Biomedical subjects

C Jasmin

Publications and source records attributed to C Jasmin.

At least 145 records · Page 8Linked to original sources

PubMed1986

Ectopic hematopoiesis in peritoneal tumor nodules induced by the myeloproliferative sarcoma virus in DBA/2 mice.

Tumor nodules composed of fibroblasts, large undifferentiated cells, granulocytes, and small lymphocytes develop in the spleens of adult DBA/2 mice infected with the myeloproliferative sarcoma virus (MPSV). They spread thereafter in the organism, and at the terminal stage of the disease they are especially numerous on the peritoneal membrane. The present study, performed on those tumor nodules to avoid contamination by exogenous hematopoietic cells, demonstrated that they were sites of granulopoiesis, which may have occurred via the local differentiation of granulomacrophage precursor cells (GM-CFC) and perhaps also from pluripotent hematopoietic stem cells, since these two populations were present in the tumor nodules (25 +/- 11 and 13 +/- 10, respectively, per 5-10(5) cells). Almost all (88%) those GM-CFC were able to clone in vitro without added colony-stimulating factor. A comparative study with the Moloney murine sarcoma virus-induced tumor indicated that the local production of hematopoiesis-stimulating factors was not sufficient to allow such ectopic granulopoiesis. These results imply the presence of a specific hematopoietic microenvironment in the MPSV-induced tumor nodules.

Animals↗

PubMed1986

[Pre and postoperative chemotherapy of osteosarcoma with an adriamycin-cisplatin combination. Risks of a neoadjuvant chemotherapy which is not sufficiently effective].

The authors evaluated a new protocol of neoadjuvant chemotherapy for osteosarcoma, easier to manage and different from T10. The good results obtained with the postoperative ADR-CDDP association led us to undertake a pilot study between 1982 and 1984, using ADR-CDDP as preoperative chemotherapy. The records of sixteen patients were available for follow-up. The average age of the patients was 19.9 years. Patients received two or three preoperative courses, and a total of six identical courses. Tolerance was good. Pain usually disappeared but this was often misleading because associated with radiological and/or clinical tumor progression, low histological necrosis or poor outcome. The continuous disease-free survival actuarial rate was less than 57 and 40% at 18 months and two years respectively. The actuarial survival rate was 87% at one year and 65% at two years respectively. Disappointing results of this preoperative protocol, compared to results with the SO4 78 or T10 protocols for example, led to publish these data early in order to underline their potential dangers. As a result, we stopped our study. The charter of pilot studies justifies this publication. As well, these data point out the necessity of very close follow-up of neoadjuvant chemotherapy by sophisticated medical imaging. Neoadjuvant chemotherapy, if ineffective, must be stopped early, and should lead to surgery, followed by adequate postoperative chemotherapy.

Adolescent↗

PubMed1986

[Experiences and perspectives on adjuvant chemotherapy in osteogenic osteosarcoma].

This article analyses the relevance of the published results of adjuvant chemotherapy in osteogenic osteosarcomas. It discusses the causation and prospects for treatment particularly the details of the chemotherapy, with reference to mono- or poly-chemotherapy, the influence of the dose and of the interval of administration, and also the value of pre- and post-operative chemotherapy. It is apparent that intensive pre-operative chemotherapy limited to 4 weeks is a reasonable mean of distinguishing the good responders. The problem of the choice of therapy for bad responders is also discussed.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

Abnormal in vitro proliferation and differentiation of T colony-forming cells in patients with lymphadenopathy syndrome.

