bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal parasitism—protozoa and helminths—in primates at the Barcelona Zoo
Authors: Gómez M. Soledad , Gracenea Mercedes , Montoliu Isabel , Feliu Carlos , Monleon Antonio , Fernandez Jesús , Enseñat Conrad
Published: September 2011

Abstract: The faunistic results regarding intestinal parasitism by protozoa and helminths in 21 primate species (three Cebidae, thirteen Cercopithecidae, one Hylobatidae, one Lemuridae, three Pongidae) are reported. The primate species were housed in four separate galleries. Six faecal samples of each host species were subjected to coprological analysis. Fifteen parasite species were detected: 11 protozoa (Entamoeba coli, E. chattoni, E. hartmanni, Iodamoeba bütschlii, Endolimax nana, Giardia intestinalis, Chilomastix mesnilii, Enteromonas hominis, Trichomonas intestinalis, Balantidium coli, and Blastocystis hominis) and 4 helminths (Ancylostoma sp., Strongyloides fuelleborni, Strongyloides sp., and Trichuris trichiura). The results reveal certain parasitic similarities between host species housed in the same gallery; however, these primate species do not always carry identical parasite species.
Leukocyte trafficking in free‐flowing cerebrospinal fluid of normal rhesus macaques (Macaca mulatta)
Authors: Hou Fang‐Yao , Coe Christopher L. , Erickson Chris
Published: September 2011

Abstract: Cellular components in free‐flowing cerebrospinal fluid (CSF) of normal rhesus macaques were characterized. Microscopic counting enumerated the total number of leukocytes, percentage of polymorphonuclear cells (PMN), leukocytes with nonspecific esterase (NSE), and those reducing nitro blue tetrazolium (NBT). Flow cytometric analysis further identified CD4, CD8, CD14, and CD20 positive leukocytes. These experiments established reliable techniques for evaluating cellular components in CSF from rhesus macaques and documented the difference in the CD4/CD8 ratio between peripheral blood (PB) and CSF compartments under normal physiological conditions.
Subcutaneous rabies vaccination of pigtail macaques
Authors: Nieves Pablo , Rodriguez Jose F. , Kessler Matt J. , Bercovitch Fred
Published: September 2011

Abstract:Nonhuman primates housed in outside cages in rabies enzootic areas should be vaccinated against rabies because of the risk of exposure to rabid wildlife. This article reports that vaccination with an inactivated rabies vaccine for domestic animals induced levels of neutralizing antibodies against rabies in pigtail macaques (Macaca nemestrina) without causing adverse reactions.
Serum and urine biochemical diversity among adult wild‐caught Aotus nancymae and Saimiri peruviensis
Authors: Weller Richard E. , Buschbom Raymond L. , Málaga Carlos A , Kimsey Barbara B. , Ragan Harvey A.
Published: September 2011

Serum and urine analytes were compared between adult wild‐caught owl monkeys (Aotus nancymae) and adult wild‐caught squirrel monkeys (Saimiri peruviensis) to determine if normative clinical pathology data were similar. An objective of the study was to confirm that species of neotropical primates are distinct with regard to physiologic parameters, and should not be considered interchangeable in biomedical research. Significant differences (P < 0.05) were noted in many serum and urine analytes between the two groups. The results suggest that reference data for wild‐caught owl monkeys are not applicable to squirrel monkeys, and the differences are sufficiently large to be of clinical significance. These findings illuminate the diversity among species of neotropical primates.
Characterization of centchroman binding protein in plasma of rhesus monkey (Macaca mulatta)
Authors: Agnihotri Anila , Srivastava A.K. , Kamboj V.P.
Published: September 2011

Centchroman, a nonsteroidal antifertility agent was studied for its binding to monkey (Macaca mulatta) plasma proteins using charcoal adsorption and electrophoretic techniques. 14C‐centchroman showed a low affinity binding and did not compete for 3H‐cortisol or 3H‐DHT binding sites in plasma. 14C‐centchroman binding protein was heat stable in nature and showed the electrophoretic pattern similar to that of albumin (Rf 0.70). Thus centchroman binds to albumin in monkey plasma which can be suggested as carrier protein for this contraceptive agent.
CD8+ cell‐mediated immune responses: Relation to disease resistance and susceptibility in lentivirus‐infected primates
Authors: Buijs L. , Bogers W.M.J.M. , Eichberg J.W. , Heeney J.L.
Published: September 2011

Abstract: Immune responses mediated by CD8+ lymphocytes have been correlated with protection from HIV infection and disease progression in humans and nonhuman primates. The CD8+ cell population is heterogeneous in terms of biological function and phenotype. We have undertaken a review of the current state of knowledge of subtypes of CD8+ cells and their role in immune responses directed to HIV and related primate lentiviruses. Differences in the pathogenesis of lentivirus infections in various primate hosts were examined and the possible roles of the various subpopulations of CD8+ lymphocytes in the resistance and/or susceptibility to lentivirus‐related disease were compared.
Flow cytometric analysis on reactivity of human T lymphocyte‐specific and cytokine‐receptor‐specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and squirrel monkey (Saimiri sciureus)
Authors: Ozwara Hastings , Niphuis Henk , Buijs Leo , Jonker Margreet , Heeney Jon L. , Bambra Charanjit S. , Thomas Alan W. , Langermans Jan A.M.
Published: September 2011

