c-Ki-ras gene amplification and malignant behavior in murine embryonal carcinoma cell lines.

Embryonal carcinoma (EC) cells are malignant components of murine teratoma tumors. To extend our earlier findings concerning c-Ki-ras amplification in the embryonal carcinoma PCC4 cell line, we examined the c-Ki-ras protooncogene and its expression in other EC cell lines. We report here that c-Ki-ras amplification is not a general feature of EC cell lines since neither PCC3, PCC6, nor F9 cell lines have an amplified copy number of this protooncogene. Furthermore, molecular analysis of three independently passaged PCC4 cell lines showed marked heterogeneity for c-Ki-ras amplification. Two PCC4 cell lines showed amplified copy number and elevated expression of c-Ki-ras whereas the original one does not, suggesting that this gene amplification occurred through laboratory passage. Malignancy in syngeneic mice of PCC4 with or without an amplified c-Ki-ras gene was also examined. Our results indicate that c-Ki-ras amplification alone is not a determining factor in the malignant behavior of EC cells.

[Immunohistochemical localization of alpha-fetoprotein in the vitelline sac of a two-week old human embryo]. / Marquage immunohistochimique de l'alpha-foetoprotéine dans le sac vitellin d'un embryon humain de deux semaines.

Histological sections of a stage 6b human embryo (13-15 days old) were immunohistochemically stained for specific alphafoetoprotein (AFP). Conspicuous AFP+ endodermal cells were observed in the yolk-sac wall using the ABC peroxidase technique, which gave consistent results on dismounted and decolorized old slides.

[Immunohistochemical localization of chorionic gonadotropin and alpha fetoprotein in polyembryomas: description and interpretation]. / Localisation immunohistochimique de la gonadotrophine chorionique et de l'alpha-foetoprotéine dans les polyembryomes: description et interprétation.

As polyembryomas are special forms of human teratomas in which numerous structures mimicking the early stages of the human embryo are conspicuous, immunoperoxidase staining of these embryoid bodies (EB) has been used to reveal the initial appearance and localization of beta HCG and AFP, respectively, in amnion and in primary yolk-sac. EB are involved in the building of various questionable patterns of teratomatous germ-cell tumours. Special emphasis has been placed on tracking yolk-sac tumour patterns through dislocating EB, using a specific anti-human AFP serum.

Molecular duality of DNA ligase in axolotl corresponds to distinctive transcriptional information.

Based upon the use of specific antibodies and sucrose gradient sedimentation analysis, the present work describes the use of the post-transcriptional equipment of the urodele egg to compare the information contained in two RNA samples extracted from respectively liver and activated axolotl eggs. It is shown that besides the normal DNA ligase activity present in the host Pleurodeles eggs, RNA can translate for the specific carried information revealing a difference between the two samples. Moreover, unlike in nuclear transplantation, the homologous DNA ligases are not mutually exclusive. These observations give a new convincing support of the genetic basis of the molecular duality of DNA ligases.

[Immunological localization of alpha-fetoprotein in the proximal endoderm and its significance in extra-embryonic differentiation of teratocarcinomas in the mouse]. / Le marquage immunologique de l'alpha-foetoprotéine dans l'endoderme proximal et sa signification dans les différenciations extra-embryonnaires des tératocarcinomes de la souris.

The ABC technique using a specific anti-mouse alpha-foetoprotein (AFP) serum permits identification of groups of extraembryonic proximal endoderm cells in certain teratocarcinomas. These AFP+ cells are always associated with trophoblastic and parietal endodermal patterns and structures. These observations strongly support the hypothesis of a common precursor to the extraembryonic tissues which appears during the first phases of egg development.

[An immunological technic (ABC immunoperoxidase) demonstrating hepatic differentiation in teratocarcinomas of the mouse]. / Une technique immunologique (immunoperoxydase ABC) permet de déceler une différenciation hépatique dans les tératocarcinomes de la souris.

The present work shows that hepatic tissue occasionally appears in certain mouse teratocarcinomas: the presence of hepatic structures in these tumours, suspected on the basis of routine histological examination, is confirmed here by the use of anti-mouse alpha-foetoprotein serum and the ABC immunoperoxidase technique.

Translocation involving chromosome 22 in Ewing's sarcoma. A cytogenetic study of four fresh tumors.

Ewing's sarcoma was described in 1921 by James Ewing as a diffuse endothelioma of bone and, for some time, was believed to be an undifferentiated type of Parker's sarcoma. At present, these two entities are thought to be distinct, the macroscopic and microscopic aspects of Ewing's sarcoma being very characteristic, although the exact cell type of this tumor remains unknown. This has lead many workers to study this sarcoma in order to recognize its origin. We thought it of interest to carry out cytogenetic investigations of our cases of Ewing's sarcoma, since very few chromosomal data on this malignancy exist in the literature [1-3].