Patients with acquired immunodeficiency syndrome (AIDS) present impaired colony growth and in vitro differentiation capacity of peripheral blood and bone marrow T colony-forming cells (T-CFC). We show that peripheral blood, bone marrow, and lymph node T-CFC from patients with persistent lymphadenopathy syndrome (LAS), a syndrome that can precede AIDS, displayed similar abnormalities. Indeed, peripheral blood T-CFC generated a low number of colonies in seven out of 12 patients, and almost no colonies were obtained from bone marrow cells of all patients. The simultaneous study of T-CFC from peripheral blood and lymph node mononuclear cells seems to provide a reliable indicator for the risk of developing AIDS. The six patients who developed AIDS displayed extremely low numbers of peripheral blood T-CFC (13 +/- 17 colonies per 5 X 10(4) cells), and in two of them, no colonies could be obtained from lymph node T-CFC. The remaining patients who had not developed AIDS displayed a higher number of peripheral blood T-CFC (141 +/- 113 per 5 X 10(4) cells) and lymph node T-CFC, which, in addition, preserved their clonogenic capacity. In some patients, peripheral blood and lymph node, but not bone marrow, T-CFC were capable of generating colonies in the absence of added growth factors or mitogens, whereas in others, colony formation was obtained with purified interleukin 2 (IL 2) alone. Both spontaneous and IL 2-induced colony formation was abrogated by a monoclonal antibody against the IL 2 receptor. Taken together, these findings suggest that at least some T-CFC expressed IL 2 receptors. Colonies generated either in the presence or in the absence of added growth factors were composed of T4+, T6+, and T8+ cells, indicating impaired in vitro T-CFC differentiation. These findings indicate that a dramatic quantitative and qualitative impairment of the proliferation and differentiation of peripheral blood and lymph node T-CFC precedes the clinical evolution from LAS to AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1986

[Digital angiography of bone sarcoma in the child].

The authors analyze the results of 50 computed angiographies made for osteosarcoma and Ewing's sarcoma. Better tolerated than conventional angiography computed angiography is also more sensitive in preoperative evaluation of effectiveness of neoadjuvant chemotherapy. Automatic subtraction, direct measuring of tumor size and vascularization density give to angiographic changes after chemotherapy the most predictive value. After conservative surgery or radiotherapy digital angiography provides most reliable local follow up.

Angiography↗

PubMed1985

Characterization of normal peripheral blood T- and B-cell colony-forming cells: growth factors(s) and accessory cell requirements for their in vitro proliferation.

The biological properties of normal peripheral lymphoid precursors were studied using separate colony assays for T- and B-cell colony-forming cells (T-CFC and B-CFC, respectively). Cell fractions, selected by complement-mediated cytotoxicity with monoclonal antibodies, were cultured in methylcellulose using different sources of growth factors containing (PHA-LCM2 and PHA-LCM7) or not (PHA-TCM) Interleukin-2 (IL-2). Well-differentiated T-cell colonies were only observed with IL-2-containing conditioned media (CM). Normal T-CFC displayed either an immature (E-T11-OKT3-Ia-) or mature (E+) phenotype, were quiescent cells presenting different radiosensitivity (D0 = 80 and 155 rads, respectively). B-CFC displayed the E-T11-OKT3-B1-Ia+ surface phenotype, were in DNA synthesis and were more radioresistant (D0 = 300 rads) than T-CFC. B-cell colonies could be obtained in the presence of allogeneic irradiated T cells and PHA-TCM, but not with IL-2-containing CM. When E-T11-OKT3- cells were seeded with PHA-TCM supplemented with increasing amounts of semipurified IL-2 in the presence of a fixed number of irradiated T cells, the B-cell colony growth (as assessed by the frequency of sIg+ colony cells) progressively decreased whereas that of T-cell colonies increased. IL-2-free CM (PHA-TCM) was able to induce T-cell colony growth from E-T11-OKT3- cells but addition of allogeneic irradiated T cells induced B-cell colony formation in a dose-dependent manner. Conversely, T cells enhanced T-cell colony growth in the presence of IL-2-containing CM. Furthermore, adherent cell depletion of E-T11-OKT3- cells inhibited T- but not B-cell colony growth. These results taken together suggest that T- and B-cell colonies derive from different progenitor cells which have different growth factor(s) and accessory cell requirements and indicate that T-cell colony growth is associated with inhibition of B-cell colony formation.