Abstract: There are relatively few monoclonal antibodies (mAb) that have been characterized for their applicability in studies on the immune system of various nonhuman primates. In the present study, we identified a large number of mAb that can be used in future immunological studies in three different nonhuman primates, i.e., chimpanzees, rhesus macaques, and squirrel monkeys. The reactivity of 161 anti‐human mAb to T‐cell antigens and cytokine receptors were tested on peripheral blood mononuclear cells (PBMC) from the three primate species by flow cytometric analysis. A total of 105 (65%), 73 (45%), and 68 (42%) antibodies reacted with PBMC from chimpanzees, rhesus macaques, and squirrel monkeys, respectively. Out of the 161 mAb, 38 reacted with all three species and 112 reacted with one or two of the species. No specific reaction was observed with mAb to receptors to GM‐CSF, 4–1BB, FLT3, FLX2, common β‐chain, IL‐1 (type I receptor), and IL‐8.
Doppler echocardiographic reference values for healthy rhesus monkeys under ketamine hydrochloride sedation
Authors: Korcarz Claudia E. , Padrid Philip A. , Shroff Sanjeev G. , Weinert Lynn , Lang Roberto M.
Published: September 2011

Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler‐Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non‐human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques.

Cardiac ultrasound is a noninvasive technique that is commonly used to serially evaluate cardiac structure and function. Recent advances in Doppler‐Echocardiography enable the ultrasonographer to perform a sophisticated noninvasive assessment of cardiovascular physiology. The Rhesus monkey is a frequently used non‐human primate animal model of human cardiovascular disease because this species closely models human anatomy and physiology. However, while this species is frequently used in cardiovascular research, standardized echocardiographic values generated from large numbers of normal Rhesus are not available. In the present study, we performed cardiac ultrasound imaging on 28 healthy Rhesus monkeys to obtain normal reference values of cardiovascular structure and function in this species. Nomograms were generated from these data by plotting parameters of cardiovascular geometry and function with body weight. These normal reference data were compared to previously reported values obtained from prior studies that used noninvasive, invasive, and morphometric techniques.
Frequency of spontaneous congenital defects in rhesus and cynomolgus macaques
Authors: Peterson P.E. , Short J.J. , Tarara R. , Valverde C. , Rothgarn E. , Hendrickx A.G.
Published: September 2011

Abstract: This paper summarizes the spontaneous incidence of congenital defects in the rhesus and cynomolgus macaque colonies (Macaca mulatta and M. fascicularis) at the California Regional Primate Research Center. The computerized database used in this analysis included fetuses, term infants, juveniles, and adults that underwent a necropsy procedure over a 14‐year period (1983–1996). The calculated malformation rates were 0.9% (40/4,390) and 0.3% (3/965) for the rhesus and cynomolgus monkey, respectively. Most of the observed malformations in both species affected the musculoskeletal and the cardiovascular systems, while a smaller number of defects were observed in the gastrointestinal, urogenital, endocrine, and central nervous systems. Inbreeding did not contribute to the spontaneous malformation incidence and there was no predilection for sex (male vs. female) or housing (indoors vs. outdoors) among the malformed cases. This spontaneous malformation database in our macaque colony aids in the interpretation of defects that occur in an experimental study as well as in the ongoing assessment of a healthy nonhuman primate breeding colony.
SIV/DeltaB670 transmission across oral, colonic, and vaginal mucosae in the macaque
Authors: Trichel Anita M. , Roberts E. Donald , Wilson Lawrence A , Martin Louis N. , Ruprecht Ruth M. , Murphey‐Corb Michael
Published: September 2011

Abstract: The primary mode of human immunodeficiency virus (HIV) transmission worldwide is by exposure to the virus at vaginal, rectal, and oral mucosal surfaces. To understand HIV/simian immunodeficiency virus (SIV) transmission events at mucosal portals of entry, we used the SIV‐macaque model to determine if mucosal surfaces function as barriers and select for particular viral genotypes. Rhesus macaques were inoculated intravaginally, intracolonically, intrarectally, or orally with the complex primary viral isolate SIV/DeltaB670. Peripheral blood mononuclear cells, collected within the first two weeks postinoculation, were cloned and sequenced from all infected macaques. In the majority of the animals analyzed, multiple genotypes were identified, independent of the route of infection. These findings suggest that the mucosal barrier may play a minor role in the genotypic selection observed during sexual transmission of HIV and emphasize the need to evaluate the viral diversity present within the mucosal secretions of chronically infected individuals.
Chemoattractant factors (IP‐10, MIP‐1α, IL‐16) mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques
Authors: Chéret Arnaud , Grand Roger Le , Caufour Philippe , Neildez Olivier , Matheux Frank , Théodora Frédéric , Boussin François , Vaslin Bruno , Dormont Dominique
Published: September 2011

Abstract: We have used semiquantitative RT‐PCR to monitor the expression of mRNA encoding chemoattractant factors IP‐10, MIP‐1α, and IL‐16 in freshly isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral replication (two weeks after experimental inoculation) and proinflammatory cytokine IL‐6 mRNA expression, high levels of MIP‐1α and IP‐10 mRNA were produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked progressive overexpression of IFN‐γ mRNA coinciding with an increase in the CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL‐16 mRNA. Our results suggest the role of chemokines IP‐10, MIP‐1α, and IL‐16 in the development of inflammatory and immune responses during the early stages of lentiviral infection.
Chimpanzee lipoprotein(A): Relationship between apolipoprotein(A) isoform size and the density profile of lipoprotein(A) in animals with different heterozygous apo(A) phenotypes
Authors: Doucet Chantal , Wickings Jean , Chapman John , Thillet Joëlle
Published: September 2011

