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Biomedical subjects

P Debre

Publications and source records attributed to P Debre.

At least 91 records · Page 5Linked to original sources
PubMed1985

Lymphadenopathy in patients at risk for acquired immunodeficiency syndrome. Histopathology and histochemistry.

Lymph node biopsies of 12 patients at high risk for acquired immunodeficiency syndrome (AIDS) with generalized lymphadenopathy (AIDS-related complex [ARC]) and seven controls with conventional lymph node hyperplasia were examined by light microscopy and immunohistochemical staining of frozen tissue. The immunohistochemical results were quantified by planimetric means. Our findings show that the T helper/T suppressor-cytotoxic (Th/Tsc) ratio in lymph nodes from ARC patients is significantly decreased with respect to controls and that this decrease precedes the change in the Th/Tsc ratio in peripheral blood. Our findings distinguish between lymphadenopathy from patients with ARC and other forms of hyperplasia; the relation to AIDS is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1984

[Acquired immunodeficiency syndrome and related syndromes. Critical analysis of biological tests of cell-mediated immunity].

In order to assess the actual value of the in vitro tests of cellular immunity performed to provide diagnostic evidence for acquired immune deficiency syndrome (AIDS) or related syndromes, we have evaluated T-lymphocyte subsets and in vitro proliferative responses. The respective profiles of 44 symptom-free homosexual men, 30 patients with AIDS and 42 patients with lymphadenopathy were compared with each other and with profiles of blood bank volunteers, using stepwise discriminant analysis. At first investigation, control homosexuals, AIDS patients and lymphadenopathy patients displayed varying degrees of the same type of immunological abnormalities. The percentage of OKT4+ cells was the most discriminant variable between blood donors and control homosexuals, AIDS or lymphadenopathy patients. The latter differed from homosexuals by a higher percent of OKT8+ cells and from AIDS patients by a lesser reduction in T-lymphocyte counts. OKT4+ cell counts differentiated AIDS patients from control homosexuals. However, none of these major discriminant variables could classify correctly more than 70% of subjects in the homosexual and in the two patient groups. Thus, a single investigation of T-lymphocyte immune parameters does not provide substantial diagnostic and prognostic evidence.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Heterogeneity of plasminogen activator expression in various Moloney virus-induced tumor cell lines. Lack of correlation with tumor growth and cell phenotype.

The aberrant expression of a plasminogen activator (PA) by Moloney virus (MuLV)-transformed mouse lymphocytes and its relation to cell phenotype and tumor growth have been studied. Nine cultured cell lines were established from neoplastic splenic and thymic tissues obtained from B10 congeneic mice inoculated with MuLV and killed when overtly leukemic. Cell surface markers were assayed by microcytotoxicity tests, the concentration of MuLV p30 and group-specific MuLV gp 70 was determined by radioimmunoassays and the expression of PA activity was assessed in a fibrin-agar plate method. PA activity of 24 h serum-free culture supernatant, intact cells or cell lysates (2 X 10(5) cells/ml) was expressed in International Units by reference to a urokinase standard curve. Tumor extension and cell morphology were investigated by histologic and cytomorphologic analysis. In all cases the cell lines were derived from T cells. PA activity is not expressed by normal lymphocytes, but variations in PA expression were observed in the transformed cells. Five out of nine transformed cell lines showed PA activity with a range of 1.3 to 9.9 IU/ml. No PA activity could be detected in the other cell lines. No correlation was found between PA expression and the cell-surface-expressed phenotype, neither was there any correlation between the PA content, the cytopathological features and the degree and type of organ infiltration. This lack of correlation indicates that there is no relation between PA activity and the expression of the transformed phenotype, and that the presence of PA activity seems to be irrelevant to the tumorigenic capacities of the transformed cell lines.

Animals↗
PubMed1984

The management of thirty immunocompromised patients with tuberculosis.

