3. The temperature curve and leucocyte count of monkeys are unsatisfactory criteria for the diagnosis of disease in those animals. 4. Monkeys frequently have transient blotchy, erythematous eruptions on the face and neck, and almost always a bran-like desquamation. 5. Monkeys are highly resistant to infection with microorganisms from human beings. PMID:19867663

Humans and monkeys use different strategies to solve the same short-term memory tasks.

PubMed

Wittig, John H; Morgan, Barak; Masseau, Evan; Richmond, Barry J

2016-11-01

The neural mechanisms underlying human working memory are often inferred from studies using old-world monkeys. Humans use working memory to selectively memorize important information. We recently reported that monkeys do not seem to use selective memorization under experimental conditions that are common in monkey research, but less common in human research. Here we compare the performance of humans and monkeys under the same experimental conditions. Humans selectively remember important images whereas monkeys largely rely on recency information from nonselective memorization. Working memory studies in old-world monkeys must be interpreted cautiously when making inferences about the mechanisms underlying human working memory. © 2016 Wittig, et al.; Published by Cold Spring Harbor Laboratory Press.

Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

PubMed

Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

2015-01-01

Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

PubMed

Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

2014-01-01

Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

Active tactile exploration using a brain-machine-brain interface.

PubMed

O'Doherty, Joseph E; Lebedev, Mikhail A; Ifft, Peter J; Zhuang, Katie Z; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A L

2011-10-05

Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses.

TNF neutralization results in disseminated disease during acute and latent M. tuberculosis infection with normal granuloma structure

PubMed Central

Lin, Philana Ling; Myers, Amy; Smith, Le’Kneitah; Bigbee, Carolyn; Bigbee, Matthew; Fuhrman, Carl; Grieser, Heather; Chiosea, Ion; Voitenek, Nikolai N.; Capuano, Saverio V.; Klein, Edwin; Flynn, JoAnne L.

2010-01-01

An increased risk of tuberculosis has been documented in humans treated with tumor necrosis factor alpha (TNF) neutralizing agents. In murine models, impaired signaling by TNF caused exacerbation of both acute and chronic infection associated with aberrant granuloma formation and maintenance. The non-human primate model of tuberculosis provides an opportunity to study immune modulation in the setting of TNF neutralization during primary and latent tuberculosis. Administration of TNF neutralizing agents prior to M. tuberculosis infection resulted in fulminant and disseminated disease by 8 weeks post-infection. Neutralization of TNF in latently infected cynomolgus macaques caused reactivation in a majority of animals as determined by gross pathology and bacterial burden. A spectrum of dissemination was noted including extrapulmonary disease. Surprisingly, monkeys who developed primary and reactivation tuberculosis after TNF neutralization had similar granuloma structure and composition compared to active control monkeys. TNF neutralization was associated with increased IL-12, decreased CCL4, increased chemokine receptor expression and reduced mycobacteria-specific IFN-γ production in blood but not to the affected mediastinal lymph nodes. Finally, the first signs of reactivation often occurred in thoracic lymph nodes. These findings have important clinical implications for determining the mechanism of TNF-neutralization-related tuberculosis. PMID:20112395

Cortical Correlates of Fitts’ Law

PubMed Central

Ifft, Peter J.; Lebedev, Mikhail A.; Nicolelis, Miguel A. L.

2011-01-01

Fitts’ law describes the fundamental trade-off between movement accuracy and speed: it states that the duration of reaching movements is a function of target size (TS) and distance. While Fitts’ law has been extensively studied in ergonomics and has guided the design of human–computer interfaces, there have been few studies on its neuronal correlates. To elucidate sensorimotor cortical activity underlying Fitts’ law, we implanted two monkeys with multielectrode arrays in the primary motor (M1) and primary somatosensory (S1) cortices. The monkeys performed reaches with a joystick-controlled cursor toward targets of different size. The reaction time (RT), movement time, and movement velocity changed with TS, and M1 and S1 activity reflected these changes. Moreover, modifications of cortical activity could not be explained by changes of movement parameters alone, but required TS as an additional parameter. Neuronal representation of TS was especially prominent during the early RT period where it influenced the slope of the firing rate rise preceding movement initiation. During the movement period, cortical activity was correlated with movement velocity. Neural decoders were applied to simultaneously decode TS and motor parameters from cortical modulations. We suggest that sensorimotor cortex activity reflects the characteristics of both the movement and the target. Classifiers that extract these parameters from cortical ensembles could improve neuroprosthetic control. PMID:22275888

Simultaneous recordings from the primary visual cortex and lateral geniculate nucleus reveal rhythmic interactions and a cortical source for γ-band oscillations.

PubMed

Bastos, Andre M; Briggs, Farran; Alitto, Henry J; Mangun, George R; Usrey, W Martin

2014-05-28

Oscillatory synchronization of neuronal activity has been proposed as a mechanism to modulate effective connectivity between interacting neuronal populations. In the visual system, oscillations in the gamma-frequency range (30-100 Hz) are thought to subserve corticocortical communication. To test whether a similar mechanism might influence subcortical-cortical communication, we recorded local field potential activity from retinotopically aligned regions in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) of alert macaque monkeys viewing stimuli known to produce strong cortical gamma-band oscillations. As predicted, we found robust gamma-band power in V1. In contrast, visual stimulation did not evoke gamma-band activity in the LGN. Interestingly, an analysis of oscillatory phase synchronization of LGN and V1 activity identified synchronization in the alpha (8-14 Hz) and beta (15-30 Hz) frequency bands. Further analysis of directed connectivity revealed that alpha-band interactions mediated corticogeniculate feedback processing, whereas beta-band interactions mediated geniculocortical feedforward processing. These results demonstrate that although the LGN and V1 display functional interactions in the lower frequency bands, gamma-band activity in the alert monkey is largely an emergent property of cortex. Copyright © 2014 the authors 0270-6474/14/347639-06$15.00/0.

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

PubMed

Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae)

PubMed Central

Schelegle, Edward S.; Gershwin, Laurel J.; Miller, Lisa A.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan P.; Walby, William F.; Omlor, Amanda M.; Buckpitt, Alan R.; Tarkington, Brian K.; Wong, Viviana J.; Joad, Jesse P.; Pinkerton, Kent B.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4+ lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA. PMID:11141508

How do primary care doctors in England and Wales code and manage people with chronic kidney disease? Results from the National Chronic Kidney Disease Audit.

PubMed

Kim, Lois G; Cleary, Faye; Wheeler, David C; Caplin, Ben; Nitsch, Dorothea; Hull, Sally A

2017-10-16

In the UK, primary care records are electronic and require doctors to ascribe disease codes to direct care plans and facilitate safe prescribing. We investigated factors associated with coding of chronic kidney disease (CKD) in patients with reduced kidney function and the impact this has on patient management. We identified patients meeting biochemical criteria for CKD (two estimated glomerular filtration rates <60 mL/min/1.73 m2 taken >90 days apart) from 1039 general practitioner (GP) practices in a UK audit. Clustered logistic regression was used to identify factors associated with coding for CKD and improvement in coding as a result of the audit process. We investigated the relationship between coding and five interventions recommended for CKD: achieving blood pressure targets, proteinuria testing, statin prescription and flu and pneumococcal vaccination. Of 256 000 patients with biochemical CKD, 30% did not have a GP CKD code. Males, older patients, those with more severe CKD, diabetes or hypertension or those prescribed statins were more likely to have a CKD code. Among those with continued biochemical CKD following audit, these same characteristics increased the odds of improved coding. Patients without any kidney diagnosis were less likely to receive optimal care than those coded for CKD [e.g. odds ratio for meeting blood pressure target 0.78 (95% confidence interval 0.76-0.79)]. Older age, male sex, diabetes and hypertension are associated with coding for those with biochemical CKD. CKD coding is associated with receiving key primary care interventions recommended for CKD. Increased efforts to incentivize CKD coding may improve outcomes for CKD patients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Primary vesicoureteral reflux: A 26-year experience in a single centre.

PubMed

Vachvanichsanong, Prayong; Dissaneewate, Pornsak; McNeil, Edward

2016-04-01

To determine the nature of primary vesicoureteral reflux (VUR) and the association of VUR with hydronephrosis and renal damage. The medical records of children ≤ 15 years diagnosed with VUR, attending the Department of Pediatrics, Prince of Songkla University, Thailand between 1987 and 2013 were reviewed. Renal ultrasound and technetium-99m dimercaptosuccinic acid renal scan (DMSA) results were examined to determine the severity of hydronephrosis and renal damage, respectively. There were 177 boys and 211 girls. 350 (90.2%) were diagnosed following urinary tract infection (UTI). The median (IQR) age at diagnosis of first VUR was 7.6 (4.3-12.2) months in boys and 18.6 (9.0-46.6) months in girls (P < 0.001). Renal ultrasound was performed in 340 patients. Hydronephrosis was found in 105 patients and 135 kidneys and 22.5% VUR kidneys and 11.0% non-VUR kidneys (P = 0.01). The severity of hydronephrosis was associated with VUR grade (44.2% of grades IV and V VUR had hydronephrosis vs 11.9% of grades I-III VUR, P < 0.001). DMSA was performed in 332 patients. Abnormalities were found in 30.1% VUR kidneys and 4.1% non-VUR kidneys (P < 0.001). Abnormal DMSA results were strongly associated with VUR grade (17.8% for VUR grades I-III vs 60.5% for VUR grades IV and V, P < 0.001). Primary VUR in this group was most commonly diagnosed following investigation of UTI and detected during infancy, earlier in boys. Hydronephrosis and renal damage were associated with severity of VUR. © 2015 Asian Pacific Society of Nephrology.

Attitudes toward kidney donation.

PubMed Central

Aghanwa, H. S.; Akinsola, A.; Akinola, D. O.; Makanjuola, R. O. A.

2003-01-01

The Renal Unit of Obafemi Awolowo University Teaching Hospital Ile-Ife in Southwest Nigeria intends commencing a kidney transplantation program. This cross-sectional study aimed at examining the willingness of Nigerians to be living-related kidney donors. Three hundred and sixteen Nigerians (96 first-degree relatives of end-stage renal disease patients, 69 rural dwellers and 151 health workers) were interviewed regarding their willingness to donate kidneys using an interview schedule designed to elicit socio-demographic information, knowledge about kidney transplantation and attitude toward kidney donation. Sixty-two percent of health workers, 52.1% of the patients' relatives and 27.1% of rural dwellers expressed willingness to donate. Higher proportions of health workers and patients' relatives--compared with the rural dwellers--were willing to donate a kidney to their children, full-siblings and parents (P<0.05). The level of awareness about kidney transplantation was highest among health workers and least among rural dwellers (P<0.001). Altruism was the primary motivation for those willing to donate a kidney. The most important reason for refusal to donate was fear of adverse health consequences. Among the rural dwellers, never-married persons were more willing than the married to donate (P<0.05). Programs aimed at increasing awareness about the safety of kidney donation, reducing adverse beliefs about kidney donation, and encouraging altruistic tendencies will increase the availability of kidney donors. PMID:12934871

Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.

PubMed

Pavkov, Meda E; Harding, Jessica L; Burrows, Nilka R

2018-03-16

Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Mild Perceptual Categorization Deficits Follow Bilateral Removal of Anterior Inferior Temporal Cortex in Rhesus Monkeys.

PubMed

Matsumoto, Narihisa; Eldridge, Mark A G; Saunders, Richard C; Reoli, Rachel; Richmond, Barry J

2016-01-06

In primates, visual recognition of complex objects depends on the inferior temporal lobe. By extension, categorizing visual stimuli based on similarity ought to depend on the integrity of the same area. We tested three monkeys before and after bilateral anterior inferior temporal cortex (area TE) removal. Although mildly impaired after the removals, they retained the ability to assign stimuli to previously learned categories, e.g., cats versus dogs, and human versus monkey faces, even with trial-unique exemplars. After the TE removals, they learned in one session to classify members from a new pair of categories, cars versus trucks, as quickly as they had learned the cats versus dogs before the removals. As with the dogs and cats, they generalized across trial-unique exemplars of cars and trucks. However, as seen in earlier studies, these monkeys with TE removals had difficulty learning to discriminate between two simple black and white stimuli. These results raise the possibility that TE is needed for memory of simple conjunctions of basic features, but that it plays only a small role in generalizing overall configural similarity across a large set of stimuli, such as would be needed for perceptual categorical assignment. The process of seeing and recognizing objects is attributed to a set of sequentially connected brain regions stretching forward from the primary visual cortex through the temporal lobe to the anterior inferior temporal cortex, a region designated area TE. Area TE is considered the final stage for recognizing complex visual objects, e.g., faces. It has been assumed, but not tested directly, that this area would be critical for visual generalization, i.e., the ability to place objects such as cats and dogs into their correct categories. Here, we demonstrate that monkeys rapidly and seemingly effortlessly categorize large sets of complex images (cats vs dogs, cars vs trucks), surprisingly, even after removal of area TE, leaving a puzzle about how this generalization is done. Copyright © 2016 the authors 0270-6474/16/360043-11$15.00/0.

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

PubMed

Schoenfeld, Heidi A; West, Tim; Verghese, Philip B; Holubasch, Mary; Shenoy, Neeta; Kagan, David; Buono, Chiara; Zhou, Wei; DeCristofaro, Marc; Douville, Julie; Goodrich, Geoffrey G; Mansfield, Keith; Saravanan, Chandra; Cumin, Frederic; Webb, Randy L; Bateman, Randall J

2017-05-15

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC (0-24h) ) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Germline transmission in transgenic Huntington's disease monkeys.

PubMed

Moran, Sean; Chi, Tim; Prucha, Melinda S; Ahn, Kwang Sung; Connor-Stroud, Fawn; Jean, Sherrie; Gould, Kenneth; Chan, Anthony W S

2015-07-15

Transgenic nonhuman primate models are an increasingly popular model for neurologic and neurodegenerative disease because their brain functions and neural anatomies closely resemble those of humans. Transgenic Huntington's disease monkeys (HD monkeys) developed clinical features similar to those seen in HD patients, making the monkeys suitable for a preclinical study of HD. However, until HD monkey colonies can be readily expanded, their use in preclinical studies will be limited. In the present study, we confirmed germline transmission of the mutant huntingtin (mHTT) transgene in both embryonic stem cells generated from three male HD monkey founders (F0) and in second-generation offspring (F1) produced via artificial insemination by using intrauterine insemination technique. A total of five offspring were produced from 15 females that were inseminated by intrauterine insemination using semen collected from the three HD founders (5 of 15, 33%). Thus far, sperm collected from the HD founder (rHD8) has led to two F1 transgenic HD monkeys with germline transmission rate at 100% (2 of 2). mHTT expression was confirmed by quantitative real-time polymerase chain reaction using skin fibroblasts from the F1 HD monkeys and induced pluripotent stem cells established from one of the F1 HD monkeys (rHD8-2). Here, we report the stable germline transmission and expression of the mHTT transgene in HD monkeys, which suggest possible expansion of HD monkey colonies for preclinical and biomedical research studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

PubMed Central

Perez-Gomez, Maria Vanessa; Sanchez-Niño, Maria Dolores; Sanz, Ana Belen; Martín-Cleary, Catalina; Ruiz-Ortega, Marta; Egido, Jesus; Navarro-González, Juan F.; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

2015-01-01

Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail. PMID:26239562

Metabolism and Tissue Distribution of Orally Administered Trichloroethylene in Male and Female Rats: Identification of Glutathione- and Cytochrome P450-Derived Metabolites in Liver, Kidney, Blood and Urine

PubMed Central

Lash, Lawrence H.; Putt, David A.; Parker, Jean C.

2006-01-01

Male and female Fischer 344 rats were administered trichloroethylene (TRI) (2, 5, or 15 mmol/kg body weight) in corn oil by oral gavage and TRI and its metabolites were measured at times up to 48 hr in liver, kidney, blood, and urine. We tested the hypothesis that sex-dependent differences in distribution and metabolism of TRI could help explain differences in toxicity. Higher levels of TRI were generally observed in tissues of males. A biphasic pattern of TRI concentration was observed in liver, kidney, and blood of both males and females, consistent with enterohepatic recirculation. Higher concentrations of cytochrome P450 (P450)-derived metabolites (chloral hydrate, trichloroacetate, trichloroethanol) were observed in livers of males than in livers of females whereas the opposite pattern was observed in kidneys. Chloral hydrate was the primary P450-derived metabolite in blood and urine of males whereas trichloroacetate was the primary P450-derived metabolite in blood and urine of females. S-(1,2-Dichlorovinyl)glutathione (DCVG) was recovered in liver and kidney of female rats only and in blood of both male and female rats, with generally higher amounts found in females. S-(1,2-Dichlorovinyl)-l-cysteine (DCVC), the penultimate nephrotoxic metabolite, was recovered in male and female liver, female kidney, male blood, and in urine of both males and females. The results demonstrate sex-dependent differences in recovery of key metabolites of TRI that may help explain differences in susceptibility to TRI-induced toxicity with both the liver and kidney as target organs. PMID:16754541

[Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

PubMed

Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

2014-02-26

Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist.

Efficacy of an Adenovirus-based Anti-cocaine Vaccine to Reduce Cocaine Self-administration and Reacqusition using a Choice Procedure in Rhesus Macaques

PubMed Central

Evans, Suzette M.; Foltin, Richard W.; Hicks, Martin J.; Rosenberg, Jonathan B.; De, Bishnu P.; Janda, Kim D.; Kaminsky, Stephen M.; Crystal, Ronald G.

2016-01-01

Immunopharmacotherapy offers an approach for treating cocaine abuse by specifically targeting the cocaine molecule and preventing its access to the CNS. dAd5GNE is a novel cocaine vaccine that attenuates the stimulant and the reinforcing effects of cocaine in rats. The goal of this study was to extend and validate dAd5GNE vaccine efficacy in non-human primates. Six experimentally naïve adult female rhesus monkeys (Macaca mulatta) were trained to self-administer 0.1 mg/kg/injection intravenous (i.v.) cocaine or receive candy; then 4 monkeys were administered the vaccine and 2 monkeys were administered vehicle intramuscularly, with additional vaccine boosts throughout the study. The reinforcing effects of cocaine were measured during self-administration, extinction, and reacquisition (relapse) phases. Serum antibody titers in the vaccinated monkeys remained high throughout the study. There was no change in the preference for cocaine over candy over a 20-week period in 5 of the 6 monkeys; only one of the 4 (25%) vaccinated monkeys showed a decrease in cocaine choice. All 6 monkeys extinguished responding for cocaine during saline extinction testing; vaccinated monkeys tended to take longer to extinguish responding than control monkeys (17.5 vs. 7.0 sessions). Vaccination substantially retarded reacquisition of cocaine self-administration; control monkeys resumed cocaine self-administration within 6–41 sessions and 1 vaccinated monkey resumed cocaine self-administration in 19 sessions. The other 3 vaccinated monkeys required between 57–94 sessions to resume cocaine self-administration even in the context of employing several manipulations to encourage cocaine reacquisition. These data suggest that the dAdGNE vaccine may have therapeutic potential for humans who achieve cocaine abstinence as part of a relapse prevention strategy. PMID:27697554

Cup tool use by squirrel monkeys.

PubMed

Buckmaster, Christine L; Hyde, Shellie A; Parker, Karen J; Lyons, David M

2015-12-01

Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool use technique to Contain (i.e., hold and control) food they reduced into fragments for consumption and to Contain water collected from a valve to drink. Food cup use was observed more frequently than water cup use. Observations indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also used a cup to Contain water. Cup use was optional and did not replace, but supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by all members of the population. Strategies monkeys used to bring food and cups together for food processing activity at preferred upper-level perching areas, in the arboreal-like environment in which they lived, provides evidence that monkeys may plan food processing activity with the cups. Specifically, prior to cup use monkeys obtained a cup first before food, or obtained food and a cup from the floor simultaneously, before transporting both items to upper-level perching areas. After food processing activity with cups monkeys rarely dropped the cups and more often placed the cups onto perching. Monkeys subsequently returned to use cups that they previously placed on perching after food processing activity. The latter behavior is consistent with the possibility that monkeys may keep cups at preferred perching sites for future food processing activity and merits experimental investigation. Reports of spontaneous tool use by squirrel monkeys are rare and this is the first report of population-level tool use. These findings offer insights into the cognitive abilities of squirrel monkeys and provide a new context for behavior studies with this genus and for comparative studies with other primates. © 2015 Wiley Periodicals, Inc.

Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

PubMed

Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

2014-05-01

Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

PubMed

Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

2002-12-01

To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

Imaging Prostate Cancer with Positron Emission Tomography

DTIC Science & Technology

2016-07-01

pool. Radioactivity was retained in kidney tissue and suggests that this is the primary route of excretion. Tumor targeting was inefficient.    15...radioactivity in hepatic tissue. Elevated levels of radioactivity were observed in kidney tissue suggesting that these radiotracers are excreted...20, 21], and its Blood 0 10 20 30 0.00 0.05 0.10 0.15 0.20 Time (h) % ID /g Liver 0 10 20 30 0.0 0.5 1.0 1.5 2.0 Time (h) % ID /g Kidney 0 10 20 30

Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer.

PubMed

Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang; Poo, Muming; Sun, Qiang

2018-02-08

Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys (Macaca fascicularis) by somatic cell nuclear transfer (SCNT). We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys. For SCNT using fetal monkey fibroblasts, 6 pregnancies were confirmed in 21 surrogates and yielded 2 healthy babies. For SCNT using adult monkey cumulus cells, 22 pregnancies were confirmed in 42 surrogates and yielded 2 babies that were short-lived. In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

Lactobacillus and Pediococcus species richness and relative abundance in the vagina of rhesus monkeys (Macaca mulatta)

PubMed Central

Gravett, Michael G.; Jin, Ling; Pavlova, Sylvia I.; Tao, Lin

2012-01-01

Background The rhesus monkey is an important animal model to study human vaginal health to which lactic acid bacteria play a significant role. However, the vaginal lactic acid bacterial species richness and relative abundance in rhesus monkeys is largely unknown. Methods Vaginal swab samples were aseptically obtained from 200 reproductive aged female rhesus monkeys. Following Rogosa agar plating, single bacterial colonies representing different morphotypes were isolated and analyzed for whole-cell protein profile, species-specifc PCR, and 16S rRNA gene sequence. Results A total of 510 Lactobacillus strains of 17 species and one Pediococcus acidilactici were identified. The most abundant species was L. reuteri, which colonized the vaginas of 86% monkeys. L. johnsonii was the second most abundant species, which colonized 36% of monkeys. The majority of monkeys were colonized by multiple Lactobacillus species. Conclusions The vaginas of rhesus monkeys are frequently colonized by multiple Lactobacillus species, dominated by L. reuteri. PMID:22429090

Lentivirus-mediated RNA interference of vascular endothelial growth factor in monkey eyes with iris neovascularization.