In a previous study [C. Doucet et al., J. Lipid Res 35:263–270, 1994], we have shown that plasma lipoprotein (a) [Lp(a)] levels were significantly elevated in a population of unrelated chimpanzees as compared to those in normolipidemic human subjects. Nonetheless, the inverse correlation between Lp(a) levels and apolipoprotein (a) [apo(a)] isoforms typical of man was maintained in the chimpanzee. In the present study, we describe the density profiles of apo B‐ and apo A1‐containing lipoproteins and of Lp(a) in chimpanzee plasmas heterozygous for apo(a) isoforms after fractionation by single spin ultracentrifugation in an isopycnic gradient. The distribution of apo(a) isoforms in the density gradient was also examined by SDS‐agarose gel electrophoresis and immunoblotting using chemiluminescence detection. In all double‐band phenotypes examined, the smallest isoform was present along the entire length of the density gradient. The density distribution of the second isoform varied according to the size difference between the respective isoforms. Two isoforms close in size (difference in apparent molecular mass ? 60 kDa) were present together in every gradient subfraction. On the contrary, when the two isoforms displayed distinct molecular mass (maximal difference in apparent molecular mass = 340 kDa), then the largest was principally present in the densest fractions of the gradient (d > 1.1 mg/ml). These observations suggest that Lp(a) particles with small apo(a) isoforms are more susceptible to interact with other lipoproteins than are Lp(a) particles with large isoforms.
Estimation of gestational ages in the common marmoset (Callithrix jacchus) from published prenatal growth curves
Authors: Tardif Suzette D. , Jaquish Cashell E. , Toal Robert L. , Layne Donna G. , Power Rachel A.
Published: September 2011

This report compares estimated gestational ages from published cubic spline curves to gestational ages estimated retrospectively from delivery dates in 28 pregnancies from ten common marmosets (Callithrix jacchus). Both CRL‐ and BPD‐based estimates of gestational age were closely correlated with delivery‐based gestational age estimates. Of the three ultrasound machines used, the one with 16 shades of gray and a sequential linear array overestimated gestational age during early pregnancy, based on CRL measures. Measures from the other two machines (64 or 264 shades of gray; linear sector and annular array or electronic phase array) were similar and resulted in a correlation of the two estimates of gestational age of 0.94 and a mean difference between the two estimates of 0.16 days with 80% of CRL‐based gestational age estimates being within ± 5 days of the delivery‐based estimate. The reliability of BPD‐based estimates of gestational age was strongly related to pregnancy outcome. BPD‐based estimates underestimated gestational age in poor outcome pregnancies (i.e., those in which infants died within 7 days of birth) but not in good outcome pregnancies. The combined CRL‐ and BPD‐based estimates on poor outcome pregnancies suggest that there was less growth in BPD in late gestation for those pregnancies that resulted in nonviable offspring. For good outcome pregnancies, the correlation between BPD‐based and delivery‐based estimates of gestational age was 0.871 and the mean difference between the two estimates was −0.06 days with 83.3% of BPD‐based estimates falling within ± 5 days of delivery‐based estimates.
Intestinal Cryptococcosis in a common marmoset (Callithrix jacchus)
Authors: Juan‐Sallés Carles , Marco Alberto , Domingo Mariano
Published: September 2011

Abstract: A five‐year‐old female common marmoset (Callithrix jacchus) died after a one‐month clinical course of nonspecific signs. Pathologic findings were acute diffuse fibrinonecrotizing enteritis and granulomatous endolymphangitis of intestinal and mesenteric lymphatic vessels. Both lesions were associated with a marked proliferation of Mayer's mucicarmine‐positive, 4 to 15 μm yeasts that were surrounded by a wide clear halo. The infection was probably acquired by oral route. Other findings included moderate multifocal granulomatous and necrotizing hepatitis and mesangial nephropathy. Although the immunological status of this marmoset was unknown, cryptococcosis might induce primary lethal intestinal infections in callitrichids.
Retinoid teratogenicity in the macaque: Verification of dosing regimen
Authors: Hendrickx A.G. , Tzimas G. , Korte R. , Hummler H.
Published: September 2011