[Translocation of chromosome 22 in Ewing's sarcoma]. / Translocation du chromosome 22 dans le sarcome d'Ewing.

The chromosomal analysis of four fresh Ewing tumours shows a translocation of the band q12 of the chromosome 22 in all the clones observed. This translocation seems to preferentially involve the band q24 of the chromosome 11. These results are in favour of a consistent translocation in Ewing's sarcoma, and are to be compared with the results obtained in other malignancies. A relation between this translocation and the location of the human oncogene c-sis on the chromosome 22 should be considered.

Factors acting upon differentiation of mouse teratoma in vivo: spontaneous differentiation and effects of interferon.

CE/44 mouse teratocarcinoma and its sublines isolated at the Institut Pasteur were studied comparatively in 129/Sv, hybrid F1 129 X NCS, and NCS strains of male and female mice with respect to the age of the animals and the type of the tumor graft (ascitic or subcutaneous solid tumor). The tumors grow more quickly and with more malignant characteristics in female mice. The tumor "takes" and growth are equally good in the hybrid F1 as in 129/Sv mice, but its maintenance in hybrid F1 is not so stable, for a tumor loss and a lessening of differentiation could be seen through the passages in this strain. In the NCS strain the tumor grows very rarely. Interferon slowed the subcutaneous tumor growth and favored neuroepithelial tissue differentiation, but allowed selective growth of one cellular type, the "trophoblastic" one, which is very malignant, and which, in the ascitic tumor, caused death in female animals by a hemorrhagic syndrome.

Ewing's sarcoma: transplantation in nude rat.

Eight Ewing's sarcoma, primary tumor or metastasis, have been transplanted in Nude Rats. These tumors grow slowly and only in female rats. One of them has been maintained for 13 months with 5 passages. It has conserved all the characteristics of the primary tumor, histologic and ultramicroscopic morphology, glycogen secretion and cytogenetic modification (11.22 translocation). The graft of Ewing's sarcoma to Nu/Nu rats is a valuable system to get more material in good condition to study the nature and the origin of Ewing's cells, to test the new chemotherapy trials and to prepare and test the monoclonal antibodies.

Maternal serum levels of sex steroid-binding protein during pregnancy.

Serum concentrations of sex steroid-binding protein (SBP) were measured by an immunodiffusion technique in a total of 133 samples from 70 healthy pregnant women, 18 puerperal women and 21 non-pregnant women. In 6 individuals, trends or serum SBP were established from multiple samples taken throughout pregnancy. Maternal serum SBP levels had increased significantly above base line values as early as by 10 weeks gestation, and attained a plateau between 25 and 30 weeks, at which time mean values were about 10-fold higher than the normal non-pregnant range, the levels then declined slightly towards term. Parallel measurements of dihydrotestosterone-binding capacity of SBP showed a good correlation between SBP content and biological activity. Six abnormal pregnancies were encountered in the present study, and in five of them the molar ratios of bound hormone to SBP concentration were much lower than the normal value, suggesting a reduced binding capacity of the protein for the hormone.

Presence of benzo[a]pyrene metabolizing activities in isolated rat liver nucleoli.

A benzo[a]pyrene (B[a]P) hydroxylase activity and epoxide hydrolase (EH) activity have been found in rat liver nucleoli obtained from untreated (C) and 3-methylcholanthrene (3-MC) pretreated rats. A comparison of the enzyme activities was made in rat nuclei and nucleoli. Light and electron microscopic observations of nucleolar preparations did not reveal significant contamination either by intact nuclei or by nuclear membranes, and glucose 6-phosphatase, a marker of microsomal activity, was not detected in our nucleolar preparations. NADPH cytochrome c-reductase could be measured in C and 3-MC nuclei and very low but detectable activity was found in the nucleoli. Nucleolar preparations revealed significant hydroxylating activity, which was inducible by 3-MC in nuclei but not in nucleoli. The presence of EH in nucleoli was demonstrated with phenanthrene 9,10-oxide and B[a]P 4,5-oxide, but the nucleolar activities were lower than those obtained using intact nuclei. The addition of 1,1,1-trichloropropene 2,3-oxide completely inhibited EH activity. Furthermore the presence of covalently-bound metabolites of B[a]P formed in isolated nucleoli was demonstrated by cytofluoromicroscopy.

Osteopetro-rickets: a new congenital bone disorder.

