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Prevalence and laparoscopic appearance of spontaneous endometriosis in the baboon (Papio anubis, Papio cynocephalus).

The prevalence of spontaneous endometriosis was investigated by laparoscopy in 52 baboons (Papio anubis and Papio cynocephalus) of proven fertility. Clinical endometriosis was diagnosed in 9 (17%) and 4 (8%) baboons with or without a previous hysterotomy, respectively. Endometriosis was confirmed by histology in 75% of these animals. The 37 endometriotic lesions were classified as typical (13%), subtle (57%), or suspicious (30%); and the percentage of histological confirmation was 100%, 61%, and 50%, respectively. Lesions were found on the uterosacral ligaments and in Douglas' pouch (46%), on the uterine peritoneum and the uterovesical fold (38%), and on uterine-omental adhesions (11%). Only 5% of the lesions were localized on the ovarian ligament, whereas ovarian endometriosis was not found. This study for the first time demonstrates that spontaneous endometriosis occurs in healthy baboons with proven fertility. It also shows that the laparoscopic appearances, the histological aspect, and the localization of the pelvic lesions are comparable to those found in women. We therefore conclude that the baboon is a good animal model for the study of endometriosis.

Animals↗

Purification of two cytochrome P450 isozymes related to CYP2A and CYP3A gene families from monkey (baboon, Papio papio) liver microsomes. Cross reactivity with human forms.

Two cytochrome P450 isozymes, FA and FI, were isolated and characterized from liver microsomes of phenobarbital-induced baboons (Papio papio). The cytochrome FA possesses the same N-terminal amino acid sequence as P450 MK2 from crab-eating monkeys (Macaca irus) and closely resembles the human P450 3A isozymes. This cytochrome was able to oxidize nifedipine and hydroxylate testosterone at the 6 beta position. The second baboon cytochrome (FI) is closely related to the P450 2A subfamily and has the same N-terminal sequence as human P450 2A7. Like human P450 2A forms, it is highly active as a coumarin 7-hydroxylase. Antibodies against P450 FA and FI cross-react with two human liver proteins of 51 kDa and 49 kDa, respectively. The concentration of the first protein in the human samples, was five-times greater than the second. However, the latter showed marked interindividual variation. In primary cultures of human hepatocytes, rifampicin is a strong inducer of the 51-kDa protein and a moderate inducer of the 49-kDa protein, while phenobarbital has the opposite effect on the two proteins.

Amino Acid Sequence↗

Phosphorylated thiamine derivatives and cortical activity in the baboon Papio papio: effect of intermittent light stimulation.

The effect of intermittent light stimulation (ILS) on the distribution of thiamine derivatives in three brain areas (occipital, motor, and premotor) was compared in photosensitive and nonphotosensitive baboons. ILS induces paroxysmal discharges in the motor and premotor areas of photosensitive animals only. In baboons submitted to ILS, thiamine triphosphate (TTP) decreases in both photosensitive and nonphotosensitive animals; thiamine monophosphate (TMP) increases in photosensitive animals, which present ILS-induced paroxysmal discharges, whereas it is unaffected in nonphotosensitive animals. The variations are the most significant in the occipital (visual) cortex. A consumption of TTP may result from electrical activity induced by light stimulation in the occipital area. No correlation between ILS-induced paroxysmal activity and a decrease in TTP contents was found. However, photosensitive animals are affected differently from nonphotosensitive animals, as their content of TMP in the cerebral cortex increases on stimulation. However, as long as the exact role of thiamine compounds in relation to membrane excitability in the nervous system remains unknown, it is impossible to conclude whether the differences observed in the metabolism of thiamine compounds are the cause or the consequence of the photosensitivity in the baboon Papio papio.

Animals↗

Excessive light sensitivity in Papio papio: its variation with age, sex, and geographic origin.

Excessive sensitivity (levels 3 and 4) in a population of 1,122 Papio papio was related with age, sex, and geographical origin. (1) Age. There was no clinical response to intermittent light stimulation under the age of 5 months. These was no difference between animals 6 months to 2 years (J1) and those aged 2 to 4 years (J2). Adult females were less often light sensitive (levels 3 and 4 = 32.9%) than immature females (52.4%). Adult males could usually not be tested, but were probably less often sensitive than immature males. (2) Sex. Immature females (J1 + J2) were more often light sensitive (52.4%) than immature males (38.1%). (3) Geographical origin. No animals from East Senegal (Sansande Region) were very light sensitive. Animals from Casamance were more often light sensitive (56.2%) than those from the Niokolo-Koba National Park (N.K.N.P.) (20%). Of two samples taken at one spot between these two regions, one group resembled the population from Casamance and the second resembled that from the N.K.N.P. This observation raises several questions about the respective roles of genetic, ecological, and ethological factors.