Antigen-Presenting Cells↗

PubMed1985

Accessory role of autologous T lymphocytes and adherent cells for the in vitro proliferation of T-cell colony-forming cells from patients with T-cell acute lymphoblastic leukemia.

Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies can proliferate in methylcellulose in the absence of added growth factors or mitogenic stimulation. Mononuclear cells (MNC) from 7 patients with T-cell acute lymphoblastic leukemia were separated into cells forming rosettes with sheep erythrocytes (E+) or not (E-). E- cells were further depleted by complement-mediated cytotoxicity with OKT3 monoclonal antibody (E-OKT3- cells). The study of their spontaneous T-cell colony-forming ability suggested that proliferation of T-CFC in the absence of added growth factors requires cellular cooperation because: (1) No colony growth was observed at low cell concentrations (up to 2 X 10(4) cells/ml) whereas at higher cell densities the number of colonies increased exponentially; (2) The plating efficiency from unfractionated MNC was higher than that from E-OKT3- or E+ cells. Irradiated autologous E+ cells enhanced the plating efficiency from blast-enriched cell fractions (E-OKT3-) when co-cultured either directly in methylcellulose or separately in a two layer assay (agar-methylcellulose), suggesting that their activity could be due to diffusible factors; (3) Adherent-cell depletion of MNC decreased colony formation. Autologous irradiated adherent cells were able to restore the plating efficiency from MNCA- cells when co-cultured directly in methylcellulose but not in separate layers; however, media conditioned by patients' A+ cells could enhance the colony growth from patients' MNCA- cells, indicating that their activity could also be mediated by constitutively released soluble factors.

Antibodies, Monoclonal↗

PubMed1985

In vitro induction of CFU-S proliferation by a non viral splenic activity from myeloproliferative sarcoma virus infected mice.

The myeloproliferative sarcoma virus (MPSV) induces a myeloproliferative syndrome in DBA/2 mice. It is characterized by a considerable increase in the number (100-fold) and in the concentration (10-fold) of pluripotent hematopoietic stem cells detected in vivo (CFU-S) in the spleens of infected animals. Prior studies have shown the presence of a mixed-colony promoting activity (MPA) in neoplastic spleens. In the presence of a small quantity of erythropoietin, MPA induces the proliferation and differentiation of pluripotent hematopoietic stem cells, detected in vitro (Mix-CFU). We tested the effect of factors produced by neoplastic spleen cells on the proliferation of day 10 CFU-S and their entry into the cell cycle. This was done by comparing the number of day 10 CFU-S present in suspensions of normal bone marrow cells incubated for 2 days on agar underlays containing cells from either normal or neoplastic spleens. Our results show the existence of an activity secreted by cells from the spleens of MPSV-infected animals which starts CFU-S cycling and which is physically distinct from MPSV. The presence of this activity, whose identity with MPA remains to be proven, would enable us to explain the proliferation of CFU-S in the course of the disease.

Animals↗

PubMed1985

Study of the 78A1 isolate of Moloney murine sarcoma virus. II. Haematopoietic tropism and tumourigenicity.

A new isolate of Moloney murine sarcoma virus (Mo-MuSV), designated 78A1, has been molecularly cloned. The cloned genome, found to be larger than that of other known isolates of the same virus is close in size to that of the myeloproliferative sarcoma virus (MPSV), also a derivative of the original Mo-MuSV/Moloney murine leukaemia virus (Mo-MuLV) complex. Until now, MPSV was the only Mo-MuSV isolate known to be capable of inducing a myeloproliferative disease associated with a tumoural syndrome when injected intravenously into sensitive mice. We compared the biological activity of our cloned virus isolate (78A1) and that of another cloned Mo-MuSV virus (HT1) whose genome is slightly smaller than that of 78A1. The helper virus (Mo-MuLV) associated with the Mo-MuSV isolates was also injected alone as control. After injection into sensitive mice only the isolate 78A1, as well as MPSV caused a tumoural syndrome invading spleen, liver and other haematopoietic organs, and the appearance of granulo-macrophage precursors not requiring exogenous stimulating factors for their proliferation and differentiation. The 78A1 virus has a longer latency period (3 months) than MPSV (several days) and does not induce a typical myeloproliferative disease.