Two lethal mutations have been described in the rat: "osteopetrosis" (op) and "toothless" (tl). The op mutant can be cured by normal bone marrow infusion, while the tl mutant cannot. We report here additional data with regard to the tl mutant. The bone disease of the tl rat as in the op rat is associated with a precocious thymic atrophy, but bone lesions are quite different. In addition to classical osteopetrosis, the tl rat displays several features of rickets: broadening of the extremities of long bones, thickening of the epiphyseal plates, presence of osteoid areas. In addition, the persistence of embryonic characters, evidenced by high levels of alpha-fetoprotein, suggests that the developmental defect of bone is part of a more general process.

[Modification of the immune response by a hepatic ferroglobulin: L alpha2-HF]. / modifications des réponses immunitaires sous l'influence d'une ferroglobuline hépatique: L' alpha2-HF

Alpha2-HF, foetal and tumorous isoferritin, the level of which is high in cancerous patients and in amniotic fluid during pregnancy, has an immunosuppressif effect on normal lymphocytic response. Its activity has been tested on blastic transformation induced by PHA, tuberculin, candidin and allgenic lymphocytes. The inhibition effect is proportional to the added quantity of alpha2-HF globulin. The antibody synthesis is depressed by alpha2-HF as demonstrated in vivo and in vitro. Iron is no responsible for the suppressif effect: the efficiency is identical with the native protein or the apo-protein. Crystallised ferritin, without sugar in its molecule on the contrary of alpha2-HF which is a glycoferroprotein, has no suppressif effect.

[Immunosuppressive effect of a human serum ferroprotein of hepatic origin: alpha-2-HF-globulin]. / Effet immunosuppresseur d'une ferroprotéine sérique humaine d'origine hépatique l'alpha 2 HF-globuline. Action sur la synthèse des anticorps in vitro

alpha 2HF, a serum ferroprotein increased during some malignant diseases, displays a suppressive effect on in vitro antibody responses, whether T-independent or T-dependent. This effect is not related to the presence of iron, nor to the macroglobulin nature of the molecule. The immunosuppressive properties of alpha 2 HF might depend on its carbohydrate moeity.

Letter: Alpha fetoprotein in amniotic fluid and maternal serum.

PIP: Additional findings concerning the evolution alpha fetoprotein (AFP) are reported in this letter. AFP levels of 440 amniotic fluids and 469 maternal sera were studied at different gestational ages. In addition, amniotic fluids and serum samples of 180 pregnant women were collected on the same day. Comparative study of amniotic fluid and maternal sera levels of AFP led to establishment of parallelism between these values from Week 17-20 of gestation. During this period, the ratio of amniotic fluid:maternal serum AFP was always between 100 and 250, whereas, it was less than 80 after Week 21 and greater than 400 before the 16th week. Fetal blood contamination of 2 samples resulted in high-for-date AFP levels, and subsequent amniocenteses were normal for AFP. In 2 twin pregnancies, the AFP value was normal in amniotic fluid and increased in maternal serum. The ratio was low for dates--about 1/2 normal. In cases with abnormalities the ratio was abnormal. High AFP levels in serum with normal amniotic values in 2 pregnant patients with renal disease were found: in these cases, the ratio was low for gestational age, but not as low as that observed in cases of intrauterine death. Ratios were too high for gestational age in cases of anencephaly and umbilical hernia.^ieng

Immunosuppresive effect of a human hepatic glycoferroprotein, alpha2H globulin. A study on the transformation of normal human lymphocytes.

A macroglycoferroprotein of hepatic orgin, alpah2H globulin, the serum level of which increases a few weeks or months before local recurrence of metastases, has been essayed for its immunosuppressive activity. The study was carried out using the lymphoblastic transformation test and was judged by tritiated thymidine incorporation and microscopic examination. PHA-induced blast transformation of 97 per cent of normal donor lymphocytes is inhibited by 100 mug/ml of alpha2H globulin. This inhibitory effect is proportional to the quantity of added alpha2H globulin. In is obvious with a concentration of 2-5 mug/ml, a frequently observed level in the serum of patient with tumours. Preincubation of lymphocytes with alpha2H globulin renders more effective the inhibitory action on PHA-induced transformation. A mechanism of competition between PHA and alpha2H globulin is suggested by preincubation and the inhibitory effect related to the doses. However, microscopic observation shows that alpha2H globulin acts on the earliest events occurring to the stimulated lymphocytes, by inhibiting cytoplasmic RNA and protein synthesis. The alpha2H globulin effect may not only have an immunosuppresive activity but it may have a more general effect, for example blocking or modifying cellular respiration.