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Biomedical subjects

L Degos

Publications and source records attributed to L Degos.

At least 235 records · Page 13Linked to original sources

Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regression, with clinical improvement in a high percentage of cases. To investigate a possible relevance of binding parameters as response markers, IFN receptor interaction on tumor cells responsive to IFN in vivo was studied. Binding of human alpha 2 IFN to circulating hairy cells was analyzed before and during IFN therapy in ten patients selected on the basis of high numbers of peripheral hairy cells. Binding experiments were carried out on Ficoll-Paque fractionated peripheral cell samples containing a majority of hairy cells. All patients reacted to recombinant alpha IFN treatment with a striking decrease in binding capacity within 12 hours after the first injection. As demonstrated by using a monoclonal antibody able to recognize alpha 2 IFN bound to its receptor, this decreased binding capacity was not due to blocking by circulating IFN but rather to a decrease in receptor number. This receptor "down-regulation" was partially reversible after the first IFN injection. However, upon prolonged IFN therapy, all patients displayed a stable state of decreased receptor expression. Down-regulation of IFN receptors can be regarded as a response marker to IFN treatment. This response marker, however, was not correlated with the clinical response within the first months of IFN therapy.

Animals↗

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗

[The chromosomal HLA region].

HLA is located on the short arm of chromosome 6. This region includes several genes which are subdivided into 4 classes: class I (with HLA-A, B, and C), class II (HLA-D region), class III (complement components) and class IV (enzymes).

Chromosome Mapping↗

[HLA typing in classical and African Kaposi's disease].

HLA A, B, C, typing have been done in 39 patients with clinically and histologically documented classical Kaposi's sarcoma. Thirty three were also typed for HLA DR antigens. Twenty seven were males, 12 were females and three ethnic groups were represented: european caucasoids 41%, north african caucasoids 38.5% and negroids 20.5%. The only statistically significant abnormality is an increase of HLA DR5 frequency (60.6 vs 26. p less than 0.001 et RR = 4.2). Such an increase has been evidenced also in AIDS patients, with or without Kaposi's sarcoma and then is not discriminant between all this different types of the disease.

Adolescent↗

[Malignant histiocytosis of pulmonary form].

Malignant histiocytosis beginning by a unique pulmonary location is most unusual. The case reported here has seemed worthy because of its strange clinical aspect, the unexpected diagnosis, and because of the way it answered completely and rapidly to the following chemotherapy: Adriamycin 50 mg/m2, Cyclophosphamide 750 mg/m2, Vincristine 2 mg one day every three weeks associated to Prednisone 100 mg/m2 the five first days. A study of literature has allowed us to review all pleuro-pulmonary location initiating malignant histiocytosis and to stress out the errors of diagnosis that can outcome in this case.

Adult↗

Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Biopsy↗

Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients.

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.

Acute Disease↗

[Treatment of acute myeloblastic leukemia in elderly patients with low-dose cytosine arabinoside].

Forty-eight patients, aged from 65 to 88 years, presenting with de novo acute myelogenous leukemia were treated with a low-dose cytarabine regimen (10 mg/sq.m subcutaneously 12-hourly for 15 to 28 days). Twenty-four complete remissions and 7 partial remissions were obtained. The complete remission rate correlated with low initial bone marrow cellularity (p less than 0.05). Bleeding occurred in 28 patients and fever was noted, also in 28 patients. Four patients died of infection during induction treatment. Fourteen patients were treated as out-patients, but regular medical supervision was necessary. The median duration of complete remission was 8 months. The median survival for all patients was 15 months. It is concluded that low-dose cytarabine is an alternative to intensive chemotherapy in elderly patients with acute myelogenous leukemia.

Aged↗

Evidence for a new HLA class II determinant present on cells from HLA-DR1 and/or -DR4 individuals.

Evidence for a new HLA class II specificity is presented. It is recognized by LE serum, which reacts with most DR1 and/or DR4 individuals (r = 0.86). Its frequency in the French population is 0.33. Absorption-elution experiments showed that the serum reactivity was not due to a mixture of anti-DR1 and anti-DR4 antibodies, but to a single antibody population which could be absorbed on and eluted from both DR1(+) or DR4(+) cells. LE specificity seemed to be expressed on DR but not on DQ molecules since the serum reacted with and could be absorbed by DR+,DQw- cells; it did not react with a DR-,DQw+ mutant cell, but did react with the DR+,DQw+ parental cell. The relationship between LE specificity and MC1 and Te23 specificities remains to be determined.

Adult↗

[HLA and myasthenia. Subdivision in 3 categories].

Genetic susceptibility (HLA types), clinical and pathological findings, amount of acetylcholine receptor antibodies and T lymphocyte subpopulations were studied in 63 patients with Myasthenia Gravis (MG). The frequency of HLA-DR5 was increased among patients (0.50 versus 0.23 in controls, pc less than 0.01, relative risk 3.3) and that of HLA-DR3 previously described as associated with MG was slightly increased (0.31 versus 0.20 in controls). The relative frequencies of two T cell subpopulations (T4 helper and T8 suppressor/cytotoxic lymphocytes) were normal in HLA-DR5 positive patients while the ratio T4/T8 was increased in other MG patients, who were HLA-DR3 (p less than 0.005). The high rate was due to an increase in the absolute number of T4 lymphocytes (p less than 0.001). HLA-DR3 patients were mostly women with early onset of a severe form of the disease, marked by the presence of thymic follicular lymphoid hyperplasia. A third genetic susceptibility to this disease was recently described in patients treated with D-penicillamine, the antigenic frequency of HLA-Bw35, DR1 is significantly increased. These 3 types of association between HLA and myasthenia gravis can be related to three different physiopathological mechanisms: the first two are probably linked to individual immunity (inductor/suppressor disequilibrium), in the third association, the mechanism is immunopharmacological.

Adult↗

[Phorbol diester induces phenotypic and functional changes in human T-lymphocyte clones].

Tumor promoting phorbol myristate acetate (PMA) induce to enhance the expression of IL2 Receptor and to decrease the antigen receptor expression on the cell surface. The same phenotypic changes are also observed when the T cell clones are stimulated by the specific ligand. In contrast to the IL2 Receptor induced by the specific antigen, the ones induced by PMA are less active.

Animals↗