PubMed

Yuan, Meng-Ke; Tao, Yong; Yu, Wen-Zhen; Kai, Wang; Jiang, Yan-Rong

2010-08-25

To explore the in vivo anti-angiogenesis effects resulting from lentivirus-mediated RNAi of vascular endothelial growth factor (VEGF) in monkeys with iris neovascularization (INV). Five specific recombinant lentiviral vectors for RNA interference, targeting Macaca mulatta VEGFA, were designed and the one with best knock down efficacy (LV-GFP-VEGFi1) in H1299 cells and RF/6A cells was selected by real-time PCR for in vivo use. A laser-induced retinal vein occlusion model was established in one eye of seven cynomolgus monkeys. In monkeys number 1, 3, and 5 (Group 1), the virus (1x10(8) particles) was intravitreally injected into the preretinal space of the animal's eye immediately after laser coagulation; and in monkeys number 2, 4, and 6 (Group 2), the virus (1x10(8) particles) was injected at 10 days after laser coagulation. In monkey number 7, a blank control injection was performed. In monkeys number 1 and 2, virus without RNAi sequence was used; in monkeys number 3 and 4, virus with nonspecific RNAi sequence was used; and in monkeys 5 and 6, LV-GFP-VEGFi1 was used. In monkey number 5, at 23 days after laser treatment, no obvious INV was observed, while fluorescein angiography of the iris revealed high fluorescence at the margin of pupil and point posterior synechiae. At 50 days after laser treatment, only a slight ectropion uvea was found. However, in the other eyes, obvious INV or hyphema was observed. The densities of new iridic vessels all significantly varied: between monkey number 5 and number 3 (36.01+/-4.49/mm(2) versus 48.68+/-9.30/mm(2), p=0.025), between monkey number 3 and monkey number 7 (48.68+/-9.30/mm(2) versus 74.38+/-9.23/mm(2), p=0.002), and between monkey number 5 and number 7 (36.01+/-4.49/mm(2) versus 74.38+/-9.23/mm(2), p<0.001). Lentivirus-mediated RNAi of VEGF may be a new strategy to treat iris neovascularization, while further studies are needed to investigate the long-term effect.

Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies.

PubMed

Murphy, Jittawadee R; Weiss, Walter R; Fryauff, David; Dowler, Megan; Savransky, Tatyana; Stoyanov, Cristina; Muratova, Olga; Lambert, Lynn; Orr-Gonzalez, Sachy; Zeleski, Katie Lynn; Hinderer, Jessica; Fay, Michael P; Joshi, Gyan; Gwadz, Robert W; Richie, Thomas L; Villasante, Eileen Franke; Richardson, Jason H; Duffy, Patrick E; Chen, Jingyang

2014-06-03

When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented. Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner. Anopheles dirus, An. crascens and a cross between these two species all were excellent vectors for P. knowlesi. High donor monkey parasitaemia was associated with poor mosquito survival. A single infected mosquito bite is likely sufficient to infect a monkey with P. knowlesi. It is possible to efficiently challenge large groups of monkeys by mosquito bite, which will be useful for P. knowlesi vaccine studies.

The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials.

PubMed

Schulman, Gerald; Berl, Tomas; Beck, Gerald J; Remuzzi, Giuseppe; Ritz, Eberhard; Shimizu, Miho; Shobu, Yuko; Kikuchi, Mami

2016-09-30

The orally administered spherical carbon adsorbent AST-120 is used on-label in Asian countries to slow renal disease progression in patients with progressive chronic kidney disease (CKD). Recently, two multinational, randomized, double-blind, placebo-controlled, phase 3 trials (Evaluating Prevention of Progression in Chronic Kidney Disease [EPPIC] trials) examined AST-120's efficacy in slowing CKD progression. This study assessed the efficacy of AST-120 in the subgroup of patients from the United States of America (USA) in the EPPIC trials. In the EPPIC trials, 2035 patients with moderate to severe CKD were studied, of which 583 were from the USA. The patients were randomly assigned to two groups of equal size that were treated with AST-120 or placebo (9 g/day). The primary end point was a composite of dialysis initiation, kidney transplantation, or serum creatinine doubling. The Kaplan-Meier curve for the time to achieve the primary end point in the placebo-treated patients from the USA was similar to that projected before the study. The per protocol subgroup analysis of the population from the USA which included patients with compliance rates of ≥67 % revealed a significant difference between the treatment groups in the time to achieve the primary end point (Hazard Ratio, 0.74; 95 % Confidence Interval, 0.56-0.97). This post hoc subgroup analysis of EPPIC study data suggests that treatment with AST-120 might delay the time to primary end point in CKD patients from the USA. A further randomized controlled trial in progressive CKD patients in the USA is necessary to confirm the beneficial effect of adding AST-120 to standard therapy regimens. ClinicalTrials.gov NCT00500682 ; NCT00501046 .

[Etiological analysis of 264 cases with chronic kidney disease stage 2 to 5 in children].

PubMed

Miao, Qianfan; Shen, Qian; Xu, Hong; Sun, Li; Tang, Xiaoshan; Fang, Xiaoyan; Liu, Haimei; Zhai, Yihui; Bi, Yunli; Wang, Xiang; Chen, Hong

2015-09-01

To study and summarize the etiology of children patients with chronic kidney disease (CKD) stage 2 to 5 seen in Children's Hospital of Fudan University from Jan. 2004 to Dec. 2013. By complying with the NKF-K/DOQI guidelines, we collected data of 264 cases of children patients with CKD stage 2-5 from Jan. 2004 to Dec. 2013 in the medical record system of Children's Hospital of Fudan University. And we retrospectively analyzed their age and CKD stage at first diagnosis, primary diseases, complications, etc. In the collected 264 cases, 52 cases (19.7%) were diagnosed at stage 2, 67 (25.4%) at stage 3, 52 (19.7%) at stage 4 and 93 (35.2%) at stage 5. For disease causes, 116 cases (43.9%) had congenital anomalies of the kidney and urinary tract (CAKUT), 61 cases (23.1%) had glomerular disease, 15 (5.7%) had hereditary kidney disease, 14 (5.3%) had other diseases and in 58 cases (22.0%) the causes of disease were unknown. In the group with age between 0 and 3.0 and 3.1 and 6.0 years, 57.1% (24 cases) and 60.0% (30 cases) had primary disease with CAKUT. In the group with age older than 10 years, 49.2% (30 cases) had primary disease with glomerular disease and 32.0% (32 cases) with unknown causes. The major cause of CKD stage 2-5 in children in our hospital during the last ten years was CAKUT (43.9%), followed by glomerular disease (23.1%). The primary diseases of CKD were significantly different between the 2 age groups. CAKUT was more common in infants and preschool children while for adolescents, glomerular disease was the major cause.

Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

PubMed

Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

2009-01-01

Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

Systems Biology of the Vervet Monkey

PubMed Central

Jasinska, Anna J.; Schmitt, Christopher A.; Service, Susan K.; Cantor, Rita M.; Dewar, Ken; Jentsch, James D.; Kaplan, Jay R.; Turner, Trudy R.; Warren, Wesley C.; Weinstock, George M.; Woods, Roger P.; Freimer, Nelson B.

2013-01-01

Nonhuman primates (NHP) provide crucial biomedical model systems intermediate between rodents and humans. The vervet monkey (also called the African green monkey) is a widely used NHP model that has unique value for genetic and genomic investigations of traits relevant to human diseases. This article describes the phylogeny and population history of the vervet monkey and summarizes the use of both captive and wild vervet monkeys in biomedical research. It also discusses the effort of an international collaboration to develop the vervet monkey as the most comprehensively phenotypically and genomically characterized NHP, a process that will enable the scientific community to employ this model for systems biology investigations. PMID:24174437

Exposure of the endangered golden monkey (Rhinopithecus roxellana) to heavy metals: a comparison of wild and captive animals.

PubMed

Liu, Qiang; Chen, Yi-Ping; Maltby, Lorraine; Ma, Qing-Yi

2015-05-01

Golden monkeys are endemic to China and of high conservation concern. Conservation strategies include captive breeding, but the success of captive breeding programs may be being compromised by environmental pollution. Heavy metal exposure of wild and captive golden monkeys living in the Qinling Mountains was assessed by measuring fecal metal concentrations (As, Cd, Cr, Co, Cu, Mn, Hg, Ni, Pb, and Zn). Captive monkeys were exposed to higher concentrations of As, Hg, Pb, and Cr than monkeys living in the wild, while high background levels of Mn led to high exposure of wild monkeys. Seasonal variations in metal exposures were detected for both wild and captive monkeys; possible reasons being seasonal changes in either diet (wild monkeys) or metal content of food (captive monkeys). Coal combustion, waste incineration, and traffic-related activities were identified as possible sources of heavy metals exposure for captive animals. Efforts to conserve this endangered primate are potentially compromised by metal pollutants derived from increasing anthropogenic activities. Providing captive animals with uncontaminated food and relocating captive breeding centers away from sources of pollution will reduce pollutant exposure; but ultimately, there is a need to improve environmental quality by controlling pollutants at source.

Hereditary Causes of Kidney Stones and Chronic Kidney Disease

PubMed Central

Edvardsson, Vidar O.; Goldfarb, David S.; Lieske, John C.; Beara-Lasic, Lada; Anglani, Franca; Milliner, Dawn S.; Palsson, Runolfur

2013-01-01

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC and PH with emphasis on childhood manifestations. PMID:23334384

Induction, management, and complications of streptozotocin-induced diabetes mellitus in rhesus monkeys.

PubMed

Kim, Jong-Min; Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Hyun-Je; Kim, Jung-Sik; Yoon, Il-Hee; Jeong, Won-Young; Lee, Ga-Eul; Kim, Min-Sun; Kim, Ju-Eun; Jin, Sang-Man; Park, Chung-Gyu

2016-11-01

Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months. Streptozotocin (immediately dissolved in normal saline, 110 mg/kg) was slowly infused via central catheter for 10 minutes in 22 rhesus monkeys. Clinical signs, complete blood count and blood chemistry were monitored to evaluate toxicity for 1 week after STZ injection. Monkey basal C-peptides were measured and intravenous glucose tolerance test was performed to confirm complete induction of DM. Exogenous insulin was subcutaneously injected to maintain blood glucose in diabetic rhesus monkeys and the complications were recorded while in insulin treatment. Severe salivation and vomiting were observed within 1 hour after STZ injection in 22 rhesus monkeys. One monkey died at 6 hours after STZ injection and the reason for the death was unknown. Pancreatitis was noticed in one monkey after STZ injection, but the monkey recovered after 5 days by medical treatment. Serum total protein and albumin decreased whereas the parameters for the liver function such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly increased (P<.05) after STZ injection, but they were resolved within 1 week. Azotemia was not observed. Monkey fasting C-peptide levels after STZ injection were <0.1 ng/mL in 18 rhesus monkeys, but 0.34, 0.22, 0.16 ng/mL in three monkeys, respectively. The value of daily insulin requirement was 0.92±0.26IU/kg/d (range=0.45-1.29) in the monkeys. Diabetic ketoacidosis was observed in one rhesus monkeys, but the monkey recovered after 24 hours by fluid and insulin treatment. Streptozotocin was effective for inducing DM in rhesus monkeys, but various adverse effects such as pancreatitis, liver toxicity or death were observed. Therefore, careful and suitable medical managements should be implemented to eliminate the risks of mortality and severe adverse effects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations

PubMed Central

Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

2014-01-01

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. PMID:24028276

Porcine platelet lysate as a supplement for animal cell culture

PubMed Central

Aldén, Anna; Gonzalez, Lorena; Persson, Anna; Christensson, Kerstin; Holmqvist, Olov

2007-01-01

A novel supplementation of cell growth media based on a porcine platelet lysate was developed for culture of animal-derived cells. The platelet lysate was produced from porcine blood and contained lysate of platelets and plasma components. It showed satisfactory microbiological integrity and it carried only low amount of endotoxins (<10 EU/mL). The porcine platelet lysate supported well proliferation of Vero (African green monkey transformed kidney epithelial cells), Chinese hamster ovary (CHO) and hybridoma cells comparable to fetal bovine serum (FBS). Platelet lysate shows promise as a viable choice over FBS as it can be produced in large quantities, high lot-to-lot consistency and with an attractive price structure. Furthermore it is a strong alternative to FBS for ethical reasons. It is expected that it can be used as a general supplementation for most animal cells for research studies on the proliferation of cells and their expression of products. PMID:19002989

Light-induced translocation of Pyronine G from mitochondria to nucleoli in monkey kidney CV-1 cells

NASA Astrophysics Data System (ADS)

Geze, Marc; Dellinger, M.; Bazin, M.; Santus, Rene C.

1996-12-01

Pyronine G (3,6-bis-N,N-dimethylaminoxanthylium chloride; PG) is a cationic dye that concentrates in mitochondria of living cells due to the high membrane potential of these organelles, similarly to rhodamine 123 and many other cationic dyes. Pyronine G also shows a preferential affinity for RNA. Upon light irradiation PG has been shown to induce cell death, but the photosensitizing properties of this molecule and the mechanism of cell death are not well understood. Microfluorometry and most particularly microspectrofluorometry are now powerful non-invasive techniques for quantitative studies of single living cells in real time which allow, for example, knowing how living cells are affected by photosensitization. To demonstrate the usefulness of image acquisition with high resolution and high sensitive camera, we present data on photosensitizer relocalization during illumination leading to functional and structural damage in the cells.

Antigenic and biologic characteristics of Venezuelan encephalitis virus strains including a possible new subtype, isolated from the Amazon region of Peru in 1971.

PubMed

Scherer, W F; Anderson, K

1975-04-01

Nine strains of Venezuelan encephalitis (VE) virus isolated from the Amazon region of Peru in 1971 were identified as antigenic subtype I based on plaque-reduction neutralization tests with four and 20 units of antibody. A tenth strain, 71D1252, was possibly a new subtype, but was related to subtypes I and III. Hemagglutinins of each strain made from infected mouse brains had optimals pHs of 6.2 and 6.4. Nine strains were pathogenic for adult hamsters and adult mice, but strain 71D1252 inapparently infected some adult hamsters and mice inoculated peripherally. Plaques of nine strains in Vero African green monkey kidney cell cultures were intermediate in size between representative epizootic and enzootic strains, but plaques of strain 71D1252 were small like epizootic strains.

POWASSAN VIRUS: MORPHOLOGY AND CYTOPATHOLOGY.

PubMed

ABDELWAHAB, K S; ALMEIDA, J D; DOANE, F W; MCLEAN, D M

1964-05-02

Powassan virus, a North American tickborne group B arbovirus, multiplied after simultaneous inoculation into bottles or tubes of virus and trypsinized suspension of continuous-line cultures of rhesus monkey kidney cells, strain LLC-MK2. Cytopathic effects comprising cell rounding and cytoplasmic vacuolation were first observed five days after inoculation. Mixture of Powassan antiserum with virus before inoculation into tissue cultures inhibited the appearance of cytopathic effects. Hemagglutinins for rooster erythrocytes, optimally at pH 6.4 and 22 degrees C., first appeared in tissue culture supernatant fluids four days after inoculation.Electron microscopic observation of thin sections of infected tissue culture cells showed virus particles 360-380 A.U. along outer cell membranes and edges of cytoplasmic vacuoles. In phosphotungstic acid negatively stained preparations, intact virus particles, 400-450 A.U. total diameter, were observed inside infected cells. In particles in which the peripheral layer became discontinuous, geometrically arranged subunits compatible with cubic symmetry were observed.

Mumps Meningoencephalitis, Toronto, 1963

PubMed Central

McLean, D. M.; Bach, Ruth D.; Larke, R. P. B.; McNaughton, G. A.

1964-01-01

Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis and 15 showed no salivary gland involvement. Cerebrospinal fluids from 18 of 40 patients yielded mumps virus by inoculation of rhesus monkey kidney cultures; 33 subjects, including 12 of the 18 virus excretors, showed rising or elevated levels of mumps antihemagglutinin during convalescence. Between May 1959 and June 1963, mumps virus was recovered from cerebrospinal fluids of 50 of 126 cases of mumps meningoencephalitis; virus isolation rates were highest during the peak incidence of mumps meningoencephalitis in winter and early spring. Mumps vaccine (inactivated) was administered to 34 parents with no history of mumps, shortly after their children developed mumps. Mumps occurred in three of 17 parents without prevaccination mumps antihemagglutinins, and in two others, but in none of 15 who had prevaccination antibodies. PMID:14120950

MUMPS MENINGOENCEPHALITIS, TORONTO, 1963.

PubMed

MCLEAN, D M; BACH, R D; LARKE, R P; MCNAUGHTON, G A

1964-02-15

Between January and June 1963, 45 children were hospitalized with mumps meningoencephalitis. Of 39 patients with laboratory evidence of mumps infection, 24 had parotitis and 15 showed no salivary gland involvement. Cerebrospinal fluids from 18 of 40 patients yielded mumps virus by inoculation of rhesus monkey kidney cultures; 33 subjects, including 12 of the 18 virus excretors, showed rising or elevated levels of mumps antihemagglutinin during convalescence. Between May 1959 and June 1963, mumps virus was recovered from cerebrospinal fluids of 50 of 126 cases of mumps meningoencephalitis; virus isolation rates were highest during the peak incidence of mumps meningoencephalitis in winter and early spring.Mumps vaccine (inactivated) was administered to 34 parents with no history of mumps, shortly after their children developed mumps. Mumps occurred in three of 17 parents without prevaccination mumps antihemagglutinins, and in two others, but in none of 15 who had prevaccination antibodies.

Protective effect of vanilloids against tert-butyl hydroperoxide-induced oxidative stress in vero cells culture.

PubMed

Rosa, Antonella; Atzeri, Angela; Deiana, Monica; Melis, M Paola; Incani, Alessandra; Corona, Giulia; Loru, Debora; Appendino, Giovanni; Dessì, M Assunta

2008-05-28

This study investigated the effect of synthetic capsiate, a simplified analogue of capsiate, and vanillyl alcohol on the oxidative stress induced by tert-butyl hydroperoxide (TBH) in a line of fibroblasts derived from monkey kidney (Vero cells). In response to the TBH-mediated oxidative stress, a reduction of the levels of total unsaturated fatty acids and cholesterol was observed, and a rise in the concentrations of conjugated dienes fatty acids hydroperoxides and 7-ketocholesterol. Pretreatment with both synthetic capsiate and vanillyl alcohol preserved Vero cells from oxidative damage and showed a remarkable protective effect on the reduction of the levels of total unsaturated fatty acids and cholesterol, inhibiting the increase of MDA, conjugated dienes fatty acids hydroperoxides, and 7-ketocholesterol. Both compounds were effective against peroxidation of cell membrane lipids induced by TBH, with synthetic capsiate essentially acting as a pro-drug of vanillyl alcohol, its hydrophilic hydrolytic derivative.

Microwave-assisted synthesis and anti-YFV activity of 2,3-diaryl-1,3-thiazolidin-4-ones.

PubMed

Sriram, Dharmarajan; Yogeeswari, Perumal; Kumar, T G Ashok

2005-09-01

The purpose of this study was to prepare several 1,3-thaizolidin-4-ones bearing variously substituted diaryl ring at C-2 and N-3 positions and evaluate them for their anti-YFV activity. Several 1,3-thaizolidin-4-ones were prepared by reacting substituted benzaldehyde with equimolar amount of an appropriate substituted aromatic amine in the presence of an excess of mercaptoacetic acid in toluene utilizing microwave irradiation. The synthesized compounds were also evaluated for their inhibitory effects on the replication of YFV in green monkey kidney (Vero) cells (ATCC CCL81), by means of a cytopathic effect reduction assay. The compound DS1 emerged as the most potent anti-YFV agent with EC50 of 6.9 microM and CC50 more than 100 microM making it more potent than ribavirin. 2,3-diaryl-1,3-thiazolidin-4-ones possess anti-YFV potency.

An erythrodermic variant of pemphigus foliaceus with puzzling histologic and immunopathologic features.

PubMed

Peterson, Jennifer D; Worobec, Sophie M; Chan, Lawrence S

2007-01-01

Pemphigus foliaceus is an autoimmune blistering disorder that affects the skin owing to autoantibodies against desmoglein 1. We employed clinical, histologic, immunopathologic, and serum laboratory studies to investigate a case of an erythrodermic variant of pemphigus foliaceus in an elderly man following treatment with bisoprolol-hydrochlorothiazide. Early histopathology revealed psoriasiform dermatitis, but later biopsies showed subcorneal and granular layer separation with neutrophilic infiltrate. Direct immunofluorescence showed intercellular deposits of immunoglobulin G throughout the epidermis, granular staining of C3 along the basement membrane zone, and fibrin and C3 deposition around the blood vessels. Indirect immunofluorescence on monkey esophagus showed a titer of greater than 1:1,280. Indirect immunofluorescence on rat bladder, antinuclear antibody, lupus panel, and kidney function panel were all negative. There are no reports in the literature of pemphigus foliaceus being induced by bisoprolol, but reports exist of propanolol resulting in drug-induced pemphigus foliaceus.

Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys

PubMed Central

Qi, Hui-Xin; Wang, Feng; Liao, Chia-Chi; Friedman, Robert M.; Tang, Chaohui; Kaas, Jon H.; Avison, Malcolm J.

2016-01-01

After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution fMRI CBV-fMRI mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6 weeks after a high cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2 weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6 weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with inter-individual differences in collateral damage to and recovery of secondary (e.g. spinothalamic) pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on the severity and duration of loss of secondary as well as primary inputs revealed by low and high intensity ES. PMID:27523450

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.

PubMed

Yang, Hongli; Reynaud, Juan; Lockwood, Howard; Williams, Galen; Hardin, Christy; Reyes, Luke; Stowell, Cheri; Gardiner, Stuart K; Burgoyne, Claude F

2017-07-01

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetics Home Reference: Joubert syndrome

MedlinePlus

... sensing the physical environment and in chemical signaling. Primary cilia are important for the structure and function of many types of cells, including brain cells (neurons) and certain cells in the kidneys and liver. Primary cilia are also necessary for the perception ...

Androgen resistance in squirrel monkeys (Saimiri spp.).

PubMed

Gross, Katherine L; Westberry, Jenne M; Hubler, Tina R; Sadosky, Patti W; Singh, Ravinder J; Taylor, Robert L; Scammell, Jonathan G

2008-08-01

The goal of this study was to understand the basis for high androgen levels in squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels were elevated compared with those of humans, even during the nonbreeding season; the highest levels occurred during the breeding season. The ratio of testosterone to dihydrotestosterone in squirrel monkeys is high during the breeding season compared to man. Squirrel monkeys may have high testosterone to compensate for inefficient metabolism to dihydrotestosterone. We also investigated whether squirrel monkeys have high androgens to compensate for low-activity androgen receptors (AR). The response to dihydrotestosterone in squirrel monkey cells transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with 28-fold in human cells. This result was not due to overexpression of cellular FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys, because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated reporter activity in a human fibroblast cell line. To test whether the inherently low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity, squirrel monkey cells were transfected with an AR expression plasmid, an AR-responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of FKBP52 decreased the EC50 or increased the maximal response to dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys likely compensate for their relatively low 5 alpha-reductase activity during the breeding season and AR insensitivity resulting from low cellular levels of FKBP52.

Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

PubMed Central

Jiang, George; Shi, Meng; Conteh, Solomon; Richie, Nancy; Banania, Glenna; Geneshan, Harini; Valencia, Anais; Singh, Priti; Aguiar, Joao; Limbach, Keith; Kamrud, Kurt I.; Rayner, Jonathan; Smith, Jonathan; Bruder, Joseph T.; King, C. Richter; Tsuboi, Takafumi; Takeo, Satoru; Endo, Yaeta; Doolan, Denise L.; Richie, Thomas L.; Weiss, Walter R.

2009-01-01

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost. PMID:19668343

A patient with MEN1 and end-stage chronic kidney disease due to Alport syndrome: Decision making on the eligibility of transplantation.

PubMed

Matrone, Antonio; Brancatella, Alessandro; Marchetti, Piero; Vasile, Enrico; Boggi, Ugo; Elisei, Rossella; Cetani, Filomena; Marcocci, Claudio; Vitti, Paolo; Latrofa, Francesco

2018-03-01

Absence of neoplastic disease in the organ-recipient is required in order to allow organ transplantation. Due to its rarity, no data regarding management of patients with Multiple endocrine neoplasia type 1 (MEN1) and end-stage renal failure candidates for kidney transplantation are available. A 36 year-old man was referred to the present hospital with MEN1, with a neuroendocrine pancreatic tumor and primary hyperparathyroidism and associated Alport syndrome with end stage renal failure. The present study aimed to establish the eligibility of the patient for a kidney transplantation. The neuroendocrine tumor had been treated with duodenopancreatectomy two years earlier and hyperparathyroidism by parathyroidectomy. The review of the literature did not provide data regarding the eligibility for kidney transplantation of patients harboring a neuroendocrine pancreatic tumor in the context of MEN1. Due to the end-stage renal failure, neuroendocrine markers were unreliable and the investigation therefore relied on imaging studies, which were unremarkable. Young age, low-grade tumor, low expression of Ki67, absence of metastatic lymph nodes, onset in the setting of a MEN1 were all positive prognostic factors of the neuroendocrine tumor. Normal serum calcium ruled out persistent primary hyperparathyroidism. Overall, hemodyalisis is known to significantly reduce life expectancy. Benefits of kidney transplantation overcome the risk of neuroendocrine tumor recurrence in a young patient bearing MEN1.

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenfeld, Heidi A., E-mail: heidi.schoenfeld@nov

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat didmore » not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50 mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p = 0.026), Aβ1-40 (35.2%; p = 0.04) and Aβtotal (29.8%; p = 0.04) acutely; this returned to normal as expected with repeated dosing for 15 days. CSF concentrations of newly generated Aβ (AUC{sub (0–24} {sub h)}) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p = 0.039) and day 15 (34.7%; p = 0.0003) and in shorter forms Aβ1-40 (23.4%; p = 0.009), Aβ1-38 (64.1%; p = 0.0001) and Aβtotal (50.45%; p = 0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300 mg/kg) or vehicle control for 39 weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings. - Highlights: • Sacubitril/valsartan reduced Aβ clearance on day 1, but not after 15 daily doses. • Sacubitril/valsartan increased CSF Aβ but did not result in increases in brain Aβ. • No Aβ brain pathology in 39 week monkey study with high dose sacubitril/valsartan.« less

A randomized, phase 2 study of ASP0113, a DNA-based vaccine, for the prevention of CMV in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor.

PubMed

Vincenti, Flavio; Budde, Klemens; Merville, Pierre; Shihab, Fuad; Peddi, V Ram; Shah, Malay; Wyburn, Kate; Cassuto-Viguier, Elisabeth; Weidemann, Alexander; Lee, Misun; Flegel, Teresa; Erdman, Jay; Wang, Xuegong; Lademacher, Christopher

2018-05-09

Cytomegalovirus (CMV) is a latent infection in most infected individuals, but can be pathogenic in immunocompromised kidney transplant recipients. ASP0113 is a DNA-based vaccine for the prevention of CMV-related mortality and end-organ disease in transplant recipients. The efficacy, safety, and immunogenicity of ASP0113 was assessed in a phase 2, double-blind, placebo-controlled study in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Transplant recipients were randomized (1:1) to receive five doses of ASP0113 (5 mg; n=75) or placebo (n=74) on Days 30/60/90/120/180 post transplant, and received prophylactic valganciclovir/ganciclovir 10-100 days post transplant. The primary endpoint was the proportion of transplant recipients with CMV viremia ≥1000 IU/mL from Day 100 through to 1 year after first study vaccine injection. There was no statistically significant difference in the primary endpoint between the ASP0113 and placebo groups (odds ratio 0.79, 95% confidence interval 0.43-1.47; p=0.307). There were similar numbers of transplant recipients with treatment-emergent adverse events between groups; however, more transplant recipients reported injection site pain in the ASP0113 group compared with placebo. ASP0113 did not demonstrate efficacy in the prevention of CMV viremia in this CMV-seronegative kidney transplant population, but demonstrated a safety profile similar to placebo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Overview of the cellular and molecular basis of kidney fibrosis

PubMed Central

Eddy, Allison A

2014-01-01

The common pathogenetic pathway of progressive injury in patients with chronic kidney disease (CKD) is epitomized as normal kidney parenchymal destruction due to scarring (fibrosis). Understanding the fundamental pathways that lead to renal fibrosis is essential in order to develop better therapeutic options for human CKD. Although complex, four cellular responses are pivotal. (1) An interstitial inflammatory response that has multiple consequences—some harmful and others healing. (2) The appearance of a unique interstitial cell population of myofibroblasts, primarily derived from kidney stromal cells (fibroblasts and pericytes), that are the primary source of the various extracellular matrix proteins that form interstitial scars. (3) Tubular epithelial cells that have variable and time-dependent roles as early responders to injury and later as victims of fibrosis due to the loss of their regenerative abilities. (4) Loss of interstitial capillary integrity that compromises oxygen delivery and leads to a vicious cascade of hypoxia–oxidant stress that accentuates injury and fibrosis. In the absence of adequate angiogenic responses, a healthy interstitial capillary network is not maintained. The fibrotic ‘scar' that typifies CKD is an interesting consortium of multifunctional macromolecules that not only change in composition and structure over time, but can be degraded via extracellular and intracellular proteases. Although transforming growth factor beta appears to be the primary driver of kidney fibrosis, a vast array of additional molecules may have modulating roles. The importance of genetic and epigenetic factors is increasingly appreciated. An intriguing but incompletely understood cardiorenal syndrome underlies the high morbidity and mortality rates that develop in association with progressive kidney fibrosis. PMID:25401038

Patient and health professional preferences for organ allocation and procurement, end-of-life care and organization of care for patients with chronic kidney disease using a discrete choice experiment.

PubMed

Davison, Sara N; Kromm, Seija K; Currie, Gillian R

2010-07-01

Clinical practice, policy and research, and the ethical bases upon which they are founded, should be systematically and transparently informed by both patient and professional values. A discrete choice experiment was utilized to understand and quantify the preferences of 351 Canadian patients and healthcare providers in relation to ethically challenging aspects of the management of chronic kidney disease (CKD): procurement and allocation of organs for transplantation, end-of-life care discussions and decision making and the identities of those providing primary care. Patients and health professionals had clear preferences for detailed prognostic information, early advance care planning, shared end-of-life decision making, coordinated models of care that enhance interaction and communication between primary and tertiary care and a more utilitarian approach of best match over first come, first served for allocating deceased donor kidneys. These data also suggest that the innovative strategies of non-directed anonymous donation and paired kidney exchange that are slowly being implemented internationally will be acceptable to both patients and healthcare providers. Current models of CKD care do not consistently reflect the preferences or priorities of either health professionals or patients.

Nephronophthisis: Disease Mechanisms of a Ciliopathy

PubMed Central

Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar

2009-01-01

Nephronophthisis (NPHP), a recessive cystic kidney disease, is the most frequent genetic cause of end-stage kidney disease in children and young adults. Positional cloning of nine genes (NPHP1-9) and functional characterization of their encoded proteins (nephrocystins) has contributed to a unifying theory that defines cystic kidney diseases as “ciliopathies”. The theory is based on the finding that all proteins mutated in cystic kidney diseases of humans or animal models are expressed in primary cilia or centrosomes of renal epithelial cells. Primary cilia are sensory organelles that connect mechanosensory, visual, and other stimuli to mechanisms of epithelial cell polarity and cell cycle control. Mutations in NPHP genes cause defects in signaling mechanisms that involve the non-canonical Wnt signaling pathway and the sonic hedgehog signaling pathway, resulting in defects of planar cell polarity and tissue maintenance. The ciliary theory explains the multiple organ involvement in NPHP, which includes retinal degeneration, cerebellar hypoplasia, liver fibrosis, situs inversus, and mental retardation. Positional cloning of dozens of unknown genes that cause NPHP will elucidate further signaling mechanisms involved. Nephrocystins are highly conserved in evolution, thus allowing the use of animal models to develop future therapeutic approaches. PMID:19118152

Outbreak of larval Echinococcus multilocularis infection in Japanese monkey (Macaca fuscata) in a zoo, Hokkaido: western blotting patterns in the infected monkeys.

PubMed

Sato, Chiaki; Kawase, Shiro; Yano, Shoki; Nagano, Hideki; Fujimoto, Satoshi; Kobayashi, Nobuyuki; Miyahara, Kazuro; Yamada, Kazutaka; Sato, Motoyoshi; Kobayashi, Yoshiyasu

2005-01-01

A high prevalence of larval Echinococcus multilocularis (Em) infection was found in zoo primates in Hokkaido, Japan. In October 1997, a Japanese monkey (Macaca fuscata) died and histopathologically diagnosed as alveolar hydatidosis. Serum samples were collected from the remaining Japanese monkeys and examined for antibodies against Em by enzyme-linked immunosorbent assay and western blotting. Serological tests showed 12 more animals of the remaining 57 monkeys were possibly infected. Ultrasonography revealed that nine of these 12 animals had a cystic lesion in the liver. The band patterns of western blotting in the monkeys were very similar to those in human.

Medication Safety Principles and Practice in CKD.

PubMed

Whittaker, Chanel F; Miklich, Margaret A; Patel, Roshni S; Fink, Jeffrey C

2018-06-18

Ensuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use. Copyright © 2018 by the American Society of Nephrology.

Primary hiperoxaluria diagnosed after kidney transplantation: report of 2 cases and literature review.

PubMed

Rios, John Fredy Nieto; Zuluaga, Monica; Higuita, Lina Maria Serna; Florez, Adriana; Bello-Marquez, Diana Carolina; Aristizábal, Arbey; Kohn, Catalina Ocampo; Zuluaga, Gustavo Adolfo

2017-01-01

Primary hyperoxaluria (PH) is a very rare genetic disorder; it is characterized by total or partial deficiency of the enzymes related to the metabolism of glyoxylate, with an overproduction of calcium oxalate that is deposited in different organs, mainly the kidney, leading to recurrent lithiasis, nephrocalcinosis and end stage renal disease (ESRD). In patients with ESRD that receive kidney transplantation alone, the disease has a relapse of 100%, with graft loss in a high percentage of patients in the first 5 years of transplantation. Three molecular disorders have been described in PH: mutation of the gene alanin glioxalate aminotransferase (AGXT); glyoxalate reductase/hydroxy pyruvate reductase (GRHPR) and 4-OH-2-oxoglutarate aldolase (HOGA1). We present two cases of patients with a history of renal lithiasis who were diagnosed with primary hyperoxaluria in the post-transplant period, manifested by early graft failure, with evidence of calcium oxalate crystals in renal biopsy, hyperoxaluria, hyperoxalemia, and genetic test compatible; they were managed with proper diet, abundant oral liquids, pyridoxine, hydrochlorothiazide and potassium citrate; however, they had slow but progressive deterioration of their grafts function until they reached end-stage chronic renal disease.

Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization.

PubMed

Cano, David A; Murcia, Noel S; Pazour, Gregory J; Hebrok, Matthias

2004-07-01

Polycystic kidney disease (PKD) includes a group of disorders that are characterized by the presence of cysts in the kidney and other organs, including the pancreas. Here we show that in orpk mice, a model system for PKD that harbors a mutation in the gene that encodes the polaris protein, pancreatic defects start to occur at the end of gestation, with an initial expansion of the developing pancreatic ducts. Ductal dilation continues rapidly after birth and results in the formation of large, interconnected cysts. Expansion of pancreatic ducts is accompanied by apoptosis of neighboring acinar cells, whereas endocrine cell differentiation and islet formation appears to be unaffected. Polaris has been shown to co-localize with primary cilia, and these structures have been implicated in the formation of renal cysts. In the orpk pancreas, cilia numbers are reduced and cilia length is decreased. Expression of polycystin-2, a protein involved in PKD, is mislocalized in orpk mice. Furthermore, the cellular localization of beta-catenin, a protein involved in cell adhesion and Wnt signaling, is altered. Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas.

Pancreas anatomy and surgical procedure for pancreatectomy in rhesus monkeys.

PubMed

Zhang, Yi; Fu, Lan; Lu, Yan-Rong; Guo, Zhi-Guang; Zhang, Zhao-Da; Cheng, Jing-Qiu; Hu, Wei-Ming; Liu, Xu-Bao; Mai, Gang; Zeng, Yong; Tian, Bo-Le

2011-12-01

The aim of this study was to investigate the pancreas anatomy and surgical procedure for harvesting pancreas for islet isolation while performing pancreatectomy to induce diabetes in rhesus monkeys. The necropsy was performed in three cadaveric monkeys. Two monkeys underwent the total pancreatectomy and four underwent partial pancreatectomy (70-75%). The greater omentum without ligament to transverse colon, the cystic artery arising from the proper hepatic artery and the branches supplying the paries posterior gastricus from the splenic artery were observed. For pancreatectomy, resected pancreas can be used for islet isolation. Diabetes was not induced in the monkeys undergoing partial pancreatectomy (70-75%). Pancreas anatomy in rhesus monkeys is not the same as in human. Diabetes can be induced in rhesus monkeys by total but not partial pancreatectomy (70-75%). Resected pancreas can be used for islet isolation while performing pancreatectomy to induce diabetes. © 2011 John Wiley & Sons A/S.

Causal prophylactic efficacy of primaquine, tafenoquine, and atovaquone-proguanil against Plasmodium cynomolgi in a rhesus monkey model.

PubMed

DiTusa, Charles; Kozar, Michael P; Pybus, Brandon; Sousa, Jason; Berman, Jonathan; Gettayacamin, Montip; Im-erbsin, Rawiwan; Tungtaeng, Anchalee; Ohrt, Colin

2014-10-01

Since the 1940s, the large animal model to assess novel causal prophylactic antimalarial agents has been the Plasmodium cynomolgi sporozoite-infected Indian-origin rhesus monkey. In 2009 the model was reassessed with 3 clinical standards: primaquine (PQ), tafenoquine (TQ), and atovaquone-proguanil. Both control monkeys were parasitemic on day 8 post-sporozoite inoculation on day 0. Primaquine at 1.78 mg base/kg/day on days (-1) to 8 protected 1 monkey and delayed parasitemia patency of the other monkey to day 49. Tafenoquine at 6 mg base/kg/day on days (-1) to 1 protected both monkeys. However, atovaquone-proguanil at 10 mg atovaquone/kg/day on days (-1) to 8 did not protect either monkey and delayed patency only to days 18-19. Primaquine and TQ at the employed regimens are proposed as appropriate doses of positive control drugs for the model at present.

Metastatic renal cell carcinoma associated with acquired cystic kidney disease 15 years after successful renal transplantation.

PubMed

Lien, Y H; Kam, I; Shanley, P F; Schröter, G P

1991-12-01

Renal cell carcinoma (RCC) is a relatively uncommon cancer in renal transplant patients. From 1968 to 1987, 101 cases of RCC of native kidneys have been reported to the Cincinnati Transplant Tumor Registry. We describe here a case of metastatic RCC associated with acquired cystic kidney disease (ACKD) 15 years after successful renal transplantation. The patient presented with a subcutaneous nodule, which led to discovery of a large primary tumor in the left kidney. ACKD was present in the atrophic right kidney. The reported cases of ACKD-associated RCC in renal transplant recipients were reviewed. Most of these cases are middle-aged men with a long posttransplant course, good graft function, and usage of azathioprine and prednisone as immunosuppressive agents. ACKD can develop or persist and progress to RCC many years after successful renal transplantation. Transplant patients with flank pain, hematuria, or other suspicious symptoms should have imaging studies of their native kidneys.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Behavioral Retardation in a Macaque with Autosomal Trisomy and Aging Mother.

ERIC Educational Resources Information Center

Waal, Frans B. M. de; And Others

1996-01-01

The social development of a female rhesus monkey was followed from birth until death, age 32 months. The monkey had an extra autosome and was hydrocephalic. The monkey showed serious motor deficiencies, delayed social development, poorly established dominance relationships, and heavy dependence on mother and kin. The monkey was, however, well…

Social Recovery of Monkeys Isolated for the First Year of Life: 1. Rehabilitation and Therapy

ERIC Educational Resources Information Center

Novak, M. A.; Harlow, H. F.

1975-01-01

This experiment demonstrated that 12-month-old monkeys reared in social isolation developed appropriate species-typical behavior through the use of adaptation, self pacing of visual input and exposure to younger "therapist" monkeys. A critical period of socialization is not indicated in the rhesus monkey. (GO)

Monkey bites among US military members, Afghanistan, 2011.

PubMed

Mease, Luke E; Baker, Katheryn A

2012-10-01

Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September-December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment.

Geophagy in brown spider monkeys (Ateles hybridus) in a lowland tropical rainforest in Colombia.

PubMed

Link, Andres; de Luna, Ana Gabriela; Arango, Ricardo; Diaz, Maria Clara

2011-01-01

Spider monkeys and howler monkeys are the only Neotropical primates that eat soil from mineral licks. Not all species within these genera visit mineral licks, and geophagy has been restricted to populations of Ateles belzebuth belzebuth,Ateles belzebuth chamek and Alouatta seniculus in western Amazonian rainforests. With the aid of a camera trap we studied the visitation patterns of a group of brown spider monkeys (Ateles hybridus) to a mineral lick at Serrania de Las Quinchas, in Colombia. Spider monkeys visited the lick frequently throughout the year, with a monthly average of 21.7 ± 7.2 visits per 100 days of camera trapping (n = 14 months). Spider monkeys visited the mineral lick almost always on days with no rain, or very little (<3 mm) rain, suggesting that proximate environmental variables might determine spider monkeys' decisions to come to the ground at the licks. This study expands the geographical occurrence of mineral lick use by spider monkeys providing additional data for future assessments on the biogeographical correlates of mineral lick use by platyrrhines. Copyright © 2011 S. Karger AG, Basel.

Rhesus monkey lens as an in vitro model for studying oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

1989-10-01

Lenses from young rhesus monkeys were incubated in the presence of H{sub 2}O{sub 2} or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that themore » mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses.« less

Causal cognition in a non-human primate: field playback experiments with Diana monkeys.

PubMed

Zuberbühler, K

2000-09-14

Crested guinea fowls (Guttera pucherani) living in West African rainforests give alarm calls to leopards (Panthera pardus) and sometimes humans (Homo sapiens), two main predators of sympatric Diana monkeys (Cercopithecus diana). When hearing these guinea fowl alarm calls, Diana monkeys respond as if a leopard were present, suggesting that by default the monkeys associate guinea fowl alarm calls with the presence of a leopard. To assess the monkeys' level of causal understanding, I primed monkeys to the presence of either a leopard or a human, before exposing them to playbacks of guinea fowl alarm calls. There were significant differences in the way leopard-primed groups and human-primed groups responded to guinea fowl alarm calls, suggesting that the monkeys' response was not directly driven by the alarm calls themselves but by the calls' underlying cause, i.e. the predator most likely to have caused the calls. Results are discussed with respect to three possible cognitive mechanisms - associative learning, specialized learning programs, and causal reasoning - that could have led to causal knowledge in Diana monkeys.

An assessment of domain-general metacognitive responding in rhesus monkeys.

PubMed

Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

2017-02-01

Metacognition is the ability to monitor and control one's cognition. Monitoring may involve either public cues or introspection of private cognitive states. We tested rhesus monkeys (Macaca mulatta) in a series of generalization tests to determine which type of cues control metacognition. In Experiment 1, monkeys learned a perceptual discrimination in which a "decline-test" response allowed them to avoid tests and receive a guaranteed small reward. Monkeys declined more difficult than easy tests. In Experiments 2-4, we evaluated whether monkeys generalized this metacognitive responding to new perceptual tests. Monkeys showed a trend toward generalization in Experiments 2 & 3, and reliable generalization in Experiment 4. In Experiments 5 & 6, we presented the decline-test response in a delayed matching-to-sample task. Memory tests differed from perceptual tests in that the appearance of the test display could not control metacognitive responding. In Experiment 6, monkeys made prospective metamemory judgments before seeing the tests. Generalization across perceptual tests with different visual properties and mixed generalization from perceptual to memory tests provide provisional evidence that domain-general, private cues controlled metacognition in some monkeys. We observed individual differences in generalization, suggesting that monkeys differ in use of public and private metacognitive cues. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of antibody to adult T-cell leukemia virus-associated antigens (ATLA) in Japanese monkeys and other non-human primates.

PubMed

Hayami, M; Komuro, A; Nozawa, K; Shotake, T; Ishikawa, K; Yamamoto, K; Ishida, T; Honjo, S; Hinuma, Y

1984-02-15

The prevalence of adult T-cell-leukemia virus (ATLV) infection was examined in Japanese monkeys living naturally in various parts of Japan and in other species of non-human primates imported into and kept in Japan. Sera of 2,650 Japanese monkeys from 41 troops throughout Japan were tested. High incidences of anti-ATLV-associated antigen (ATLA)-positive monkeys were found in most troops, not only in the endemic area of human ATL(Southwestern Japan), but also in non-endemic areas. The incidence of sero-positive individuals increased gradually with age, reaching a maximum when the animals became adult, indicating age dependency, like that found by epidemiological studies on humans. Anti-ATLA antibodies were also detected in 90 of 815 sera of imported non-human primates of 33 species other than Japanese monkeys. All the anti-ATLA sero-positive monkeys were Catarrhines (Old World monkeys), mainly macaques of Asian origin. Some sero-positive monkeys were also found among animals of African origin, but no antibody was detected in Prosimians and Platyrrhines (New World monkeys). The clear-cut difference between the geographical distribution of sero-positive simians and that of humans indicates the improbability of direct transmission of ATLV from simians to humans.

Molecular characterization of Blastocystis isolates from children and rhesus monkeys in Kathmandu, Nepal.