Age Factors↗

Effects of tetrahydrocannabinols on kindled amygdaloid seizures and photogenic seizures in Senegalese baboons, Papio papio.

Intraperitoneal injections of delta 8-tetrahydrocannabinol (THC) and delta 9-THC failed to affect myoclonic response to photic stimulation in Senegalese baboons (Papio papio). However, both isomers of THC exerted dose-related antiepileptic effects upon established kindled convulsions provoked by electrical stimulation of amygdala in the same species. Delta 9-THC was more potent than delta 8-THC, in terms of both antiepileptic effects and general toxicity. The antiepileptic effects of the THC isomers appear to be due mainly to the suppression of propagation of the induced afterdischarge to distant cerebral structures, although high doses also seem to suppress afterdischarge at the site of stimulation.

Amygdala↗

Electroencephalographic and behavioral effects of a GABA agonist (muscimol) on photosensitive epilepsy in the baboon, papio papio.

Muscimol, 0.25-1.0 mg/kg, i.v., was administered acutely to 4 adolescent baboons, Papio papio, that show photically induced epilepsy. On the EEG, slowing of background rhythms was associated with the appearance of spikes, polyspikes, and recurring symmetrical spike-wave complexes. These changes were maximal 0.5-2 hr after muscimol injection. Regular testing with intermittent light stimulation showed either no change from control responses or a more severe epileptiform EEG 0.1-3 hr after muscimol. Photically induced myoclonus was not modified by muscimol. Despite its GABA-abonist properties, muscimol is not an effective anticonvulsant.

Animals↗

Action of progabide in the photosensitive baboon, Papio papio.

Progabide is a GABA agonist which is nontoxic and crosses the blood-brain barrier. Progabide was tested in naturally and allylglycine-induced photosensitive baboons (Papio papio). Intravenous injection of various doses (30 to 100 mg/kg) of progabide induced a protective effect against intermittent light stimulation (25 Hz) in both test situations. This protection lasted 10 to 120 min. This duration was dose-dependent and was generally shorter in allylglycine-treated than in naturally photosensitive baboons. At all doses, progabide reinforced rhythmic activities in the frontorolandic and occipital regions. At doses greater than 50 mg/kg, progabide produced a mild sedation with somnolence and myorelaxation, all effects which could be reversed by sensory stimulation. These data confirm the anticonvulsant properties of progabide in another animal model.

Allylglycine↗

Limbic kindling in the forebrain-bisected photosensitive baboon, Papio papio.

When forebrain-bisected photosensitive baboons, Papio papio, were kindled from the amygdala or hippocampus, bilateralization of convulsive seizure proved difficult, and the final stage of bisymmetrical and bisynchronous convulsive seizure unique to this species did not develop despite more than twice the number of kindling stimulations required for its development in nonbisected baboons. At the secondary site amygdala, convulsive seizure development was suppressed. Findings of the present and previous studies suggest that the corpus callosum plays: (a) a major, if not an exclusive, role in convulsive seizure bilateralization ; and (b) a critical role in the development of primarily generalized convulsive seizures unique to this epileptic baboon. Finally, in the absence of the corpus callosum (and the hippocampal commissure) the transhemisphere seizures suppressing effect generated by amygdaloid kindling appears to be mediated through the subcortical pathway which presumably exists in the brainstem.

Amygdala↗

The influence of light stimulation on subcortical potentials evoked by single flashes in photosensitive Papio papio.

Visual evoked potentials (VEPs) from the frontorolandic (FR) cortex and from subcortical nuclei (colliculi superioris, pulvinar, corpori geniculati lateralis, centrum medianum, ventralis lateralis) and from pontine reticular formation were analyzed in Papio papio monkeys rendered photosensitive by a subconvulsant dose of allylglycine. The VEPs induced by single flashes were compared statistically with those induced by flashes preceded by trains of intermittent light stimulation (ILS). This latter mode of stimulation provoked the appearance of paroxysmal VEPs (PVEPs) in the FR cortex with the same morphology as the spikes and waves induced in this area by the ILS. The aim of our research was to provide evidence for the possible implication of the subcortical structures which we have studied in the elaboration of PVEPs and thus of spikes and waves. The VEPs recorded at the thalamic and pontine levels were modified when PVEPs were present. These modifications varied according to the site, but subcortical VEPs were never paroxysmal. In structures with visual functions (colliculi superioris, corpori geniculati lateralis), the VEPs were modified by the ILS, but showed more marked changes when PVEPs were present. Thus, these structures may contribute to the genesis of PVEPs. In the other structures (centrum medianum, ventralis lateralis, and pontine reticular formation), modifications of the VEPs occurred only when PVEPs were present. Thus, these structures would be only secondarily involved. We also present preliminary results concerning the effects of lesioning the pulvinar and the ventralis lateralis on the susceptibility of the FR cortex to produce spikes and waves during ILS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of macular and peripheral retina coagulation on photosensitive epilepsy in the forebrain bisected baboon, Papio papio.

