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Biomedical subjects

N de Tribolet

Publications and source records attributed to N de Tribolet.

At least 145 records · Page 8Linked to original sources
PubMed1989

Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2.

Transforming growth factor (TGF)-beta 1 is a polypeptide that is assumed to play a fundamental role in the growth of both normal and neoplastic cells. TGF-beta 2 is a closely related polypeptide, originally described as glioblastoma cell-derived T cell suppressor factor (G-TsF) due to its immunosuppressive activity. Expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 was examined in tumor cells and was found to be different in several cell lines and tissues that were tested. Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection. The coordinate expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 in glioblastoma was not paralleled by secretion of both polypeptides as only G-TsF/TGF-beta 2 but not TGF-beta 1 was identified in supernatants of glioblastoma cells. These data provide evidence for a post-transcriptional level of regulation for production of the two forms of TGF-beta. As mRNA for G-TsF/TGF-beta 2 was also identified in fresh surgically removed human glioblastoma tissue, G-TsF/TGF-beta 2 may also be secreted within the tumor in vivo. Unlike glioblastoma, human fetal brain tissues or adult brain specimens studied did not express detectable levels of TGF-beta mRNA. Impaired cell-mediated immunity is an established finding in patients with glioblastoma. Secretion of G-TsF/TGF-beta 2 by tumor cells in vivo may contribute to decreased immune surveillance for tumor development, as well as neovascularization of the tumor tissue.

Adult↗
PubMed1989

Antitumor activity and surface phenotypes of human glioma-infiltrating lymphocytes after in vitro expansion in the presence of interleukin 2.

The present study describes a method for in vitro expansion and characterization of antitumor-reactive lymphoid cells isolated from human malignant astrocytomas. Glioma-infiltrating lymphocytes were separated from 24 glioma specimens and cultured in medium containing interleukin 2 (50 to 2000 units/ml). Within 20 to 42 days after the initiation of culture, 20 of 24 cultures of glioma-derived lymphocytes expanded with a substantial increase in cell numbers, of at least 5 x 10(8) cells up to 5 x 10(9), with a simultaneous elimination of contaminating autologous glioma cells. The expanding glioma-derived lymphocytes consisted of 90 +/- 8% (SD) CD3+ T-cells including both CD4+ and CD8+ subpopulations. CD16 was expressed on 4 +/- 5% of the cells and three cultures studied exhibited 14% +/- 1 of Leu-19-positive cells. After 4 to 8 weeks of proliferation, interleukin 2 receptor expression decreased from 36 +/- 28% to less than 10% and the lymphocytes ceased to grow in all cultures. Glioma-derived effector lymphocytes could lyse almost all the autologous tumor targets as well as allogeneic glioma cells. The cytotoxic activity of long-term cultured peripheral blood lymphocytes obtained from the same patients appeared to be similar to that of glioma-derived lymphocytes in killing autologous tumor cells. In summary, glioma-derived lymphocytes expanded in bulk culture with high concentrations of interleukin 2 (2000 units/ml) consisted predominantly of T-lymphoblasts with the ability to kill autologous glioma cells. The tumor-infiltrating lymphocytes could be expanded to sufficient numbers for possible use in the adoptive immunotherapy of malignant gliomas.

Adult↗
PubMed1989

[Intracranial pressure determination in neuro-traumatology. Indications, interpretation and complications].

Intracranial pressure (ICP) monitoring in patients with severe head injury is useful in understanding the physiopathology of cerebral contusion, proper planning of treatment and assessment of prognosis. ICP should be monitored in patients with severe head injury presenting with coma, signs of brainstem involvement and an abnormal CT-scan. ICP values must be considered in conjunction with other parameters, especially blood pressure. Normal ICP does not rule out the development of intracranial hematoma, thus emphasizing the importance of clinical examination and of control CT-scans if the patients are paralyzed and artificially ventilated. Monitoring should be discontinued as soon as possible since, the complication rate correlates with the duration of ICP monitoring.

Age Factors↗
PubMed1989

[The surgical treatment of lumbar canal stenosis].