Animals↗

PubMed1985

Enhanced cloning efficiency of murine rhabdomyosarcoma cells after chlorozotocin treatment: relationship with enhanced lung metastasis.

The effect of chlorozotocin [(CZT) CAS: 54749-90-5; 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-gluco-pyranose] was studied on a series of tumor cells, cultured or extracted fresh primary or transplanted tumors, by means of clonogenic assay. The ability of most rat rhabdomyosarcoma cells to form colonies in soft agar was enhanced when exposed to the water-soluble nitrosourea chloride CZT. The tumor cells tested were derived from a) several primary tumors induced in WAG rats by colloidal nickel, then cultured and exposed to CZT early during in vitro passage; b) the 9-4 tumor, also Ni-induced but maintained in long-term culture; and c) the Ni-induced 9-4/0 tumor, maintained by transplantation in syngeneic rats. No inhibition of colony formation was observed in any of the cell lines even at high concentrations of CZT. Adriamycin, chosen as a control treatment, strongly inhibited the cloning efficiency (CE) of the tumor cells. In vivo, the weekly injection of 10 mg CZT/kg body weight into syngeneic rats bearing transplanted tumors led to an enhancement of lung metastasis formation. The CZT enhancement of CE of tumor cells and its relationship to increased in vivo tumor metastasis is discussed.

Animals↗

PubMed1985

Abnormal in vitro proliferation and differentiation of T colony forming cells in AIDS patients and clinically normal male homosexuals.

T cell colonies were generated from the peripheral blood and bone marrow of 11 patients with acquired immune deficiency syndrome (AIDS), 17 normal male and female heterosexuals and seven clinically normal male homosexuals. Mononuclear cells were cultured in methylcellulose both in the absence and presence of interleukin-2 (IL-2) containing conditioned medium. Clinically normal homosexuals showed a low number of T4+ (P less than 0.01) but not T8+ cells. The number of T cell colony forming cells (T-CFC) from both AIDS patients and homosexuals was significantly (P less than 0.01) reduced compared to T-CFC from normal heterosexuals. In seven and four out of 11 AIDS patients, T-CFC from peripheral blood and bone marrow, respectively, were able to generate colonies in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies from AIDS patients as well as induced colonies from normal homosexuals were composed of immature cells bearing the T3+, T4+, T6+ T8+ surface phenotype, unlike colonies from normal heterosexuals which displayed mature cells bearing the T3+ T4+ T6- and T3+ T8+ T6- surface phenotype. Moreover, most T-CFC from primary spontaneous and induced colonies had lost their self-renewal capacity either in the absence or the presence of added growth factors. These results suggest that early impairment of T-CFC may play a predominant role in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1985

T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia.

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non-Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.

Acid Phosphatase↗

PubMed1984

Colony formation in the absence of added growth factors by peripheral blood T-cell colony-forming cells of patients with T-cell malignancies.

Clonogenic cells from peripheral blood of 13/16 patients with T-cell malignancies generated colonies in methylcellulose in absence of added growth factors or mitogenic stimulation. Spontaneous colonies were also obtained from purified cell fractions (E-OKT3- and/or E+ cells) in 73% and 57% of the patients, respectively. No spontaneous colony growth was observed with mononuclear cells of patients with solid tumors, non-T-cell leukemias or normal subjects. Colonies consisted of acid-phosphatase-positive, myeloperoxidase-and PAS-negative lymphoblasts bearing T-cell surface markers. Although the phenotype of pooled colony cells from either unfractionated mononuclear cells or E-OKT3- -derived colonies varied from patient to patient, the colonies, like fresh leukemic cells, were mostly composed of relatively immature cells as assessed by the high proportion (greater than 40%) of OKT6+ and OKT10+ cells and the low proportion (less than 40%) of OKT3+ and/or E+ cells. Cytogenetic analysis of colony cells revealed either normal metaphases or chromosome anomalies similar to those observed in fresh leukemic cells. Moreover, cells from primary colonies exhibited a capacity for self-renewal in the absence of added growth factors.