Abstract: To further define teratogenicity associated with 13‐cis‐retinoic acid (13‐cis‐RA) in the cynomolgus monkey, the drug was orally administered on three different treatment regimens. Experiment (Exp.) 1 (2.5 mg/kg/day, gestational day [GD] 12–27, n = 11) investigated the teratogenicity of a single daily dose of 13‐cis‐RA administered shortly after embryo implantation. Pharmacokinetic sampling was done to determine retinoid profiles on the first (GD12) and last (GD27) days of treatment. Exposure to 13‐cis‐RA during early organogenesis in Exp. 2 (2.5 mg/kg/day, GD20–27, and 2 × 2.5 mg/kg/day, GD28–30, n = 5) investigated the potential adverse effects of 13‐cis‐RA on the developing limb. The use of multiple doses of 13‐cis‐RA in Exp. 3 (2 × 2.5 mg/kg/day, GD26–27, n = 5) investigated the necessity of double dosing on the induction of retinoid embryopathy in the macaque. Malformations of retinoid target organs as well as embryolethality were most prevalent when single daily doses of 13‐cis‐RA were administered during pre‐ and early organogenesis in Exp. 1. Moreover, multiple doses on GD26–27 failed to induce any manifestation of abnormal development in Exp. 3. These results confirm that the lowest observed adverse effect level (LOAEL) in macaques is 2.5 rather than 5.0 times greater than that observed in human pregnancies. Exposure during forelimb development (GD20–30) in Exp. 2 was unsuccessful in inducing defects of this skeletal region, although defects in several retinoid target organs (i.e., cerebellum and internal ear) were present, indicating that a teratogenic threshold was achieved. Pharmacokinetic analysis of 13‐cis‐RA and its metabolites on GD12 and 27 in Exp. 1 showed considerable exposure to the administered drug and its 4‐oxo‐metabolite. In contrast, the exposure to all‐trans‐RA was negligible. The results support the use of a specific treatment schedule in early gestation in the macaque as the most appropriate model for characterizing the teratogenic potential of retinoids in humans.
Gastrointestinal tumors observed in nonhuman primates at the German primate center
Authors: Brack Manfred
Published: September 2011

Abstract: Twenty‐six gastrointestinal tumors were observed in twenty‐three nonhuman primates during routine necropsies at the German Primate Center, Göttingen. The majority (15 cases) were colorectal mucoid adenocarcinomas in cotton‐top tamarins (Saguinus oedipus), which in two animals were associated with gastric adenomas. Three cases of small intestinal mucoid adenocarcinomas occurred in common marmosets (Callithrix jacchus). One colonic leiomyoma was observed in a dwarf galago (Galagoides demidovii) and another one in a cotton top tamarin. Singular findings were a tubular adeno‐carcinoma of the ileo‐caecal valve in a saddle‐backed tamarin (Saguinus fuscicollis) and a lymphosarcoma of jejunum, ileum, and colon in another saddle‐backed tamarin. Multiple tubular adeno‐carcinomas of the colonic diverticles occurred in an aged rhesus monkey (Macaca mulatta). The findings are discussed in comparison to the situation in man.
The role of type‐1 and type‐2 T‐helper immune responses in HIV‐1 vaccine protection
Authors: Heeney Jonathan L , van Gils Mariëlle E. , van der Meide Peter , Morghen Carlo de Giuli , Ghioni Cristina , Gimelli Margherita , Raddelli Antonio , Davis David , Akerblom Lennart , Morein Bror
Published: September 2011

Abstract: The dichotomy of type‐1 and type‐2 T‐helper (Th) immune responses is thought to be an obstacle to develop Human immunodeficiency virus‐type‐1 (HIV‐1) vaccines capable of inducing effective cellular as well as humoral immune responses. Macaca mulatta were immunized using two different HIV‐1sf2 envelope vaccine strategies, based on either immune‐stimulating complexes (ISCOM) or chimeric Fowlpox (FP) vaccines. One month following the third immunization all animals were heterologously challenged with simian/human immunodeficiency virus (SHIVsf13). Vaccinated monkeys, which were protected had the highest levels of both type‐1 and type‐2 HIV‐1 specific T‐helper cell (Th) responses in addition to the highest homologous and heterogenous virus neutralizing antibodies. To determine how long Th responses persisted and if they correlated with protection, animals were re‐challenged after waiting for four months without re‐boosting. Macaques which maintained the highest gp120‐specific type‐1 (IFN‐γ) responses were protected, while there was evidence of viral clearance in two others. These findings demonstrate the importance of both or mixed type‐1 and type‐2 Th responses in HIV‐1 vaccine induced immunity while suggesting a possible role of persistent type‐1 responses in maintaining protective immunity over time.
Natural history of SIVmac BK28 and H824 infection in Macaca nemestrina
Authors: Mulvania Thera , Coon Eva , Kuller LaRene , Agy Michael B. , Morton William R. , Mullins James I.
Published: September 2011

Abstract: The natural histories of disease progression induced by two closely related molecular clones of SIVmac were evaluated to determine the utility of these viruses for modeling fast and slow progression to AIDS in Macaca nemestrina. Viral and immune parameters were measured to determine differential progression. Survival time, viral load and CD4+ T cell decline all were indicative of distinct rates of progression, while early measurements of interferon‐gamma (IFNγ) producing cells did not indicate significant differences.
Fetal growth in the baboon during the second half of pregnancy
Authors: Tame J.D. , Winter J.A. , Li C. , Jenkins S. , Giussani D.A. , Nathanielsz Peter W.
Published: September 2011

The normal growth profile of critical fetal organs through the last third of gestation has not been documented in detail in human fetuses or the fetus of any nonhuman primate species. Recent epidemiological studies in human pregnancy suggest that fetal growth plays a major role in the programming of life‐long health by modifying cardiovascular, pancreatic, brain, and liver growth. The present study aimed to produce a detailed database of individual organ growth in the fetal baboon in late gestation. Fetal organ weights were obtained from 43 baboon fetuses between 121 and 177 days of gestation. Various organs (brain, heart, kidney, femur, intestines, and spinal cord) showed no sign of slowed growth in late gestation while growth of others (lung, liver, stomach, and bladder) accelerated in late gestation. The fetal adrenal and thymus showed a decrease in growth rate over the final 20 and 10 days of gestation respectively. These observations provide a database that will permit analysis of factors responsible for regulation of normal and altered fetal organ development in this important experimental species.
Plasma and red blood cell total phospholipid fatty acid status of nonpregnant female Vervet monkeys (Cercopithecus aethiops) on a high carbohydrate maintenance diet
Authors: Tichelaar H.Y. , van Jaarsveld P.J. , Smuts C.M. , Marais M. , Mdhluli M.C. , Kruger M. , Benadé A.J.S.
Published: September 2011