Between 1978 and 1981, 30 of 870 bacteriologically confirmed cases of tuberculosis occurred in immunocompromised hosts. One year after the diagnosis, 11 patients were dead, only 2 of them of tuberculosis. In the other 19 patients, the course of tuberculosis under standard chemotherapy was the same as in nonimmunocompromised hosts. Among the 24 patients still alive more than 2 months after the diagnosis of tuberculosis, the treatment of the underlying disease was changed in 14 patients to avoid worsening of the course of tuberculosis; 5 patients died and 4 kidney transplant carriers rejected their transplants. The treatment of the underlying disease was not changed in 10 patients: all of these remained alive 1 yr later, and 2 were kidney transplant carriers who did not reject their transplants. We conclude that the clinical response of the immunocompromised tuberculous host was good and that treatment of the underlying disease should not be modified.

Adult↗
PubMed1984

Differential inhibition of human antigen-specific T cell clone proliferative responses by distinct monoclonal anti-HLA-DR antibodies.

The inhibition of diphtheria toxoid and varidase-specific T cell clones from a single DR 6/7 donor by eight distinct monoclonal anti-HLA-DR antibodies was tested in proliferative assays. These moAb were selected because they had been previously defined for their ability: 1) to react with Ia molecules; 2) to recognize similar or different epitopes; 3) to share or not share idiotypic specificities. Our results show a distinct inhibition pattern for each clone tested. Furthermore, the various moAb could be classified into three groups according to their inhibitory effect on T cell proliferation. These data suggest: a) an epitopic restriction by class II antigens of antigen-specific human T cell clone proliferation; and b) the recognition of functional epitopes on the human Ia-like antigens by some but not all moAb studied.

Antibodies, Monoclonal↗
PubMed1984

Critical analysis of T cell subset and function evaluation in patients with persistent generalized lymphadenopathy in groups at risk for AIDS.

In order to determine whether there exists a distinct immunological profile that discriminates between healthy homosexual men and those expressing persistent generalized hyperplastic lympadenopathy GHL and which of the observed abnormalities in GHL would be most indicative of patients who would eventually develop AIDS, we evaluated T lymphocyte subset and in vitro proliferative responses. The respective profiles of 44 symptom free homosexual men (HC), 42 patients with GHL and 30 cases of AIDS were compared to that of blood bank volunteers (BBV) and to each other, using stepwise discrimination analysis. HC, GHL and AIDS patients demonstrated upon their first investigation varying degrees of the same type of abnormal immunological characteristics. The percentage of OKT4+ cells was the most discriminant variable between BBV and HC, GHL or AIDS. GHL was distinguished from HC primarily by a higher percentage of OKT8+ cells and from AIDS by higher T lymphocyte counts, while the OKT4+ cell count discriminated between AIDS and HC. However, none of these major discriminant variables could classify correctly more than 71% within the HC and the two patient groups. Thus, there exists a continuity between GHL and AIDS in the range of observed immunological abnormalities without clearcut boundaries. This, together with the existence of abnormal background values in HC will not permit a single investigation of T lymphocyte immune parameters to provide substantial diagnostic and prognostic evidence.

Acquired Immunodeficiency Syndrome↗
PubMed1984

T-lymphocyte progenitors in man: biochemical characterization of a colony promoting activity (CPA) active on immature precursors.

PHA-stimulated lymphocyte supernatants (P-SUP) containing colony promoting activity (CPA) and interleukin-2 (IL-2) were found to drive T-lymphocyte precursor cells (OKT4-OKT8- blood cells) into colonies of mature T cells in agar. Ammonium sulphate precipitation followed by gel filtration on Sephadex G-75 showed that both IL-2 activity and CPA coeluted in the 21,000 MW fraction. Chromatofocusing on a PBE 94 gel equilibrated between pH 7.4 and 4.2 showed that CPA coeluted with the two main peaks of IL-2 (pI 7.2, pI 6.7). Adsorption of IL-2 activity by more than 97% on different T-cell lines did not completely abolish CPA. These results suggest that other(s) factor(s) with the same biochemical characteristics as IL-2 play a role in the induction of growth and differentiation of immature T-cell precursors.

