Expression of mRNAs for alpha-fetoprotein (AFP) and albumin and incorporation of AFP and docosahexaenoic acid in baboon fetuses.

alpha-Fetoprotein and albumin, two members of a multigene family, reversibly bind fatty acids with high affinity. The origin of alpha-fetoprotein (AFP) and albumin present in fetal tissues other than the liver and yolk sac is a subject of controversy. In this work, we have searched for the presence of the albumin and AFP mRNA molecules in different fetal organs of the baboon (Papio cinocephalus), using a highly sensitive gel-blot hybridization assay with human albumin and AFP cDNA probes. Large amounts of albumin and AFP mRNA molecules were found in the fetal liver; significant quantities were also present in the gastrointestinal tract and in the kidney. No detectable levels were found in the other tissues examined (brain, skin, spleen, pancreas, muscle, heart, thymus, placenta, and amnion). After injection of radiolabeled AFP into pregnant baboons, all fetal tissues took up the protein. White adipose tissue, kidney, intestine, lung, liver, and cerebral cortex showed a great uptake of exogenous AFP. [14C]Docosahexaenoic acid (22:6, n-3), injected at the same time, was actively transferred from the maternal compartment across the placenta and incorporated into cellular lipids by all fetal tissues and particularly by liver (around 70% of total incorporation). The levels of [14C]docosahexaenoic acid per gram of tissue increased in the order: maternal blood less than placenta less than fetal liver, indicating a selective accumulation of this fatty acid by the fetus. These results indicate that intracellular AFP in non-hepatic tissues of the developing baboon is, for the most part, of plasma origin.

Increased phagocytic activity of peripheral blood monocytes after intravenous injection of phospholipase A2 to monkeys.

One of the expressions of the activity of phagocytic cells such as monocytes or macrophages is a burst of increased oxidative activity on stimulation. The free oxygen radicals liberated, mainly O2- and H2O2, lead to chemoluminescence, which is thus a measure of activation. Chemoluminescence also depends on arachidonic acid metabolism, and this depends on phospholipase A2 (PLA2). We modified monocyte activity in monkeys by injecting them i.v. with this enzyme and observed that 30 min after injection, the phagocytic activity of peripheral blood monocytes and the chemoluminescence they emitted was greater than that of controls. We suggest that PLA2 may act as an in vivo immunomodulator in mammals.

[Anatomical and microbiological study of the conditions for baboon-man liver xenograft]. / Etude anatomique et microbiologique des conditions d'une xénogreffe hépatique babouin-homme.

This work assesses the anatomical and infectious problems of heteroplastic transplantation from a baboon to a man. The study was carried out with 30 baboons of the primatology laboratory of the CNRS. The aspects studied included the anatomic structure and the biology of the liver, the microbial and parasitic population, and the serological features. Out of these 30 animals, 8 were selected as potential donors.

Use of Old World monkeys for acquired immunodeficiency syndrome research.

Mangabeys, macaques, and baboons persistently infected with human immunodeficiency virus (HIV)-2 NIH-DZ demonstrated no signs of immunodeficiency disease after 6-11 months following seroconversion. Thus Old World monkeys provide an animal model to investigate the effects of passive immunization (anti-HIV-2 antibodies) on HIV infection in primates.

Persistent HIV-2 infection of rhesus macaque, baboon, and mangabeys.

Six monkeys of three different species (mangabey, macaque and baboon) were infected with human immunodeficiency type 2 (HIV-2) NIH-DZ using intraperitoneal or intravenous injections of cell-free HIV-2 or autologous HIV-2-infected cells with no prior immunostimulation. Viral expression was demonstrated by reverse transcriptase activity in cells after coculture with human peripheral blood lymphocytes or by electron microscopy. Serum was analyzed by western blot, enzyme-linked immunosorbent assay (detection of antigen and antibody), and neutralization assay carried out using immunofluorescence techniques. The 6 inoculated animals seroconverted during the 1st month after inoculation and remained persistently infected after 6-11 months. We also observed proviral DNA by genomic analysis in the six tested samples. No sign of immunodeficiency disease has been observed so far. The data suggest that HIV-2 infection of nonhuman primates provides an acceptable animal model to investigate vaccination or specific immunotherapeutic procedures.

Intracellular alpha-fetoprotein and albumin in the developing nervous system of the baboon.

The intracellular presence of alpha-fetoprotein (AFP) and of albumin in the brain and other neural derivatives of three Baboon fetuses (9,13 and 17 weeks of gestational age, respectively), was demonstrated by immunocytochemical techniques. The largest localization of both proteins was observed in the 9 week old fetus, where most neural tube and neural crest derivatives showed intracytoplasmic labelling. The staining decreased abruptly in the 17 week old fetus. In the brain, of the youngest fetus examined, the penetration of AFP and albumin into the cerebral wall is transependymal. The route seems to possess differential activity since IgG molecules never appeared internalized in spite of their presence, like AFP and albumin, in the choroid plexus and the ventricular spaces of this fetus. It is also worth noting that the labelling declines as myelination and glial cell development progress. The wide distribution of AFP and albumin labelling supports the conclusion that the intracellular uptake of these proteins is probably general in immature nervous structures. Attention is brought to the binding and transport of polyunsaturated fatty acids by AFP and albumin as a possible explanation for the transitory presence of these proteins in the developing nervous system.

Oestrogen receptor in the baboon endometrium: cytosolic receptor, detection, characterization and variation of its concentration during the menstrual cycle.

