Search PubMed⌕ Search

Biomedical subjects

C Jasmin

Publications and source records attributed to C Jasmin.

At least 109 records · Page 6Linked to original sources

Defective uptake of alpha-fetoprotein (AFP) and transferrin (Tf) by PHA-activated peripheral blood lymphocytes from patients with AIDS and related syndromes.

Serum alpha-fetoprotein (AFP) and transferrin (Tf) are actively endocytosed by many growing cells during ontogenic and neoplastic growth, but also by peripheral T lymphocytes upon mitogen activation. AFP and Tf uptake occurs through receptor-mediated endocytosis. The purpose of the present work was to assess whether the expression and functional activity of AFP and Tf receptors are impaired in mitogen-activated T cells from several groups of HIV-1 seropositive (HIV+) individuals. Forty HIV+ cases were studied, including 12 patients with AIDS, 12 with lymphoadenopathy syndrome (LAS), as well as 16 asymptomatic homosexuals (As). Quantification of AFP and Tf uptake was carried out by fluorescence-activated cell sorting (FACS) using fluoresceinated derivatives of these proteins. Compared with healthy blood donors, the three HIV-1 seropositive groups exhibited clear impairment in the ability of their peripheral blood mononuclear cells (PBMC) to internalize AFP and Tf. The decrease in mean values of AFP uptake correlates roughly with the severity of the clinical status. Although these observations need to be confirmed after a much wider study groups, the AFP-Tf-endocytosis assay presented here clearly reveals early defective functions of mitogen-responsive T cells in disease-free subjects and may provide the basis for a prognostic test. The pathophysiological implications of these facts are discussed in relation to the structural and/or metabolic activities of fatty acids and iron, the ligands carried by AFP and Tf, respectively.

AIDS-Related Complex↗

Evidence for a link between certain psychological factors and the risk of breast cancer in a case-control study. Psycho-Oncologic Group (P.O.G.).

The relationship between psychosomatic characteristics and the risk of breast cancer was studied in women aged from 35 to 65 years, presenting with a clinically palpable breast tumor. To permit a double-blind design, the psychosomatic evaluation obtained by a long open-ended interview was completed before any diagnostic procedure. On the basis of this evaluation, the psychosomatician concluded that the patient was at high or low risk of serious disease. Several other psychological parameters were also recorded, and the diagnosis was then established by cytology or histology. Nineteen of the 77 patients finally included in the study had histologically verified breast cancer. The relative risk (RR) of breast cancer associated with psychosomatic factors was estimated by multivariate unconditional logistic regression, taking into account age at interview, family history of breast cancer, parity and age at first delivery. A significant relationship (p = 0.02) was found between psychosomatic prognosis and the relative risk of breast cancer. Both the low and high risk groups identified by the psychosomaticians had a similar mean age (46.1 versus 47.6 years). Fundamental mental structure played a predominant role in the risk of breast cancer, since no case was observed among the 18 patients with well organized neurosis, and all the 19 malignant tumors were observed among patients with poorly organized neurosis or psychosis (RR = 7.8, p = 0.009). In addition, excessive self-esteem (RR = 10.0, p = 0.02), hysterical disposition (RR = 7.5, p = 0.02), and unresolved recent grief (RR = 8.2, p = 0.05), were found to be significantly related to the risk of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phase I-II constant infusion of adriamycin (doxorubicin) by ambulatory pump delivery system in heavily pretreated (including adriamycin) breast cancer patients.

