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N Genetet

Publications and source records attributed to N Genetet.

At least 19 recordsLinked to original sources

The prognostic value of plasma viremia in HIV-infected patients under AZT treatment: a two-year follow-up study.

To determine the prognostic value of plasma viremia in long-term zidovudine (AZT)-treated HIV-infected patients, HIV-1 plasma viremia (PV) was quantified in 28 HIV-infected patients before and during AZT long-term treatment; the follow-up also included p24 antigenemia and CD4 cell counts. The variations of these markers during the follow-up period, the correlation with the clinical outcome (progressors versus nonprogressors), and the discrepancies between PV and surrogate markers were then analyzed. A significant and stable decrease in PV titer was observed in only nonprogressors (Friedman test, p < 0.005). At the end of follow-up, 11 (73%) of the 15 non-progressors were PV responders (patients who remained or became PV- long-term), whereas all the 13 progressors were PV nonresponders (patients who remained or became PV+). These results indicated a strong correlation between PV and clinical outcome (Fischer's exact test, p < 0.0001). The persistence, increase, or reappearance of viral replication appeared to be an important predictor of poor clinical outcome in HIV-infected patients under AZT treatment. This finding could provide a rational basis to help the clinician's decision in the clinical treatment of HIV-infected patients.

Acquired Immunodeficiency Syndrome

Ex vivo studies of polymorphonuclear neutrophils from patients with early-onset periodontitis (III). CR3 and LFA-1 expression by peripheral blood and gingival crevicular polymorphonuclear neutrophils.

In this study, we assessed the LFA-1 (CD18/CD11a) and CR3 (CD18/CD11b) expression on peripheral polymorphonuclear leukocytes (PB-PMN) and crevicular fluid polymorphonuclear leukocytes (CF-PMN), by subjects with a healthy periodontium (n = 7), gingivitis (n = 8), early-onset periodontitis (n = 17) and adult periodontitis (n = 8). Using flow cytometry analysis, the %s of CD18, CD11a and CD11b positive cells and the absolute numbers of fluorescent molecules were determined. No significant difference could be found among the 4 groups, for these 2 kinds of parameters, in PB-PMN or CF-PMN. However, a great difference could be noted between the results obtained from PB-PMN and those obtained from CF-PMN. The %s of positive CF-PMN were significantly lower than those of PB-PMN for the 3 sub-units (p < 0.001). The levels of CD18 and CD11b expressed by CF-PMN were higher than those expressed by PB-PMN and the difference was significant for CD11b (p < 0.001). On the contrary, the level of CD11a expressed on CF-PMN was significantly lower than that expressed by PB-PMN (p < 0.001). Hence, our current results show that early-onset periodontitis PMN can be quite normal and this fact is not surprising insofar as, in our study, these cells were perfectly functional and all the subjects were in good health. We concluded that the analysis of the leukocyte adhesion receptors expression on PB-PMN does not appear useful for helping to establish a differential diagnosis between the different forms of periodontitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Relevance of 10 Caucasian HLA haplotypes in searches for unrelated bone marrow donors for 100 patients from a single center.

Unrelated donor searches for 100 Caucasian patients were referred to France Greffe de Moëlle Registry (FGM) from September 1987 (24,600 donors) to December 1993 (71,500 donors, 61% DR typed). After DR typing of HLA-A,B matched donors, unsuccessful searches were extended to other European Registries for 36 patients. Twenty two patients had a donor (FGM: 19, other Registries: 3) selected on: (1) HLA-A,B and DRB,DQB1 split identity; and (2) unidirectional relative response < 5% in MLR performed twice. Estimated probability of finding a compatible donor at 9 months in FGM was 12% (s.e. +/- 4%) and 25% at 2 years (s.e. +/- 6%). This probability was stringently dependent on a phenoidentity to one very common HLA-A,B,DR or B,DR haplotype (25% at 9 months when present, representing 19 of 19 patients with a compatible donor). Without this phenoidentity, the probability was zero per cent (P = 0.0001) in FGM searches and < 4% (n = 1) in extended searches. The MLR test was shown to be insensitive for screening for DPB1 mismatches. Clinical status influenced the probability of finding a compatible donor at one year ranging from 9% +/- 9% for ALL to 23% +/- 8% for CML (NS). Disregarding DPB1 mismatches is the most efficient way of increasing search efficiency.

