[Malignant non-Hodgkin lymphoma: a prospective study of the value of esophagogastroduodenal fibroscopy in the initial staging].
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Biomedical subjects
Publications and source records attributed to J Dumont.
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Intracellular cavities characterized by the presence of microvilli have been identified in dispersed thyroid cells. These structures resembling follicular lumina were called intracellular lumina or ICL. Freshly dispersed cells did not contain ICL. At 37 degrees C, ICL formation was a rapid process. After 60 min of incubation, ICL were present in 15 to 20% of the cells; the number of ICL remained rather constant during 3 to 4 h of incubation. In the presence of thyrotropin, the number of ICL increased with time to reach a value ranging from 40 to 60 ICL per 100 cells after 4 h of incubation. ICL formation was also increased in the presence of dibutyryl cyclic AMP (2 mM). Vinblastine (30 microM), a microtubule-disrupting agent and monensin (30 microM), an ionophore inhibiting Golgi functions blocked the formation of ICL in control and thyrotropin-stimulated cells. Cycloheximide (0.5 mM) and puromycin (0.5 mM) did not inhibit ICL formation in either control or thyrotropin stimulated cells. The iodination capacity of ICL was studied by quantitative electron microscopic autoradiography after incubation of thyroid cells with 125 I-iodide for 2 to 60 min. Radioiodinated products appeared first in ICL. After 1 h of labeling autoradiographic grains were found mainly in ICL (60-70%) and over the cytoplasm. The labeling of ICL was heterogeneous; ICL contained either few or numerous overlapping grains. Whatever the labeling time, a high proportion of ICL (70-80%) were labeled. The labeling of ICL as well as the labeling over the cytoplasm was increased in the presence of thyrotropin and almost completely inhibited in the presence of an iodide trapping inhibitor: sodium perchlorate. Pulse-chase experiments revealed that thyrotropin stimulated the discharge of 125 I-labeled material from ICL.
A non-Hodgkin's lymphoma was observed in a patient who had been treated for Hodgkin's disease (HD). The initial treatment consisted of radiotherapy alone, but following three subsequent relapses, both chemotherapy and radiotherapy were administered several times. Twenty years later, the biopsy of an isolated cervical lymph node revealed a non-Hodgkin's lymphoma. The histologic subtype was immunoblastic. Cytogenetic studies of the tumoral cells revealed a t(8;14)(q24;q32) translocation. At the same time, multiple chromosomal rearrangements were observed in peripheral blood lymphocytes, especially t(7;14)(q35;q12), which was noted in 6 of 53 mitoses. This anomaly, frequently observed in patients with ataxia telangiectasia or severe immunodeficiency, has not previously been described in such circumstances.
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A 23 year old man with severe idiopathic aplasia, who had previously been unsuccessfully treated with oxymetholone for a period of 6 months, received two intravenous (IV) infusions of bone marrow cells from his HLA identical brother. He was given 200 mg/kg anti-lymphocyte globulins (ALG) IV, followed by a first infusion of 13 X 10(9) nucleated cells IV, but no improvement was observed. Three months later, he was treated with cyclophosphamide (25 mg/kg over 4 days) followed by a second infusion of 18 X 10(9) nucleated cells IV of the same donor. Within a four month period there was evidence of complete marrow reconstitution, and the patient has experienced no relapse of the disease during the subsequent 13 years follow up period. The mechanism of the recovery is unclear: no evidence of graft acceptance could be established. The respective roles of ALG, cyclophosphamide and/or bone marrow infusions are discussed.
The association of B cell chronic lymphocytic leukemia and pure red cell aplasia in a 42 year-old patient led to the discovery of a thymic enlargement. After six weeks treatment including steroids, cyclophosphamide and three courses of plasma exchange without improvement, surgical thymectomy was followed by a reticulocytosis and remission of the red cell aplasia. The tumor was a thymolipoma. Characteristics of this are thymic tumor, his connections with pure red cell aplasia and in vitro differentiation of erythroid progenitors are discussed.
