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At least 1,513 records · Page 84Linked to original sources
PubMed1992

Therapeutic efficacy of HI-6 in soman-poisoned marmoset monkeys.

The therapeutic efficacy of the oxime HI-6 against intoxication with the irreversible cholinesterase (ChE) inhibitor soman was tested in marmoset monkeys. Five out of six marmosets, intoxicated with 5 x LD50 soman and treated immediately with diazepam (0.2 mg.kg-1 iv) and 15 sec later with atropine (0.5 mg.kg-1 im) and HI-6 (50 mg.kg-1 im), survived for more than 24 hr. One of these animals died after 4 days. In the HI-6-treated marmosets blood ChE activity was inhibited at a rate slower than that in three animals treated similarly but with saline instead of HI-6. The latter marmosets died within 8 min after soman. HI-6 achieved its plasma peak 5 min after injection and was eliminated with a t1/2 of about 40 min. In a second experiment similarly treated marmosets were euthanized at 5 min (three saline-treated animals) or at 10 min (three HI-6-treated animals) after the soman intoxication to enable the determination of acetylcholinesterase (AChE) activities in diaphragm and brain tissue. In addition, in these animals blood AChE and butyrylcholine esterase (BuChE) activities were determined. Low AChE activities were encountered in diaphragms and brains. These levels were not significantly different between saline- and HI-6-treated marmosets. In vitro treatment with HI-6 at 40 min after soman still led to an increase of the AChE activity, which was significant in diaphragm, suggesting that postmortem AChE inhibition had occurred. The ratio of AChE to BuChE in blood was significantly enhanced in HI-6-treated animals, indicating that HI-6 preferentially reactivated AChE. It is concluded that (i) HI-6 is an effective treatment against soman poisoning in marmosets and (ii) AChE reactivation or protection by HI-6 contributed to the survival of the animals.

Acetylcholinesterase↗
PubMed1981

The relationship of DNA excision repair of ultraviolet-induced lesions to the maximum life span of mammals.

Physical and chemical agents present in the environment can potentially damage mammalian DNA. Such damage is known in some cases to be repaired by the process of DNA excision repair. This process has been extensively studied utilizing the repair of ultraviolet irradiation damage as a model system. In this study we have used this system and the 5-bromodeoxyuridine photolysis assay to measure DNA excision repair in cells derived from 21 mammalian species. We have attempted to relate the DNA repair proficiencies and the average size of the repaired regions seen in the cell cultures with the various maximum life spans of the mammals studied. There was an approximate linear correlation between life span of the mammals and the number of DNA excision repair sites measured 20-22 hours following ultraviolet irradiation of the cell cultures. Several deviations from the linear relationships were observed which remain largely unexplained. The size of the repaired regions was shown not to be related to the maximum life spans of the mammals tested.

Animals↗
PubMed1992

Histochemical characterization of the aging microvasculature in the human and other mammalian and non-mammalian vertebrates by the periodic acid-Schiff reaction.

Prior histochemical studies with the periodic acid-Schiff (PAS) reaction have shown altered biochemical composition in a limited part of the microvasculature (MV) in aging in two species of laboratory animals. We therefore studied, with the PAS reaction, all the components of the MV in multiple tissues from various immature, adult and aged mammals, including human, and immature and aged nonmammalian vertebrates. We now demonstrate that there is an altered biochemical composition of capillaries, arterioles and venules in various tissues with aging. These are first detectable somewhat beyond half the life-span in man (greater than 45 years), marmoset (5 years) and dog (8 years) and seen in old fish, reptiles and birds. The capillary wall is increasingly PAS+; in arterioles there are focal PAS+ areas in the media which increase in size and number with age and become hyalinized masses. The non-muscular venules are increasingly PAS+ apparently due to a polysaccharide staining of connective tissue elements. These histochemical changes in the MV with aging are in the extracellular matrix and appear to be a specific manifestation of aging in vertebrates. The consequences of such changes in MV aging may be important physiologically.

Adolescent↗
PubMed1994

The gastrointestinal absorption of neptunium, plutonium and americium in a primate (C. jacchus).

Mixtures of Np, Pu and Am were administered to primates (C. jacchus) by gastric intubation to measure their fractional gastrointestinal absorption (f1 values). The values obtained were about 2 x 10(-3) and 1 x 10(-3), respectively, for Np and Pu administered as the citrate, and 2 x 10(-3) and 6 x 10(-4), respectively, for Pu and Am in potato. The significance of these values in terms of absorption in humans is discussed.

