The role of mononuclear phagocytes in HTLV-III/LAV infection.

Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.

[Spontaneous transformation and long term culture of foetal mouse glial cells (author's transl)]. / Transformation spontanée et maintien prolongé in vitro de cellules gliales d'embryons de souris.

Six cell lines originated from foetal mouse brain were maintained in vitro for more than two years. The morphology of most of these cultures suggests their glial character. This is corroborated, for some lines, by the presence of specific glial protein (Glial fibrillary acidic protein, or GFAP). Five out of these lines remained not transplantable in animals during all the experiments. However one of them went through a spontaneous transformation at the eleventh population doubling. This culture, after transformation remained glial and when injected in animals, induced GFAP containing tumors.

[Chemical cancerization of hamster embryo cells in mass culture]. / Sur la cancérisation chimique de cellules d'embryon de hamster en culture de masse

For periods between 24 and 72 hours mass cultures of hamster embryo cells were put in contact with the following carcinogens: 7,10-dimethylbenz (c) acridine (2 mug/ml), benzo (a) pyrene (0,1 mug/ml), 7-methyl benz (a) anthracene (5 and 10 mug/ml), 3-methyl-cholanthrene (0,1 mum/ml), and 7,12-dimethyl benz (a) anthracene (0,05 mug/ml). The cancerisation of cells thus treated was demonstrated by hamster grafting as soon as 4 1/2 months post-treatment. By contrast neither the cells treated by benzo (e) pyrene (non-carcinogenic in animals) nor those of the two control lines resulted in tumours when grafted into hamsters even after culture for 8 and 15 months. These transformed and malignant cultures differ from the controls by their rapid uncontrolled growth and in their morphology. Moreover the morphological characteristics of transformation are evident as soon as 2 months after treatment and for the majority of the compounds studied well before cancerization is demonstrable by hamster grafts. During the course of the first 2 months toxic effects of the compounds are evident in the partial destruction of the cultures and by the appearance of colonies composed in part of cells in disorderly growth. The cells of these colonies when isolated and returned to culture do not survive beyond 4 or 5 passages. Moreover grafts of cultures at 30 days after exposure to carcinogens has never resulted in tumour in the hamster host.

[Lymphography as an investigation method for bladder cancer in adults]. / Intérêt de la lymphographie dans le bilan pré-thérapeutique des cancers vésicaux de l'adulte.

The use of lymphography as an investigational method in bladder cancer is a controversial subject. Results of a personal series of 90 cases, including 50 that were histologically confirmed, are compared with those reported in the published literature. Results were fairly different from those previously described, as though there was a lower sensitivity (43 as against 85 p. cent in the literature), specificity was much higher (100 as against 94 p. cent) as well as positive predictive value (100 as against 69 p. cent). This improvement was mainly due to the use of Piver and Wallace's assessment criteria, and results should be improved still further in the future by more frequent use of needle puncture cytology. Even with the increasing employ of the scanner, lymphography still remains a precise method for investigating bladder cancer.

[In vitro malignant transformation of hamster lung cells by 2-chlorobutadiene]. / Transformation in vitro de cellules de poumons de jeunes hamsters par le chloro-2 butadiène (CB).

Normal Hamster lung cells from an established line were treated with 1-500 microgram . ml-1 2-chlorobutadiene. Those treated with 1 microgram . ml-1 of the compound showed malignant transformations 14 weeks after treatment. The treatment with higher concentrations did not accelerate the transformation process.

[Spontaneous growth of suspended hamster embryonic cells transformed in vitro by methyl-7 benzo(a)anthracene]. / Crossance spontanée en suspension de cellules d'embryon de hamster cancérisées in vitro par le méthyl-7 benzo(a) anthracéne

A transformed and malignant cell line was obtained by treatment of secondary hamster embryo cells with 7-methyl benz(a)anthracene (10 mug/ml of medium). Later on these cells acquired the capacity to grow spontaneously in suspension and form "spheroids". The evolution of this cell line showed similarities between the carcinogenic process in vitro and in vivo.

Normal and benzo(a)pyrene-transformed fetal mouse brain cells. II. Ultrastructural study.

An ultrastructural study was performed on normal and Benzo(a)-pyrene(B(a)P)-transformed fetal mouse brain cells. Early subcultures of a strain initiated from whole brain presented three cell types in vitro: astroglial, poorly differentiated glial, and spongioblastic types. After B(a)P-treatment, there was an exclusive transformation and the growth of neuroglia sometimes without gliofibrillary maturation, but with the presence of glial fibrillary acidic protein (GFAP) in the cytoplasm. Early subcultures of another strain initiated from cortex only presented poorly differentiated neuroglial cells. After transformation, cell maturation as evidenced by gliofibrillogenesis and GFAP production by these cells was observed. In both cases, the potentiality of glial differentiation after in vitro malignant transformation by a chemical carcinogen seemed preserved.