A cytosolic oestrogen receptor from baboon endometria was detected and partially characterized. The apparent dissociation constant for oestradiol was 1.5 x 10(-10)--4 x 10(-10) mol/l. Steroids that competed with the [3H]oestradiol binding to the receptor were oestradiol and ethynyloestradiol greater than oestriol greater than oestrone; progesterone, testosterone and corticosterone were not competitors. The [3H]oestradiol-receptor complexes migrated as a 3-3.5S peak during sucrose density-gradient centrifugation when endometrial samples were taken during either the proliferative or the secretory phase. A 7S peak was observed for samples taken at the period of ovulation. A [3H]oestradiol exchange technique was used to detect changes in the receptor concentration during the menstrual cycle. This concentration which was high during the early follicular phase fell sharply before the ovulatory peak of ovarian oestrogens. It remained at a base level during the early secretory phase and then rose during the last days of the cycle to the same concentration as that measured at the beginning of the cycle.

Nuclear receptor for oestrogen in the baboon endometrium: detection, characterization and variation in its concentration during the menstrual cycle.

The present paper describes studies conducted to detect and characterize the nuclear receptor for oestrogen in the baboon endometrium. Only 10% of the [3H]oestradiol nuclear receptor complexes were extracted with a 0.5 M-KCl solution. This solubilized receptor migrated as a 4.4S peak during 5-20% sucrose gradient centrifugation. The oestrogen receptor was not bound to oestrogen in the nuclei under normal physiological conditions. Using an unlabelled competitor addition technique with intact nuclei the variation in oestrogen-receptor concentration of baboon endometrium during the menstrual cycle was measured. This concentration increased slightly during the first week of the cycle, being maximal on day 7 before ovulation (2500 molecules/cell), then decreasing gradually, reaching the lowest level (300 molecules/cell) on day 5 after ovulation, where it remained until the end of the cycle.

Natural antibodies to EBV-VCA antigens in common marmosets (Callithrix jacchus) and response after EBV inoculation.

Healthy common marmosets from two separate colonies, one in England and one in France, were found to have antibodies cross-reacting with Epstein-Barr virus structural antigens (EBV-VCA). All seropositive animals were at least 2 years old. Experimental EBV infection of marmosets of different ages led to seroconversion of inoculated weanlings. Adult animals either developed antibody for the first time or showed an increase in their existing titers. Both control and infected animals developed a progressive interstitial nephritis. The lymphocytic infiltration was more extensive, diffuse and immature in appearance in inoculated animals, but no definite evidence of lymphoproliferative disease or lymphoma was found.

Preclinical and phase I studies of malonatoplatinum.

After preclinical toxicologic study in baboons, we are conducting a phase I trial of malonatoplatinum, starting with 3 mg/kg and now reaching 1 mg/kg. Toxicity, mainly hematologic, was mild and our study was mainly limited by poor solubility. Regressions, which have been rare in the advanced-tumor patients, have been observed in three patients considered as clinically resistant to cisdichlorodiammino-platinum (DDP). Malonatoplatinum pharmacokinetics appeared similar to those of DDP as far as total platinum is concerned.

Isolation and characterization of a new simian foamy virus serotype from lymphocytes of a Papio cynocephalus baboon.

A new type of syncytium-forming (foamy) virus was isolated from peripheral lymphocytes of a Papio cynocephalus baboon after cocultivation with a rhesus monkey cell line. The isolate was characterized by cytopathogenic effect, host range, electron microscopy, reverse transcriptase activity and physical and chemical properties. Seroneutralization tests indicate that the new isolate is antigenically distinct from the other nine known simian foamy virus serotypes.

Scanning electron microscopy of ejaculated baboon (Papio anubis) spermatozoon.

Scanning electron microscopy has been used in order to provide the morphological study including comparative measurements of the main parts of the Baboon spermatozoon. If the dimensions of the head and the mid-piece are fairly close to the human spermatozoon, the Baboon spermatozoon is practically twice as long as the human one. In the Baboon spermatozoon, the head appears smooth with only a light ransversal furrow at the level of its posterior third, which probably marks the limit of the posterior border of the equatorial segment. The mid-piece, a conical trunk, is larger in its anterior part than at the level of its posterior extremity. The end-piece appears very short as compared with the total length of the sperm cell. The technical modalities of the preparation and the possibility of artifacts are briefly discussed.

In vitro transforming activity of EBV. I-Establishment and properties of two EBV strains (M81 and M72) produced by immortalized Callithrix jacchus lymphocytes.

In vitro transformation of Callithrix jacchus marmoset lymphocytes was achieved with a nasopharyngeal carcinoma (NPC) derived Epstein-Barr virus (EBV) strain, HKLY-28. Two permanent and virus producing lymphoblastoid cell lines, M81 and M72, were obtained. Comparison between the original HKLY-28 line and both M81 and M72 lines showed that passage in the marmosets lymphocytes greatly enhanced viral production and transforming activity of the virus as observed in cottontop derived B95.8 lymphoblastoid line.

[Action of cytotoxic drugs on normal hepatic tissue in the baboon. Immediate and late lesions]. / Action de médicaments cytotoxiques sur le tissu hépatique normal du babouin. Lésions immédiates et tardives

The perfusion of cytotoxic drugs in the treatment of inoperable tumours of liver is used even in children. The experiment described here was planned to study the effect of three cytotoxic drugs (5. Fluorouracil, Méthotrexate and S.P.I.) on the liver of healthy baboons. The drugs were introduced by perfusion through the hepatic artery. Liver biopsies were performed at the end of the treatment and 15 and 60 days later. In order to avoid acute toxic effects, low doses of the drugs must be given during the first five days. The therapeutic dose can then be increased and maintained for variable periods. Of the three products tested, the toxicity increases in the following order: S.P.I., 5 F U. and Methotrexate.