Americium↗
PubMed1994

Inhibition of human platelet aggregation by GR91669, a prototype fibrinogen receptor antagonist.

In order to produce more potent and specific fibrinogen receptor (GpIIb/IIIa) antagonists, the Arg-Gly of a chemical series based upon Arg-Gly-Asp was replaced by alkyl chains of varying lengths. The most potent in this series, GR91669, inhibited aggregation of human gel-filtered platelets (GFP) in vitro induced by ADP or the thromboxane A2 mimetic, U46619, with IC50 values of 200nM and 500nM respectively and was selected for further studies. Its inhibitory effects on GFP were reversed by addition of excess fibrinogen. The compound also inhibited ADP- or U46619-induced platelet aggregation in human whole blood (IC50 values of 700nM in both cases). 125I-Fibrinogen binding to ADP-stimulated platelets was inhibited by GR91669 with an IC50 (65nM) similar to that against platelet aggregation. GR91669 (1mM) did not inhibit U46619-induced platelet shape change or 14C-5HT secretion from platelets stimulated by collagen, U46619 or thrombin. Therefore GR91669 inhibits aggregation but has no significant effect on stimulus-response events, a profile consistent with fibrinogen receptor blockade. In addition, GR91669 (1mM), unlike echistatin or Gly-Arg-Gly-Asp-Ser, did not disrupt vitronectin recptor-dependent attachment of cultured HUVECS in vitro and similarly did not inhibit Mac-1 dependent adhesion of human granulocytes. Thus, of the integrins tested, GR91669 appears to be specific for GpIIb/IIIa. Following intravenous administration to marmosets of 1 or 10 mg/kg GR91669, ADP (10 microM)-induced platelet aggregation ex vivo was abolished for 15 and 60 minutes respectively. Greater than 50% inhibition was maintained for 30 minutes and 2 hours respectively. GR91669, therefore appears to be a potent, specific fibrinogen receptor antagonist in vitro and which is also active in vivo.

Amino Acid Sequence↗
PubMed1984

Delineation of lymphocyte subsets in lymph nodes of nonhuman primates.

Monoclonal antibodies which recognize specific surface antigens on human lymphocytes were used with an avidin-biotin immunoperoxidase technique to stain lymph nodes from nonhuman primates. Cells in lymph nodes from three macaque species and two new-world primate species could be stained to define T11, T4, T8, and B1 lymphocyte subsets. This approach will facilitate the study of many important spontaneous and experimentally induced diseases of nonhuman primates.

Animals↗
PubMed1990

The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates.

The selective 5-HT3 receptor antagonist, onansetron, has been assessed in three tests of cognition in the mouse, rat and marmoset. In a habituation test in the mouse, ondansetron facilitated performance in young adult and aged animals, and inhibited an impairment in habituation induced by scopolamine, electrolesions or ibotenic acid lesions of the nucleus basalis magnocellularis. Arecoline failed to improve basal performance in young adult mice but inhibited the impairment caused by scopolamine and lesions of the nucleus basalis magnocellularis. In the T-maze reinforced alternation task in rats, ondansetron and arecoline antagonised a scopolamine-induced impairment. In an object discrimination and reversal learning task in the marmoset, assessed using a Wisconsin General Test Apparatus, ondansetron improved performance in a reversal learning task. We conclude that ondansetron potently improves basal performance in rodent and primate tests of cognition and inhibits the impairments in performance caused by cholinergic deficits.

Aging↗
PubMed1991

The effects of umespirone as a potential anxiolytic and antipsychotic agent.

Umespirone was compared to buspirone, diazepam and clozapine as a potential anxiolytic and antipsychotic agent. In the mouse black and white test box, umespirone was considerably more potent than diazepam or buspirone to reduce aversive responding, tolerance to its effects was not observed and sedation was absent, a chronic treatment and withdrawal was not associated with an anxiogenic profile, and umespirone prevented the behavioural consequences of withdrawal from diazepam. Umespirone also had an anxiolytic profile of action in the tests of rat social interaction and in the marmoset exposed to a human threat. Both umespirone and clozapine reduced the hyperactivity induced by the infusion of dopamine into the nucleus accumbens of rat. In radioligand binding assays umespirone demonstrated nanomolar affinity for the alpha 1-adrenoceptor and the 5-HT1A and dopamine D2 receptors. It is concluded that umespirone may present as a novel psychotropic agent with anxiolytic and antipsychotic potential.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset.