Cell Differentiation↗
PubMed1983

Syngeneic anti-idiotypes against monoclonal anti-HLA-DR antibodies: characterization of recurrent idiotopes.

Monoclonal anti-HLA-DR antibody (anti-DR mAb) reactivity was investigated at the idiotypic level; three syngeneic anti-idiotype (Id) sera were raised against three monomorphic anti-DR mAb (206, BM 50, and D 1.12). The syngeneic anti-Id responses exhibited some differences in their intensity and the idiotypic determinants recognized by the three anti-Id sera were localized, at least in part, on the antigen combining site of the respective anti-DR mAb. Idiotype analysis of 24 anti-DR mAb was performed with these anti-Id sera by Id-binding inhibition assays. Idiotypic cross-reactivity was demonstrated for 12 out of the 24 anti-DR mAb, indicating a large degree of idiotypic recurrence. Analysis of the cross-inhibition patterns led us to define at least five sets of recurrent idiotopes: one set cross-reacting with anti-206 Id, the second with both anti-BM 50 and anti-D 1.12 Id, the third with anti-BM 50 Id only, the fourth with anti-D 1.12 Id only, and a fifth set was shared by D 1.12 and NE 4. Eleven monomorphic anti-DR mAb and one polymorphic anti-DR 3 mAb (16.23) did not cross-react with the three anti-Id sera. These results suggest that the mouse antibody response to monomorphic determinants on human Ia antigens is based on a limited number of recurrent idiotopes. In two cases, recurrent idiotopes could be related to a similar anti-DR mAb fine specificity. These anti-Id provide useful reagents to classify and compare anti-DR mAb.

Animals↗
PubMed1981

Genetic control of antinuclear antibodies in mice inoculated with the moloney leukaemia virus.

The production of antinuclear antibodies (ANA) was studied after inoculation with Moloney leukaemia virus (M-MuLV) in different H-2 congenic strains of mice. Using a new sensitive method for ANA detection, it was demonstrated that M-MuLV-induced ANA were genetically controlled by several different factors. A high viral production was first required for ANA triggering. Among viremic animals both high and low ANA producers were observed. H-2 and non H-2-linked genes were involved in the control of M-MuLV-induced ANA; these genes were different from those involved in the control of viremia. The H2b haplotype was associated with an increased ANA response, the transmission of the responder phenotype being intermediate. Non-H-2-linked genes must also control M-MuLV-induced ANA, as demonstrated in mice having the same H-2 haplotypes, since with equivalent viremias they produced different amounts of ANA. No linkage with X chromosome was found.

Animals↗
PubMed1981

Incidence and phenotypic heterogeneity of Moloney virus-induced leukemias: a multigenic control.

The incidence of leukemias was established in mice of different inbred strains inoculated with Moloney leukemia virus (M-MuLV), and a complex genetic control was found. To characterize the different steps of the host-virus relationship further, the degree of viremia, the appearance of leukemia, organ involvement, and the surface phenotype of leukemic cells were studied in individual mice. The results demonstrate that: a) The viremia was controlled by H-2 and non-H-2 genes. Three H-2 genes located in the I and D or T region of the MHC behave like immune-response genes controlling the specific antiviral immune response. Other gene(s) mapped outside the complex also affected the virus production. Both sets of genes influenced leukemia incidence, since leukemias were observed only in highly viremic strains. b) Additional non-H-2 genes, which were not involved in viremia control, were determinants in the induction of malignancies because some sensitive strains do not become leukemic despite high levels of viremia. c) The anatomical type of Moloney virus-induced leukemias varied according to the non-H-2 background. Most of the leukemias arising in B10 congeneic mice involved the thymus and were frequently limited to this organ, whereas BALB mice preferentially developed splenic leukemias. d) In a given inbred strain, the leukemias arising in different animals frequently expressed different phenotypes. It can be concluded that Moloney virus-induced leukemia is a multistep process, viral production being necessary but not sufficient in and of itself to induce a malignant transformation.

Animals↗
PubMed1979

Identification of a pure splenic form of chronic lymphocytic leukaemia.