Repeat lymphography in children with Hodgkin's disease.

Repeat lymphography was performed in 37 children less than 16 years old with histologically proven Hodgkin's disease. The repeat studies had the same lymphatic cannulation success rates as the first lymphogram; one patient had a bilaterally unsuccessful repeat study, which left 36 for analysis. Both first and repeat lymphograms were negative in 33% of children, whereas a negative lymphogram became positive for tumor in 39%. The remaining 28% had a positive first lymphogram, with an equal incidence of positive and negative repeat studies. Reactive hyperplasia was seen in 16.7%, and post-therapeutic lymph node alteration in 22%, of all cases. Of the 22 children studied for routine opacification or because of suspected but unproved relapse, 10 (45%) had positve repeat studies. The repeat lymphogram in these patients was of utmost importance in initiating therapy. Nine of 14 patients studied for documented clinical relapse had positive repeat studies.

Experiment with 659 consecutive lymphograms in children.

Between 1963 and January 30, 1975, 659 children under 16 years of age were referred for bipedal lymphography at the Institut Gustave-Roussy. Approximately one-third were under 5 years of age. The vast majority had documented malignant disease. Successful bilateral lymphatic cannulation and lymph nodd opacification were accomplished in 86.7% of all children. Another 11.6% had successful unilateral lymphograms, which usually provided sufficient information to be considered as diagnostic stldies. In only 1.7% of all children was the study unsuccessful bilaterally. Lymphatic cannulation failure rates progressively decreased as the child increased in age. There were five "allergic" reactions (0.75%), one of which was considered life-threatening, and one instance (0.15%) of a transient neurological deficit. No permanent sequelae or deaths were attributed to the lymphogram.

Lymphography in the staging, treatment planning, and surveillance of ovarian dysgerminomas.

Ovarian dysgerminomas are distinguished from other ovarian neoplasms by their rarity, their predilection for metastases via lymphatic pathways, and their radiosensitivity and favorable prognosis. After the initial surgery, which provides the histologic diagnosis and defines the local extent of pelvic involvement, lymphography is the single most useful tool to determine whether retroperitoneal lymph nodes are involved. Results of the study guide the radiotherapeutic approach, including field size and dosage. In an unselected group of 31 previously untreated patients, 10 had positive lymphograms. The response to therapy and the detection of relapse of disease may be evaluated by monitoring the residually opacified lymph nodes with surveillance abdominal radiographs. If necessary, a repeat lymphogram can be performed. The 2 year survival rate of 84% for ovarian dysgerminomas is lower than that for testicular seminomas, probably due to later recognition of the tumor. Failuresare related to local extension or to hematogenous dissemination.

Lymphography in childhood rhabdomyosarcomas.

Forty-one children with subdiaphragmatic rhabdomyosarcoma underwent bipedal lymphography. Twenty-two (53.5%) of the lymphograms were interpreted as being positive. In our series, the lower limbs were the most common primary site of involvement, were more frequently involved by the alveolar histologic subtype which carries a poor prognosis, and were associated with a higher incidence of lymph node metastases. Positive lymphographic findings in this group of children were similar to those seen in both adults and children with other solid tumors, i.e., the presence of discrete lymph node filling defects. However, in 3 cases, abnormalities more characteristic of lymphoma were identified. Evaluation of lymph node metastases as demonstrated by lymphography has prognostic significance.

[Radiological aspects of cancer of the breast in men (author's transl)]. / Aspects radiologiques du cancer du sein chez l'homme.

The radiological signs of malignant mammary tumours in men, which are similar to those observed in women, are reviewed. Several points have to be remembered, however; the common retro-mammillary location, the frequent nodular character, the skin involvement and the usual mamillary retraction, and, finally, the absence of characteristic microcalcifications. The interest of mammography to rate T in the TNM classification is also mentioned.

Metabolism of benzo[a]pyrene by brain microsomes of fetal and adult rats and mice. Induction by 5,6 benzoflavone, comparison with liver and lung microsomal activities.