Previous studies have shown that the protracted infusion of adriamycin (ADM) by the ambulatory delivery system can significantly decrease both the cardiac and hematological toxicity caused by intermittent bolus administration. We treated 27 patients with metastatic breast cancer who had been heavily pretreated with regimens including ADM. Treatment consisted of 15- or 25-day courses of ADM at a mean dose of 3.8 mg/m2 (2.2-4.5 mg/m2) infused by programmable portable pump. Early cardiac toxicity was detected by echocardiography-Doppler. Two-dimensional echocardiography made possible the detection of interventricular septum hypokinetics, an early sign of a decrease of systolic function of the left ventricle. Despite the very high cumulative dose of ADM (mean dose 777.79 mg/m2, range 282-1647 mg/m2) received by these patients, no clinical heart failure was observed. Most frequently observed complications were oral mucositis, Grade 2 and 3 (10 patients), and complications related to the drug delivery system (15/137 courses). Hematological toxicity was minimal. Seven Grade 2 and five Grade 3 (but no Grade 4) alopecia were observed. Objective response was obtained in four of 24 patients (17%) evaluated for response, (only 21 were fully evaluable): one complete response and three partial responses (duration: 6.6, 7 and 11 months, respectively). Stabilization was seen in 14 patients lasting three to 26 months. The performance status and symptoms of nine of the patients (37%) was significantly improved. Our results show that continuous infusion of ADM is well tolerated and provides palliation to patients with metastatic breast cancer. It merits a trial as first-line treatment.

Adult↗

Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection.

We and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 x 10(4) cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infected patients. However, CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients' cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PHA + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.

Antigens, CD↗

Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages.

Recent studies have shown that IL-2R are composed of at least two polypeptide chains of 55 kDa (Tac or alpha-chain) and 70 to 75 kDa (p70 or beta-chain). The association of both chains forms high affinity IL-2R, whereas each chain alone binds IL-2 with a low (alpha-chain) or intermediate (beta-chain) affinity. So far, the p70 peptide has been found, in the absence of the Tac peptide, on the surface of lymphoid cells of T, B, or NK lineage. In this study, we investigated whether leukemic cells of various hemopoietic lineages expressed the p70 IL-2-binding protein. We found that both fresh leukemic cells obtained from patients, and cells from established leukemic lines of T cells, B cell, and myeloid origin constitutively expressed a p70 IL-2-binding protein on their surface, as detected by affinity cross-linking of radioiodinated IL-2. IL-2 binding and cross-linking to these cells was completely inhibited in the presence of an excess unlabeled rIL-2, but not with an anti-Tac mAb. Binding experiments on pre-B and myeloid cell lines revealed intermediate affinity IL-2R, whereas both high and intermediate affinity IL-2R were detected in T leukemic cells. The intermediate affinity binding of 125I-rIL-2 to the leukemic cell lines MOLT4 and Reh6 was inhibited by the TU27 mAb, which recognized the p75 chain of IL-2R. Moreover, the TU27 mAb could stain the K562, KM3, and MOLT4 (weakly) cell lines by indirect immunofluorescence. A high dose of rIL-2 (400 U/ml) enhanced the proliferation of cells from one out of three patients with acute myeloblastic leukemia, but it did not induce differentiation of the cells in any of three cases. Thus the finding of p70 IL-2-binding molecules on immature lymphoid and nonlymphoid hemopoietic cells should disclose new biologic functions for IL-2.

Cell Differentiation↗

Acquisition of tumorigenic potential in the human myoepithelial HBL100 cell line is associated with decreased expression of HLA class I, class II and integrin beta 3 and increased expression of c-myc.

The human breast cell line HBL100 acquires the capacity to invade normal tissues and to replace them by proliferation in vitro only at high passage levels (HPL). These cells therefore are a useful model for studying tumor progression in vitro. We have analyzed the expression of cell-surface markers supposed to be involved in the control of the neoplastic process. Quantitative flow cytometry has revealed that: (1) spontaneous expression of HLA class-I antigens strongly decreases in HPL HBL100 cells vs. LPL cells, which parallels amplification and over-expression of c-myc oncogene; (2) HLA DR antigens can be induced by IFN-gamma in LPL but not in HPL HBL100 cells; (3) HBL100 cells secrete a soluble protein factor which specifically inhibits HLA DR induction by IFN-gamma even in heterologous cell systems; (4) 50% of LPL HBL100 cells express integrin beta 3, whereas HPL HBL100 cells lose this antigen; (5) this cell line is myoepithelial in origin, since 100% of HBL100 cells exhibit the CD10 antigen. Our data stress a role of HLA antigens, of some integrins and of c-myc in the acquisition of malignant potential by myoepithelial mammary cells of the HBL100 line.

Biomarkers, Tumor↗

Impaired in-vitro proliferation of hemopoietic precursors in HIV-1-infected subjects.

