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Biomedical subjects

B Varet

Publications and source records attributed to B Varet.

At least 91 records · Page 5Linked to original sources

Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy.

Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord.

Adult↗

Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients.

Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented.

Adolescent↗

Erythropoietin: sites of synthesis and regulation of secretion.

Erythropoietin (Epo) is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. The major site of Epo production is the kidney, while the liver is the main extrarenal site of Epo production. Within these organs, the cells synthesizing Epo were identified by using in situ hybridization in hypoxic animals with an increased Epo mRNA expression. Epo-producing cells in the kidney were peritubular cells, most likely endothelial cells of the cortex and outer medulla. Glomerular and tubular cells were not labeled. In three patients with renal adenocarcinomas associated with polycythemia, in situ hybridization showed a strong labeling of the tumor cells. Epo secretion is stimulated by hypoxia, which is detected by an oxygen sensor located in the kidney. This oxygen sensor has been recently shown to be an heme protein. At the Epo gene level, studies to identify cis-acting DNA sequences, and trans-activation factors for inducible kidney and liver Epo expression are being pursued.

Animals↗

Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion.

The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.

Adult↗

Tumor cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia.

One to five percent of human renal cell carcinomas are associated with polycythemia. It is generally assumed that polycythemia results from the secretion of erythropoietin (Epo) by the malignant cells. However, there is no direct proof supporting this hypothesis. Three patients with typical renal adenocarcinoma and polycythemia were studied. All three exhibited high Epo serum levels as measured by radioimmunoassay (RIA). A strong Epo signal was observed on Northern blot analysis of total RNA extracted from the renal tumors. The Epo message seemed to be of normal size and no Epo gene rearrangement was observed with the restriction enzymes tested. Using the in situ hybridization technique, a significant labeling was constantly observed on the tumor cells. Immunohistochemical studies showed that these tumor cells, known to be of tubular origin, were labeled by an anti-cytokeratin antibody and therefore were of epithelial nature. Thus, this study demonstrated that malignant cells of tubular origin were able to produce Epo constitutively, whereas in the mouse hypoxic kidney, peritubular cells (probably capillary endothelial cells) were the major site of Epo synthesis.

Adenocarcinoma↗

Erythroid cultures and erythropoietin assay. Clinical and diagnostic value.

In vitro cultures of erythroid progenitors and radioimmunoassay of erythropoietin (Epo) are 2 recently available techniques. It is possible to assess their relevance in various hematological disorders. Erythroid cultures can be performed in the investigation of polycythemias, pure red cell aplasias (PRCA) and refractory anemias. In primary polycythemias "spontaneous" colonies appear in vitro whereas this phenomenon is never observed in secondary polycythemias. These so called "spontaneous" colonies have been demonstrated with a lower incidence in all myeloproliferative disorders. Therefore, if the absence of spontaneous colonies does not permit us to eliminate the presence of a myeloproliferative syndrome aside from polycythemia vera, their presence does seem pathognomonic of a myeloproliferative disorder. In acquired chronic pure red cell aplasia in adults, a strong correlation is found between the in vitro growth of erythroid colonies and the results of immuno-suppressive treatment. In refractory anemias erythroid cultures do not have either diagnostic, or prognostic interest. Serum epo level does not have a high discriminatory value in distinguishing between primary and secondary erythrocytosis. Indeed in PV, the Epo level is generally low or normal, in secondary polycythemias Epo level is high or normal. There is an important overlap between the two groups. Epo level determination can have a therapeutic incidence. Administration of recombinant Epo seems justified only in patients both sufficiently anemic to warrant transfusions and in whom Epo level is low in comparison with the degree of anemia.

Erythroid Precursor Cells↗

Erythropoietin: physiology and clinical experience.

Erythropoietin is a glycoprotein hormone of primarily renal origin that promotes the proliferation and differentiation of erythrocyte precursors. Technological advances have resulted in the production of recombinant hormone suitable for therapeutic use and have permitted significant progress in the characterization of the physiologic and pathologic processes involved in endogenous erythropoietin production. In situ hybridization studies have shown that erythropoietin production in the hypoxic kidney occurs primarily in peritubular cells, most likely endothelial cells. In renal carcinoma associated with polycythemia, however, erythropoietin mRNA has been detected in the tumor cells, which are tubular in origin. New information regarding the biochemistry of the erythropoietin receptor has been gleaned subsequent to the cloning of the gene encoding the receptor; however, much remains to be learned about the interaction of the hormone with its target cells. With regard to clinical experience, recombinant erythropoietin has been shown to correct the anemia associated with chronic renal failure in patients requiring dialysis, having a significant beneficial effect on the overall physical and psychological state of the patient; the major adverse effect of such treatment is hypertension. The role of recombinant erythropoietin in predialysis patients, patients with anemias of other origin, and other clinical settings is currently being evaluated.

Anemia↗

Cellular localization of erythropoietin gene transcription.

Erythropoietin producing cells were identified in the murine hypoxic kidney by in situ hybridization. The positive cells were peritubular cells, most likely endothelial cells of the cortex and outer medulla. Glomerular and tubular cells were not labelled. In three patients with renal adenocarcinomas associated with polycythemia, a strong Epo message was observed on Northern blot analysis. Using in situ hybridization, a strong labelling was observed in all cases on the tumor cells which are of tubular origin.

Animals↗

ets-1 and ets-2 proto-oncogene expression in human leukemia cells and cell lines.

c-ets-1 and c-ets-2 are 2 proto-oncogenes known to be possibly involved in some human myelomonocytic leukemias. However, very few studies concern c-ets-1 and c-ets-2 RNA expression in human hematologic malignancies. We have studied 18 leukemic patients, and 10 cell lines for their ets RNA contents. c-ets-1 was strongly expressed in 5 and c-ets-2 in 8 of the 18 patients. All the cell lines expressed both c-ets-1 and c-ets-2 RNAs. This expression was highly variable from one patient to another, and from one cell line to another, regardless of the cellular leukemia subtype. The variability of this expression in patients may reflect differences in the proliferative potential of leukemic cells.

Adult↗