The effects of macular and peripheral retina coagulation were examined in photosensitive baboons, Papio papio (PP), with or without forebrain bisection. The temporal part of the macula and surrounding retina of the left eye were coagulated with an Argon laser and later confirmed histologically. In forebrain nonbisected baboons, intermittent light stimulation of the operated eye produced bisymmetrical and bisynchronous spikes and waves and self-sustained seizures. In forebrain-bisected baboons intermittent light stimulation of the operated eye produced spikes and waves and self-sustained seizures localized to the contralateral hemisphere. Subsequent stimulation of the nonoperated eye in the same animal produced spikes and waves and seizures either bilaterally or only in the opposite hemisphere when stimulation took place during the postictal silent period in the first hemisphere. In both cases, the tonic phase of the seizure was always bilateral but asymmetrical as shown by electromyographic recordings. Based on these data, it has been hypothesized that the tonic phase is mediated, in part, through crossed interreticular pathways, by one or both cerebral hemispheres. However, data are also compatible with a possible origin of the tonic phase of the seizure being partly localized in the medial frontal cortex. Results demonstrated (1) the usefulness of laser coagulation of the temporal portion of the macula and retina for the study of the functional independence between two cerebral hemispheres, (2) the critical role of the corpus callosum (CC) in bisynchronization and generalization of the intermittent light stimulation (ILS)-induced seizure, (3) independent excitability of each cerebral hemisphere by the ILS, and (4) the critical role of cortical visual afferents for inducing epileptic phenomena in this species.

Animals↗

Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio.

Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Effect of DN-1417 on photosensitivity and cortically kindled seizure in Senegalese baboons, Papio papio.

The effect of DN-1417, a thyrotropin-releasing hormone (TRH) analogue, on photosensitivity and cortically kindled seizures was examined in seven Senegalese baboons (Papio papio). Intravenous (i.v.) administration of 2 mg/kg had no effect on either photosensitivity or cortically kindled seizures. When this agent was administered intracisternally, both the photomyoclonic response and cortically kindled seizures were suppressed for 4-5 days. A study of the transcallosal response also showed a long-lasting attenuation of the early positive wave (P1) amplitude (peak latency, 5-10 ms) elicited by a single stimulus after cisternal injection of DN-1417. These findings are consistent with the assumption that endogenous TRH is involved in suppression of epileptic seizures.

Animals↗

Cingulate kindling in Senegalese baboons, Papio papio.

Kindling of the cingulate cortex in the Senegalese baboon Papio papio led to a protracted nonconvulsive seizure state characterized by immobile staring with (anterior cingulate, AC) or without (posterior cingulate, PC) widening of eyelids and neck flexion, followed by postictal visual searching behavior. Despite early bilateral spread of EEG discharges, ictal and interictal patterns remained persistently asymmetric. Secondary generalization was rapid and predictable once contralateral lower facial twitching associated with sustained adversion developed. After the primary site had been kindled, stimulation of the contralateral homotopic posterior cingulate cortex readily produced afterdischarge. However, it remained localized and kindling growth did not occur. The findings suggest that (a) the cingulate cortex can support nonconvulsive seizures; (b) cingulate seizures are accompanied by asymmetric convexity EEG discharges indicating its lateralized onset; (c) further evolution to convulsive seizures after kindling of cingulate cortex requires access to the ipsilateral frontocentral cortex responsible for facial twitching; and (d) the development of focal epileptogenesis at one cingulate site interferes with clinical seizure development at the homotopic contralateral site.

Adolescent↗

Assessment of cell-mediated immunity against coxsackievirus B3-induced myocarditis in a primate model (Papio papio).

Delayed hypersensitivity and myocarditis were induced in five baboons (Papio papio) after inoculation with myocarditic murine coxsackievirus B3 (CVB3m). By means of the [3H]thymidine incorporation assay and the agarose droplet cell migration inhibition assay, specific cell-mediated immunity was detected in all five animals against viral antigens and/or KCl-extractable soluble antigens extracted from the heart of a CVB3m-inoculated baboon. KCl-extracted antigens from normal baboon heart tissues, as well as KCl-extracted antigens from spleen or liver tissues from a CVB3m-inoculated baboon, failed to stimulate baboon peripheral blood lymphocytes or inhibit the migration of baboon peritoneal exudate cells. The appearance of dissimilar antigen(s) in extracts of heart tissues from CVB3m-inoculated baboons which did not contain infectious CVB3m parallels the appearance of novel KCl-extractable antigen(s) induced by CVB3m in murine heart tissues (Paque et al., J. Immunol. 120:1672-1678). The animal model described represents the first systematic evaluation of cell-mediated immunity in CVB3m-induced myocarditis in primates and suggests that a similar phenomenon may occur in humans.