In a retrospective study of the results, 2 and 4 years after operation, of 52 cases of narrow lumbar canal, the most frequent preoperative symptoms were low back pain (82.7%), neurogenic claudication (61.5%) and sciatica (61.5%). 21 patients had a herniated disk in addition to the narrow canal. Sciatica was more frequent in this group than in narrow lumbar canal alone, where neurogenic claudication was more frequent. All patients underwent decompressive laminectomy, most often at level L4-L5. No spondylodesis was required. After 4.9 months, 84% of the patients were improved or cured. After more than 2 years 90% of the patients were cured of low back pain and 92% were cured of sciatica, but 22% were still under limitation in walking.

Adult↗
PubMed1989

Immunology of gliomas.

The treatment of cerebral gliomas continues to challenge neurosurgeons and research scientists. The lack of major success with chemotherapy and radiation therapy has given rise to further investigation into the biology of these tumors and host reactions to them. Much of this research has centered upon the evaluation of tumor cell antigenicity and on both the humoral and cellular immune responses to gliomas. Contrary to previous considerations, evidence suggests that astrocytes, glioma cells, and tumor endothelial cells may all have pivotal roles in the initiation and prolongation of both local and systemic immune responses to the tumor. In this review we will discuss the immunobiology of the glioma with specific reference to the interactions between the tumor and the host immune system. In addition, ideas for potential therapeutic manipulation of the host-glioma immune interactions will be reviewed, stressing potential pitfalls and risks.

Antibody Formation↗
PubMed1989

Symptomatic xanthogranuloma of the third ventricle: report of two cases and review of the literature.

Two patients with symptomatic xanthogranuloma of the third ventricle are presented. Both presented with a short history of increased intracranial pressure owing to hydrocephalus secondary to obstruction of the foramina of Monro. Computed tomography scanning demonstrated in both cases a round hypoisodense nonenhancing mass localized in the third ventricle, with dilatation of the lateral ventricles. Macroscopically complete surgical removal by a right transventricular approach was achieved in both patients. Eleven cases of xanthogranulomas of the third ventricle, including our own, have been published in the literature. The pathogenesis, clinical and radiological features, differential diagnosis, and treatment of this rare benign lesion are briefly discussed.

Adult↗
PubMed1989

Effects of propranolol on resting metabolic rate after severe head injury.

Postabsorptive resting metabolic rate (RMR), measured by indirect calorimetry, and the effect of iv propranolol administration were studied in 12 nonseptic patients with severe head injury by means of indirect calorimetry. Before propranolol RMR was moderately increased (126 +/- 10.4% of predicted values) whereas urinary excretion of catecholamines was markedly elevated (p less than .01 vs. normal values). RMR was significantly correlated with both resting heart rate (HR) (r = .72, p less than .01) and 24-h urinary N excretion (r = .85, p less than .001). The administration of iv propranolol (0.1 mg/kg) produced a rapid decrease in HR (-10 +/- 4%, p less than .001) and in RMR (-6.1 +/- 2.3%, p less than .001). Further administration of propranolol produced no additional reduction in either HR or RMR. We conclude that severely head-injured patients are moderately hypermetabolic in resting and postabsorptive conditions, and that acute iv propranolol administration induces a reduction of about one quarter of the resting hypermetabolism.

Adolescent↗
PubMed1989

Immunohistochemical and in vitro functional analysis of pineal-germinoma infiltrating lymphocytes: report of a case.

The present study describes the phenotypic and functional analysis of tumor-infiltrating lymphocytes isolated from a germinoma located in the pineal region. Tumor-infiltrating lymphocytes were separated from the germinoma and cultured in medium containing IL-2 (1000 U/ml). An immunohistochemical analysis of frozen sections revealed that 90% of the germinoma-infiltrating lymphocytes were CD3-positive T cells expressing CD4, CD8, and HLA Class I and Class II antigens, but were negative for CD16, CD20, CD23, CD25 and CD14 antigens. After in vitro cultivation in the presence of high concentrations of IL-2, the lymphocytes proliferated for 2 weeks, showing marked DNA synthesis. In addition, the lymphocytes could lyse NK-resistant allogeneic target cells. These results provide evidence for a potential role of germinoma-infiltrating lymphocytes in vivo, and suggest that the lymphocytes may control the growth of autochthonous tumor cells by killing those that are not restricted to the major histocompatibility complex.