Nonhuman primates are of interest as models of human physiology to study the effect of multiple pregnancies on birth weight. Reference plasma and red blood cell (RBC) total phospholipids fatty acids were established in nonpregnant breeding female Vervet monkeys. Twenty‐three clinically healthy nonpregnant Vervet monkeys (Cercopithecus aethiops), contained in a controlled closed environment and consuming a high carbohydrate diet (68 E%) that contained 20 E% fat and 12 E% protein were sampled for blood during a cross‐sectional study. A low intake of ω3 fatty acids was reflected by a high ω6/ω3 ratio (66:1) of the diet. Inverse relations were seen between plasma and RBC total phospholipid fatty acids, 18:2ω6, 20:3ω6, and 20:4ω6, which suggested selective incorporation in membranes. Low levels of 20:5ω3 and 22:6ω3 of plasma and RBC total phospholipids render Vervet monkeys as ideal subjects to study the effect of ω3 fatty acid supplementation on pregnancy outcomes.

Tichelaar HY, van Jaarsveld PJ, Smuts CM, Marais M, Mdhluli MC, Kruger M, Benadé AJS. Plasma and red blood cell total phospholipid fatty acid status of nonpregnant female Vervet monkeys (Cercopithecus aethiops) on a high carbohydrate maintenance diet. J Med Primatol 1998; 27:240–243. © Munksgaard, Copenhagen
Fatal outbreaks of proliferative enteritis caused byLawsonia intracellularisin young colony‐raised rhesus macaques
Authors: Klein E.C. , Gebhart C.J. , Duhamel G.E.
Published: September 2011

Abstract:Ten juvenile rhesus monkeys (Macaca mulatta) died acutely in two separate disease outbreaks. The animals had segmental thickening of the distal ileum with associated proliferative, rugous appearing mucosae. Microscopically, necrosis, exudative inflammation, mucosal ulceration, and crypt hyperplasia were present. Intracellular organisms were seen histochemically and ultrastructurally, and were confirmed to beLawsonia intracellularisusing a specific immunohistochemical method. Proliferative enteropathic conditions caused byL. intracellularisare reported in an ever‐increasing range of hosts, suggesting that the infection may exist unrecognized in an even greater array of species, possibly including man.
Localization of immunoreactive testosterone and 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase in cynomolgus monkey (Macaca fascicularis) testes during postnatal development
Authors: Liang Ji‐Hong , Sankai Tadashi , Yoshida Takashi , Cho Fumiaki , Yoshikawa Yasuhiro
Published: September 2011

Abstract: The age‐related expression of testosterone and 3β‐HSD in the testes of cynomolgus monkeys was detected using light‐microscopic immunocytochemistry. Intense deposits of immunoreactive testosterone were labeled in parts of Leydig cells in neonatal, late infantile, pubertal, and adult testes, and only a few Leydig cells in early infantile testes. The immunoreactive 3β‐HSD was labeled in parts of Leydig cells and in all Sertoli cells in neonatal, late infantile, pubertal, and adult testes, whereas only a few Leydig cells, but no Sertoli cells, were labeled in early infantile testes. The fluctuations of testosterone and 3β‐HSD expression in testes correlated well with those already observed plasma testosterone levels during postnatal development in cynomolgus monkeys.
Unrearable litters and prenatal reduction of litter size in the common marmoset (Callithrix jacchus)
Authors: Windle Colin P. , Baker Harry F. , Ridley Rosalind M. , Oerke Ann‐Kathrin , Martin Robert D.
Published: September 2011

Abstract: It is widely believed that common marmosets (Callithrix jacchus) typically give birth to twins under natural conditions. In captivity, however, births of triplets or even larger litters are common, although parents rarely succeed in rearing more than two offspring. The traditional interpretation is that captive conditions, notably the ready availability of food, have led to increased reproductive output, perhaps involving a higher ovulation rate. The present paper provides evidence, combined from ultrasound examinations between ovulation and birth and hysterotomies conducted during the late embryonic and early fetal phase, that the litter size can be progressively reduced during pregnancy without spontaneous abortion. There is an unusually long lag phase prior to the onset of embryonic growth in common marmosets; the fetal stage does not begin until day 80 of the 144‐day pregnancy. Reduction in litter size occurs during embryonic stages (up to day 80), and continues into the fetal stages. These results indicate that the common marmoset is adapted for flexible modification of litter size between ovulation and birth. The high incidence of triplet births in captive colonies may therefore be an expression of an adapted natural developmental process under artificial circumstances.
A cerebral primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus)
Authors: Johnson Eugene H. , Chima Sylvester C. , Muirhead David E.
Published: September 2011