We have recently proposed a new staging system for chronic lymphocytic leukaemia (CLL) in which patients with isolated splenomegaly are classified into a distinct stage (stage II). Twenty-three such patients (from two institutions) have been studied without recorded death in a follow-up of 18 months to 30 years. This favourable prognosis justifies separation of these 'pure splenic forms' (SCLL) which must be distinguished from what Galton has termed prolymphocytic leukaemia (PL). This distinction can be made on the basis of three criteria: (i) Clinically, SCLL has a slow uneventful course and neither anaemia and/or thrombocytopenia: (ii) cytologically PL can be distinguished from other forms of CLL though atypical forms of CLL may be confused with the former; and (iii) the study of surface membrane immunoglobulins (SmIg) showed that while lymphocytes from most patients with both PL and SCLL bore uniform SmIg, suggesting a monoclonal B-cell proliferation, there was a major quantitative difference in that whereas PL lymphocytes had a number of antigenic sites close to that of normal lymphocytes (mean: 82 000 sites per cell), SCLL lymphocytes had a drastically reduced number of sites. It is our opinion that this is an important criterion for the differential diagnosis between PL and SCLL.

Aged↗
PubMed1979

Genetic control of sensitivity to Moloney leukemia virus in mice. II. Mapping of three resistant genes within the H-2 complex.

The level of viremia and the appearance of leukemias were studied after inoculation wtih Moloney leukemia virus (M-MuLV) in different H-2 congenic strains of mice. The viremia was regularly measured on individual mice with a radioimmunoassay of the major internal virion component p30. Three genes within the major histocompatibility complex controlled the level of circulating virus. Two of them, called Rmv.1 and Rmv.2, appear to be located in the I region, respectively, in the IA, and the IC-S or G regions. The third gene, Rmv.3, was mapped to the D end of the complex in the D or T region. Crosses between resistant and sensitive strans demonstrated that the H-2 associated resistance was inherited as a dominant or semi-dominant Mendelian trait. Rmv.1, Rmv.2, and Rmv.3 were shown to complement for resistance in trans when the hybrids between sensitive strains were examined. A good correlation was found between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. Nevertheless, additional non-H-2 genes must control viremia and/or the appearance of leukemia since, despite high levels of viremia, some sensitive strains do not become leukemic.

Animals↗
PubMed1978

Chronic lymphatic leukaemia: cellular effects of glucocorticoids in vitro.

Glucocorticoid receptor levels and steroid induced inhibition of nucleic acid precursors have been examined in lymphocytes from 27 patients at different stages of chronic lymphatic leukaemia. No correlation can be found between the level of glucocorticoid receptors and the stage of the disease. On the other hand, a significant difference (P less than 0.02) was found between stage O and stage III/IV patients, in terms of the in vitro effect of dexamethasone on [3H] uridine incorporation.

Adult↗
PubMed1975

[Waldenstrôm's macroglobulinemia. Developmental and prognostic study].

The course of 27 cases of Waldenström's macroglobuilinemia was observed during at least 2 years or until death. A worsening occurred in half of the patients, with 7 deaths before 2 years. 10 patients improved under therapy, with only two deaths later. The more frequent complications were infections, but other complications, haemorragic, neurologic, osseous and renal were also observed. A haemoglobin initial level higher than 9 g % and a significant decrease of lymphocyte blood count under chemotherapy seem to be of good prognosis.

Adult↗
PubMed1975

[Waldenström's macroglobulinemia with preserved antierythrocyte and antilipoprotein antibody activity].

One case of Waldenström's macroglobulinemia is reported, in which the monoclonal IgM has an antibody activity against stored red cells, beta-lipoproteins and mammalian glomeruli. The antibody activity is observed with the purified IgM molecule, which cross reacts with the three antigens, and with the Fab piece. The study of the cross reactions shows that the antibody recognizes similar rather than identical antigens. This observation is to be added to the few cases already published of antibody against stored red cells, and of Waldenström's macroglobulinemia with antibody activity. The physiopathology of the occurrence of a M component with such an activity is discussed.

Blood Preservation↗