Adolescent↗

PubMed1984

Induction of cellular DNA polymerases in a Burkitt lymphoma-derived cell line by treatment with 5-iododeoxyuridine.

Cellular DNA polymerases of a Burkitt lymphoma-derived cell line (P3HR-1) were found to be greatly induced by treatment of the cells with 5-iododeoxyuridine (IUdR) at a concentration which induces Epstein-Barr virus (EBV) early antigen (EA) expression. The activities of all the DNA Polymerases alpha, beta and gamma in P3HR-1 cells increased 7-9 fold by exposure of the cells to IUdR (25 micrograms/ml) for 3 days, while the EBV-coded DNA polymerase activity in the cell remained undetectable under the assay conditions employed. Under the same culture conditions with IUdR, EA-positive P3HR-1 cells increased to 16.6% which was much higher than that of the non-treated control cells (0.32%). On the other hand, another Burkitt lymphoma cell line, Raji, had very low incidence (1.27%) of EA induction by IUdR-treatment and the level of DNA polymerase activities remained almost unchanged. From these results it seems that the increase in DNA polymerase activity during the treatment of P3HR-1 cells with IUdR is closely related to high incidence of EA expression in these Burkitt lymphoma cells. Also, the finding has revealed yet unknown effect of IUdR on cultured cells and provides a useful tool to obtain a large quantity of the induced cellular DNA polymerases from the P3HR-1 and KB cells.

Burkitt Lymphoma↗

PubMed1984

In vivo acute hematotoxicity of N,N'-bis[N-(2-chloroethyl)-N-nitrosocarbamoyl]cystamine (CNCC), a new nitrosourea analog.

The in vivo hematotoxic effects on different hemopoietic cell compartments of a new nitrosourea analog CNCC were compared to another glycosidyl derivative, RFCNU. Bone marrow microenvironment in liquid culture, bone marrow and splenic colony-forming units in agar culture (GM-CFUc), relative spleen index, and spleen and bone marrow cellularity were evaluated in young adult (DBA/2 X C57B1/6)F1 mice. The drugs, dissolved in olive oil, were injected ip at either the minimal or the median or the maximal dose of the "maximally efficient dose range." A single administration of CNCC induced a dramatic depopulation of bone marrow and spleen within 12 and 24 hr and significantly reduced the GM-CFUc in both organs. A rapid recovery of both the total cell number and GM-CFUc was observed between Days 2 and 5 (kinetic experiment). The comparison of toxicity of 20 to 50 mg/kg CNCC and 15 to 30 mg/kg (2-chloroethyl)ribopyranosyl-3-nitrosourea RFCNU at Day 1 and Day 5 showed that the bone marrow microenvironment was modified by the effect of oil and was further impaired by CNCC in a concentration-dependent fashion. In contrast RFCNU had less effect on the microenvironment. Similarly, the bone marrow GM-CFUc population was reversibly impaired by CNCC in a dose-dependent fashion, and again RFCNU had less effect. In the spleen both drugs provoked a higher toxic effect than in the bone marrow; on Day 1 they decreased the GM-CFUc population by 1 to 2 log. On Day 5 a compensatory regeneration was obtained in all cases except the highest tolerable CNCC dose, whose effect was more delayed.

Acute Disease↗

PubMed1984

Heterogeneity of peripheral blood T-cell colony-forming cells in patients with T-cell malignancies.