Patients with acquired immunodeficiency syndrome (AIDS) and persistent lymphadenopathy syndrome (LAS) display significant hematological abnormalities of one or more cell lineages. In order to understand the pathophysiologic mechanisms leading to these abnormalities we studied the proliferation capacity of pluripotent and committed hemopoietic precursors using in-vitro colony assays. Anemia, leukopenia and thrombopenia were relatively frequent findings in HIV-infected subjects irrespectively of the patients' clinical status. The colony growth capacity of AIDS patients' GM-CFU and BFU-E was significantly decreased whereas no GEMM-CFU colonies could be obtained. There was no correlation between the number of BFU-E and GM-CFU colony number and the hemoglobin or the absolute number of polynuclear cells, respectively. The plating efficiency of both committed and pluripotent hematopoietic precursors from HIV infected patients could not be enhanced when additional exogenous recombinant GM-CSF, human interleukin 3 or erythropoietin were added in contrast to normal patients' cells. In addition, the impaired colony growth of these precursors could not be restored after adherent or T-cell depletion or the addition of normal allogenic irradiated adherent or/and T cells. Since this colony growth abnormality was also detected in HIV seropositive asymptomatic subjects our findings strongly suggest that the in-vitro growth of hematopoietic precursors is affected early after HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Replication of the human immunodeficiency virus 1 and impaired differentiation of T cells after in vitro infection of bone marrow immature T cells.

HIV-1 infection in vitro of normal bone marrow mononuclear cells (BMMC) depleted of mature T cells was studied. BMMC depleted of either CD3, CD2, or both could replicate HIV-1 irrespective of the presence of macrophages/monocytes. Infected bone marrow cells were shown to differentiate during the culture into CD3+, CD4+, CD8+, and CD1+ cells, whereas noninfected BMMC gave rise to CD3+, CD4+, and CD8+ cells. Moreover, 9-14% of the cells also expressed the viral proteins p24 and gp120 on their surface. Double staining studies revealed that 72 and 83% of the CD4+ cells expressed the gp120 and p24, respectively, suggesting that virus replication occurred in CD4+ cells. T cell colony growth from infected BMMC, either unfractionated or depleted of mature T cells, was impaired in a time-dependent manner, and the differentiation capacity of T cell precursors was abnormal. Colony cells displayed an immature cell phenotype (CD1+ cells) and the viral proteins gp120 and/or p24 could also be detected on CD1+ cells. In addition, pooled colony cells derived from infected CD2- and CD3-depleted BMMC could infect normal mitogen-activated lymphocytes in coculture experiments. These findings strongly suggest that HIV-1 can infect immature bone marrow T cells and be transmitted to the progeny, but the massive viral replication occurs only when the cells differentiate toward CD4+ cells.

Antigens, Differentiation, T-Lymphocyte↗

Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a European multicentre study.

Between October 1987 and November 1988, 95 European patients with metastatic renal cell carcinoma have been treated with recombinant interleukin-2 (rIL-2) (EuroCetus) at 18 X 10(6) IU/m2/day (equivalent to 3 X 10(6) Cetus Units/m2/day) according to the West schedule in two trials. 1. Forty-two patients received rIL-2 alone. Median time between initial diagnosis and metastases was three months. Eighty-one percent of the patients had at least two involved sites at inclusion and 86% underwent prior nephrectomy. Twenty-seven patients (64%) received two successive courses. Over 80% of the planned dose was administered in 69% and 44% of patients during courses 1 and 2, respectively. Fever, hypotension, weight gain, rise in creatinine level, hepatic disturbances, anaemia and thrombocytopenia were commonly observed but resolved promptly after completion of therapy. No toxic death was recorded. Two (6%) complete responses (CR), four (13%) partial responses (PR), four stable diseases (SD) and 22 progressive diseases (PD) were observed. The response rate is 6/32 (19%); the median progression-free survival time is not reached at 218+ days (92-394). 2. Fifty-three patients received rIL-2 with lymphokine-activated killer (LAK) cells. Median time from primary diagnosis to metastases was three months. Eighty-five percent of patients had at least two involved sites though 73% had previously undergone nephrectomy. Forty patients (75%) received two successive induction courses. Most patients, i.e. respectively, 77% and 60%, were given at least 80% of the planned dose during courses 1 and 2. Median numbers of LAK cells infused were 13.1 and 11.6 X 10(9) nucleated cells per course, respectively. Toxicity was not different from that described above; no toxic death occurred; five CR (10%), nine PR (18%), 11 SD and 26 PD were observed. The response rate is 14/51 (27%) and the median progression-free survival time is not reached at 7.2+ months (3-13.1). In conclusion, rIL-2, with or without LAK cells, is obviously active on metastatic renal cell carcinoma. The difference in response rate between the two trials is not statistically significant but has to be paralleled with the difference in dose received by the patients rather than with the addition of a cellular therapy. Toxicity was always manageable and reversible. The association of rIL-2 with other lymphokines should represent a major issue to improve the response rate and will be considered in further European studies.