Using brain, lung and liver microsomes as the enzyme source in in vitro assays, benzo[a]pyrene (B[a]P) metabolism was studied in fetuses and dams of mice (C57B1/6) and rats (WAG). Separation and quantitation of B[a]P metabolites were performed by h.p.l.c. Microsomal preparations were tested for cytochrome P-450 dependent O-dealkylation of 7-ethoxycoumarin and epoxide hydrolase activities. Another parameter measured included the conjugation of 1-chloro-2,4 dinitrobenzene to glutathione by cytosolic glutathione-S-transferase activity. The induction of B[a]P metabolism was studied after treatment of animals with 5,6-benzoflavone (BF). Mixed function oxygenase, epoxide hydrolase and glutathione-S-transferase activities were transplacentally inducible after dams were treated with BF. Metabolic activation of B[a]P by fetal brain microsomes was lower in both species than that by fetal lung and liver microsomes, but it was higher in fetuses than in adults. All metabolites of B[a]P increased after BF treatment; the production of 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (7,8-dihydrodiol B[a]P) was higher in brain microsomes from BF-treated rats than that in mice. In stimulated rats, the formation of 7,8-dihydrodiol B[a]P by fetal brain microsomes were higher than that by fetal lung microsomes, whereas in mice, the opposite was observed. These data suggest that initiation could occur in utero, and partially explain the species-specific differences in susceptibility to transplacental tumorigenesis by polycyclic aromatic hydrocarbons by differences in biotransformation in the target organ.

[Trials of in vitro propagation of the scrapie agent in mouse nerve cells]. / Essais de propagation in vitro de l'agent scrapie dans des cellules nerveuses de souris.

We attempted to propagate the Scrapie agent in vitro in glia and neuroblastoma cells of Mice. Four out of seven assays of infection were positive, i.e. after several passages in vitro yielding at most a 10(9) fold final dilution of the original material, the extracts of each of the four cultures, when injected intracerebrally into CD1 Mice, produced a deadly disease displaying the clinical and pathological signs characteristic of Scrapie.

Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS.

Primary cultures from a brain biopsy specimen of a human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) seropositive patient with progressive dementia contained small numbers of monocytoid cells and showed reverse transcriptase activity that persisted for as long as 100 days. Electron microscopy of these cells revealed the presence of HTLV-III/LAV virions. Subcultured cells removed from primary cultures by trypsinization were nonspecific esterase negative and did not express virus or show evidence of HTLV-III/LAV proviral sequences, while those remaining in the original flasks were nonspecific esterase positive and continued to produce virus. Virus from primary cultures was transmitted to peripheral blood-derived monocyte-macrophages and T cells. Virus production in T-cell cultures was transient while the monocyte-macrophages, like the primary cultures, produced virus for at least 120 days. Infection of several brain-derived cells with this and another HTLV-III/LAV isolate failed to demonstrate virus replication. These results indicate that the HTLV-III/LAV-infected cells recovered from the brain of this patient are cells of the mononuclear phagocyte series.

[Ovarian dysgerminoma: clinical signs, assessment, and therapeutic indications, with reference to 30 observations]. / Les dysgerminomes de l'ovaire. Signes cliniques, bilan, indications thérapeutiques à propos de 30 observations.

Thirty cases of ovarian seminomas in patients aged for the most part between 10 and 20 years were studied at the Gustave-Roussy Institute between 1957 and 1970. In 10 per cent of cases both ovaries were involved. They were revealed by menstrual disorders, acute cystic twisting, signs of abdomino-pelvic compression, or a change in the general state of health. Lymphograms were made for the 25 most recent cases. They showed pathological signs in 35 per cent of cases. The role of the lymphogram is of prime importance in the suveillance of nonirradiated patients, making it possible for them to have remedial treatment. Surgery ensures excision of the tumour and indicates the degree of abdominal extension. During a second operation, it is possible to transpose a healthy ovary to avoid castration. The methods of ganglion irradiation, which should be systematic, are discussed in relation to the results of the operation and of the lymphogram. In 80 per cent of cases, the patients were alive after two years and slightly more than half of them had maintained ovarian function.

[Effect of a microsomal system on the toxicity and on the interactions of various polycyclic carconogenic hydrocarbons with cells in culture]. / Effet d'un systme microsomal sur le pouvoir toxique et sur l'interaction de certains hydrocarbures polycycliques cancérogènes avec des cellules en culture

The addition of a liver microsomal system (extracted from phenobarbital pretreated hamster livers) to hamster embryo cell cultures, together with a carcinogenic hydrocarbon, reduces the hydrocarbon toxicity and increases the velocity of hydrocarbon uptake by cells.

[In vitro modification of the morphology and the growth of cells infected with scrapie (author's transl)]. / Modifications in vitro de la morphologie et de la croissance de cellules infectées par l'agent scrapie.

Seven cell lines originated either in brains or in neuroblastomas of Mice, were infected with Scrapie. After 12 to 16 in vitro passages, 6 lines out of 7 showed changes of their morphology, and of their growth, resembling those occurring in the course of a malignant transformation. The Scrapie infected cells acquired the capacity to form 2 to 4 times more colonies in liquid medium than the controls, and to develop large tridimensional colonies in semisolid medium. The role of Scrapie in these changes is discussed.