PubMed

Yoshikawa, Hisao; Wu, Zhiliang; Pandey, Kishor; Pandey, Basu Dev; Sherchand, Jeevan Bahadur; Yanagi, Tetsuo; Kanbara, Hiroji

2009-03-23

To investigate the possible transmission of Blastocystis organisms between local rhesus monkeys and children in Kathmandu, Nepal, we compared the subtype (ST) and sequence of Blastocystis isolates from children with gastrointestinal symptoms and local rhesus monkeys. Twenty and 10 Blastocystis isolates were established from 82 and 10 fecal samples obtained from children and monkeys, respectively. Subtype analysis with seven sequence-tagged site (STS) primers indicated that the prevalence of Blastocystis sp. ST1, ST2 and ST3 was 20%, 20% and 60% in the child isolates, respectively. In contrast to human isolates, ST3 was not found in monkey isolates and the prevalence of ST1 and ST2 was 50% and 70%, respectively, including three mixed STs1 and 2 and one isolate not amplified by any STS primers, respectively. Since Blastocystis sp. ST2 has been reported as the most dominant genotype in the survey of Blastocystis infection among the various monkey species, sequence comparison of the 150bp variable region of the small subunit rRNA (SSU rRNA) gene was conducted among ST2 isolates of humans and monkeys. Sequence alignment of 24 clones developed from ST2 isolates of 4 humans and 4 monkeys showed three distinct subgroups, defined as ST2A, ST2B and ST2C. These three subgroups were shared between the child and monkey isolates. These results suggest that the local rhesus monkeys are a possible source of Blastocystis sp. ST2 infection of humans in Kathmandu.

Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.

PubMed

Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

2014-06-01

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. © 2013 The Authors. APMIS published by John Wiley & Sons Ltd.

Distribution and abundance of sacred monkeys in Igboland, southern Nigeria.

PubMed

Baker, Lynne R; Tanimola, Adebowale A; Olubode, Oluseun S; Garshelis, David L

2009-07-01

Although primates are hunted on a global scale, some species are protected against harassment and killing by taboos or religious doctrines. Sites where the killing of sacred monkeys or the destruction of sacred groves is forbidden may be integral to the conservation of certain species. In 2004, as part of a distribution survey of Sclater's guenon (Cercopithecus sclateri) in southern Nigeria, we investigated reports of sacred monkeys in the Igbo-speaking region of Nigeria. We confirmed nine new sites where primates are protected as sacred: four with tantalus monkeys (Chlorocebus tantalus) and five with mona monkeys (Cercopithecus mona). During 2004-2006, we visited two communities (Akpugoeze and Lagwa) previously known to harbor sacred populations of Ce. sclateri to estimate population abundance and trends. We directly counted all groups and compared our estimates with previous counts when available. We also estimated the size of sacred groves and compared these with grove sizes reported in the literature. The mean size of the sacred groves in Akpugoeze (2.06 ha, n = 10) was similar to others in Africa south of the Sahel, but larger than the average grove in Lagwa (0.49 ha, n = 15). We estimated a total population of 124 Sclater's monkeys in 15 groups in Lagwa and 193 monkeys in 20 groups in Akpugoeze. The Akpugoeze population was relatively stable over two decades, although the proportion of infants declined, and the number of groups increased. As Sclater's monkey does not occur in any official protected areas, sacred populations are important to the species' long-term conservation. Despite the monkeys' destruction of human crops, most local people still adhere to the custom of not killing monkeys. These sites represent ideal locations in which to study the ecology of Sclater's monkey and human-wildlife interactions. (c) 2009 Wiley-Liss, Inc.

Comprehensive Evaluation for Substrate Selectivity of Cynomolgus Monkey Cytochrome P450 2C9, a New Efavirenz Oxidase.

PubMed

Hosaka, Shinya; Murayama, Norie; Satsukawa, Masahiro; Uehara, Shotaro; Shimizu, Makiko; Iwasaki, Kazuhide; Iwano, Shunsuke; Uno, Yasuhiro; Yamazaki, Hiroshi

2015-07-01

Cynomolgus monkeys are widely used as primate models in preclinical studies, because of their evolutionary closeness to humans. In humans, the cytochrome P450 (P450) 2C enzymes are important drug-metabolizing enzymes and highly expressed in livers. The CYP2C enzymes, including CYP2C9, are also expressed abundantly in cynomolgus monkey liver and metabolize some endogenous and exogenous substances like testosterone, S-mephenytoin, and diclofenac. However, comprehensive evaluation regarding substrate specificity of monkey CYP2C9 has not been conducted. In the present study, 89 commercially available drugs were examined to find potential monkey CYP2C9 substrates. Among the compounds screened, 20 drugs were metabolized by monkey CYP2C9 at a relatively high rates. Seventeen of these compounds were substrates or inhibitors of human CYP2C9 or CYP2C19, whereas three drugs were not, indicating that substrate specificity of monkey CYP2C9 resembled those of human CYP2C9 or CYP2C19, with some differences in substrate specificities. Although efavirenz is known as a marker substrate for human CYP2B6, efavirenz was not oxidized by CYP2B6 but by CYP2C9 in monkeys. Liquid chromatography-mass spectrometry analysis revealed that monkey CYP2C9 and human CYP2B6 formed the same mono- and di-oxidized metabolites of efavirenz at 8 and 14 positions. These results suggest that the efavirenz 8-oxidation could be one of the selective markers for cynomolgus monkey CYP2C9 among the major three CYP2C enzymes tested. Therefore, monkey CYP2C9 has the possibility of contributing to limited specific differences in drug oxidative metabolism between cynomolgus monkeys and humans. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Aged monkeys as a partial model for Parkinson's disease.

PubMed

Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E

2011-09-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. Copyright © 2011 Elsevier Inc. All rights reserved.

Aged monkeys as a partial model for Parkinson's disease

PubMed Central

Hurley, P.J.; Elsworth, J.D.; Whittaker, M.C.; Roth, R.H.; Redmond, D.E.

2011-01-01

Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, eating problems, delayed initiation of movement, and poverty of movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies. PMID:21620883

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

PubMed

Fitzgerald, Julie C; Basu, Rajit K; Akcan-Arikan, Ayse; Izquierdo, Ledys M; Piñeres Olave, Byron E; Hassinger, Amanda B; Szczepanska, Maria; Deep, Akash; Williams, Duane; Sapru, Anil; Roy, Jason A; Nadkarni, Vinay M; Thomas, Neal J; Weiss, Scott L; Furth, Susan

2016-12-01

The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. One hundred twenty-eight PICUs in 26 countries. Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. None. One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Analysis of Urinary Calculi Using Infrared Spectroscopic Imaging

NASA Astrophysics Data System (ADS)

Sablinskas, Valdas; Lesciute, Daiva; Hendrixson, Vaiva

2009-06-01

Kidney stone disease is a cosmopolitan disease, occurring in both industrialized and developing countries and mainly affecting adults aged 2060 years. The formation of kidney stones is a process that includes many factors. Its primary and contributing pathogenic factors are genetic, nutritional and environmental, but also include personal habits. Information about the chemical structure of kidney stones is of great importance to the treatment of the kidney diseases. The usefulness of such information was first recognized in early 1950s. Analysis of urinary stones by various chemical methods, polarization microscopy, x-ray diffraction, porosity determination, solid phase NMR, and thermo analytical procedures have been widely used. Unfortunately, no one method is sufficient to provide all the clinically useful information about the structure and composition of the stones. Infrared spectroscopy can be considered a relatively new method of kidney stone analysis. It allows to identify any organic or inorganic molecules the constituents of kidney stones. So far this method had never been used to collect information about kidney stone component patterns in Lithuania. Since no epidemiological studies have been performed in this field, the medical treatment of kidney stone disease is empirical and often ineffective in hospitals around the country. The aim of this paper is to present some results of analysis of kidney stones extracted from local patients using FTIR spectroscopical microscopy.

Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Jeffrey W., E-mail: jeffrey.fisher@fda.hhs.gov; Twaddle, Nathan C.; Vanlandingham, Michelle

A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 {mu}g d6-BPA/kg (). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from and , the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Voelkel et al., 2002). Voelkel et al. were unable to detect the aglycone BPA in plasma, but were able to detectmore » BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Voelkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. -- Highlights: Black-Right-Pointing-Pointer A bisphenol A (BPA) PBPK model for the infant and adult monkey was constructed. Black-Right-Pointing-Pointer The hepatic metabolic rate of BPA increased with age of the monkey. Black-Right-Pointing-Pointer The systemic clearance rate of metabolites increased with age of the monkey. Black-Right-Pointing-Pointer Gut wall metabolism of orally administered BPA was substantial across all ages of monkeys. Black-Right-Pointing-Pointer Aglycone BPA plasma concentrations were predicted in humans orally given oral doses of deuterated BPA.« less

Widespread and evolutionary analysis of a MITE family Monkey King in Brassicaceae.

PubMed

Dai, Shutao; Hou, Jinna; Long, Yan; Wang, Jing; Li, Cong; Xiao, Qinqin; Jiang, Xiaoxue; Zou, Xiaoxiao; Zou, Jun; Meng, Jinling

2015-06-19

Miniature inverted repeat transposable elements (MITEs) are important components of eukaryotic genomes, with hundreds of families and many copies, which may play important roles in gene regulation and genome evolution. However, few studies have investigated the molecular mechanisms involved. In our previous study, a Tourist-like MITE, Monkey King, was identified from the promoter region of a flowering time gene, BnFLC.A10, in Brassica napus. Based on this MITE, the characteristics and potential roles on gene regulation of the MITE family were analyzed in Brassicaceae. The characteristics of the Tourist-like MITE family Monkey King in Brassicaceae, including its distribution, copies and insertion sites in the genomes of major Brassicaceae species were analyzed in this study. Monkey King was actively amplified in Brassica after divergence from Arabidopsis, which was indicated by the prompt increase in copy number and by phylogenetic analysis. The genomic variations caused by Monkey King insertions, both intra- and inter-species in Brassica, were traced by PCR amplification. Genomic sequence analysis showed that most complete Monkey King elements are located in gene-rich regions, less than 3kb from genes, in both the B. rapa and A. thaliana genomes. Sixty-seven Brassica expressed sequence tags carrying Monkey King fragments were also identified from the NCBI database. Bisulfite sequencing identified specific DNA methylation of cytosine residues in the Monkey King sequence. A fragment containing putative TATA-box motifs in the MITE sequence could bind with nuclear protein(s) extracted from leaves of B. napus plants. A Monkey King-related microRNA, bna-miR6031, was identified in the microRNA database. In transgenic A. thaliana, when the Monkey King element was inserted upstream of 35S promoter, the promoter activity was weakened. Monkey King, a Brassicaceae Tourist-like MITE family, has amplified relatively recently and has induced intra- and inter-species genomic variations in Brassica. Monkey King elements are most abundant in the vicinity of genes and may have a substantial effect on genome-wide gene regulation in Brassicaceae. Monkey King insertions potentially regulate gene expression and genome evolution through epigenetic modification and new regulatory motif production.

Transmission of Staphylococcus aureus from Humans to Green Monkeys in The Gambia as Revealed by Whole-Genome Sequencing.

PubMed

Senghore, Madikay; Bayliss, Sion C; Kwambana-Adams, Brenda A; Foster-Nyarko, Ebenezer; Manneh, Jainaba; Dione, Michel; Badji, Henry; Ebruke, Chinelo; Doughty, Emma L; Thorpe, Harry A; Jasinska, Anna J; Schmitt, Christopher A; Cramer, Jennifer D; Turner, Trudy R; Weinstock, George; Freimer, Nelson B; Pallen, Mark J; Feil, Edward J; Antonio, Martin

2016-10-01

Staphylococcus aureus is an important pathogen of humans and animals. We genome sequenced 90 S. aureus isolates from The Gambia: 46 isolates from invasive disease in humans, 13 human carriage isolates, and 31 monkey carriage isolates. We inferred multiple anthroponotic transmissions of S. aureus from humans to green monkeys (Chlorocebus sabaeus) in The Gambia over different time scales. We report a novel monkey-associated clade of S. aureus that emerged from a human-to-monkey switch estimated to have occurred 2,700 years ago. Adaptation of this lineage to the monkey host is accompanied by the loss of phage-carrying genes that are known to play an important role in human colonization. We also report recent anthroponotic transmission of the well-characterized human lineages sequence type 6 (ST6) and ST15 to monkeys, probably because of steadily increasing encroachment of humans into the monkeys' habitat. Although we have found no evidence of transmission of S. aureus from monkeys to humans, as the two species come into ever-closer contact, there might be an increased risk of additional interspecies exchanges of potential pathogens. The population structures of Staphylococcus aureus in humans and monkeys in sub-Saharan Africa have been previously described using multilocus sequence typing (MLST). However, these data lack the power to accurately infer details regarding the origin and maintenance of new adaptive lineages. Here, we describe the use of whole-genome sequencing to detect transmission of S. aureus between humans and nonhuman primates and to document the genetic changes accompanying host adaptation. We note that human-to-monkey switches tend to be more common than the reverse and that a novel monkey-associated clade is likely to have emerged from such a switch approximately 2,700 years ago. Moreover, analysis of the accessory genome provides important clues as to the genetic changes underpinning host adaptation and, in particular, shows that human-to-monkey switches tend to be associated with the loss of genes known to confer adaptation to the human host. Copyright © 2016 Senghore et al.

Capuchin monkeys' use of human and conspecific cues to solve a hidden object-choice task.

PubMed

Essler, Jennifer L; Schwartz, Lindsay P; Rossettie, Mattea S; Judge, Peter G

2017-09-01

Learning by watching others can provide valuable information with adaptive consequences, such as identifying the presence of a predator or locating a food source. The extent to which nonhuman animals can gain information by reading the cues of others is often tested by evaluating responses to human gestures, such as a point, and less often evaluated by examining responses to conspecific cues. We tested whether ten brown capuchin monkeys (Cebus [Sapajus] apella) were able to use cues from monkeys and a pointing cue from a human to obtain hidden rewards. A monkey could gain access to a reward hidden in one of two locations by reading a cue from a conspecific (e.g., reaching) or a human pointing. We then tested whether they could transfer this skill from monkeys to humans, from humans to monkeys, and from one conspecific to another conspecific. One group of monkeys was trained and tested using a conspecific as the cue-giver and was then tested with a human cue-giver. The second group of monkeys was trained and tested with a human cue-giver and was then tested with a monkey cue-giver. Monkeys that were successful with a conspecific cue-giver were also tested with a novel conspecific cue-giver. Monkeys learned to use a human point and conspecific cues to obtain rewards. Monkeys that had learned to use the cues of a conspecific to obtain rewards performed significantly better than expected by chance when they were transferred to the cues of a novel conspecific. Monkeys that learned to use a human point to obtain rewards performed significantly better than expected by chance when tested while observing conspecific cues. Some evidence suggested that transferring between conspecific cue-givers occurred with more facility than transferring across species. Results may be explained by simple rules of association learning and stimulus generalization; however, spontaneous flexible use of gestures across conspecifics and between different species may indicate capuchins can generalize learned social cues within and partially across species.

Glycan Encapsulated Gold Nanoparticles Selectively Inhibit Shiga Toxins 1 and 2

PubMed Central

Kulkarni, Ashish A.; Fuller-Schaefer, Cynthia; Korman, Henry; Weiss, Alison A.; Iyer, Suri S.

2011-01-01

Shiga toxins (Stx) released by Escherichia coli O157:H7 and Shigella dysentriae, cause life-threatening conditions that include hemolytic-uremic syndrome (HUS), kidney failure and neurological complications. Cellular entry is mediated by the B subunit of the AB5 toxin, which recognizes cell surface glycolipids present in lipid raft like structures. We developed gold glyconanoparticles that present a multivalent display similar to the cell surface glycolipids to compete for these toxins. These highly soluble glyconanoparticles were nontoxic to the Vero monkey kidney cell line and protected Vero cells from Stx-mediated toxicity in a dose dependent manner. The inhibition is highly dependent on the structure and density of the glycans; selective inhibition of Stx1 and the more clinically relevant Stx2 was achieved. Interestingly, natural variants of Stx2, Stx2c and Stx2d, possessing minimal amino acid variation in the receptor binding site of the B subunit or changes in the A subunit were not neutralized by either the Stx1- or Stx2-specific gold glyconanoparticles. Our results suggest that tailored glyconanoparticles that mimic the natural display of glycans in lipid rafts could serve as potential therapeutics for Stx1 and Stx2. However, a few amino acid changes in emerging Stx2 variants can change receptor specificity, and further research is needed to develop receptor mimics for the emerging variants of Stx2. PMID:20669970

Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration.

PubMed

Thompson, James D; Kornbrust, Douglas J; Foy, Jeffrey W-D; Solano, Elisabeth C R; Schneider, David J; Feinstein, Elena; Molitoris, Bruce A; Erlich, Shai

2012-08-01

We report the toxicological and pharmacokinetic properties of the synthetic, small interfering RNA I5NP following intravenous administration in rodents and nonhuman primates. I5NP is designed to act via the RNA interference (RNAi) pathway to temporarily inhibit expression of the pro-apoptotic protein p53 and is being developed to protect cells from acute ischemia/reperfusion injuries such as acute kidney injury that can occur during major cardiac surgery and delayed graft function that can occur following renal transplantation. Following intravenous administration, I5NP was very rapidly cleared from plasma was distributed predominantly to the kidney, with very low levels in liver and other tissues. Doses of 800 mg/kg I5NP in rodents, and 1,000 mg/kg I5NP in nonhuman primates, were required to elicit adverse effects, which in the monkey were isolated to direct effects on the blood that included a sub-clinical activation of complement and slightly increased clotting times. In the rat, no additional adverse effects were observed with a rat analogue of I5NP, indicating that the effects likely represent class effects of synthetic RNA duplexes rather than toxicity related to the intended pharmacologic activity of I5NP. Taken together, these data support clinical testing of intravenous administration of I5NP for the preservation of renal function following acute ischemia/reperfusion injury.

Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s).

PubMed

Miyamoto, J; Kaneko, H; Takamatsu, Y

1986-06-01

In accordance with in vivo findings, of the four chiral isomers of fenvalerate (S-5602 Sumicidin, Pydrin, [RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-chlorophenyl)isovalerate), only the [2R, alpha S]-isomer (B-isomer) yielded cholesteryl [2R]-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) in the in vitro study using several tissue homogenates of mice, rats, dogs, and monkeys. There were species differences in the extent of CPIA-cholesterol-ester formation, with mouse tissues showing relatively higher activity than those of other animals. The kidney, brain, and spleen of mice showed relatively higher capacities to form this ester compared to other tissues, and the enzyme activity was mainly localized in microsomal fractions. The CPIA-cholesterol ester did not seem to be produced by three known biosynthetic pathways of endogenous cholesterol esters--acyl-CoA:cholesterol O-acyltransferase (ACAT), lecithin:cholesterol O-acyltransferase (LCAT), and cholesterol esterase. Carboxyesterase(s) of mouse kidney microsomes solubilized by digitonin hydrolyzed only the B alpha-isomer of fenvalerate, yielding CPIA, whereas they yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. Thus, it appears that the stereoselective formation of the CPIA-cholesterol ester results from the stereoselective formation of the CPIA-carboxyesterase complex only from the B alpha-isomer, which subsequently undergoes cleavage by cholesterol to yield the CPIA-cholesterol ester.

Natural Plasmodium infection in monkeys in the state of Rondônia (Brazilian Western Amazon)

PubMed Central

2013-01-01

Background Simian malaria is still an open question concerning the species of Plasmodium parasites and species of New World monkeys susceptible to the parasites. In addition, the lingering question as to whether these animals are reservoirs for human malaria might become important especially in a scenario of eradication of the disease. To aid in the answers to these questions, monkeys were surveyed for malaria parasite natural infection in the Amazonian state of Rondônia, Brazil, a state with intense environmental alterations due to human activities, which facilitated sampling of the animals. Methods Parasites were detected and identified in DNA from blood of monkeys, by PCR with primers for the 18S rRNA, CSP and MSP1 genes and sequencing of the amplified fragments. Multiplex PCR primers for the 18S rRNA genes were designed for the parasite species Plasmodium falciparum and Plasmodium vivax, Plasmodium malariae/Plasmodium brasilianum and Plasmodium simium. Results An overall infection rate of 10.9% was observed or 20 out 184 monkey specimens surveyed, mostly by P. brasilianum. However, four specimens of monkeys were found infected with P. falciparum, two of them doubly infected with P. brasilianum and P. falciparum. In addition, a species of monkey of the family Aotidae, Aotus nigriceps, is firstly reported here naturally infected with P. brasilianum. None of the monkeys surveyed was found infected with P. simium/P. vivax. Conclusion The rate of natural Plasmodium infection in monkeys in the Brazilian state of Rondônia is in line with previous surveys of simian malaria in the Amazon region. The fact that a monkey species was found that had not previously been described to harbour malaria parasites indicates that the list of monkey species susceptible to Plasmodium infection is yet to be completed. Furthermore, finding monkeys in the region infected with P. falciparum clearly indicates parasite transfer from humans to the animals. Whether this parasite can be transferred back to humans and how persistent the parasite is in monkeys in the wild so to be efficient reservoirs of the disease, is yet to be evaluated. Finding different species of monkeys infected with this parasite species suggests indeed that these animals can act as reservoirs of human malaria. PMID:23731624

Vacillation, indecision and hesitation in moment-by-moment decoding of monkey motor cortex

PubMed Central

Kaufman, Matthew T; Churchland, Mark M; Ryu, Stephen I; Shenoy, Krishna V

2015-01-01

When choosing actions, we can act decisively, vacillate, or suffer momentary indecision. Studying how individual decisions unfold requires moment-by-moment readouts of brain state. Here we provide such a view from dorsal premotor and primary motor cortex. Two monkeys performed a novel decision task while we recorded from many neurons simultaneously. We found that a decoder trained using ‘forced choices’ (one target viable) was highly reliable when applied to ‘free choices’. However, during free choices internal events formed three categories. Typically, neural activity was consistent with rapid, unwavering choices. Sometimes, though, we observed presumed ‘changes of mind’: the neural state initially reflected one choice before changing to reflect the final choice. Finally, we observed momentary ‘indecision’: delay forming any clear motor plan. Further, moments of neural indecision accompanied moments of behavioral indecision. Together, these results reveal the rich and diverse set of internal events long suspected to occur during free choice. DOI: http://dx.doi.org/10.7554/eLife.04677.001 PMID:25942352

Otolithic influences on extraocular and intraocular muscles

NASA Technical Reports Server (NTRS)

Gernandt, B. E.