Carcinoma, Renal Cell↗

[Value of a new induction protocol in Ewing's sarcoma. Apropos of 35 cases].

The use of a protocol of induction in Ewing's sarcoma based on the sequential association of Cyclophosphamide (150 mg/m2 for 7 days) and Adriamycin (35 mg/m2 on day 8) has shown that: 1. The clinical and radiological response (scan + MRI) even when complete is not predictive of the quality of the histological response. 2. For the histological response to be predictive, it must be evaluated on a complete monobloc resection. 3. A sustained, complete remission is more frequent after systematic extratumoral monobloc surgery and appropriate postoperative chemotherapy. When these conditions are respected, a complete remission rate of 88% at 30 months can be expected.

Adolescent↗

[Comparative study of 3 successive treatment protocols of osteogenic osteosarcoma in children, adolescents and young adults. Apropos of 100 cases].

Three therapeutic protocols were used successively for the treatment of osteogenic osteosarcoma since 1978. The first protocol associated initial surgery and 12 months of chemotherapy and was applied to 41 patients with good results in adults but poor results in children. A protocol introducing adjuvant chemotherapy based on the association of adriamycin-cisplatinum gave very disappointing results first in children and then in adults. The protocol based on HD MTX gave much more encouraging results: the long version (3 months preoperative chemotherapy) was effective in good responders but did not influence the course of poor responders. The shortened version of this protocol, derived from the T 10 Rosen protocol (1 month preoperative chemotherapy conservative surgery and appropriate peri- and postoperative chemotherapy) seems to transform the prognosis of osteosarcoma. Our current results indicate a complete primary remission rate of 89% at one year, and 83% at 33 months.

Adolescent↗

Tetrahydroaminoacridine in HIV infections. The THA Study Group.

On the basis of a similarity between certain neurological symptoms of AIDS and Alzheimer's disease, the authors studied the effects of tetrahydroaminoacridine (THA) in 9 patients with HIV infection. After 2 months of treatment, the preliminary results showed a significant increase in CD4 lymphocyte count as well as a decrease in p24 antigen level in 8 patients, of whom 4 became negative for the p24 antigen.

Acquired Immunodeficiency Syndrome↗

Histopathologic studies on myeloproliferative sarcoma virus (MPSV) induced leukemias and hemangiosarcoma in Jar-2 rats.

It is well known that MPSV induces myeloproliferative syndrome (MPS) in mice. Intravenous one shot inoculation of myeloproliferative sarcoma virus (MPSV) with Friend murine leukemia virus (F-MuLV) as a helper in newborn Jar-2 rats (on the second neonatal day) yielded hematopoietic malignancies in all the treated rats (25/25 rats) after 2 weeks' latency. MPS appeared from the 14th day in 14 rats. In the midst of the myeloproliferative field of the spleen and bone marrow, myeloblastic or myeloblastic-erythroblastic foci were observed. From 19th day, acute myeloblastic leukemia occurred in 3 rats and erythroleukemia in 8 rats. MPSV induced first MPS which remained as such or later developed into acute leukemia. Myelofibrosis as seen in mice was not observed. In addition, hemangiosarcoma of the brain, spinal cord and spleen appeared in 15 rats from the 24th day, and were often multiple. MPSV can yield the tumor only in newborn rats, and target cells of MPSV are not only hematopoietic cells but also endothelial cells of the brain, spinal cord and occasionally spleen.

Animals↗