The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.

Animals↗
PubMed1992

Behavioural effects of anxiogenic agents in the common marmoset.

The effects of the anxiogenic agents FG7142, caffeine, pentylenetetrazole, and amphetamine were assessed in two anxiety situations in the marmoset, first in an "anxiogenic" test based on the animal's response to a human observer standing in front of the home cage and second in a low-anxiety situation where animals behaviour was videotaped in the absence of the observer. In response to the human observer, the anxiolytic agent diazepam (0.1-2.5 mg/kg, SC) was shown to reduce the intensity of behaviours such as postures, while increasing time spent on the cage front. In this test, with the exception of amphetamine, which only modified responding at stereotypic doses, the anxiogenic agents failed to modify marmoset behaviour. In contrast, in the low-anxiety filming protocol the anxiogenic agents consistently reduced measures of locomotor activity while increasing the amount of time animals spent in the nest box. It is suggested that the low-anxiety protocol may be useful to evaluate drug-induced anxiogenesis and in studies of withdrawal from chronic anxiolytic treatment or drugs of abuse.

Amphetamine↗
PubMed1995

Differential distribution of mRNA for the alpha- and beta-subunits of chorionic gonadotrophin in the implantation stage blastocyst of the marmoset monkey.

We studied the expression of mRNA encoding the alpha- and beta-subunits of marmoset chorionic gonadotrophin (mCG) in implantation stage blastocysts and in a trophoblastic cell line derived from such blastocysts. In this investigation in situ hybridization was carried out using digoxygenin-labelled riboprobes to localize the subunit transcripts. The trophoblastic cell line, known to secrete bioactive mCG, was used as a positive control. Marmoset uterine embryos were cultured to hatched blastocysts and following growth on Matrigel or plastic were processed for in situ hybridization at developmental stages ranging from 13-15 days post-conception. In serial sections mCG-beta mRNA was detected mainly in polar trophoblast. The mRNA for mCG-alpha was expressed more uniformly in polar and mural trophoblast. Transcripts for the beta-subunit were not expressed, or present as weak signals, in the inner cell mass (ICM) and endoderm. However, low levels of mRNA for mCG-alpha were detected in the ICM and visceral endoderm. We have concluded that mRNA for mCG-beta was primarily localized to patches of syncytiotrophoblast at the embryonic pole and sparsely distributed in mural trophoblast, while the transcripts for mCG-alpha were distributed more uniformly in differentiating cytotrophoblast and syncytium, and at much lower levels in ICM and early endoderm.

Animals↗
PubMed1990

Screening procedure for assessment of ototoxicity in the common marmoset.

Detection of drug-induced ototoxicity in safety evaluation studies of novel chemical entities is rarely attempted. Where such examinations are included, they usually rely on reflex testing. The Brainstem Auditory Evoked Response can be measured with the use of externally positioned electrodes, and it monitors electrophysiologic responses to sound from the cochlear nerve and associated structures of the 8th cranial nerve. These responses have been reproducibly measured in sedated marmosets and the method shown to be a sensitive detector of hearing loss caused by loop diuretics or aminoglycoside antibiotics. additionally, where hearing damage is reversible, recovery can also be monitored. It is proposed that where a sensitive marker for ototoxicity is considered necessary as part of a multifaceted study investigating in vivo drug safety, this procedure may prove advantageous over existing methods.

Animals↗
PubMed1991

A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4.