Adult↗
PubMed1989

Chiasmal apoplexy: haemorrhage from a cavernous malformation in the optic chiasm.

We present a patient who experienced sudden onset of orbital headache, visual loss and bitemporal visual field defect. MRI of the optic chiasm suggested a diagnosis of haemorrhage and hence a vascular malformation. Pterional craniotomy revealed an intrachiasmatic haematoma with a cavernous angioma. The malformation was totally excised and vision improved after surgery. The syndrome of chiasmal apoplexy is discussed.

Adult↗
PubMed1989

The implications of the heterogeneous distribution of Ki-67 labelled cells in meningiomas.

Ki-67 monoclonal antibody reacts with a nuclear protein only expressed in proliferating cells. In order to evaluate the applicability of Ki-67 in meningiomas we determined the index of labelled cells in 52 biopsies. Two counting methods were used to calculate the labelling index. The mean Ki-67 index was determined by the number of positive Ki-67 cells in three randomly chosen fields divided by the total number of cells in the three fields. The preparations were also screened for the area with the highest percentage of positive Ki-67 cells, yielding the 'highest' Ki-index. The three patients who developed a recurrence did not show an elevated Ki-67 index by any of the two counting methods. Because of the differences observed between the two counting methods and the differences of the Ki-67 indices in the three randomly chosen fields we performed a statistical analysis to evaluate the possibility of a heterogeneous distribution of Ki-67 positive cells in meningiomas. Homogeneity was rejected if the data showed no Poisson distribution. We found that five of the 13 tumours which had a mean Ki-67 index greater than 1.00% were heterogeneous (38.4%). One of the highest differences between the two counting methods (5.05%) was noted in the only tumour with local signs of malignancy. Our results indicate a heterogeneity of the labelling of Ki-67 in histologically benign meningiomas and emphasise the importance of representative sampling. More attention should be paid to this heterogeneity for cell kinetic studies in brain tumours, and one should be aware that regrowth is not only determined by the proliferative capacity.

Antibodies, Monoclonal↗
PubMed1989

Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor beta 2.

Human glioblastoma cells secrete an inhibitory factor termed "glioblastoma-derived T-cell suppressor factor" (G-TsF). A member of the transforming growth factor beta (TGF beta) family, G-TsF is identical to TGF beta 2. The present study investigated the effect of G-TsF/TGF beta 2 on the proliferative and cytotoxic properties of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). The results demonstrate that the IL-2 (5 to 20 U/ml)-dependent proliferative response of glioma-derived TIL's was inhibited 70% to 85% by G-TsF/TGF beta 2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNF alpha) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNF alpha nor interferon gamma was able to reduce the inhibitory effect of TGF beta 2 on TIL proliferation. In addition, TGF beta 2 suppressed 60% to 100% the cytotoxic response of glioma-derived TIL's against several tumor targets, including autologous glioma cells, and the suppressive effect was shown to be reduced by increasing concentrations of IL-2.

Brain Neoplasms↗
PubMed1988

Immunohistological and functional analyses of lymphoid infiltrates in human glioblastomas.

An immunohistological analysis of tumor tissue obtained from seven patients with malignant gliomas demonstrated varying levels of lymphoid cell infiltration. The tumor infiltrating lymphocytes obtained from each sample were cultured in vitro by a limiting dilution technique. In three of the cases studied many tumor infiltrating lymphocyte microcultures selectively lysed autologous glioblastoma cells but did not lyse allogeneic gliomas, natural killer-resistant fresh melanoma cells or K562 target cells. These cultures were found to consist of CD 3+ cells. In six cases studied a variable number of microcultures lysed both autologous tumor and K562 target cells only. A minority of the microcultures studied were cytolytic for allogeneic glioma cells and fresh melanoma target cells. The cytolytic activity expressed by tumor infiltrating lymphocytes against autologous tumor cells was significantly greater (P less than 0.001) than that obtained by the corresponding peripheral blood lymphocytes cultured in a similar manner. The present immunohistological and functional studies suggest that there is an immune response to human glioblastomas in vivo with an accumulation of cells with antitumor activity at the tumor site.