Abstract: An adult squirrel monkey with a history of long‐term exposure to microwave radiation was found at necropsy to have a malignant tumor of the right cerebral cortex. Gross examination revealed a mass with expanding borders in the right frontoparietal cortex with compression of the adjacent lateral ventricle. Microscopy revealed a tumor composed of sheets of moderate‐sized cells, resembling an oligodendroglioma, with clear cytoplasm and central nuclei interrupted by delicate vasculature. Malignant features were present in the form of marked nuclear pleomorphism, frequent mitotic figures, and focal necrosis. A neuronal cell origin for this tumor was supported by immunohistochemical analysis, which revealed immunopositivity for neurofilament proteins and neuron‐specific enolase. Staining for vimentin and glial fibrillary acid protein was negative, except in reactive astrocytes at the tumor margins and adjacent to intra‐tumoral blood vessels. Antibody activity against Ki‐67 antigen, a marker of rapidly proliferating tumor cells, and p53 oncoprotein was strongly positive, indicative of the aggressive and malignant nature of this tumor. The tumor was diagnosed as a cerebral primitive neuroectodermal tumor.
Anti‐human red cell monoclonal antibodies produced by macaque–mouse heterohybridomas: Their reactivity with human and nonhuman primate erythrocytes
Authors: Blancher A. , Roubinet F. , Reld M. , Socha W.W.
Published: September 2011

Abstract: Eighteen monoclonal antibodies (Mabs) against human red blood cells (RBCs) produced by macaque–mouse heterobybridomas gave uniformly positive reactions with all human samples except for some with particular null phenotypes. Based on reactions with latter cells, the human antigenic targets of 11 antibodies could be identified: six were specific for glycophorin‐related antigens (Wrb, Ena, Ge4), and each of the five remaining antibodies showed one of the following specificities: CD55, CD44, CD59, Kell, and Rh proteins. Four Mabs recognized the Vc antigen of the chimpanzee V‐A‐B‐D system. Six macaque Mabs detected polymorphisms in chimpanzee, gorilla, orangutan, and gibbon that did not correspond to any known blood group in these animals, while other Mabs gave monomorphic reactions with ape RBCs. The reagents produced by macaque hybridomas are useful tools not only for human blood grouping tests, but also for tracing the relationships among blood group antigens of man and anthropoid apes.
In vivo adaptation of SHIVSF162: Chimeric virus expressing a NSI, CCR5‐specific envelope protein
Authors: Tan Rei Chin How , Harouse Janet M. , Gettie Agegnehu , Cheng‐Mayer Cecilia
Published: September 2011

Abstract: The chemokine receptor CCR5 is known to be a critical determinant of human immunodeficiency virus (HIV) transmission and pathogenesis in the human host. Towards the development of a macaque model to evaluate the efficacy of vaccines and therapeutics against infection with CCR5‐specific viruses, and to delineate the pathogenic properties of such viruses, we constructed a chimeric simian human immunodeficiency virus, SHIVSF162, containing the env, tat, rev, and vpu genes from HIV‐1SF162 (R5, MT/NSI) in the context of the molecular clone simian immunodeficiency virus, SIVmac239. Virus generated from this molecular clone was used to intravenously infect two juvenile macaques, followed by three consecutive serial blood/bone marrow transfusions. Animals infected with parental SHIVSF162 (P1) had detectable levels of viral replication (as determined by p27gag production) within days of infection; however, viral set‐points fell below detection by Week 3. Late passage animals (P3 and P4) had a two‐log increase in the level of plasma p27gag antigen. These results demonstrate that in vivo serial passage of the R5‐specific SHIVSF162 enhanced its replicative capacity.
The disruption of macaque CD4 + T‐cell repertoires during the early simian immunodeficiency virus infection
Authors: Zhou Dejiang , Kou ZhongChen , Ibegbu Chris , Shen Yun , Lee‐Parritz David , Shen Ling , Sehgal Prabhat K. , McClure Harold M. , Morrison Paul , Bogle Christine , Sehgal Neetu , Nahmias Andre J. , Chen Zheng W.
Published: September 2011

Abstract: T‐cell receptor (TCR) complementarity determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4 + T‐cell repertoires during the primary infection. Rhesus and pig‐tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4 + peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple‐length distribution to one‐ or two‐length dominance in the selected TCR Vβ‐expressing CD4 + PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4 + T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4 + T‐cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus‐induced clonal dominance can contribute to the disruption of CD4 + T‐cell repertoires.
An anti‐HIV strategy combining chemotherapy and therapeutic vaccination
Authors: Rosenwirth B. , Bogers W.M.J.M. , Nieuwenhuis I.G. , Ten Haaft P. , Niphuis H. , Kuhn E.M. , Bischofberger N. , Erfle V. , Sutter G. , Berglund P. , Liljestrom P. , Uberla K. , Heeney J.L.
Published: September 2011