Some peripheral blood clonogenic T-cells from patients with T-cell malignancies can generate colonies in methylcellulose in the absence of added growth factors or mitogen stimulation (T-CFCs). T-CFC from these patients were also able to form colonies in semi-solid media in the presence of added growth factors (T-CFCi). T-CFCs, in contrast to T-CFCi, were highly clonogenic cells possessing self-renewal capacity in the absence of added growth factors. T-CFCs were in cell cycle and more sensitive to Ara-C or ADM (D10 = 0.009 and 0.025 microgram/ml respectively than T-CFCi (D10 = 1 and 2 micrograms/ml respectively). Furthermore, T-CFCs were more radiosensitive (Do less than 1.1 Gy) than T-CFCi (Do less than 5 Gy). T-cell precursors from patients with immature blast cells (E-, OKT3-, OKT6+, OKT10+) were independent of added growth factors for their in vitro proliferation whereas in cases with mature blast cells (E+, OKT3+) T-CFC were significantly more dependent. These observations strongly suggest that T-CFCs and T-CFCi represent different cell subsets. The phenotype of pooled induced and spontaneous T-cell colonies was highly individualized. However, colonies contained a significant proportion of relatively immature T-cells as assessed by the proportion of OKT6+, OKT10+, OKT3+ and E+ cells. The phenotype of colony cells was quite similar to that observed on fresh leukemic cells suggesting a defect of the in vitro differentiation of both T-CFCs and T-CFCi.

Adolescent↗

PubMed1984

Modulation by the polyoxotungstate HPA-23 of Epstein-Barr virus early antigen expression in Raji cells treated with iododeoxyuridine.

The polyoxotungstate HPA-23 was found to exert a differential effect on the induction of Epstein-Barr virus early antigen in Raji cells induced with 5-iodo-2'-deoxyuridine (IUdR). Thus, treatment of Raji cells concomitantly with IUdR and HPA-23 inhibited early antigen expression, and the extent of inhibition was proportional to the duration of treatment with HPA-23. In contrast, pretreatment of Raji cells with HPA-23 prior to induction with IUdR stimulated early antigen expression in exponentially multiplying but not in stationary-phase cells. HPA-23 alone had no effect on early antigen expression in Raji cells. Activation of the latent Epstein-Barr virus genome by IUdR is dependent upon incorporation of the thymidine analogue into cellular DNA during the S-phase of the cell cycle. Synthesis of Epstein-Barr virus DNA also takes place during S-phase, suggesting a possible participation in this process of cellular DNA polymerase alpha which is thought to be responsible for cellular DNA replication and the activity of which increases several-fold during S-phase. Treatment of Raji cells with HPA-23 caused a marked decrease in DNA polymerase alpha activity, which could result in an inhibition of IUdR incorporation leading to the observed reduction of early antigen expression in cells treated concomitantly with IUdR and HPA-23.

Antigens, Viral↗

PubMed1984

Action of temperature-sensitive mutants of myeloproliferative sarcoma virus suggests that fibroblast-transforming and hematopoietic transforming viral properties are related.

The myeloproliferative sarcoma virus is molecularly related to the Moloney sarcoma virus (Pragnell et al., J. Virol. 38:952-957, 1981), but causes both fibroblast transformation in vitro and leukemic changes--including spleen focus formation--in adult mice. The fibroblast transforming properties of myeloproliferative sarcoma virus were used to select viral temperature-sensitive mutants at 39.5 degrees C, the nonpermissive temperature. These mutants are temperature sensitive in the maintenance of the transformed state. This was also shown by cytoskeletal changes of the infected cells at permissive and nonpermissive temperatures. Viruses released from cells maintained at both the permissive and nonpermissive temperature are temperature sensitive in fibroblast transformation functions. All temperature-sensitive mutants show only a low reversion rate to wild-type transforming function. The myeloproliferative sarcoma virus temperature-sensitive mutants are inefficient in causing leukemic transformation (spleen enlargement, focus formation) in mice at the normal temperature. A method to maintain a low body temperature (33 to 34 degrees C) in mice is described. One temperature-sensitive mutant was checked at low body temperature and did not induce leukemia. These data thus indicate that the same or related viral functions are responsible for hematopoietic and fibroblast transformation.

Animals↗