Aged↗
PubMed1988

Effects of recombinant human tumor necrosis factor-alpha on the surface phenotype and the growth of human malignant glioma cell lines.

Human malignant glioma cell lines and clones were incubated with various concentrations of recombinant human TNF-alpha, either alone or in combination with recombinant human IFN-gamma. The surface expression of HLA-ABC (class I) antigens and beta 2-microglobulin, was significantly enhanced by TNF-alpha alone on every cell line and clone tested. After incubation with both TNF-alpha and IFN-gamma, the surface expression of HLA-ABC antigens was only slightly higher than that observed with each cytokine alone. In contrast to IFN-gamma, TNF-alpha had no effect on the surface expression of HLA-DR (class II) antigens. Moreover, the surface expression of HLA-DR induced by IFN-gamma was unaffected by TNF-alpha. The increased expression of HLA-ABC antigens after treatment with TNF-alpha or IFN-gamma correlated with increased levels of HLA-ABC-specific mRNA. In addition, TNF-alpha, like IFN-gamma, selectively enhanced the surface expression of a tumor-associated antigen, Me14-D12, while it had no effect on the expression of various other surface antigens. In the absence of actinomycin D, TNF-alpha exhibited no direct cytotoxic/cytostatic effect on the glioma cell lines tested. These results indicate that TNF-alpha can enhance the surface expression of HLA-ABC antigens on human glioma cells in the absence of a direct cytotoxic/cytostatic effect.

Animals↗
PubMed1988

The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta 2 inhibits the generation of lymphokine-activated killer (LAK) cells.

Glioblastoma cells release factors (G-TsF) which inhibit T-cell proliferation. The G-TsF is a novel member of the transforming growth factor beta family and is identical to TGF beta 2. The effect of G-TsF and TGF beta 2 on the induction of LAK cell activity was investigated by culturing PBL obtained from normal blood donors and brain tumour patients in varying concentrations (50-500 U/ml) of interleukin 2 (IL2) alone or IL2 plus G-TsF/TGF beta 2 (1 ng/ml) for 4 days. Subsequent cytolytic activity was measured against autologous and allogeneic glioblastoma targets, fresh NK-resistant melanoma cells and K562 cells. G-TsF/TGF beta 2 purified from glioblastoma cell cultures and TGF beta 2 isolated from porcine platelets significantly suppressed the generation of LAK cell activity, and the inhibitory effect could be reduced by higher concentrations of IL2. The suppressive effect of TGF beta 2 was most significant during the early stages of LAK cell generation and no inhibitory effect was seen when TGF beta 2 was added directly to the cytotoxicity assay. These results suggest that human glioblastomas may exert an inhibitory influence on the generation of an immune response in vivo through the production of G-TsF/TGF beta 2, and that the inhibitory effect may be modified by IL2.

Cytotoxicity, Immunologic↗
PubMed1988

Comparative localization of murine monoclonal antibody Me1-14 F(ab')2 fragment and whole IgG2a in human glioma xenografts.

Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to normal tissues. In this study, we have examined the in vivo localization of radioiodinated MAb Me1-14, a murine immunoglobulin G2a (IgG2a) reactive with gliomas, and its F(ab')2 fragment in s.c. and intracranial xenografts of human glioma cell line D-54 MG in athymic mice. The radiolabeled F(ab')2 fragment of Me1-14 was demonstrated to possess in vitro binding affinity and immunoreactivity comparable to that of whole IgG. Direct comparison of IgG and F(ab')2 biodistribution in s.c. xenograft-bearing mice showed higher tumor: normal tissue ratios of the F(ab')2 fragment compared to IgG. In intracranial tumor-bearing mice paired-label analysis using a nonspecific protein control showed earlier specific tumor localization by the F(ab')2 fragment of Me1-14 compared to IgG. Blood-to-tumor transfer constants (K1) derived for Me1-14 F(ab')2 were significantly greater than those for whole Me1-14 (P = 0.01). Estimated radiation dosimetry revealed that 131I-labeled Me1-14 F(ab')2 would deliver higher radiation doses to tumor than to normal tissues. These studies demonstrate that the F(ab')2 fragment of Me1-14 may be a potential agent for immune-directed brain tumor diagnosis and therapy.

Animals↗