Bone Marrow Transplantation

Immunological study in primary intestinal lymphangiectasia.

Primary intestinal lymphangiectasia is a rare congenital condition associated with protein-losing enteropathy. Hypogammaglobulinemia and lymphopenia secondary to this condition are frequent but infectious complications are not. So far few immunological studies have been made in these patients. We report here the results of such a study carried out in two adolescents. Both patients presented with a dramatic decrease in serum gammaglobulins, especially IgG and IgA, and in peripheral blood lymphocytes, especially CD4 T helper cells. From a functional standpoint, the proliferative response to certain mitogens was reduced. A decrease in in vitro production of immunoglobulins by B lymphocytes may be due to a faulty T/B cell cooperation. Histological examination of duodenal biopsy specimens revealed a decreased number of intraepithelial lymphocytes. Colonoscopy revealed nodular lymphoid hyperplasia in the terminal ileum, confirmed by endoscopic biopsy. The role of these abnormalities in the development of infectious complications and lymphoma is underscored.

Adolescent

Interferon production in severe hemophiliacs with and without HIV antibodies.

The interferon (IFN) system, both serum IFN levels and the in vitro IFN production, was investigated in 38 clinically asymptomatic multitransfused hemophiliacs, half positive and half negative for HIV antibodies. In most patients, no circulating IFN was detected; similar levels of IFN-alpha were obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai virus both in hemophiliacs and controls, while production of IFN-gamma following stimulation with phytohemagglutin (PHA) was diminished in a large number of patients irrespective of their HIV serology. These data indicate that the deficiency in IFN-gamma generation is not only related to HIV contamination but may be a direct consequence of the chronic antigenic stimulation through Factor VIII concentrates.

HIV Seropositivity

Surface markers in adult acute myeloblastic leukemia: correlation of CD19+, CD34+ and CD14+/DR--phenotypes with shorter survival. Groupe d'Etude Immunologique des Leucémies (GEIL).

The immunophenotype of blast cells was investigated in a multicentric study of 154 adult acute myeloblastic leukemias (AMLs). A panel of 27 monoclonal antibodies (MoAbs) was tested in indirect immunofluorescence. Expression of CD14 (UCHM1), CD19 (SB4), CD36 (OKM5), and HLA-DR were associated with higher mean leucocyte counts. CD14 expression correlated with low hemoglobin level and the absence of CD33 (MY9) with low platelet counts. Extramedullary disease was associated with CD16 (Leu11b) and HLA-DR antigen positivity. The study of relationships between surface markers and FAB criteria confirmed the predominant expression of CD14 in the M5 sub-group (p less than 0.000001) and the association of CD19 and CD36 with monocytic M4/M5 subgroups (respectively p less than 0.00002 and p less than 0.000001). All patients received an induction therapy including an anthracycline and cytarabine. The median follow-up was 13 months. The achievement of complete remission (CR) was inversely correlated with CD34 (B13C5) and CD19 expression: CR was obtained in 31 of 59 (53%) CD34-positive AML versus 64 of 75 (85%) CD34-negative cases (p less than 0.0001) and 11 of 24 (46%) CD19-positive versus 95 of 122 (78%) CD19-negative cases (p less than 0.01). In univariate analysis, a longer survival was associated with CD33 expression and the combined phenotypes CD36+/CD19- and CD16+/CD14-. Conversely, the CD18(IOT18)+/CDw65(VIM2)- phenotype was related to shorter survival. The expression of CD19, of CD34, and of the combined phenotype CD14+/DR--correlated with shorter survival as demonstrated both in univariate and multivariate analysis (p less than 0.03 in each case in multivariate analysis).