Animals↗

Divergent simian T-cell lymphotropic virus type 3 (STLV-3) in wild-caught Papio hamadryas papio from Senegal: widespread distribution of STLV-3 in Africa.

Among eight samples obtained from a French primatology research center, six adult guinea baboons (Papio hamadryas papio), caught in the wild in Senegal, had a peculiar human T-cell leukemia virus type 2 (HTLV-2)-like Western blot seroreactivity (p24(+), GD21(+), K55(+/-)). Partial sequence analyses of the tax genes (433 bp) indicated that these baboons were infected by a novel divergent simian T-cell lymphotropic virus (STLV). Analyses of the complete proviral sequence (8,892 bp) for one of these strains (STLV-3/PPA-F3) indicate that this STLV was highly divergent from the HTLV-1 (61.6% of nucleotide similarity), HTLV-2 (61.2%), or STLV-2 (60.6%) prototype. It was, however, much more closely related to the few other known STLV-3 strains, exhibiting 87 and 89% of nucleotide similarity with STLV-3/PHA-PH969 (formerly PTLV-L/PH969) and STLV-3/CTO-604, respectively. The STLV-3/PPA-F3 sequence possesses the major HTLV or STLV open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat comprises only two 21-bp repeats. In all phylogenetic analyses, STLV-3/PPA-F3 clustered together in a highly supported single clade with the other known strains of STLV-3, indicating an independent evolution from primate T-cell lymphotropic virus type 1 (PTLV-1) and PTLV-2. The finding of a new strain of STLV-3 in a West African monkey (Guinea baboon) greatly enlarges the geographical distribution and the host range of species infected by this PTLV type in the African continent. The recent discovery of several different STLV-3 strains in many different African monkey species, often in contact with humans, strongly suggests potential interspecies transmission events, as it was described for STLV-1, between nonhuman primates but also to humans.

Amino Acid Sequence↗

New gene assignments and syntenic groups in the baboon (Papio papio).

MDH2, SOD2, PEPS, and ITPA were assigned to Papio papio chromosomes 3, 4, 5, and 10, respectively, by their concordant segregation with previously assigned gene markers in a set of baboon X mouse somatic cell hybrids. The linkage of NP, IDH2, SORD, MPI, and PKM2 was confirmed, and three other independently segregating markers (MDH1, ACY1, and PEPB) were identified. Syntenic groups described in the baboon are compared to those found in man and in the rhesus monkey.

Animals↗

Red cell and serum enzymes of Guinea baboon (Papio papio).

Variants of some erythrocyte and serum enzymes have been studied among several blood samples of Guinea baboon (Papio papio). Variation occurred in two red cell enzymes, G6PD and NADH diaphorase, and in serum esterase. All studied animals had a complete uniformity in other enzyme systems (acP, 6PGD, CA, AK, and cholinesterase at E1 locus). Data obtained in the present work have been discussed and compared with those reported among other baboon species.

Acid Phosphatase↗

Neurophysiology of photically induced epilepsy in Papio papio.

This chapter critically reviews arguments supporting the role of the frontal cortex in light-sensitive epilepsy of the baboon Papio papio in the light of the most recent neurophysiological research. In particular, it is known that spontaneous or ILS-induced paroxysmal discharges, as well as generalized seizures, originate in the frontorolandic cortical region. In this region during ILS, neurons behave in the same manner as hyperexcitable neurons in focal epileptogenic lesions of animals and man. Aso, section of the corpus callosum causes deterioration or even destruction of the synchronization that exists naturally between the two frontorolandic areas. Lastly experimental focal irritative lesions enhance light sensitivity if they are located in the frontorolandic region and inhibit it if they are located in the occipital cortex. Opposing these arguments are those that support the important role the occipital cortex plays, since its ablation makes excessive light sensitivity in the baboon disappear. Studies of the primary and nonprimary visual messages and pathways have also contributed evidence. In particular, demonstration of the existence of large numbers of direct occipitofrontal connections may help reconcile the two opposing arguments. Other evidence favoring the role of the frontal cortex is furnished by the still fragmentary studies on activation of the motor pathways and by studies in neuropharmacology. The significance and value of this type of epilepsy as an animal model of the generalized reflex epilepsies of man are discussed.

Aluminum↗