Abstract: Combination chemotherapy using potent anti‐retroviral agents has led to significant advances in the clinical management of human immunodeficiency virus (HIV) disease. However, the emergence of multiple drug‐resistant mutants, the high need for compliance to adhere to demanding drug‐dosing schemes, and the remaining toxic side‐effects of drugs make the perspective of life‐long treatment unattractive and possibly unrealistic. Therefore, means must be sought to shorten the time span during which treatment is necessary. Such means could be to stimulate an efficient immune response during the period of low virus load and restored CD4 + cell levels, which might be capable of keeping the virus under long‐lasting control after treatment is stopped. Here we tested this concept of combined chemotherapy/therapeutic vaccination in a non‐human primate model. Rhesus macaques chronically infected with the chimeric simian/human immunodeficiency virus (SHIV) containing the HIV type 1 (HIV‐1) HXBc2 gene for reverse transcriptase (RT) in the genomic background of simian immunodeficiency virus (SIV)mac239 (RT‐SHIV) were treated with (R)‐9‐(2‐phosphonylmethoxypropyl)adenine (PMPA), a potent anti‐HIV drug. When virus load had decreased significantly, we immunized with SIV genes env, gag/pol, rev, tat, and nef inserted in two different expression vector systems. Four weeks after the second immunization, drug treatment was stopped. Animals were monitored to determine if virus load stayed low or if it increased again to the original levels and if CD4 + T‐cell levels remained stable. Humoral and cellular immune responses were also measured. This combined chemotherapy/therapeutic vaccination regimen induced a significant reduction in the steady‐state level of viremia in one out of two chronically infected rhesus macaques. Chemotherapeutic treatment alone did not achieve reduction of viremia in two chronically infected animals. The nature of the immune responses assumed to have been induced by vaccination in one out of the two monkeys remains to be elucidated.
Antigen‐specific humoral and cellular immune responses can be modulated in rhesus macaques through the use of IFN‐γ, IL‐12, or IL‐18 gene adjuvants
Authors: Kim Jong J. , Nottingham Liesl K. , Tsai Anthony , Lee Daniel J. , Maguire Henry C. , Oh Jim , Dentchev Tzvete , Manson Kelledy H. , Wyand Michael S. , Agadjanyan Michael G. , Ugen Kenneth E. , Weiner David B.
Published: September 2011

Abstract: DNA or nucleic acid immunization has been shown to induce both antigen‐specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced and modulated by the use of molecular adjuvants. To engineer the immune response in vivo towards more T‐helper (Th)1‐type cellular responses, we investigated the co‐delivery of inteferon (IFN)‐γ, interleukin (IL)‐12, and IL‐18 genes along with DNA vaccine constructs. We observed that both antigen‐specific humoral and cellular immune responses can be modulated through the use of cytokine adjuvants in mice. Most of this work has been performed in rodent models. There has been little confirmation of this technology in primates. We also evaluated the immunomodulatory effects of this approach in rhesus macaques, since non‐human primates represent the most relevant animal models for human immunodeficiency virus (HIV) vaccine studies. As in the murine studies, we also observed that each Th1 cytokine adjuvant distinctively regulated the level of immune responses generated. Co‐immunization of IFN‐γ and IL‐18 in macaques enhanced the level of antigen‐specific antibody responses. Similarly, co‐delivery of IL‐12 and IL‐18 also enhanced the level of antigen‐specific Th proliferative responses. These results extend this adjuvant strategy in a more relevant primate model and support the potential utility of these molecular adjuvants in DNA vaccine regimens.
Efforts to broaden HIV‐1‐specific immunity by boosting with heterologous peptides or envelope protein and the influence of prior exposure to virus
Authors: Verschoor Ernst J. , Davis David , van Gils Mariëlle , Koopman Gerrit , Mooij Petra , Oostermeijer Herman , Haaft Peter Ten , Verstrepen Babs , Rosenwirth B. , Morein Bror , Barnett Susan W. , Heeney Jonathan L.
Published: September 2011

Abstract: In two previous studies, we have demonstrated the successful protection of human immunodeficiency virus type 1 (HIV‐1)‐vaccinated rhesus macaques from challenge with SHIVSF13 with envelop immunogens derived from the closely related HIV‐1SF2 strain. Here we report on two follow‐up studies in which we aimed to broaden immunity in order to elicit protection from a more diverse heterologous challenge with SHIVSF33. In the first study, animals were boosted once with HIV‐1SF33 V2 and V3 peptides that were cross‐linked to influenza immunestimulating complexes (ISCOMs). In the second study, monkeys were boosted twice at 12‐week intervals, using a heterologous recombinant gp120 derived from HIV‐1SF33 that was either incorporated into ISCOMs or mixed with the MF59 adjuvant. In both studies, the animals were challenged with 50 monkey infectious doses of SHIVSF33 4 weeks after the final boost. All controls became readily infected with the heterologous challenge virus SHIVSF33. Neither boosting with heterologous SF33 peptides or gp120 afforded protection from infection to SF2‐vaccinated animals that had previously resisted SHIVSF13 challenge. These results demonstrate the importance of developing vaccine strategies that are capable of generating broad immune responses early in the immunization protocol. Furthermore, these findings may illustrate the potential pitfalls of early antigenic sin.
Measurement of serum bone‐specific alkaline phosphatase activity in cynomolgus macaques
Authors: Brommage Robert , Allison Carolyn , Stavisky Ronda , Kaplan Jay
Published: September 2011

Abstract: Serum levels of bone‐specific alkaline phosphatase activity (B‐ALP) in cynomolgus monkeys were evaluated as an index of elevated bone turnover following ovariectomy. The enzyme immunoassay 96‐well microtiter plate B‐ALP assay, developed by Metra Biosystems (Mountain View, CA) for human use, was employed and compared with a standard automated assay measuring total serum levels of alkaline phosphatase activity (T‐ALP). The B‐ALP assay was first validated for use in these monkeys. Ovariectomy led to increased bone turnover as indicated by approximately 2‐fold higher activity in both assays and this elevation was inhibited by daily estradiol administration. Although both assays provided generally similar results, several monkeys were observed to have greatly elevated values of T‐ALP but not B‐ALP. This discrepancy is believed to result from high levels of the liver isoform of alkaline phosphatase in monkeys with hepatic dysfunction, which are not detected by the B‐ALP assay.
Irsogladine maleate regulates epithelial barrier function in tumor necrosis factor‐α‐stimulated human gingival epithelial cells
Authors: Fujita T. , Yumoto H. , Shiba H. , Ouhara K. , Miyagawa T. , Nagahara T. , Matsuda S. , Kawaguchi H. , Matsuo T. , Murakami S. , Kurihara H.
Published: September 2011