1973-01-01

Selective stimulation of utricular gravireceptors leads to gross activation of the bulbar reticular formation where a strong interaction with evoked spino-bulbo-spinal reflex activity occurs. The utricular neurons encountered by microelectrodes in the lateral vestibular nuclei show four types of elicited activity; two of these display an increased firing rate, and two exhibit pronounced inhibitory effects. Application of a stimulus of long duration and constant intensity to the utricle has shown that rapid adaptation of the peripheral receptors is a prominent feature. The effects of selective utricular stimulation upon eye movements, as recorded by the corneoretinal potential method, have been studied in experiments on cats and monkeys and it can be firmly stated that prolonged stimulation of the utricle can evoke strong primary nystagmus, followed by a secondary nystagmus at the cessation of stimulation. The action of utricular stimulation on ocular reflexes has been examined further, with particular attention to evoked pupillary reactions in both cats and monkeys: constriction during the fast phase of the brisk conjugate eye movement, and dilatation during the flow phase.

[Chronic kidney disease in Primary Health Care: prevalence and associated risk factors].

PubMed

Salvador González, Betlem; Rodríguez Pascual, Mercedes; Ruipérez Guijarro, Laura; Ferré González, Antonia; Cunillera Puertolas, Oriol; Rodríguez Latre, Luisa M

2015-04-01

To determine the prevalence of chronic kidney disease and associated risk factors in subjects over 60 years of age, as well as its staging by determining the glomerular filtration rate (GFR). Cross-sectional observational study. Primary Health Care. Patients≥60 years of age who were seen in 40 Primary Health Care centres with serum creatinine measured in a central laboratory between January 1 and December 31, 2010. kidney transplant, home care. Social-demographic and anthropometric data, cardiovascular risk factors, and diseases established according to electronic clinical records. Serum creatinine was measured using standardised Jaffe kinetic method, and GFR estimated with MDRD-4-IDMS and CKD-EPI. A total of 97,665 subjects (57.3% women, median age 70.0 years [Q1: 65.0, Q3: 77.0]). GFR-MDRD prevalence<60=15.1% (16.6% in women, 13.2% in men; P<.001) and increased with age. Multivariate analysis showed a positive association between GFR-MDRD<60 and age (OR=1.74; 95% CI 1.70 to 1.77), hypertension (OR=2.18; 95% CI 2.08 to 2.30), heart failure (OR=2.03; 95% CI 1.83 to 2.25), atrial fibrillation (OR=1.57; 95% CI 1.41 to 1.76), ischaemic heart disease (OR=1.40; 95% CI 1.30 to 1.50), peripheral arterial disease (OR=1.31; 95% CI 1.09 to 1.57), dyslipidaemia (OR=1.28; 95% CI 1.23 to 1.33), diabetes (OR=1.26; 95% CI 1.17 to 1.34), and stroke (OR=1.17; 95% CI 1.09 to 1.25). The GFR-CKD-EPI model showed an increase in OR with age and male sex, that became significant as a chronic kidney disease risk factor. Chronic kidney disease has considerable prevalence in subjects≥60 years seen in Primary Health Care, more in women, and increasing with age. Hypertension, more than diabetes, was the main associated cardiovascular risk factor. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

HLA-DQ Mismatching and Kidney Transplant Outcomes.

PubMed

Leeaphorn, Napat; Pena, Jeremy Ryan A; Thamcharoen, Natanong; Khankin, Eliyahu V; Pavlakis, Martha; Cardarelli, Francesca

2018-05-07

Recent evidence suggests that HLA epitope-mismatching at HLA-DQ loci is associated with the development of anti-DQ donor-specific antibodies and adverse graft outcomes. However, the clinical significance of broad antigen HLA-DQ mismatching for graft outcomes is not well examined. Using the United Network Organ Sharing/the Organ Procurement and Transplantation Network (UNOS/OPTN) data, patients with primary kidney transplants performed between 2005 and 2014 were included. Patients were classified as having either zero HLA-DQ mismatches, or one or two HLA-DQ mismatches. Primary outcomes were death-censored graft survival and incidence of acute rejection. A total of 93,782 patients were included. Of these, 22,730 (24%) and 71,052 (76%) received zero and one or two HLA-DQ mismatched kidneys, respectively. After adjusting for variables including HLA-ABDR, HLA-DQ mismatching was associated with a higher risk of graft loss in living kidney donor recipients with an adjusted hazard ratio (HR) of 1.18 (95% confidence interval [95% CI], 1.07 to 1.30; P <0.01), but not in deceased kidney donor recipients (HR, 1.05; 95% CI, 0.98 to 1.12; P =0.18) ( P value for interaction <0.01). When taking cold ischemic time into account, HLA-DQ mismatching was associated with a higher risk of graft loss in deceased kidney donor recipients with cold ischemic time ≤17 hours (HR, 1.12; 95% CI, 1.02 to 1.27; P =0.002), but not in deceased kidney donor recipients with cold ischemic time >17 hours (HR, 0.97; 95% CI, 0.88 to 1.06; P =0.49) ( P value for interaction <0.01). Recipients with one or two HLA-DQ mismatched kidneys had a higher incidence of acute rejection at 1 year, with adjusted odds ratios of 1.13 (95% CI, 1.03 to 1.23; P <0.01) in deceased donor and 1.14 (95% CI, 1.03 to 1.27; P =0.02) in living donor kidney transplant recipients. Specific donor-DQ mismatches seemed to be associated with the risk of acute rejection and graft failure, whereas others did not. HLA-DQ mismatching is associated with lower graft survival independent of HLA-ABDR in living donor kidney transplants and deceased donor kidney transplants with cold ischemia time ≤17 hours, and a higher 1-year risk of acute rejection in living and deceased donor kidney transplants. Copyright © 2018 by the American Society of Nephrology.

Monkey Bites among US Military Members, Afghanistan, 2011

PubMed Central

Baker, Katheryn A.

2012-01-01

Bites from Macaca mulatta monkeys, native to Afghanistan, can cause serious infections. To determine risk for US military members in Afghanistan, we reviewed records for September–December 2011. Among 126 animal bites and exposures, 10 were monkey bites. Command emphasis is vital for preventing monkey bites; provider training and bite reporting promote postexposure treatment. PMID:23017939

Monkeys Match and Tally Quantities across Senses

ERIC Educational Resources Information Center

Jordan, Kerry E.; MacLean, Evan L.; Brannon, Elizabeth M.

2008-01-01

We report here that monkeys can actively match the number of sounds they hear to the number of shapes they see and present the first evidence that monkeys sum over sounds and sights. In Experiment 1, two monkeys were trained to choose a simultaneous array of 1-9 squares that numerically matched a sample sequence of shapes or sounds. Monkeys…

Get the Monkey off Your Back

ERIC Educational Resources Information Center

Ciabattini, David; Custer, Timothy J.

2008-01-01

Monkeys are the problems that need solutions, the tasks that need to be accomplished, the decisions that need to be made, and the actions that need to be taken. According to a theory, people carry monkeys around on their backs until they can successfully shift their burden to someone else and the monkey leaps from one back to the next. Managers…

Motion Sickness-Induced Food Aversions in the Squirrel Monkey

NASA Technical Reports Server (NTRS)

Roy, M. Aaron; Brizzee, Kenneth R.

1979-01-01

Conditioned aversions to colored, flavored water were established in Squirrel monkeys (Saimiri sciureus) by following consumption with 90 min of simultaneous rotational and vertical stimulation. The experimental group (N= 13) drank significantly less of the green, almond-flavored test solution than did the control group (N=14) during three post-treatment preference testing days. Individual differences were noted in that two experimental monkeys readily drank the test solution after rotational stimulation. Only two of the experimental monkeys showed emesis during rotation, yet 10 monkeys in this group developed an aversion. These results suggest that: (1) motion sickness can be readily induced in Squirrel monkeys with simultaneous rotational and vertical stimulation, and (2) that conditioned food aversions are achieved in the absence of emesis in this species.

Managing cancer risk and decision making after kidney transplantation.

PubMed

Webster, A C; Wong, G; Craig, J C; Chapman, J R

2008-11-01

Kidney transplant recipients are at higher risk of cancer at most sites, and cancer after transplantation causes considerable morbidity and mortality. To optimize long-term patient outcomes, clinicians balance the prospect of graft failure and dialysis, with competing risks of diabetes, cardiovascular and cerebrovascular disease and the risk of malignancy. In this paper we critically examine the assumptions underpinning primary prevention, immunization, chemoprevention and screening programs, and highlight considerations when applying evidence to the kidney transplant population, and suggest a clinical research agenda that aims to define a rational approach to managing posttransplant cancer risk.

Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

PubMed

Wang, Feng; Chen, Minggui; Yan, Yin; Zhaoping, Li; Li, Wu

2015-09-30

Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue induced a transient increase of neuronal responses to the probe at the cued location during 40-100 ms after the onset of neuronal responses to the probe. This facilitation diminished and disappeared after repeated presentations of the same cue but recurred for a new cue of a different color. In another task to detect the probe, relative shortening of monkey's reaction times for the validly cued probe depended on the SOA in a way similar to the cue-induced V1 facilitation, and the behavioral and physiological cueing effects remained after repeated practice. Flashing two cues simultaneously in the two opposite visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal responses, and shortened the animal's reaction time, to a subsequent visual probe stimulus at the same location. However, the enhancement of the neural responses diminished after repeated exposures to this flash if the animal was not required to react to the probe. Moreover, a second, simultaneous, flash at another location weakened the neuronal and behavioral effects of the first one. These findings revealed, beyond the observations reported so far, the effects of exogenous attention in the brain. Copyright © 2015 the authors 0270-6474/15/3513419-11$15.00/0.

Feedforward and recurrent processing in scene segmentation: electroencephalography and functional magnetic resonance imaging.

PubMed

Scholte, H Steven; Jolij, Jacob; Fahrenfort, Johannes J; Lamme, Victor A F

2008-11-01

In texture segregation, an example of scene segmentation, we can discern two different processes: texture boundary detection and subsequent surface segregation [Lamme, V. A. F., Rodriguez-Rodriguez, V., & Spekreijse, H. Separate processing dynamics for texture elements, boundaries and surfaces in primary visual cortex of the macaque monkey. Cerebral Cortex, 9, 406-413, 1999]. Neural correlates of texture boundary detection have been found in monkey V1 [Sillito, A. M., Grieve, K. L., Jones, H. E., Cudeiro, J., & Davis, J. Visual cortical mechanisms detecting focal orientation discontinuities. Nature, 378, 492-496, 1995; Grosof, D. H., Shapley, R. M., & Hawken, M. J. Macaque-V1 neurons can signal illusory contours. Nature, 365, 550-552, 1993], but whether surface segregation occurs in monkey V1 [Rossi, A. F., Desimone, R., & Ungerleider, L. G. Contextual modulation in primary visual cortex of macaques. Journal of Neuroscience, 21, 1698-1709, 2001; Lamme, V. A. F. The neurophysiology of figure ground segregation in primary visual-cortex. Journal of Neuroscience, 15, 1605-1615, 1995], and whether boundary detection or surface segregation signals can also be measured in human V1, is more controversial [Kastner, S., De Weerd, P., & Ungerleider, L. G. Texture segregation in the human visual cortex: A functional MRI study. Journal of Neurophysiology, 83, 2453-2457, 2000]. Here we present electroencephalography (EEG) and functional magnetic resonance imaging data that have been recorded with a paradigm that makes it possible to differentiate between boundary detection and scene segmentation in humans. In this way, we were able to show with EEG that neural correlates of texture boundary detection are first present in the early visual cortex around 92 msec and then spread toward the parietal and temporal lobes. Correlates of surface segregation first appear in temporal areas (around 112 msec) and from there appear to spread to parietal, and back to occipital areas. After 208 msec, correlates of surface segregation and boundary detection also appear in more frontal areas. Blood oxygenation level-dependent magnetic resonance imaging results show correlates of boundary detection and surface segregation in all early visual areas including V1. We conclude that texture boundaries are detected in a feedforward fashion and are represented at increasing latencies in higher visual areas. Surface segregation, on the other hand, is represented in "reverse hierarchical" fashion and seems to arise from feedback signals toward early visual areas such as V1.

An Investigation of Primary Student Teachers' Drawings of the Human Internal Organs

ERIC Educational Resources Information Center

Çakici, Yilmaz

2018-01-01

The aim of this study is to investigate primary student teachers' drawings of the human internal organs, e.g. location, size and presence of organs (heart, lungs, stomach, liver, kidneys, pancreas and intestines etc.) This research was conducted with 104 primary teacher candidates studying in the Faculty of Education at Trakya University during…

Renal Extra Skeletal Mesenchymal Chondrosarcoma: A Case Report.

PubMed

Salehipour, Mehdi; Hosseinzadeh, Masood; Sisakhti, Afshin Molaei; Parvin, Vahid Abdol Mohammadi; Sadraei, Amin; Adib, Ali

2017-05-01

Primary mesenchymal chondrosarcoma of the Kidney is an extremely rare entity and very few cases have been reported in literature. We report a 22-year-old male with a right renal mass; after radical nephrectomy, pathologic examination revealed primary extra skeletal mesenchymal chondrosarcoma.

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

PubMed

Ponce, R; Armstrong, K; Andrews, K; Hensler, J; Waggie, K; Heffernan, J; Reynolds, T; Rogge, M

2005-01-01

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Renal calyceal anatomy characterization with 3-dimensional in vivo computerized tomography imaging.

PubMed

Miller, Joe; Durack, Jeremy C; Sorensen, Mathew D; Wang, James H; Stoller, Marshall L

2013-02-01

Calyceal selection for percutaneous renal access is critical for safe, effective performance of percutaneous nephrolithotomy. Available anatomical evidence is contradictory and incomplete. We present detailed renal calyceal anatomy obtained from in vivo 3-dimentional computerized tomography renderings. A total of 60 computerized tomography urograms were randomly selected. The renal collecting system was isolated and 3-dimensional renderings were constructed. The primary plane of each calyceal group of 100 kidneys was determined. A coronal maximum intensity projection was used for simulated percutaneous access. The most inferior calyx was designated calyx 1. Moving superiorly, the subsequent calyces were designated calyx 2 and, when present, calyx 3. The surface rendering was rotated to assess the primary plane of the calyceal group and the orientation of the select calyx. The primary plane of the upper pole calyceal group was mediolateral in 95% of kidneys and the primary plane of the lower pole calyceal group was anteroposterior in 95%. Calyx 2 was chosen in 90 of 97 simulations and it was appropriate in 92%. Calyx 3 was chosen in 7 simulations but it was appropriate in only 57%. Calyx 1 was not selected in any simulation and it was anteriorly oriented in 75% of kidneys. Appropriate lower pole calyceal access can be reliably accomplished with an understanding of the anatomical relationship between individual calyceal orientation and the primary plane of the calyceal group. Calyx 2 is most often appropriate for accessing the anteroposterior primary plane of the lower pole. Calyx 1 is most commonly oriented anterior. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine

PubMed Central

Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

2016-01-01

Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species. PMID:27479072

Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images

PubMed Central

Chang, Liangtang; Zhang, Shikun; Poo, Mu-ming; Gong, Neng

2017-01-01

Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal. PMID:28193875

Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

PubMed

Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

2016-01-01

Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images.

PubMed

Chang, Liangtang; Zhang, Shikun; Poo, Mu-Ming; Gong, Neng

2017-03-21

Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.

Corollary discharge contributes to perceived eye location in monkeys

PubMed Central

Cavanaugh, James; FitzGibbon, Edmond J.; Wurtz, Robert H.

2013-01-01

Despite saccades changing the image on the retina several times per second, we still perceive a stable visual world. A possible mechanism underlying this stability is that an internal retinotopic map is updated with each saccade, with the location of objects being compared before and after the saccade. Psychophysical experiments have shown that humans derive such location information from a corollary discharge (CD) accompanying saccades. Such a CD has been identified in the monkey brain in a circuit extending from superior colliculus to frontal cortex. There is a missing piece, however. Perceptual localization is established only in humans and the CD circuit only in monkeys. We therefore extended measurement of perceptual localization to the monkey by adapting the target displacement detection task developed in humans. During saccades to targets, the target disappeared and then reappeared, sometimes at a different location. The monkeys reported the displacement direction. Detections of displacement were similar in monkeys and humans, but enhanced detection of displacement from blanking the target at the end of the saccade was observed only in humans, not in monkeys. Saccade amplitude varied across trials, but the monkey's estimates of target location did not follow that variation, indicating that eye location depended on an internal CD rather than external visual information. We conclude that monkeys use a CD to determine their new eye location after each saccade, just as humans do. PMID:23986562

Task switching in rhesus macaques (Macaca mulatta) and tufted capuchin monkeys (Cebus apella) during computerized categorization tasks.

PubMed

Smith, Travis R; Beran, Michael J

2018-05-31

The present experiments extended to monkeys a previously used abstract categorization procedure (Castro & Wasserman, 2016) where pigeons had categorized arrays of clipart icons based upon two task rules: the number of clipart objects in the array or the variability of objects in the array. Experiment 1 replicated Castro and Wasserman by using capuchin monkeys and rhesus monkeys and reported that monkeys' performances were similar to pigeons' in terms of acquisition, pattern of errors, and the absence of switch costs. Furthermore, monkeys' insensitivity to the added irrelevant information suggested that an associative (rather than rule-based) categorization mechanism was dominant. Experiment 2 was conducted to include categorization cue reversals to determine (a) whether the monkeys would quickly adapt to the reversals and inhibit interference from a prereversal task rule (consistent with a rule-based mechanism) and (b) whether the latency to make a response prior to a correct or incorrect outcome was informative about the presence of a cognitive mechanism. The cue reassignment produced profound and long-lasting performance deficits, and a long reacquisition phase suggested the involvement of associative learning processes; however, monkeys also displayed longer latencies to choose prior to correct responses on challenging trials, suggesting the involvement of nonassociative processes. Together these performances suggest a mix of associative and cognitive-control processes governing monkey categorization judgments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Do capuchin monkeys (Cebus apella) diagnose causal relations in the absence of a direct reward?

PubMed

Edwards, Brian J; Rottman, Benjamin M; Shankar, Maya; Betzler, Riana; Chituc, Vladimir; Rodriguez, Ricardo; Silva, Liara; Wibecan, Leah; Widness, Jane; Santos, Laurie R

2014-01-01

We adapted a method from developmental psychology to explore whether capuchin monkeys (Cebus apella) would place objects on a "blicket detector" machine to diagnose causal relations in the absence of a direct reward. Across five experiments, monkeys could place different objects on the machine and obtain evidence about the objects' causal properties based on whether each object "activated" the machine. In Experiments 1-3, monkeys received both audiovisual cues and a food reward whenever the machine activated. In these experiments, monkeys spontaneously placed objects on the machine and succeeded at discriminating various patterns of statistical evidence. In Experiments 4 and 5, we modified the procedure so that in the learning trials, monkeys received the audiovisual cues when the machine activated, but did not receive a food reward. In these experiments, monkeys failed to test novel objects in the absence of an immediate food reward, even when doing so could provide critical information about how to obtain a reward in future test trials in which the food reward delivery device was reattached. The present studies suggest that the gap between human and animal causal cognition may be in part a gap of motivation. Specifically, we propose that monkey causal learning is motivated by the desire to obtain a direct reward, and that unlike humans, monkeys do not engage in learning for learning's sake.

Quantity judgments of sequentially presented food items by capuchin monkeys (Cebus apella).

PubMed

Evans, Theodore A; Beran, Michael J; Harris, Emily H; Rice, Daniel F

2009-01-01

Recent assessments have shown that capuchin monkeys, like chimpanzees and other Old World primate species, are sensitive to quantitative differences between sets of visible stimuli. In the present study, we examined capuchins' performance in a more sophisticated quantity judgment task that required the ability to form representations of food quantities while viewing the quantities only one piece at a time. In three experiments, we presented monkeys with the choice between two sets of discrete homogeneous food items and allowed the monkeys to consume the set of their choice. In Experiments 1 and 2, monkeys compared an entirely visible food set to a second set, presented item-by-item into an opaque container. All monkeys exhibited high accuracy in choosing the larger set, even when the entirely visible set was presented last, preventing the use of one-to-one item correspondence to compare quantities. In Experiment 3, monkeys compared two sets that were each presented item-by-item into opaque containers, but at different rates to control for temporal cues. Some monkeys performed well in this experiment, though others exhibited near-chance performance, suggesting that this species' ability to form representations of food quantities may be limited compared to previously tested species such as chimpanzees. Overall, these findings support the analog magnitude model of quantity representation as an explanation for capuchin monkeys' quantification of sequentially presented food items.

Corollary discharge contributes to perceived eye location in monkeys.

PubMed

Joiner, Wilsaan M; Cavanaugh, James; FitzGibbon, Edmond J; Wurtz, Robert H

2013-11-01

Despite saccades changing the image on the retina several times per second, we still perceive a stable visual world. A possible mechanism underlying this stability is that an internal retinotopic map is updated with each saccade, with the location of objects being compared before and after the saccade. Psychophysical experiments have shown that humans derive such location information from a corollary discharge (CD) accompanying saccades. Such a CD has been identified in the monkey brain in a circuit extending from superior colliculus to frontal cortex. There is a missing piece, however. Perceptual localization is established only in humans and the CD circuit only in monkeys. We therefore extended measurement of perceptual localization to the monkey by adapting the target displacement detection task developed in humans. During saccades to targets, the target disappeared and then reappeared, sometimes at a different location. The monkeys reported the displacement direction. Detections of displacement were similar in monkeys and humans, but enhanced detection of displacement from blanking the target at the end of the saccade was observed only in humans, not in monkeys. Saccade amplitude varied across trials, but the monkey's estimates of target location did not follow that variation, indicating that eye location depended on an internal CD rather than external visual information. We conclude that monkeys use a CD to determine their new eye location after each saccade, just as humans do.

Species-Specific Involvement of Integrin αIIbβ3 in a Monoclonal Antibody CH12 Triggers Off-Target Thrombocytopenia in Cynomolgus Monkeys.

PubMed

Zhang, Yiting; Sun, Jianhua; Tan, Minjia; Liu, Yongzhen; Li, Qian; Jiang, Hua; Wang, Huamao; Li, Zonghai; Wan, Wei; Jiang, Hualiang; Lu, Henglei; Wang, Bingshun; Ren, Jin; Gong, Likun

2018-04-07

CH12 is a novel humanized monoclonal antibody against epidermal growth factor receptor variant III (EGFRvIII) for cancer treatment. Unfortunately, in pre-clinical safety evaluation studies, acute thrombocytopenia was observed after administration of CH12 in cynomolgus monkeys, but not rats. More importantly, in vitro experiments found that CH12 can bind and activate platelets in cynomolgus monkey, but not human peripheral blood samples. Cynomolgus monkey-specific thrombocytopenia has been reported previously; however, the underlying mechanism remains unclear. Here, we first showed that CH12 induced thrombocytopenia in cynomolgus monkeys through off-target platelet binding and activation, resulting in platelet destruction. We subsequently found that integrin αIIbβ3 (which is expressed on platelets) contributed to this off-target toxicity. Furthermore, three-dimensional structural modeling of the αIIbβ3 molecules in cynomolgus monkeys, humans, and rats suggested that an additional unique loop exists in the ligand-binding pocket of the αIIb subunit in cynomolgus monkeys, which may explain why CH12 binds to platelets only in cynomolgus monkeys. Moreover, this study supported the hypothesis that the minor differences between cynomolgus monkeys and humans can confuse human risk assessments and suggests that species differences can help the prediction of human risks and avoid losses in drug development. Copyright © 2018. Published by Elsevier Inc.