Antigens, CD

Sertoli cells are the site of interleukin-1 alpha synthesis in rat testis.

To elucidate the cellular origin of interleukin-1 (IL-1) in the mammalian testis, we assayed IL-1 activity in culture media of Sertoli cells collected from rats at 20, 35 and 45 days of age as well as in culture media of interstitial, peritubular and germ cells from adult rats. IL-1 was detected in Sertoli cell culture media isolated from 35- and 45-day-old rats. At 45 days approximately twice as much IL-1 was produced than at 35 days. In contrast, IL-1 activity was not detected in 20-day-old rat Sertoli cell culture media nor in interstitial, peritubular and germ cell culture media. The Sertoli cell IL-1 activity was specifically neutralized by an IL-1 alpha antiserum. It is concluded that Sertoli cells produce IL-1 alpha and that this production increases during sexual maturation.

Animals

Does peripheral blood T-lymphocyte population distribution in sarcoidosis provide a prognostic clue?

In its pulmonary form, sarcoidosis generally resolves spontaneously, but it may lead to fibrosis of the lung. The clinical, radiological and functional tests, as well as activity markers such as the serum angiotensin converting enzyme, intrathoracic uptake of 67Gallium and the cytological data provided by bronchoalveolar lavage are only the expressions at any given time of a disease which is constantly progressing and only partly express its evolutive potential. The authors studied the distribution of T-lymphocyte subsets in the peripheral blood and from bronchoalveolar lavage. 32 patients were included in the study. They were suffering from acute or chronic sarcoidosis of the mediastinum and lungs and were divided into 2 groups according to clinical, radiological and pulmonary function criteria; Group A (n = 19) included regressive forms (minimum follow up 2 years) and group B (n = 13) the progressive untreated forms. Lymphopenia with a decrease in the percentage of CD3 cells was found in both groups. The percentage of CD4 cells is significantly lower in group B (28 +/- 11%) than in group A (45 +/- 8%) (p < 0.01) or in the control population (46 +/- 8%) (p < 0.01). The percentage of CD8 cells is higher in group B (30 +/- 8%) than in group A (18 +/- 6%). This results in a CD4/CD8 ratio which is significantly reduced in group B (1 +/- 0.5) when compared with group A (2.72 +/- 0.8) (p < 0.01) and the control group (2.17 +/- 0.8) (p < 0.01), the difference between group A and the controls being minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Interferon production in severe hemophiliacs with and without HIV antibodies.

The interferon (IFN) system, both serum IFN levels and the in vitro IFN production, was investigated in 38 clinically asymptomatic multitransfused hemophiliacs, half positive and half negative for HIV antibodies. In most patients, no circulating IFN was detected; similar levels of IFN-alpha were obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai virus both in hemophiliacs and controls, while production of IFN-gamma following stimulation with phytohemagglutin (PHA) was diminished in a large number of patients irrespective of their HIV serology. These data indicate that the deficiency in IFN-gamma generation is not only related to HIV contamination but may be a direct consequence of the chronic antigenic stimulation through Factor VIII concentrates.

HIV Seropositivity

Induction of angiotensin converting enzyme in cultured human monocytes by a factor present in the bronchoalveolar lavage fluid of sarcoidosis patients.