Fujita T, Yumoto H, Shiba H, Ouhara K, Miyagawa T, Nagahara T, Matsuda S, Kawaguchi H, Matsuo T, Murakami S, Kurihara H. Irsogladine maleate regulates epithelial barrier function in tumor necrosis factor‐α‐stimulated human gingival epithelial cells. J Periodont Res 2012; 47: 55–61. © 2011 John Wiley & Sons A/S

Background and Objective:  As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin‐1 and E‐cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans‐stimuated chemokine secretion and E‐cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions.

Material and methods:  We examined the permeability, and the expression of claudin‐1 and E‐cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)‐α, with or without IM.

Results:  TNF‐α increased the permeability of HGECs, and IM abolished the increase. TNF‐α reduced the expression of E‐cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF‐α disrupted claudin‐1 expression in HGECs, and IM reversed this effect.

Conclusion:  The results suggest that IM reverses the TNF‐α‐induced disruption of the gingival epithelial barrier by regulating E‐cadherin and claudin‐1.
Mast cells and elastosis in ultraviolet‐irradiated hairless mice
Authors: Kaarsen L. L. , Poulsen T. D. , de Olivarius F. Fine , Wulf H. C.
Published: September 2011

Earlier studies of ultraviolet (UV) irradiated hairless mice have suggested a relation between elastosis and mast cells. To examine whether such a relation exists, we examined groups of hairless mice irradiated with equal doses of UV. The narrow UV bands had peaks at 292, 300, 307, 317 and 336 nm. The groups were irradiated 5 times per week during 1 year. It was shown that the shorter the wavelengths, the more pronounced was the degree of elastosis. Sections from dorsal skin were prepared for light microscopy and stained with orcein, making it possible to detect the elastosis at the same time as the mast cells. We used a projection microscope and a computer analyzing system connected to a video scanner for the calculations. The mast cell count was higher in the irradiated groups than in the control group. The number of mast cells was higher in the groups irradiated with the shortest wavelengths (292 and 300 nm). In groups irradiated with wavelengths shorter than 307 nm a subepidermal clearance zone containing significantly fewer mast cells than the rest of the upper dermal layer was found. We suggest that the mast cells might have a digesting function, as this layer was cleared of elastotic fibers and few mast cells were seen here.
Combination of methoxsalen and ultraviolet B (UVB) versus UVB radiation alone in treatment of psoriasis: a bilateral comparison study
Authors: Morison W. L.
Published: September 2011

A bilateral comparison study of the therapeutic effects of broad‐band ultraviolet (UVB) (FS‐40 Sunlamp bulbs) radiation versus UVB radiation plus methoxsalen was conducted in patients with psoriasis. Ten patients were given up to 30 exposures to the two treatments on paired, similarly affected limbs. There was no detectable difference in the response of limbs treated with UVB plus methoxsalen versus UVB phototherapy alone although all patients did show a therapeutic response. Other areas of the body treated with methoxsalen and broad‐band UVA radiation (PUVA bulbs) responded more rapidly and to a greater extent than areas exposed to UVB radiation.
Human protoporphyria: genetic heterogeneity at the ferrochelatase locus
Authors: Ostasiewicz L. T. , Huang J.‐L. , Wang X. , Piomelli S. , Poh‐Fitzpatrick M. B.
Published: September 2011

Inherited deficiency of ferrochelatase results in erythropoietic protoporphyria (EPP). Genetic heterogeneity at the locus for human ferrochelatase was investigated. Analysis of genomic DNA of patients with EPP and of control subjects by restriction endonuclease techniques using ten different enzymes detected polymorphisms only at sites recognized by EcoRI, HincII, PstI and TaqI. None of these polymorphisms alone was specific for expression of the disease since each was observed in control subjects as well. Three of these polymorphisms (at EcoRI, HinII and PstI sites) were always associated, indicating linkage. These and other studies demonstrate that the ferrochelatase gene is markedly heterogeneous. It is not yet clear whether some of the mutations associated with these polymorphisms contribute to expression of EPP.
Ambulatory monitoring of ultraviolet erythema in photosensitive subjects
Authors: Saunders P. J. , Diffey B. L.
Published: September 2011

Little is known about whether patients with photosensitive disorders exhibit a different ultraviolet erythema time course from subjects with a normal response to sunlight. We have described the application of an instrument for ambulatory monitoring of the development of ultraviolet erythema by a reflectance method in a group of patients with chronic actinic dermatitis (CAD) and in a group of normal subjects. Investigations of the time course have been reported previously but the techniques used relied upon manual measurement. Consequently sampling frequencies have been considerably lower than the one‐minute sample rate used here. We have not demonstrated any difference in the rate at which erythema develops and peaks between patients with CAD and subjects with a normal response to sunlight.