Do Capuchin Monkeys (Cebus apella) Diagnose Causal Relations in the Absence of a Direct Reward?

PubMed Central

Edwards, Brian J.; Rottman, Benjamin M.; Shankar, Maya; Betzler, Riana; Chituc, Vladimir; Rodriguez, Ricardo; Silva, Liara; Wibecan, Leah; Widness, Jane; Santos, Laurie R.

2014-01-01

We adapted a method from developmental psychology [1] to explore whether capuchin monkeys (Cebus apella) would place objects on a “blicket detector” machine to diagnose causal relations in the absence of a direct reward. Across five experiments, monkeys could place different objects on the machine and obtain evidence about the objects’ causal properties based on whether each object “activated” the machine. In Experiments 1–3, monkeys received both audiovisual cues and a food reward whenever the machine activated. In these experiments, monkeys spontaneously placed objects on the machine and succeeded at discriminating various patterns of statistical evidence. In Experiments 4 and 5, we modified the procedure so that in the learning trials, monkeys received the audiovisual cues when the machine activated, but did not receive a food reward. In these experiments, monkeys failed to test novel objects in the absence of an immediate food reward, even when doing so could provide critical information about how to obtain a reward in future test trials in which the food reward delivery device was reattached. The present studies suggest that the gap between human and animal causal cognition may be in part a gap of motivation. Specifically, we propose that monkey causal learning is motivated by the desire to obtain a direct reward, and that unlike humans, monkeys do not engage in learning for learning’s sake. PMID:24586347

Direct comparison of (+/-) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans.

PubMed

Mueller, Melanie; Kolbrich, Erin A; Peters, Frank T; Maurer, Hans H; McCann, Una D; Huestis, Marilyn A; Ricaurte, George A

2009-06-01

The present study compared the disposition and metabolism of the recreational drug (+/-) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4-methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

Nuclear-mitochondrial incompatibility in interorder rhesus monkey-cow embryos derived from somatic cell nuclear transfer.

PubMed

Kwon, Daekee; Koo, Ok-Jae; Kim, Min-Jung; Jang, Goo; Lee, Byeong Chun

2016-10-01

Monkey interorder somatic cell nuclear transfer (iSCNT) using enucleated cow oocytes yielded poor blastocysts development and contradictory results among research groups. Determining the reason for this low blastocyst development is a prerequisite for optimizing iSCNT in rhesus monkeys. The aim of this study was to elucidate nuclear-mitochondrial incompatibility of rhesus monkey-cow iSCNT embryos and its relationship to low blastocyst development. Cytochrome b is a protein of complex III of the electron transport chain (ETC). According to meta-analysis of amino acid sequences, the homology of cytochrome b is 75 % between rhesus monkeys and cattle. To maintain the function of ETC after iSCNT, 4n iSCNT embryos were produced by fusion of non-enucleated cow oocytes and rhesus monkey somatic cells. The blastocyst development rate of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Formation of reactive oxygen species (ROS) is an indirect indicator of ETC activity of cells. The ROS levels of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Collectively, rhesus monkey iSCNT embryos reconstructed with cow oocytes have nuclear-mitochondrial incompatibility due to fundamental species differences between rhesus monkeys and cattle. Nuclear-mitochondrial incompatibility seems to correlate with low ETC activity and extremely low blastocyst development of rhesus monkey-cow iSCNT embryos.

Rhesus monkey heart rate during exercise

NASA Technical Reports Server (NTRS)

Delorge, J.; Thach, J. S., Jr.

1972-01-01

Various schedules of reinforcement and their relation to heart rates of rhesus monkeys during exercise are described. All the reinforcement schedules produced 100 per cent or higher increments in the heart rates of the monkeys during exercise. Resting heart rates were generally much lower than those previously reported, which was attributed to the lack of physical restraint of the monkeys during recording.

Genome Editing of Monkey.

PubMed

Liu, Zhen; Cai, Yijun; Sun, Qiang

2017-01-01

Gene-modified monkey models would be particularly valuable in biomedical and neuroscience research. Virus-based transgenic and programmable nucleases-based site-specific gene editing methods (TALEN, CRISPR-cas9) enable the generation of gene-modified monkeys with gain or loss of function of specific genes. Here, we describe the generation of transgenic and knock-out (KO) monkeys with high efficiency by lentivirus and programmable nucleases.

[Hybrids of human and monkey adenoviruses (adeno-adeno hybrids) that can reproduce in monkey cells: biological and molecular genetic peculiarities].

PubMed

Grinenko, N F; Savitskaia, N V; Pashvykina, G V; Al'tshteĭn, A D

2003-06-01

A highly oncogenic monkey adenovirus SA7(C8) facilitates the reproduction of human adenovirus type 2 (Ad2) in monkey cells. Upon mixed infection of monkey cells with both viruses, these viruses recombine producing defective adeno-adeno hybrids Ad2C8 serologically identical to Ad2 and capable of assisting Ad2 to reproduce in monkey cells. Ad2C8 and Ad2 form an intercomplementary pair inseparable in monkey cells. Unlike oncogenic SA7(C8), Ad2C8 is a nononcogenic virus for hamsters but is able to induce tumor antigens of this virus (T and TSTA). Molecular genetic analysis of 68 clones of adeno-adeno hybrids revealed that the left part of their genome consists of Ad2 DNA, and the right part contains no less than 40% of the viral SA7(C8) genome where E2A, E3, and E4 genes are located. Apparently, the products of these genes contribute to the composition of adenoviral tumor antigens, while the E4 gene is involved in complementation of monkey and human adenoviruses and makes a contribution to host range determination of these viruses.

Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

PubMed

Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

2013-01-01

Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

Simian immunodeficiency virus infections in vervet monkeys (Clorocebus aethiops) at an Australian zoo.

PubMed

Joy, A; Vogelnest, L; Middleton, D J; Dale, C J; Campagna, D; Purcell, D F; Kent, S J

2001-06-01

A number of monkey species, including African green monkeys and African vervet monkeys (Chlorocebus aethiops), are frequently infected in the wild and in captivity with a Simian immunodeficiency virus strain, SIVagm, a primate lentivirus. Up to 50% of African green monkeys are estimated to be infected with SIVagm. SIV strains are very closely related to HIV-2 strains, which are a cause of AIDS in humans, predominantly in western Africa, although cases in Australia have also been reported. It is generally thought that SIV is non-pathogenic in several natural hosts, including African green monkeys. Nevertheless many SIV strains induce a profound immunodeficiency virtually identical to HIV-1 induced AIDS in humans when administered to Asian macaque species such as rhesus (Macaca mulatta) or pigtailed macaques (M nemestrina). SIV infection of Asian macaque species is frequently employed as an animal model for AIDS vaccine studies. In November 1996 a group of 10 African vervet monkeys were imported from the USA for display at Victoria's Open Range Zoo in Werribee. Two animals in this group of monkeys later developed a fatal gastroenteric illness. These diagnoses led us to initiate SIV testing of the colony.

Microbial translocation and skeletal muscle in young and old vervet monkeys.

PubMed

Kavanagh, Kylie; Brown, Richelle N; Davis, Ashley T; Uberseder, Beth; Floyd, Edison; Pfisterer, Bianca; Shively, Carol A

2016-06-01

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

Removal of focal segmental glomerulosclerosis (FSGS) factor suPAR using CytoSorb.

PubMed

Schenk, Heiko; Müller-Deile, Janina; Schmitt, Roland; Bräsen, Jan Hinrich; Haller, Hermann; Schiffer, Mario

2017-12-01

Treatment of primary focal segmental glomerulosclerosis (FSGS) and its recurrence after kidney transplantation associated with rapid deterioration of kidney function remains to be challenging despite advances in immunosuppressive therapy. The presence of circulating factors has been postulated to be a pivotal player in the pathogenesis of FSGS, although suPAR and CLCF-1 have been identified as the most promising causative factors. The potential therapeutic effect of suPAR elimination in an FSGS patient using CytoSorb, a hemoadsorption device that gained attention in the cytokine elimination in septic patients, was studied. Efficiency of total plasma exchange to remove suPAR was determined. CytoSorb hemoadsorption caused a 27.33% reduction of the suPAR level in a single treatment, whereas total plasma exchange showed a suPAR level reduction of 25.12% (n = 3; 95% confidence interval, 0.2777-0.8090; P < 0.01), which may indicate therapeutic potential in the treatment of primary FSGS and its recurrence in a kidney transplant. © 2017 Wiley Periodicals, Inc.

Permissive hypofiltration

PubMed Central

2012-01-01

Acute kidney injury (AKI) is a syndrome with a multitude of causes and is associated with high mortality and a permanent loss of renal function. Our current understanding of the most common causes of AKI is limited, and thus a silver bullet therapy remains elusive. A change in the approach to AKI that shifts away from the primary composite endpoint of death/dialysis, and instead focuses on improving survival and mitigating permanent renal damage, is likely to be more fruitful. We suggest that the current approach of augmenting renal function by increasing the renal blood flow or glomerular filtration rate during AKI may actually worsen outcomes. Analogous to the approach towards adult respiratory distress syndrome that limits ventilator-induced lung injury, we propose the concept of permissive hypofiltration. The primary goals of this approach are: resting the kidney by providing early renal replacement therapy, avoiding the potentially injurious adverse events that occur during AKI (for example, fluid overload, hypophosphatemia, hypothermia, and so forth), and initiating therapies focused on improving survival and mitigating permanent loss of kidney function. PMID:22839207

Equilibrium-Based Movement Endpoints Elicited from Primary Motor Cortex Using Repetitive Microstimulation

PubMed Central

Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.

2014-01-01

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) is increasingly being used to deduce how the brain encodes coordinated muscle activity and movement. However, the full movement repertoire that can be elicited from the forelimb representation of primary motor cortex (M1) using this method has not been systematically determined. Our goal was to acquire a comprehensive M1 forelimb representational map of movement endpoints elicited with HFLD-ICMS, using stimulus parameters optimal for evoking stable forelimb spatial endpoints. The data reveal a 3D forelimb movement endpoint workspace that is represented in a patchwork fashion on the 2D M1 cortical surface. Although cortical maps of movement endpoints appear quite disorderly with respect to movement space, we show that the endpoint locations in the workspace evoked with HFLD-ICMS of two adjacent cortical points are closer together than would be expected if the organization were random. Although there were few obvious consistencies in the endpoint maps across the two monkeys tested, one notable exception was endpoints bringing the hand to the mouth, which was located at the boundary between the hand and face representation. Endpoints at the extremes of the monkey's workspace and locations above the head were largely absent. Our movement endpoints are best explained as resulting from coactivation of agonist and antagonist muscles driving the joints toward equilibrium positions determined by the length–tension relationships of the muscles. PMID:25411500

Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.

PubMed

Tran, Simon D; Sugito, Takayuki; Dipasquale, Giovanni; Cotrim, Ana P; Bandyopadhyay, Bidhan C; Riddle, Kathryn; Mooney, David; Kok, Marc R; Chiorini, John A; Baum, Bruce J

2006-10-01

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, H.; Hamada, M.; Kato, F.

1985-09-01

Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCAmore » and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.« less

Comparative anatomy of the arm muscles of the Japanese monkey (Macaca fuscata) with some comments on locomotor mechanics and behavior.

PubMed

Aversi-Ferreira, Tales Alexandre; Aversi-Ferreira, Roqueline A G M F; Bretas, Rafael Vieira; Nishimaru, Hiroshi; Nishijo, Hisao

2016-08-01

The anatomical literature on the genus Macaca has focused mainly on the rhesus monkey. However, some aspects in the positional behaviors of the Japanese monkey may be different from those in rhesus monkey, suggesting that the anatomical details of these species are divergent. Four thoracic limbs of Macaca fuscata adults were dissected. The arm muscles in Japanese macaques are more similar to rhesus monkeys and Papio; these characteristics are closer to those of bearded capuchins than apes, indicating more proximity of this genus to New World primates. The anatomical features observed favor quadrupedal locomotor behaviors on the ground and in arboreal environments. Japanese monkeys, rhesus monkeys, and bearded capuchins, which share more primitive characteristics in their arm muscles, present features that favor both arboreal and quadrupedal locomotor behaviors, whereas apes, mainly Pan and Gorilla, which spend more time on the ground, present more quadrupedal specializations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed

Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

2017-06-01

The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed Central

Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

2017-01-01

Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

Change Detection by Rhesus Monkeys (Macaca mulatta) and Pigeons (Columba livia)

PubMed Central

Elmore, L. Caitlin; Magnotti, John F.; Katz, Jeffrey S.; Wright, Anthony A.

2012-01-01

Two monkeys learned a color change-detection task where two colored circles (selected from a 4-color set) were presented on a 4×4 invisible matrix. Following a delay, the correct response was to touch the changed colored circle. The monkeys' learning, color transfer, and delay transfer were compared to a similar experiment with pigeons. Monkeys, like pigeons, showed full transfer to four novel colors, and to delays as long as 6.4 s, suggesting they remembered the colors as opposed to perceptual based attentional capture process that may work at very short delays. The monkeys and pigeons were further tested to compare transfer to other dimensions. Monkeys transferred to shape and location changes, unlike the pigeons, but neither species transferred to size changes. Thus, monkeys were less restricted in their domain to detect change than pigeons, but both species learned the basic task and appear suitable for comparative studies of visual short-term memory. PMID:22428982

Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

NASA Technical Reports Server (NTRS)

Stone, W. H.; Saphire, D. G.; Hackleman, S. M.; Braun, A. M.; Pennington, P.; Scheffler, J.; Wigle, J. C.; Cox, A. B.

1994-01-01

We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

THE COURSE OF ACUTE INTESTINAL INFECTIONS IN MONKEYS DURING THE ACTION OF IONISING RADIATION (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stasilevich, Z.K.

1963-04-01

The influence of sublethal x irradiation on the susceptibility of monkeys to acute intestinal infections (paratyphoid B fever, Heidelberg's salmonellosis and colienteritis) was studied. Experiments were carried out on 46 macaque monkeys, aged 2 1/2 to 3 yr. In monkeys subjected to a dose of 300 r there was an elevated susceptibility to paratyphoid B fever; however, the infectious process was not aggravated. Irradiation of animals with a similar dose aggravated the infectious process in Heidelberg's salmonellosis. In monkeys with colienteritis the above dose did not influence the natural immunity of animals to this disease. A clinically marked disease (colienteritis),more » with a lethal outcome was induced in monkeys irradiated with a dose of 445 r. (auth)« less

Hypothalamic-pituitary-adrenal axis physiology and cognitive control of behavior in stress inoculated monkeys.

PubMed

Parker, Karen J; Buckmaster, Christine L; Lindley, Steven E; Schatzberg, Alan F; Lyons, David M

2012-01-01

Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated monkeys: (a) mount neurobiological responses equivalent to non-inoculated monkeys when the stressor is of sufficient intensity, and (b) continue to exhibit enhanced cognitive control as young adults compared to non-inoculated monkeys. These results suggest that stress inoculation protocols alter the appraisal of and response to moderate stressors as less threatening and permanently enhance cognitive control, at least through early adulthood. These data therefore support the notion that the stress inoculation phenotype reflects stress resilience rather than stress pathology.

Urinary sodium excretion and kidney failure in non-diabetic chronic kidney disease

PubMed Central

Fan, Li; Tighiouart, Hocine; Levey, Andrew S.; Beck, Gerald J.; Sarnak, Mark J.

2014-01-01

Current guidelines recommend under 2g/day sodium intake in chronic kidney disease, but there are few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-hour urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-hour urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 and the composite outcome was reached in 723. In the primary analyses there was no association between 24-hour urine sodium and kidney failure [HR 0.99 (95% CI 0.91–1.08)] nor on the composite outcome [HR 1.01 (95% CI 0.93–1.09),] each per 1g/day higher urine sodium. In exploratory analyses there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a 2-slope model, when urine sodium was under 3g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1g/day, and lower risk of kidney failure in those with baseline proteinuria of 1g/day or more. There was no association between urine sodium and kidney failure when urine sodium was 3g/day or more. Results were consistent using first baseline and time-dependent urine sodium. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored. PMID:24646858

Examining internet-delivered cognitive behaviour therapy for patients with chronic kidney disease on haemodialysis: A feasibility open trial.

PubMed

Chan, Ramony; Dear, Blake F; Titov, Nick; Chow, Josephine; Suranyi, Michael

2016-10-01

Treating depression among patients with chronic kidney disease (CKD) is imperative because of its high prevalence and health-related costs. However, many patients with CKD experience significant barriers to effective face-to-face psychological treatments. Internet-delivered cognitive behaviour therapy (iCBT) may help overcome the treatment barriers. The aim of the present study was to explore the acceptability and preliminary efficacy of iCBT for depression and anxiety among patients with CKD on haemodialysis. A single-group open trial design involving 22 patients on dialysis and an established iCBT treatment for anxiety and depression was employed. The primary outcomes were symptoms of depression, anxiety and general psychological distress. The secondary and tertiary outcomes were disability, quality of life, kidney disease-related loss and kidney disease burden. A generalised estimation equation modelling technique was employed. Clinically significant improvements (avg. % of improvement) were observed in the primary outcomes of depression (34%), anxiety (31%) and general distress (26%), which were maintained or further improved to 3-month follow-up. Improvements were also observed for quality of life (12%) and kidney disease-related loss (30%). However, no improvements in disability and kidney disease burden were found. High levels of acceptability were reported and relatively little clinician time (99.45min; SD=14.61) was needed to provide the treatment. The present results provide encouraging support for the potential of iCBT as an innovative way of increasing access to effective psychological treatment for CKD patients. These results provide much needed support for further research in this area. Australian and New Zealand Clinical Trials Registry: ACTRN12613000103763. Copyright © 2016 Elsevier Inc. All rights reserved.

Coping with missing data in phase III pivotal registration trials: Tolvaptan in subjects with kidney disease, a case study.

PubMed

Ouyang, John; Carroll, Kevin J; Koch, Gary; Li, Junfang

2017-07-01

Missing data cause challenging issues, particularly in phase III registration trials, as highlighted by the European Medicines Agency (EMA) and the US National Research Council. We explore, as a case study, how the issues from missing data were tackled in a double-blind phase III trial in subjects with autosomal dominant polycystic kidney disease. A total of 1445 subjects were randomized in a 2:1 ratio to receive active treatment (tolvaptan), or placebo. The primary outcome, the rate of change in total kidney volume, favored tolvaptan (P < .0001). The key secondary efficacy endpoints of clinical progression of disease and rate of decline in kidney function also favored tolvaptan. However, as highlighted by Food and Drug Administration and EMA, the interpretation of results was hampered by a high number of unevenly distributed dropouts, particularly early dropouts. In this paper, we outline the analyses undertaken to address the issue of missing data thoroughly. "Tipping point analyses" were performed to explore how extreme and detrimental outcomes among subjects with missing data must be to overturn the positive treatment effect attained in those subjects who had complete data. Nonparametric rank-based analyses were also performed accounting for missing data. In conclusion, straightforward and transparent analyses directly taking into account missing data convincingly support the robustness of the preplanned analyses on the primary and secondary endpoints. Tolvaptan was confirmed to be effective in slowing total kidney volume growth, which is considered an efficacy endpoint by EMA, and in lessening the decline in renal function in patients with autosomal dominant polycystic kidney disease. Copyright © 2017 John Wiley & Sons, Ltd.

VASCULARIZED COMPOSITE ALLOGRAFT TRANSPLANT SURVIVAL IN MINIATURE SWINE: IS MHC TOLERANCE SUFFICIENT FOR ACCEPTANCE OF EPIDERMIS?

PubMed Central

Cetrulo, Curtis L.; Torabi, Radbeh; Scalea, Joseph R.; Shimizu, Akira; Leto Barone, Angelo A.; Gillon, Brad C.; Tasaki, Masayuki; Leonard, David A.; Cormack, Taylor A.; Villani, Vincenzo; Randolph, Mark A.; Sachs, David H.; Yamada, Kazuhiko

2014-01-01

Background We have previously reported that MGH miniature swine which had accepted class-I mismatched kidneys long-term (LT) following 12 days of high dose Cyclosporine (CyA), uniformly accepted donor-MHC matched kidneys without immunosuppression but rejected donor-MHC matched split-thickness skin grafts (STSG) by day 25, without changes in renal graft function or anti-donor in vitro responses. We have now tested whether this “split tolerance” would also be observed for the primarily-vascularized skin of vascularized composite allografts (VCAs). Methods Group 1 animals (n=3) received donor-MHC matched VCAs <70 days following primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched t KTx followed by a donor-matched VCA >200 days after primary KTx. Results Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of 3 recipients of VCAs including epidermis in Group 2 accepted all components of the VCAs (>200 days). The other two recipients lost only the epidermis at day 45 and 85, with survival of the remainder of the VCA long-term. Conclusions All tissues of a VCA are accepted long-term on animals tolerant of class-I mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared to STSG, but not indefinite. Exposure of tolerant animals to second donor-matched kidneys prior to VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney. PMID:24056624

Hydroxyproline metabolism in mouse models of primary hyperoxaluria

PubMed Central

Holmes, Ross P.; Cramer, Scott D.; Takayama, Tatsuya; Salido, Eduardo

2012-01-01

Primary hyperoxaluria type 1 (PH1) and type 2 (PH2) are rare genetic diseases that result from deficiencies in glyoxylate metabolism. The increased oxalate synthesis that occurs can lead to kidney stone formation, deposition of calcium oxalate in the kidney and other tissues, and renal failure. Hydroxyproline (Hyp) catabolism, which occurs mainly in the liver and kidney, is a prominent source of glyoxylate and could account for a significant portion of the oxalate produced in PH. To determine the sensitivity of mouse models of PH1 and PH2 to Hyp-derived oxalate, animals were fed diets containing 1% Hyp. Urinary excretions of glycolate and oxalate were used to monitor Hyp catabolism and the kidneys were examined to assess pathological changes. Both strains of knockout (KO) mice excreted more oxalate than wild-type (WT) animals with Hyp feeding. After 4 wk of Hyp feeding, all mice deficient in glyoxylate reductase/hydroxypyruvate reductase (GRHPR KO) developed severe nephrocalcinosis in contrast to animals deficient in alanine-glyoxylate aminotransferase (AGXT KO) where nephrocalcinosis was milder and with a lower frequency. Plasma cystatin C measurements over 4-wk Hyp feeding indicated no significant loss of renal function in WT and AGXT KO animals, and significant and severe loss of renal function in GRHPR KO animals after 2 and 4 wk, respectively. These data suggest that GRHPR activity may be vital in the kidney for limiting the conversion of Hyp-derived glyoxylate to oxalate. As Hyp catabolism may make a major contribution to the oxalate produced in PH patients, Hyp feeding in these mouse models should be useful in understanding the mechanisms associated with calcium oxalate deposition in the kidney. PMID:22189945

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

PubMed

Lorenzo, V; Alvarez, A; Torres, A; Torregrosa, V; Hernández, D; Salido, E

2006-09-01

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

An Anti-HIV-1 V3 Loop Antibody Fully Protects Cross-Clade and Elicits T-Cell Immunity in Macaques Mucosally Challenged with an R5 Clade C SHIV

PubMed Central

Lakhashe, Samir K.; Humbert, Michael; Sholukh, Anton; Hemashettar, Girish; Wong, Yin Ling; Yoon, John K.; Wang, Wendy; Novembre, Francis J.; Villinger, Francois; Ibegbu, Chris; Patel, Kalpana; Corti, Davide; Agatic, Gloria; Vanzetta, Fabrizia; Bianchi, Siro; Heeney, Jonathan L.; Sallusto, Federica; Lanzavecchia, Antonio; Ruprecht, Ruth M.