Human peripheral blood monocytes synthesize a low level of angiotensin converting enzyme (ACE) when cultured in vitro for six days. If cell-free bronchoalveolar lavage fluid from sarcoidosis patients was included with the monocytes during culture, the monocyte ACE level increased significantly in a dose dependent manner. In contrast, the cell-free bronchoalveolar lavage fluid from control subjects and patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis raised basal monocyte levels little, if at all. These results suggested that sarcoid lavage fluid contains a soluble ACE-inducing factor (AIF) that was absent or present in much lower concentrations in the bronchoalveolar lavage fluid of the other patients studied. Initial attempts to characterize this AIF indicated an apparent molecular weight of greater than 5000 daltons as determined by Amicon ultrafiltration. The AIF was stable to heating at 56 degrees for 1 hour. This finding demonstrated that lavage ACE was not responsible for the AIF activity since lavage ACE is inactivated under these conditions. Gamma-interferon (macrophage-activating factor) was also eliminated as the agent responsible for AIF activity since gamma-interferon decreased rather than increased monocyte ACE. In summary, bronchoalveolar lavage fluid from sarcoid patients contains a soluble factor (AIF) that induces ACE in cultured monocytes. Action of this factor in vivo may be responsible for the increased ACE levels seen in the monocyte-derived epithelioid granuloma cells of sarcoidosis.

Adult

Does immunodeficiency in uremic patients promote dialysis-related amyloidosis?

The present study was undertaken to evaluate the immune function of 5 hemodialysis patients with dialysis-related amyloidosis as compared to 6 without, both groups having a dialytic age from 7 to 21 years, and 5 healthy controls. We investigated serum levels of immunoglobulins (IgG, IgA, IgM), made skin tests and measured peripheral lymphocyte subsets using monoclonal antibodies. 1) The absolute numbers of T3, T4 and T8 cells were significantly lower in hemodialysis patients than controls and T3, T4 cells were lower in patients with amyloidosis than in those without: T3 (m +/- SD/microliter), 387 +/- 253 vs 744 +/- 207 (p = 0.03); T4, 262 +/- 115 vs 589 +/- 297 (p = 0.04). 2) Serum levels of IgG and IgM were significantly lower in patients with amyloidosis than in the others: IgG (m +/- SD, g/l), 10.2 +/- 1.4 vs 15.4 +/- 3.2 (p less than 0.001); IgM, 0.65 +/- 0.28 vs 1.65 +/- 0.37 (p less than 0.001). 3) Delayed hypersensitivity studied by skin tests showed less than 3 positive antigens in 4/5 patients with amyloidosis against 1/6 patients without. These data suggest there is a marked defect of T-cell help in uremic patients with dialysis-related amyloidosis.

Adult

Murine monoclonal antibody suitable for use as an Rh reagent, anti-e.

The production by the hybridoma technique of a monoclonal antibody which behaves as an anti-e agglutinin is described. A reagent was made from ascitic fluid diluted in RPMI 1640 culture medium and bovine serum albumin. All red blood cells bearing the e antigen were agglutinated; no reactivity was recorded with untreated EE red cells suspensions. However, cross-reactivity was observed with enzyme-pretreated EE cells. The characteristics of this monoclonal antibody are described and are in accordance with the standard references.

Animals

Immunological parameters in Graves' disease: are they useful for indication and monitoring of antithyroid drug treatment?

This paper reviews the available published data on studies of a correlation between the presence or intensity of measurable immunological abnormalities or markers in Graves' disease and the outcome after a course of antithyroid drug. The following parameters are discussed: circulating anti-thyroid-stimulating hormone receptor antibodies; antitubulin antibodies; human lymphocyte antigens, and repartition of T-lymphocyte subsets. At the present time no single parameter has any real practical value for individual patients either to indicate or monitor antithyroid drug therapy. The more useful information remains the anti-thyroid-stimulating hormone receptor level at the end of treatment which, if elevated, is predictive of relapse. Several areas of research, however, appear promising.

Antithyroid Agents

[Anomalies of cellular immunity in Graves' disease treated by synthetic antithyroid drugs: effects on prognosis].

The involvement of humoral immunity mechanism in etiology of Graves' disease was observed for the first time in 1956. Twenty years later cellular auto-immune dysfunction was also described. To day, there is evidence for suppressor T cell deficiency and decrease in T suppressor lymphocytes in Graves' disease and cell mediated immunity might be one of the most important point in the pathogenesis of Graves disease. For the future, cellular auto-immune dysfunction might be used to predict the evolution of the disease and to choice the best therapeutic scheme.

Antithyroid Agents