The availability of rat thyroglobulin cDNA clones was exploited to study the regulation of thyroglobulin gene transcription by thyrotropin (TSH). Groups of rats were subjected to treatments leading to reduction or increase in the rat serum TSH (rTSH) levels. Thyroid gland nuclei were isolated, incubated in vitro in the presence of 32P-labeled uridine triphosphate, and thyroglobulin transcripts were quantitated by hybridization to immobilized rat thyroglobulin cDNA clones. Transcription of the thyroglobulin gene was found to be very active in thyroid nuclei from control animals. It represented about 10% of total RNA polymerase II activity. Chronic hyperstimulation of the thyroid glands with endogenous rTSH was achieved in rats treated with the goitrogen propylthiouracil. No significant increase of thyroglobulin gene transcription could be measured in thyroid nuclei from these animals. On the contrary, a dramatic decrease in thyroglobulin gene transcription was observed in those animals in which endogenous rTSH levels had been suppressed by hypophysectomy or by the administration of triiodothyronine. Injection of exogenous bovine TSH in such animals readily restored transcriptional activity of the gene. Our results identify transcription as an important regulatory step involved in TSH action. They suggest that normal TSH levels induce close to maximal expression of the thyroglobulin gene but that continuous presence of TSH is required in order to maintain the gene in an activated state.
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Eighty-five patients with nodular lymphoma diagnosed between 1968 and 1975 were followed up for long periods and were treated by either conventional methods (local radiotherapy and single drug chemotherapy) or by more intensive therapeutic regimens, such as initial combined M.O.P.P. therapy and maintenance treatment with chlorambucil with or without further courses of M.O.P.P. Long-term follow-ups have brought to light some interesting points concerning the prognosis. Dissemination of the disease and large-cell histological pattern were, as already known, unfavourable factors. Neither age nor sex, nor bone-marrow involvement seemed to have any influence. Obtaining complete remissions improved the prognosis, but intensifying the initial and maintenance treatments proved disappointing: the survival rate remained the same, and the incidence of drug induced leukaemias was high. Indeed, relapses appeared to be less responsive to treatment when the patient had initially received multiple chemotherapy. However, in view of the high death rate of the disease (one-third of the patients in this series died within the first 5 years), trying new therapeutic regimens in the hope of obtaining better results, as has been done in Hodgkin's disease, would be fully justified.
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Natural killer cell activity, which represents the spontaneous cytotoxicity of lymphocytes toward tumor cells, has been measured in 173 tumor-bearing patients and 25 healthy volunteers; no significant difference was found in mean natural killer cell activity between the two groups. The parameters of interferon-induced activation of natural killer cells were studied in order to provide a suitable test for monitoring the effect of interferon in clinical trials. The three interferons tested (leukocyte, lymphoblastoid, and fibroblast) were equally active in inducing spontaneous cytotoxicity of lymphocytes from all healthy individuals and tumor-bearing patients studied. Incubation for one hr with 100 units of interferon was sufficient to increase spontaneous cytotoxicity activity, the maximum effect being obtained when lymphocytes were incubated with 1000 units of any of the interferons used. This effect was blocked with the appropriate antiinterferon sera. The target cells for interferon seem to be positive Fc gamma receptor lymphocytes.
In 18 cases of drug-induced acute leukemia, electron microscopy brought out a number of anomalies found in all hematopoietic cell lines. They are described here for the erythroblastic line. Some of these anomalies occur in the cytoplasm (like siderosomes, iron-containing mitochondria, glycogen spots, various dense inclusions, and nuclear-cytoplasmic asynchronism; others occur in the nucleus (such as plurinucleated cells, fragility of nuclear membrane, and nuclear clefts and blebs). Nuclear clefts and blebs may also be found in granulocytic and megakaryocytic cell lines. Their structural aspect suggests a relationship with chromosomal abnormalities, particularly with synaptonemal complexes. Unusual karyotypes, observed in two cases, give weight to such a hypothesis. The cell injury caused by alkylating agents, including DNA lesion, is most likely closely related to this particular pattern of drug-induced leukemias.
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Five cases of acute myeloblastic leukaemia (AML) arising in the course of non-Hodgkin's lymphoma (NHL) are described. The initial lymphoma was nodular lymphoid poorly differentiated in 4 cases. All patients were under chemotherapy for at least 28 months, and 3 of them were irradiated. AML was diagnosed 44 to 78 months after NHL and was heralded in 3 cases by a preleukaemia phase of pancytopenia. The leukaemia was typically myeloblastic in 2 cases and difficult to classify in 3 cases. Death occurred rapidly in 4 patients. The actuarial risk was 4.5% at 5 years. Since AML's occur mainly in NHL's, the management of this type of lymphoma with favourable prognosis ought to be reevaluated.