2011-01-01

Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient “Hit and Run” infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target. PMID:21483815

Dissecting the mechanisms of squirrel monkey (Saimiri boliviensis) social learning

PubMed Central

Holmes, AN; Williams, LE; Brosnan, SF

2013-01-01

Although the social learning abilities of monkeys have been well documented, this research has only focused on a few species. Furthermore, of those that also incorporated dissections of social learning mechanisms, the majority studied either capuchins (Cebus apella) or marmosets (Callithrix jacchus). To gain a broader understanding of how monkeys gain new skills, we tested squirrel monkeys (Saimiri boliviensis) which have never been studied in tests of social learning mechanisms. To determine whether S. boliviensis can socially learn, we ran “open diffusion” tests with monkeys housed in two social groups (N = 23). Over the course of 10 20-min sessions, the monkeys in each group observed a trained group member retrieving a mealworm from a bidirectional task (the “Slide-box”). Two thirds (67%) of these monkeys both learned how to operate the Slide-box and they also moved the door significantly more times in the direction modeled by the trained demonstrator than the alternative direction. To tease apart the underlying social learning mechanisms we ran a series of three control conditions with 35 squirrel monkeys that had no previous experience with the Slide-box. The first replicated the experimental open diffusion sessions but without the inclusion of a trained model, the second was a no-information control with dyads of monkeys, and the third was a ‘ghost’ display shown to individual monkeys. The first two controls tested for the importance of social support (mere presence effect) and the ghost display showed the affordances of the task to the monkeys. The monkeys showed a certain level of success in the group control (54% of subjects solved the task on one or more occasions) and paired controls (28% were successful) but none were successful in the ghost control. We propose that the squirrel monkeys’ learning, observed in the experimental open diffusion tests, can be best described by a combination of social learning mechanisms in concert; in this case, those mechanisms are most likely object movement reenactment and social facilitation. We discuss the interplay of these mechanisms and how they related to learning shown by other primate species. PMID:23638347

Viral vector-based reversible neuronal inactivation and behavioral manipulation in the macaque monkey

PubMed Central

Nielsen, Kristina J.; Callaway, Edward M.; Krauzlis, Richard J.

2012-01-01

Viral vectors are promising tools for the dissection of neural circuits. In principle, they can manipulate neurons at a level of specificity not otherwise achievable. While many studies have used viral vector-based approaches in the rodent brain, only a few have employed this technique in the non-human primate, despite the importance of this animal model for neuroscience research. Here, we report evidence that a viral vector-based approach can be used to manipulate a monkey's behavior in a task. For this purpose, we used the allatostatin receptor/allatostatin (AlstR/AL) system, which has previously been shown to allow inactivation of neurons in vivo. The AlstR was expressed in neurons in monkey V1 by injection of an adeno-associated virus 1 (AAV1) vector. Two monkeys were trained in a detection task, in which they had to make a saccade to a faint peripheral target. Injection of AL caused a retinotopic deficit in the detection task in one monkey. Specifically, the monkey showed marked impairment for detection targets placed at the visual field location represented at the virus injection site, but not for targets shown elsewhere. We confirmed that these deficits indeed were due to the interaction of AlstR and AL by injecting saline, or AL at a V1 location without AlstR expression. Post-mortem histology confirmed AlstR expression in this monkey. We failed to replicate the behavioral results in a second monkey, as AL injection did not impair the second monkey's performance in the detection task. However, post-mortem histology revealed a very low level of AlstR expression in this monkey. Our results demonstrate that viral vector-based approaches can produce effects strong enough to influence a monkey's performance in a behavioral task, supporting the further development of this approach for studying how neuronal circuits control complex behaviors in non-human primates. PMID:22723770

Effects of local myopic defocus on refractive development in monkeys.

PubMed

Smith, Earl L; Hung, Li-Fang; Huang, Juan; Arumugam, Baskar

2013-11-01

Visual signals that produce myopia are mediated by local, regionally selective mechanisms. However, little is known about spatial integration for signals that slow eye growth. The purpose of this study was to determine whether the effects of myopic defocus are integrated in a local manner in primates. Beginning at 24 ± 2 days of age, seven rhesus monkeys were reared with monocular spectacles that produced 3 diopters (D) of relative myopic defocus in the nasal visual field of the treated eye but allowed unrestricted vision in the temporal field (NF monkeys). Seven monkeys were reared with monocular +3 D lenses that produced relative myopic defocus across the entire field of view (FF monkeys). Comparison data from previous studies were available for 11 control monkeys, 8 monkeys that experienced 3 D of hyperopic defocus in the nasal field, and 6 monkeys exposed to 3 D of hyperopic defocus across the entire field. Refractive development, corneal power, and axial dimensions were assessed at 2- to 4-week intervals using retinoscopy, keratometry, and ultrasonography, respectively. Eye shape was assessed using magnetic resonance imaging. In response to full-field myopic defocus, the FF monkeys developed compensating hyperopic anisometropia, the degree of which was relatively constant across the horizontal meridian. In contrast, the NF monkeys exhibited compensating hyperopic changes in refractive error that were greatest in the nasal visual field. The changes in the pattern of peripheral refractions in the NF monkeys reflected interocular differences in vitreous chamber shape. As with form deprivation and hyperopic defocus, the effects of myopic defocus are mediated by mechanisms that integrate visual signals in a local, regionally selective manner in primates. These results are in agreement with the hypothesis that peripheral vision can influence eye shape and potentially central refractive error in a manner that is independent of central visual experience.

Comparative study of the oxidation of propranolol enantiomers in hepatic and small intestinal microsomes from cynomolgus and marmoset monkeys.

PubMed

Shimizudani, Takeshi; Nagaoka, Kenjiro; Hanioka, Nobumitsu; Yamano, Shigeru; Narimatsu, Shizuo

2010-01-05

Oxidative metabolism of propranolol (PL) enantiomers (R-PL and S-PL) to 4-hydroxypropranolol (4-OH-PL), 5-OH-PL and N-deisopropylpropranolol (NDP) was examined in hepatic microsomes from cynomolgus and marmoset monkeys and in small intestinal microsomes from monkeys and humans. In hepatic microsomes, levels of oxidation activities were similar between the two monkey species, and substrate enantioselectivity (R-PLS-PL) was seen in the formation of NDP in cynomolgus monkeys and humans and in the formation of 5-OH-PL in marmosets. The formation of the three metabolites in cynomolgus monkeys and the formation of NDP in marmosets were biphasic, while the formation of 4-OH-PL in humans was monophasic. From the inhibition experiments using CYP antibodies, CYP2C9 and 2C19 were thought to be involved as N-deisopropylases and CYP2D6 and 3A4 as 4-hydroxylases in human small intestine. Furthermore, CYP1A, 2C and 3A enzymes could be involved in cynomolgus monkeys and CYP2C and 3A enzymes in marmosets. These results indicate that the oxidative profile of PL in hepatic and small intestinal microsomes differ considerably among cynomolgus monkeys, marmosets and humans.

A survey for Cyclospora spp. in Kenyan primates, with some notes on its biology.

PubMed

Eberhard, M L; Njenga, M N; DaSilva, A J; Owino, D; Nace, E K; Won, K Y; Mwenda, J M

2001-12-01

From March 1999 through August 2000, 511 stool samples collected from 11 different primate species in 10 geographically distinct locations in Kenya, East Africa, were screened for the presence of Cyclospora spp. oocysts. Positive samples (43/102, 42%) were identified in vervet monkeys (Cercopithecus aethiops) in 4 of 4 locations; 19/206 (9%) in yellow and olive baboons (Papio cynocephalus, P. anubis, respectively) in 5 of 5 locations; and 19/76 (25%) in black and white colobus monkeys (Colobus angolensis, C. guereza, respectively) from 2 of 3 locations. DNA sequences obtained from 18 S rRNA coding regions from respective subsets of these positive samples were typed as Cyclospora cercopitheci (samples from Cercopithecus aethiops). Cyclospora papionis (samples from Papio cynocephalus and P. anubis), and Cyclospora colobi (samples from Colobus angolensis and C. guereza). Cyclospora oocysts were not detected in samples collected from patas, highland sykes, lowland sykes, blue sykes, DeBrazza, or red-tailed monkeys. A coded map showing the geographic location of the collected samples is given. Stool samples from 1 troop of vervet monkeys were collected over a 12-mo period. Positive samples ranged between 21 and 63%. These results suggest that there is no strongly marked seasonality evident in Cyclospora infection in monkeys as has been noted in human infection. This is further confirmed by the recovery of positive samples collected from vervet monkeys, baboons, and colobus monkeys at all times of the year during this survey. This absence of seasonality in infection is especially notable because of the extreme weather patterns typical of Kenya, where marked rainy and dry seasons occur. A second noteworthy observation is that the striking host specificity of the Cyclospora species initially described was confirmed in this survey. Baboons were only infected with C. papionis, vervet monkeys with C. cercopitheci, and colobus monkeys with C. colobi, despite geographic overlaps of both the monkey and parasite species and wide geographic distribution of each parasite and monkey host.

HIV-1 Tat-based vaccines: from basic science to clinical trials.

PubMed

Fanales-Belasio, Emanuele; Cafaro, Aurelio; Cara, Andrea; Negri, Donatella R M; Fiorelli, Valeria; Butto, Stefano; Moretti, Sonia; Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Tripiciano, Antonella; Sernicola, Leonardo; Scoglio, Arianna; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; Ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Vardas, Eftyhia; Magnani, Mauro; Laguardia, Elena; Caputo, Antonella; Titti, Fausto; Ensoli, Barbara

2002-09-01

Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.

[Pharmacological profiles of latanoprost (Xalatan), a novel anti-glaucoma drug].

PubMed

Nomura, S; Hashimoto, M

2000-05-01

Latanoprost is a novel prostaglandin F2 alpha (PGF2 alpha) derivative. Topically applied latanoprost into the glaucomatous monkey eyes lowered intraocular pressure (IOP). Latanoprost, however, failed to produce the hypotensive effect in either rabbit or cat eyes. This species difference may be attributed to its high selectivity for the FP receptor and differences in prostaglandin receptor subtypes existed in the eye amongst these species. In ligand binding studies with bovine corpus luteum cell membranes, the Kd value for the FP receptor of latanoprost was the same as that for PGF2 alpha, 2.8 nM. Latanoprost augmented uveoscleral outflow (Uv) in monkeys without affecting trabecular outflow or outflow facility like PGF2 alpha. Although the precise mechanism of the increase in Uv is not fully understood, it is suggested that a decrease in extracellular matrix components in ciliary muscle may contribute to the increase in Uv. On the other hand, an increase in blood flow at the optic nerve head and neuroprotective action in addition to the IOP lowering effect may contribute to the efficacy of latanoprost in glaucoma therapy. Only tolerable conjunctival hyperemia was seen in rabbits. A phase III clinical trial revealed latanoprost (0.005%) once daily produced sustained reduction of IOP in ocular hypertension or primary open-angle glaucoma patients to a greater extent than timolol did. Furthermore, the effects of latanoprost on aqueous humor dynamics in normal human volunteers were similar to those in monkeys, indicating that latanoprost lowers IOP by the increase in Uv in humans.

Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial.

PubMed

Ederoth, Per; Dardashti, Alain; Grins, Edgars; Brondén, Björn; Metzsch, Carsten; Erdling, André; Nozohoor, Shahab; Mokhtari, Arash; Hansson, Magnus J; Elmér, Eskil; Algotsson, Lars; Jovinge, Stefan; Bjursten, Henrik

2018-04-01

Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.

Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Agodoa, Lawrence Y.; Astor, Brad C.; Bakris, George L.; Cleveland, William H.; Charleston, Jeanne; Contreras, Gabriel; Faulkner, Marquetta L.; Gabbai, Francis B.; Gassman, Jennifer J.; Hebert, Lee A.; Jamerson, Kenneth A.; Kopple, Joel D.; Kusek, John W.; Lash, James P.; Lea, Janice P.; Lewis, Julia B.; Lipkowitz, Michael S.; Massry, Shaul G.; Miller, Edgar R.; Norris, Keith; Phillips, Robert A.; Pogue, Velvie A.; Randall, Otelio S.; Rostand, Stephen G.; Smogorzewski, Miroslaw J.; Toto, Robert D.; Wang, Xuelei

2013-01-01

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) PMID:20818902

Urinary biomarkers may provide prognostic information for subclinical acute kidney injury after cardiac surgery.

PubMed

Albert, Christian; Albert, Annemarie; Kube, Johanna; Bellomo, Rinaldo; Wettersten, Nicholas; Kuppe, Hermann; Westphal, Sabine; Haase, Michael; Haase-Fielitz, Anja

2018-06-01

This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery-asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. Patients enrolled (N = 200), originated a German multicenter study (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI. Primary end point was acute renal replacement therapy or in-hospital mortality. Long-term end points among others included 5-year mortality. Patients with single-biomarker-positive subclinical AKI (RIFLE negative) were identified. We controlled for systemic inflammation using C-reactive protein test. Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and interleukin 6) were identified as independent predictors of the primary end point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6 positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and 48.0% more cases, respectively, with likely subclinical AKI (biomarker positive/RIFLE negative) additionally to cases with RIFLE positivity alone. Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin or interleukin 6 positive) had increased risk of primary end point (adjusted hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [P = .013] and hazard ratio, 6.27; 95% confidence interval, 1.12-35.21 [P = .037]), respectively. Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase-associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence interval, 1.4-67.3 [P = .033] and odds ratio, 14.7; 95% confidence interval, 2.0-109.2 [P = .011], respectively). Three percent to 11% of patients appear to be influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney biomarker-defined short-term outcomes appeared to translate into long-term outcomes. Urinary kidney biomarkers identified RIFLE-negative patients with high-risk subclinical AKI as well as a higher risk subgroup of patients among RIFLE-AKI-positive patients. These findings support the concept that urinary biomarkers define subclinical AKI and higher risk subpopulations with worse long-term prognosis among standard patients with AKI. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

Dissociation of item and source memory in rhesus monkeys.

PubMed

Basile, Benjamin M; Hampton, Robert R

2017-09-01

Source memory, or memory for the context in which a memory was formed, is a defining characteristic of human episodic memory and source memory errors are a debilitating symptom of memory dysfunction. Evidence for source memory in nonhuman primates is sparse despite considerable evidence for other types of sophisticated memory and the practical need for good models of episodic memory in nonhuman primates. A previous study showed that rhesus monkeys confused the identity of a monkey they saw with a monkey they heard, but only after an extended memory delay. This suggests that they initially remembered the source - visual or auditory - of the information but forgot the source as time passed. Here, we present a monkey model of source memory that is based on this previous study. In each trial, monkeys studied two images, one that they simply viewed and touched and the other that they classified as a bird, fish, flower, or person. In a subsequent memory test, they were required to select the image from one source but avoid the other. With training, monkeys learned to suppress responding to images from the to-be-avoided source. After longer memory intervals, monkeys continued to show reliable item memory, discriminating studied images from distractors, but made many source memory errors. Monkeys discriminated source based on study method, not study order, providing preliminary evidence that our manipulation of retention interval caused errors due to source forgetting instead of source confusion. Finally, some monkeys learned to select remembered images from either source on cue, showing that they did indeed remember both items and both sources. This paradigm potentially provides a new model to study a critical aspect of episodic memory in nonhuman primates. Copyright © 2017 Elsevier B.V. All rights reserved.

Social Status in Monkeys: Effects of Social Confrontation on Brain Function and Cocaine Self-Administration.

PubMed

Gould, Robert W; Czoty, Paul W; Porrino, Linda J; Nader, Michael A

2017-04-01

Individual differences in response to social stress and environmental enrichment may contribute to variability in response to behavioral and pharmacological treatments for drug addiction. In monkeys, social status influences the reinforcing effects of cocaine and the effects of some drugs on cocaine self-administration. In this study, we used male cynomolgus macaques (n=15) living in established social groups to examine the effects of social confrontation on the reinforcing effects of cocaine using a food-drug choice procedure. On the test day, a dominant or subordinate monkey was removed from his homecage and placed into another social pen; 30 min later he was studied in a cocaine-food choice paradigm. For the group, following social confrontation, sensitivity to cocaine reinforcement was significantly greater in subordinate monkeys compared with dominant animals. Examining individual-subject data revealed that for the majority of monkeys (9/15), serving as an intruder in another social group affected cocaine self-administration and these effects were dependent on the social rank of the monkey. For subordinate monkeys, sensitivity to the reinforcing effects of cocaine increased while sensitivity decreased in dominant monkeys. To investigate potential mechanisms mediating these effects, brain glucose metabolism was studied in a subset of monkeys (n=8) using [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) with positron emission tomography. Dominant and subordinate monkeys displayed distinctly different patterns of brain glucose metabolism in their homecage, including areas associated with vigilance and stress/anxiety, respectively, and during social confrontation. These data demonstrate that, depending on an individual's social status, the same social experience can have divergent effects on brain function and cocaine self-administration. These phenotypic differences in response to social conditions support a personalized treatment approach to cocaine addiction.

Pulse register phonation in Diana monkey alarm calls

NASA Astrophysics Data System (ADS)

Riede, Tobias; Zuberbühler, Klaus

2003-05-01

The adult male Diana monkeys (Cercopithecus diana) produce predator-specific alarm calls in response to two of their predators, the crowned eagles and the leopards. The acoustic structure of these alarm calls is remarkable for a number of theoretical and empirical reasons. First, although pulsed phonation has been described in a variety of mammalian vocalizations, very little is known about the underlying production mechanism. Second, Diana monkey alarm calls are based almost exclusively on this vocal production mechanism to an extent that has never been documented in mammalian vocal behavior. Finally, the Diana monkeys' pulsed phonation strongly resembles the pulse register in human speech, where fundamental frequency is mainly controlled by subglottal pressure. Here, we report the results of a detailed acoustic analysis to investigate the production mechanism of Diana monkey alarm calls. Within calls, we found a positive correlation between the fundamental frequency and the pulse amplitude, suggesting that both humans and monkeys control fundamental frequency by subglottal pressure. While in humans pulsed phonation is usually considered pathological or artificial, male Diana monkeys rely exclusively on pulsed phonation, suggesting a functional adaptation. Moreover, we were unable to document any nonlinear phenomena, despite the fact that they occur frequently in the vocal repertoire of humans and nonhumans, further suggesting that the very robust Diana monkey pulse production mechanism has evolved for a particular functional purpose. We discuss the implications of these findings for the structural evolution of Diana monkey alarm calls and suggest that the restricted variability in fundamental frequency and robustness of the source signal gave rise to the formant patterns observed in Diana monkey alarm calls, used to convey predator information.

Social Status in Monkeys: Effects of Social Confrontation on Brain Function and Cocaine Self-Administration

PubMed Central

Gould, Robert W; Czoty, Paul W; Porrino, Linda J; Nader, Michael A

2017-01-01

Individual differences in response to social stress and environmental enrichment may contribute to variability in response to behavioral and pharmacological treatments for drug addiction. In monkeys, social status influences the reinforcing effects of cocaine and the effects of some drugs on cocaine self-administration. In this study, we used male cynomolgus macaques (n=15) living in established social groups to examine the effects of social confrontation on the reinforcing effects of cocaine using a food-drug choice procedure. On the test day, a dominant or subordinate monkey was removed from his homecage and placed into another social pen; 30 min later he was studied in a cocaine-food choice paradigm. For the group, following social confrontation, sensitivity to cocaine reinforcement was significantly greater in subordinate monkeys compared with dominant animals. Examining individual-subject data revealed that for the majority of monkeys (9/15), serving as an intruder in another social group affected cocaine self-administration and these effects were dependent on the social rank of the monkey. For subordinate monkeys, sensitivity to the reinforcing effects of cocaine increased while sensitivity decreased in dominant monkeys. To investigate potential mechanisms mediating these effects, brain glucose metabolism was studied in a subset of monkeys (n=8) using [18F]fluorodeoxyglucose ([18F]FDG) with positron emission tomography. Dominant and subordinate monkeys displayed distinctly different patterns of brain glucose metabolism in their homecage, including areas associated with vigilance and stress/anxiety, respectively, and during social confrontation. These data demonstrate that, depending on an individual’s social status, the same social experience can have divergent effects on brain function and cocaine self-administration. These phenotypic differences in response to social conditions support a personalized treatment approach to cocaine addiction. PMID:28025974

Nutritional benefits of Crematogaster mimosae ants and Acacia drepanolobium gum for patas monkeys and vervets in Laikipia, Kenya.

PubMed

Isbell, Lynne A; Rothman, Jessica M; Young, Peter J; Rudolph, Kathleen

2013-02-01

Patas monkeys (Erythrocebus patas) are midsized primates that feed extensively on the gum of Acacia drepanolobium and the ants are housed in swollen thorns of this Acacia. Their diet resembles that expected more of smaller bodied primates. Patas monkeys are also more like smaller bodied primates in reproducing at high rates. We sought to better understand the convergence of patas monkeys with smaller bodied primates by comparing their feeding behavior on ants and gum with that of closely related, sympatric vervets (Chlorocebus pygerythrus), and analyzing the nutrient content of the gum of A. drepanolobium and of Crematogaster mimosae, the most common ant species eaten by patas monkeys in Laikipia, Kenya. All occurrences of feeding and moving during focal animal sampling revealed that 1) patas monkeys seek A. drepanolobium gum but vervets avoid it; 2) both species open swollen thorns most often in the morning when antsare less active; 3) patas monkeys continually feed onswollen thorns and gum while moving quickly throughout the day, whereas vervets reduce their consumption of these items and their travel rate at mid-day, and; 4) vervets eat young swollen thorns at a higher rate than patas monkeys. Patas monkeys are able to spend little time acquiring substantial amounts of energy, protein, and minerals from A. drepanolobium gum and C. mimosae ants each day. These findings, when coupled with evidence of causes of infant and adult female mortality, suggest that reproductive success of female patas monkeys is more immediately affected by illness, disease, interactions between adults and infants, and access to water than by food. Copyright © 2012 Wiley Periodicals, Inc.

Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis.