The CD4 molecule is a relatively non-polymorphic 55 kDa glycoprotein expressed on a subset of T lymphocytes. A common African allele of CD4 has been identified by non-reactivity with the monoclonal antibody, OKT4. The genetic basis for the OKT4- polymorphism of CD4 is unknown. In the present paper, the structure of the CD4 molecule from an homozygous CD4OKT4- individual was characterized at the molecular level. The size of the CD4OKT4- protein and mRNA were indistinguishable from those of the OKT4+ allele. The polymerase chain reaction (PCR) was used to map the structure of CD4OKT4- cDNAs by amplifying overlapping DNA segments and to obtain partial nucleotide sequence after asymmetric amplification. PCR was then used to clone CD4OKT4- cDNAs spanning the coding region of the entire, mature CD4 protein by amplification of two overlapping segments followed by PCR recombination. The nucleotide sequence of CD4OKT4- cDNA clones revealed a G----A transition at bp 867 encoding an arginine----tryptophan substitution at amino acid 240 relative to CD4OKT4+. Expression of a CD4OKT4- cDNA containing only this transition, confirmed that the arginine----tryptophan substitution at amino acid 240 ablates the binding of the mAb OKT4. A positively charged amino acid residue at this position is found in chimpanzee, rhesus macaque, mouse and rat CD4 suggesting that this mutation may confer unique functional properties to the CD4OKT4- protein.

Alleles↗
PubMed1994

The lack of v-src involvement in tumorigenicity of marmoset cells transformed in vitro with Rous sarcoma virus.

The transformation of nonhuman primate marmoset cells by Rous sarcoma virus of Schmidt-Ruppin strain (RSV-SR) generates transformants which lack tumorigenicity in allo- and xenogeneic hosts. Marmoset cells acquire this property when they are transformed by RSV rescued from non-tumorigenic allogeneic cells. One of the rescued RSV, when used to infect marmoset kidney cells in vitro, yielded transformants which became tumorigenic in adult allogeneic hosts. Cytogenetic and molecular analyses of transformants revealed progressive genetic changes from cell diploidy to aneuploidy and from the presence to the loss of v-src during propagation in vitro. The loss of v-src in transformed cells coincided with the evolution of aneuploid cell clone with specific marker chromosome (M1). Although both early passage diploid and late passage aneuploid transformants were tumorigenic, the induced tumors originated from different type of cells. Tumors induced by diploid- and v-src-positive transformants were derived predominantly from the host cells, while tumors induced by late-passage transformants and with deleted v-src originated from an aneuploid cell clone that contained a rearranged M1 marker chromosome. These results suggest that besides the v-src oncogene, proviral integration can facilitate chromosomal rearrangements that contribute to tumorigenic transformation of nonhuman primate cells in vitro.

Aneuploidy↗
PubMed1994

A modified procedure for the propagation of wild type Epstein-Barr virus in cultures of marmoset blood cells.

Productive infection of marmoset blood mononuclear cells by the Epstein-Barr virus was generally achieved by the co-cultivation method. By introducing 2 modifications, the success rate of infection was increased from 6% to 79%. The modifications consisted of the selection of human lymphocyte donors to serve as carriers of Epstein-Barr virus in cocultures, and the addition of cyclosporin A to culture media. So far, 10 of 10 wild type oropharyngeal EBV have been propagated successfully in cultures of marmoset blood mononuclear cells by the modified procedure. Fragment length polymorphism study failed to reveal any difference between viral genomes in human lymphocytes and that in marmoset blood mononuclear cells. Antigenic analysis of 8 wild strains showed that all were related to the B95-8 strain of Epstein-Barr virus by the neutralization test.

Animals↗
PubMed1983

Structural development of the lateral geniculate nucleus and visual cortex in monkey and man.

This study concerns the development of the primary visual pathway of the primate. The lateral geniculate nucleus (LGN) is the principal thalamic relay to the visual cortex (area 17), and its neurons have similar morphological characteristics in both monkey and man, as identified by Golgi impregnation. The commonest neuron is the multipolar with a radiate or tufted dendritic tree; next is the bipolar neuron with two or three diametrically opposed dendritic trunks. Less frequent are neurons with beaded dendrites and others with fine, axon-like dendritic processes, possibly interneurons. The dendritic tree of all neurons remains generally within a lamina, but some dendrites cross interlaminar zones. LGN neurons are identifiable before birth and differ from their adult form by the presence of immature features, especially numerous dendritic and somatic spines, most frequent at birth in monkeys and at about 4 months postnatally in man. They disappear almost completely by 3 months in monkeys and 9 months in man. The human LGN has reached its 'adult' volume by this age. Two stages in the development of the human area 17 can be defined. The first is marked by a rapid growth to its 'adult' volume by about 4 months, and by intense synaptogenesis beginning in the foetus and reaching a maximum around 8 months. The second stage is one of stabilization in the volume of area 17 and loss of synapses to reach 'adult' synaptic density around 11 years, at about 60% of the maximum values.

Adolescent↗