PubMed

Rubinstein, Samuel; Cornell, Robert F; Du, Liping; Concepcion, Beatrice; Goodman, Stacey; Harrell, Shelton; Horst, Sara; Lenihan, Daniel; Slosky, David; Fogo, Agnes; Langone, Anthony

2017-09-01

Light chain (AL) amyloidosis frequently involves the kidney, causing significant morbidity and mortality. A pathologic scoring system with prognostic utility has not been developed. We hypothesized that the extent of amyloid deposition and degree of scarring injury on kidney biopsy, could provide prognostic value, and aimed to develop pathologic scoring tools based on these features. This is a case-control study of 39 patients treated for AL amyloidosis with biopsy-proven kidney involvement at a large academic medical center. Our novel scoring tools, composite scarring injury score (CSIS) and amyloid score (AS) were applied to each kidney biopsy. The primary outcome was progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12-month landmark analysis. At 12 months, nine patients had progressed to ESKD. Patients with an AS ≥7.5 had a significantly higher cumulative incidence of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13-0.64). Using a 12-month landmark analysis, AS correlated with progression to ESKD. These data suggest that a kidney biopsy, in addition to providing diagnostic information, can be the basis for a pathologic scoring system with prognostic significance.

Should pediatric patients wait for HLA-DR-matched renal transplants?

PubMed

Gritsch, H A; Veale, J L; Leichtman, A B; Guidinger, M K; Magee, J C; McDonald, R A; Harmon, W E; Delmonico, F L; Ettenger, R B; Cecka, J M

2008-10-01

Graft survival rates from deceased donors aged 35 years or less among all primary pediatric kidney transplant recipients in the United States between 1996 and 2004 were retrospectively examined to determine the effect of HLA-DR mismatches on graft survival. Zero HLA-DR-mismatched kidneys had statistically comparable 5-year graft survival (71%), to 1-DR-mismatched kidneys (69%) and 2-DR-mismatched kidneys (71%). When compared to donors less than 35 years of age, the relative rate of allograft failure was 1.32 (p = 0.0326) for donor age greater than or equal to age 35. There was no statistical increase in the odds of developing a panel-reactive antibody (PRA) greater than 30% at the time of second waitlisting, based upon the degree of HLA-A, -B or -DR mismatch of the first transplant, nor was there a 'dose effect' when more HLA antigens were mismatched between the donor and recipient. Therefore, pediatric transplant programs should utilize the recently implemented Organ Procurement and Transplantation Network's (OPTN)allocation policy, which prioritizes pediatric recipients to receive kidneys from deceased donors less than 35 years of age, and should not turn down such kidney offers to wait for a better HLA-DR-matched kidney.

The surgical management of upper tract stone disease among spinal cord-injured patients.

PubMed

Welk, B; Shariff, S; Ordon, M; Catharine Craven, B; Herschorn, S; Garg, A X

2013-06-01

Retrospective cohort study, using linked, population-based health-care data. To describe the incidence, management and outcomes of surgically treated kidney stones after spinal cord injury (SCI). To evaluate the impact of a past history of kidney stones on the occurrence of kidney stones. Ontario, Canada. A total of 5121 patients were followed a median of 4 years after an incident SCI (occurring between 2002 and 2011). The primary outcome was surgical intervention for upper tract kidney stones. In follow-up, 66 patients (1.3%) had 89 episodes of surgically treated kidney stones. Treatments included: ureteroscopic lithotripsy (34%), ureteral stent/percutaneous nephrostomy (30%), shockwave lithotripsy (19%) or percutaneous nephrolithotripsy (17%). Following stone treatment, the 30-day mortality rate was low, and the 30-day admission rate to an intensive care unit was 12%. A history of surgically treated kidney stones before SCI (compared with no such history) was associated with a higher risk of kidney stones after SCI (27 vs 3 per 1000 person-years; adjusted hazard ratio 14.74, 95% confidence interval 5.69-38.22). During intermediate follow-up after SCI, surgically treated upper tract kidney stones occur in 1.3% of patients. Ureteroscopy with lithotripsy is the most common treatment. A history of surgically managed kidney stones before SCI portends a higher risk of stones after SCI.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

Observational learning from tool using models by human-reared and mother-reared capuchin monkeys (Cebus apella).

PubMed

Fredman, Tamar; Whiten, Andrew

2008-04-01

Studies of wild capuchins suggest an important role for social learning, but experiments with captive subjects have generally not supported this. Here we report social learning in two quite different populations of capuchin monkeys (Cebus apella). In experiment 1, human-raised monkeys observed a familiar human model open a foraging box using a tool in one of two alternative ways: levering versus poking. In experiment 2, mother-raised monkeys viewed similar techniques demonstrated by monkey models. A control group in each population saw no model. In both experiments, independent coders detected which technique experimental subjects had seen, thus confirming social learning. Further analyses examined fidelity of copying at three levels of resolution. The human-raised monkeys exhibited fidelity at the highest level, the specific tool use technique witnessed. The lever technique was seen only in monkeys exposed to a levering model, by contrast with controls and those witnessing poke. Mother-reared monkeys instead typically ignored the tool and exhibited fidelity at a lower level, tending only to re-create whichever result the model had achieved by either levering or poking. Nevertheless this level of social learning was associated with significantly greater levels of success in monkeys witnessing a model than in controls, an effect absent in the human-reared population. Results in both populations are consistent with a process of canalization of the repertoire in the direction of the approach witnessed, producing a narrower, socially shaped behavioural profile than among controls who saw no model.

Orientation perception in rhesus monkeys (Macaca mulatta).

PubMed

Wakita, Masumi

2008-07-01

It was previously demonstrated that monkeys divide the orientation continuum into cardinal and oblique categories. However, it is still unclear how monkeys perceive within-category orientations. To better understand monkeys' perception of orientation, two experiments were conducted using five monkeys. In experiment 1, they were trained to identify either one cardinal or one oblique target orientation out of six orientations. The results showed that they readily identified the cardinal target whether it was oriented horizontally or vertically. However, a longer training period was needed to identify the oblique target orientation regardless of its degree and direction of tilt. In experiment 2, the same monkeys were trained to identify two-oblique target orientations out of six orientations. These orientations were paired, either sharing the degree of tilt, direction of tilt, or neither property. The results showed that the monkeys readily identified oblique orientations when they had either the same degree or direction of tilt. However, when the target orientations had neither the same degree nor direction of tilt, the animals had difficulty in identifying them. In summary, horizontal and vertical orientations are individually processed, indicating that monkeys do not have a category for cardinal orientation, but they may recognize cardinal orientations as non-obliques. In addition, monkeys efficiently abstract either the degree or the direction of tilt from oblique orientations, but they have difficulty combining these features to identify an oblique orientation. Thus, not all orientations within the oblique category are equally perceived.

Sequential responding and planning in capuchin monkeys (Cebus apella).

PubMed

Beran, Michael J; Parrish, Audrey E

2012-11-01

Previous experiments have assessed planning during sequential responding to computer generated stimuli by Old World nonhuman primates including chimpanzees and rhesus macaques. However, no such assessment has been made with a New World primate species. Capuchin monkeys (Cebus apella) are an interesting test case for assessing the distribution of cognitive processes in the Order Primates because they sometimes show proficiency in tasks also mastered by apes and Old World monkeys, but in other cases fail to match the proficiency of those other species. In two experiments, eight capuchin monkeys selected five arbitrary stimuli in distinct locations on a computer monitor in a learned sequence. In Experiment 1, shift trials occurred in which the second and third stimuli were transposed when the first stimulus was selected by the animal. In Experiment 2, mask trials occurred in which all remaining stimuli were masked after the monkey selected the first stimulus. Monkeys made more mistakes on trials in which the locations of the second and third stimuli were interchanged than on trials in which locations were not interchanged, suggesting they had already planned to select a location that no longer contained the correct stimulus. When mask trials occurred, monkeys performed at levels significantly better than chance, but their performance exceeded chance levels only for the first and the second selections on a trial. These data indicate that capuchin monkeys performed very similarly to chimpanzees and rhesus monkeys and appeared to plan their selection sequences during the computerized task, but only to a limited degree.

Diabetes Mellitus Accelerates Aβ Pathology in Brain Accompanied by Enhanced GAβ Generation in Nonhuman Primates

PubMed Central

Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Yanagisawa, Katsuhiko; Kimura, Nobuyuki

2015-01-01

Growing evidence suggests that diabetes mellitus (DM) is one of the strongest risk factors for developing Alzheimer’s disease (AD). However, it remains unclear why DM accelerates AD pathology. In cynomolgus monkeys older than 25 years, senile plaques (SPs) are spontaneously and consistently observed in their brains, and neurofibrillary tangles are present at 32 years of age and older. In laboratory-housed monkeys, obesity is occasionally observed and frequently leads to development of type 2 DM. In the present study, we performed histopathological and biochemical analyses of brain tissue in cynomolgus monkeys with type 2 DM to clarify the relationship between DM and AD pathology. Here, we provide the evidence that DM accelerates Aβ pathology in vivo in nonhuman primates who had not undergone any genetic manipulation. In DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices, even in monkeys younger than 20 years. Biochemical analyses of brain revealed that the amount of GM1-ganglioside-bound Aβ (GAβ)—the endogenous seed for Aβ fibril formation in the brain—was clearly elevated in DM-affected monkeys. Furthermore, the level of Rab GTPases was also significantly increased in the brains of adult monkeys with DM, almost to the same levels as in aged monkeys. Intraneuronal accumulation of enlarged endosomes was also observed in DM-affected monkeys, suggesting that exacerbated endocytic disturbance may underlie the acceleration of Aβ pathology due to DM. PMID:25675436

Macaque monkeys can learn token values from human models through vicarious reward.

PubMed

Bevacqua, Sara; Cerasti, Erika; Falcone, Rossella; Cervelloni, Milena; Brunamonti, Emiliano; Ferraina, Stefano; Genovesio, Aldo

2013-01-01

Monkeys can learn the symbolic meaning of tokens, and exchange them to get a reward. Monkeys can also learn the symbolic value of a token by observing conspecifics but it is not clear if they can learn passively by observing other actors, e.g., humans. To answer this question, we tested two monkeys in a token exchange paradigm in three experiments. Monkeys learned token values through observation of human models exchanging them. We used, after a phase of object familiarization, different sets of tokens. One token of each set was rewarded with a bit of apple. Other tokens had zero value (neutral tokens). Each token was presented only in one set. During the observation phase, monkeys watched the human model exchange tokens and watched them consume rewards (vicarious rewards). In the test phase, the monkeys were asked to exchange one of the tokens for food reward. Sets of three tokens were used in the first experiment and sets of two tokens were used in the second and third experiments. The valuable token was presented with different probabilities in the observation phase during the first and second experiments in which the monkeys exchanged the valuable token more frequently than any of the neutral tokens. The third experiments examined the effect of unequal probabilities. Our results support the view that monkeys can learn from non-conspecific actors through vicarious reward, even a symbolic task like the token-exchange task.

On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta).

PubMed

Reilly, Mark P; Berndt, Sonja I; Woods, James H

2016-11-01

The present study investigated the role of drug-paired stimuli in controlling the behavior of rhesus monkeys. Systematic observations were made with nine monkeys who had a history of drug self-administration; they had been lever pressing to produce intravenous infusions of various drugs. These observations revealed that the stimulus light co-occurring with drug infusion produced robust and cue-directed behavior such as orienting, touching and biting. Experiment 1 showed that this light-directed behavior would occur in naïve monkeys exposed to a Pavlovian pairing procedure. Four monkeys were given response-independent injections of cocaine. In two monkeys, a red light preceded cocaine injections by 5 s, and a green light co-occurred with the 5-s cocaine injections. In the other two monkeys, the light presentations and cocaine injections occurred independently. Light-directed behavior occurred in all four monkeys within the first couple of trials and at high levels but decreased across sessions. The cocaine-paired stimulus maintained behavior longer and at higher levels than the uncorrelated stimuli. Furthermore, light-directed behavior was not maintained when cocaine was replaced with saline. Light-directed behavior did not occur in the absence of the lights. When these monkeys were subsequently trained to lever press for cocaine, light-directed behavior increased to levels higher than previously observed. Behavior directed towards drug-paired stimuli is robust, reliable and multiply determined; the mechanisms underlying this activity likely include Pavlovian conditioning, stimulus novelty, habituation and operant conditioning.

Reproducibility of carbachol stimulated accommodation in rhesus monkeys.

PubMed

Wendt, Mark; Glasser, Adrian

2012-06-01

Approaches are being explored to restore accommodation to the presbyopic eye. Some of these approaches can be tested in monkeys by stimulating accommodation in various ways including using carbachol iontophoresis. Knowledge of the repeatability of carbachol iontophoresis stimulated accommodation in the monkey phakic eye is necessary to understand the variability of this method of evaluating accommodation. Data from 9 to 10 separate carbachol iontophoresis experiments performed on phakic eyes from 8 monkeys were retrospectively analyzed. For each experiment, carbachol was applied iontophoretically to the eyes of anesthetized monkeys and refraction generally measured every two minutes until accommodation reached a plateau. Repeated experiments were performed in each monkey over periods ranging from 10 to 18 months. Maximum accommodation measured for each monkey ranged from 11.1 D to 18.3 D with standard deviations from 0.8 D to 2.1 D and differences in accommodative amplitude varying from 2.2 D to 7.5 D. Time to reach maximum accommodation ranged from 18 to 64 min in individual experiments. Averaged time-courses indicate that maximum accommodation is generally achieved between 10 and 20 min after carbachol administration. Although carbachol iontophoresis is considered a reliable method to stimulate maximum accommodation in anesthetized monkeys, the amplitude achieved typically varies by more than 2 D. Presbyopia treatments evaluated in this way in phakic monkeys would need to show an increase in accommodation of over 2 D to clearly demonstrate that the treatments work when being tested with carbachol iontophoresis stimulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Do you see what I see? A comparative investigation of the Delboeuf illusion in humans (Homo sapiens), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

PubMed

Parrish, Audrey E; Brosnan, Sarah F; Beran, Michael J

2015-10-01

Studying visual illusions is critical to understanding typical visual perception. We investigated whether rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella) perceived the Delboeuf illusion in a similar manner as human adults (Homo sapiens). To test this, in Experiment 1, we presented monkeys and humans with a relative discrimination task that required subjects to choose the larger of 2 central dots that were sometimes encircled by concentric rings. As predicted, humans demonstrated evidence of the Delboeuf illusion, overestimating central dots when small rings surrounded them and underestimating the size of central dots when large rings surrounded them. However, monkeys did not show evidence of the illusion. To rule out an alternate explanation, in Experiment 2, we presented all species with an absolute classification task that required them to classify a central dot as "small" or "large." We presented a range of ring sizes to determine whether the Delboeuf illusion would occur for any dot-to-ring ratios. Here, we found evidence of the Delboeuf illusion in all 3 species. Humans and monkeys underestimated central dot size to a progressively greater degree with progressively larger rings. The Delboeuf illusion now has been extended to include capuchin monkeys and rhesus monkeys, and through such comparative investigations we can better evaluate hypotheses regarding illusion perception among nonhuman animals. (c) 2015 APA, all rights reserved).

Performing monkeys of Bangladesh: characterizing their source and genetic variation.

PubMed

Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

2016-04-01

The acquisition and training of monkeys to perform is a centuries-old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations, and may escape from their owners or may be released into other populations. In order to determine whether this tradition involving the acquisition and movement of animals has influenced the population structure of free-ranging rhesus macaques in Bangladesh, we first characterized the source of these monkeys. Biological samples from 65 performing macaques collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16 %) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89 %) were transitions, and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise differences for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. The collection of performing monkeys from India was also evident.

Performing monkeys of Bangladesh: characterizing their source and genetic variation

PubMed Central

Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

2016-01-01

The acquisition and training of monkeys to perform is a century's old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations and may escape from their owners or be released into other populations. In order to determine whether this tradition, that involves the acquisition and movement of animals, has influenced the population structure of free-ranging rhesus macaques in Bangladesh we first characterized the source of these monkeys. Biological samples from 65 performing macaques, collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16%) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89%) were transitions and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise difference for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. Collection of performing monkeys from India was also evident. PMID:26758818

Aortic intimal sarcoma masquerading as bilateral renal artery stenosis.

PubMed

Sethi, Supreet; Pothineni, Naga Krishna; Syal, Gaurav; Ali, Syed Mujtaba; Krause, Michelle W

2013-01-01

Aortic intimal sarcoma is a rare tumor with poor prognosis. The most common manifestations are thromboembolic phenomena and vascular obstruction. We present a case of aortic intimal sarcoma causing bilateral renal artery stenosis which manifested as resistant hypertension and acute kidney inury. Multiple attempts to stent the renal arteries were unsuccessful. Eventually the patient developed acute limb ischemia and oliguric kidney failure as complications of the primary tumor.

Oxalate, inflammasome, and progression of kidney disease

PubMed Central

Ermer, Theresa; Eckardt, Kai-Uwe; Aronson, Peter S.; Knauf, Felix

2016-01-01

Purpose of review Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. Recent findings The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. Summary The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials. PMID:27191349

Determinants of graft survival in pediatric and adolescent live donor kidney transplant recipients: a single center experience.

PubMed

El-Husseini, Amr A; Foda, Mohamed A; Shokeir, Ahmed A; Shehab El-Din, Ahmed B; Sobh, Mohamed A; Ghoneim, Mohamed A

2005-12-01

To study the independent determinants of graft survival among pediatric and adolescent live donor kidney transplant recipients. Between March 1976 and March 2004, 1600 live donor kidney transplants were carried out in our center. Of them 284 were 20 yr old or younger (mean age 13.1 yr, ranging from 5 to 20 yr). Evaluation of the possible variables that may affect graft survival were carried out using univariate and multivariate analyses. Studied factors included age, gender, relation between donor and recipient, original kidney disease, ABO blood group, pretransplant blood transfusion, human leukocyte antigen (HLA) matching, pretransplant dialysis, height standard deviation score (SDS), pretransplant hypertension, cold ischemia time, number of renal arteries, ureteral anastomosis, time to diuresis, time of transplantation, occurrence of acute tubular necrosis (ATN), primary and secondary immunosuppression, total dose of steroids in the first 3 months, development of acute rejection and post-transplant hypertension. Using univariate analysis, the significant predictors for graft survival were HLA matching, type of primary urinary recontinuity, time to diuresis, ATN, acute rejection and post-transplant hypertension. The multivariate analysis restricted the significance to acute rejection and post-transplant hypertension. The independent determinants of graft survival in live-donor pediatric and adolescent renal transplant recipients are acute rejection and post-transplant hypertension.

Acute Problems of Virology and Prophylaxis of Viral Diseases,

DTIC Science & Technology

Contents: Immunogenic activity of attenuated variant of langat virus in experiments with monkeys; Evaluation of various methods of immunization of...monkeys by variant Tr-21-237 of the langat virus; A study of residual pathogenicity of attenuated variant Tr-21-237 of langat virus in experiments...with monkeys; Pathomorphological indexes of residual neurovirulence of the attenuated variant Tr-21-237 of langat virus in experiments with monkeys.

Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Jinghua; Eng, J.; Yalow, R.S.

1990-12-01

It was reported two decades ago that insulin was not detectable in the glucose-stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled park insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report the authors describe the purification and amino acid sequences of squirrel monkey insulinmore » and glucagon. They demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in their immunoassay system is only a few percent of that of human insulin. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species.« less

Muscle Feasibility for Cosmos Rhesus

NASA Technical Reports Server (NTRS)

Edgerton, V. Reggie (Principal Investigator); Roland, Roy R.; Hodgson, John A.

1994-01-01

The following tasks were proposed for the Cosmos project: 1) Complete recordings of all preflight candidates during performance of a foot pedal motor control task while in the space capsule mock-up. 2) Complete recordings of all preflight candidates during locomotion and postural tasks. 3) Complete recordings of 24-hour spontaneous cage activity in the two flight monkeys before and after flight and of at least three control (non-flight) monkeys after the flight has been completed. 4) Complete recordings of the foot pedal and motor control tasks during flight and postflight as scheduled. 5) Complete recordings of the vertical drop test pre, during and postflight for the two flight and three control monkeys. 6) Complete recordings of locomotion and posture tests of the two flight monkeys postflight. 7) Complete recordings of locomotion and postural tests of at least three control (non-flight) monkeys during the postflight period. 8) Recalibrate buckles of the two flight and of at least three control monkeys postflight. 9) Complete analysis of the 24 hour EMG recordings of all monkeys. 10) Complete analysis of the foot pedal, locomotor and postural motor control tasks for the two flight and three control monkeys. It was proposed that efforts in the first postflight year be concentrated on the two flight animals and three postflight animals.

Immunization with Recombinant Helicobacter pylori Urease in Specific-Pathogen-Free Rhesus Monkeys (Macaca mulatta)

PubMed Central

Solnick, Jay V.; Canfield, Don R.; Hansen, Lori M.; Torabian, Sima Z.

2000-01-01

Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and documented to be free of H. pylori were vaccinated with orogastric (n = 4) or intramuscular (n = 5) urease. Two control monkeys were sham vaccinated. All monkeys were challenged with a rhesus monkey-derived strain of H. pylori, and the effects of vaccination were evaluated by use of quantitative cultures of gastric tissue, histology, and measurement of serum immunoglobulin G (IgG) and salivary IgA. Despite a humoral immune response, all monkeys were infected after H. pylori challenge, and there were no differences in the density of colonization. Immunization with urease therefore does not fully protect against challenge with H. pylori. An effective vaccine to prevent H. pylori infection will require different or more likely additional antigens, as well as improvements in the stimulation of the host immune response. PMID:10768944

Goal-directed tail use in Colombian spider monkeys (Ateles fusciceps rufiventris) is highly lateralized.

PubMed

Nelson, Eliza L; Kendall, Giulianna A

2018-02-01

Behavioral laterality refers to a bias in the use of one side of the body over the other and is commonly studied in paired organs (e.g., hands, feet, eyes, antennae). Less common are reports of laterality in unpaired organs (e.g., trunk, tongue, tail). The goal of the current study was to examine tail use biases across different tasks in the Colombian spider monkey ( Ateles fusciceps rufiventris ) for the first time (N = 14). We hypothesized that task context and task complexity influence tail laterality in spider monkeys, and we predicted that monkeys would exhibit strong preferences for using the tail for manipulation to solve out-of-reach feeding problems, but not for using the tail at rest. Our results show that a subset of spider monkeys solved each of the experimental problems through goal-directed tail use (N = 7). However, some tasks were more difficult than others, given the number of monkeys who solved the tasks. Our results supported our predictions regarding laterality in tail use and only partially replicated prior work on tail use preferences in Geoffroy's spider monkeys ( Ateles geoffroyi ). Overall, skilled tail use, but not resting tail use, was highly lateralized in Colombian spider monkeys. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Monkey-based research on human disease: the implications of genetic differences.

PubMed

Bailey, Jarrod

2014-11-01

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.