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Biomedical subjects

J Millan

Publications and source records attributed to J Millan.

At least 37 records · Page 2Linked to original sources
PubMed1993

T-cell stimulation with purified mycobacterial antigens in patients and healthy subjects infected with Mycobacterium leprae: secreted antigen 85 is another immunodominant antigen.

Peripheral blood leucocytes from 9 paucibacillary and 12 multibacillary leprosy patients, from 18 healthy controls and from 34 healthy leprosy contacts were stimulated with three mycobacterial heat shock proteins with respective molecular weights of 70, 65 and 18 kDa and with the secreted 30-32 kDa protein, also called antigen 85. Antigen 85 was found to be the most powerful T-cell antigen (as measured by lymphoproliferation and IFN-gamma secretion), eliciting a positive response in all (100%) paucibacillary patients and in all lepromin-positive controls and contacts. The three heat shock proteins (hsp) were less active T-cell stimuli. Reactivity to the 70 kDa hsp was found in only 44% of the paucibacillary patients, in 80% of the lepromin-positive controls and in 60% of the lepromin-positive leprosy contacts. The 65 kDa hsp stimulated T cells in 89% of the paucibacillary patients and in 80% of the lepromin-positive controls and contacts. Responsiveness to the 18 kDa hsp, finally, was clearly more frequent in tuberculoid leprosy patients (78%) than in lepromin-positive controls (40%) or lepromin-positive leprosy contacts (4%). T-cell reactivity of 8 lepromin-negative controls, of 9 lepromin-negative contacts and of 12 multibacillary leprosy patients was low to all the antigens tested. Although proliferative and IFN-gamma responses were generally closely related, some subjects demonstrated a dissociation of these two immune parameters. Our data confirm previous findings on the powerful T-cell stimulatory properties of antigen 85 during M. leprae infection and suggest that this antigen is indeed a potentially protective T-cell immunogen.

Antigens, Bacterial↗
PubMed1993

Leprosy reversal reaction in HIV-positive patients.

We report two cases of leprosy in HIV-infected patients who, by their clinical, histological and immunological features, enhance the evidence that HIV-positive leprosy does not differ from nonHIV-positive leprosy. Moreover, extensive studies of reversal reactions in HIV-positive patients might be of great interest in determining the exact pathogenesis of this leprosy reactional state.

Adult↗
PubMed1992

Asymptomatic nerve hypertrophy in lepromatous leprosy: a clinical, electrophysiological and morphological study.

In order to learn more about early nerve lesions observed in leprosy, we performed a clinical, electrophysiological and morphological study in seven patients with untreated lepromatous leprosy, palpably enlarged radial cutaneous nerve and preserved sensation in the corresponding territory. The conduction velocity of the cutaneous radial nerve, which was decreased in all patients, did not significantly differ from that of a group of patients with lepromatous leprosy, hypertrophy of the radial cutaneous nerve and sensory loss. In contrast, the sensory action potential was significantly lower in patients with sensory loss, which demonstrates that axon loss is more important than demyelination in producing sensory loss. In all patients nerve enlargement was due to thickening of the epineurium and of the perineurium subsequent to inflammatory infiltrates and proliferation of fibroblasts and perineurial cells. In several fascicles, the inflammatory infiltrates and the infected cells infiltrated endoneurial connective tissue septa and blood vessels. Mycobacteria leprae were abundant in perineurial cells, fibroblasts, macrophages, Schwann cells and endothelial cells, and lymphocytic vasculitis present in all cases. The average density of myelinated fibres was 2600 SD 880 fibres/mm2 (control: 7700 fibres/mm2), with marked differences between individual fascicles, versus 420 fibres/mm2 in patients with nerve hypertrophy and sensory loss (range 0-2080 fibres/mm2). Single fibre preparations showed that segmental demyelination predominated in two patients, axonal degeneration in one, while inflammatory infiltrates and proliferation of connective tissue adhering to individual fibres were prominent in the others.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Anti-peripheral nerve antibodies in leprosy patients recognize an epitope shared by the M. leprae 65 kDa heat shock protein.

Binding of leprosy sera to peripheral nerve from different species (mouse, guinea pig and rabbit) was evaluated by ELISA. A majority of sera, whatever the clinical form of leprosy, bind to these antigens. Absorption with Mycobacterium bovis BCG demonstrated that these antibodies recognize cross-reactive epitopes between peripheral nerve and mycobacteria. In immunoblot analysis, both leprosy patient sera and a monoclonal antibody directed at the 65 kDa heat shock protein of M. leprae were shown to react with a heat-shock 67-68 kDa sciatic nerve protein. Binding of the monoclonal antibody to this sciatic nerve antigen was prevented by incubation with lepromatous patient sera, showing that some peripheral nerve epitopes recognized by patient antibodies are shared by the 65 kDa heat shock protein of M. leprae.

Animals↗
PubMed1992

Humoral responses against the 85A and 85B antigens of Mycobacterium bovis BCG in patients with leprosy and tuberculosis.

Immunoglobulin G antibodies against the 85A and 85B components of the Mycobacterium bovis BCG antigen 85 complex separated by isoelectric focusing were investigated in serum samples from 129 patients representing the major forms of leprosy, 111 tuberculous patients, and 153 healthy subjects. For both of the antigens, a higher degree of staining was observed for lepromatous leprosy patients and patients with active tuberculosis than for the other groups. Because sera from some healthy subjects recognized the 85A antigen, we suggest that antigen 85B is the most useful component of the antigen 85 complex for the serodiagnosis of the multibacillary forms of leprosy or of the active forms of tuberculosis.

Antibodies, Bacterial↗
PubMed1992

[Detecting and monitoring leprosy neuropathy: which test to chose?].

The purpose of the study is to propose a simple and reproducible test for assessing nerve damage in leprosy. It is applied to the sensory branch of the radial nerve of leprosy patients, prior to any treatment. Skin sensitivity is measured by means of a needle, a drop of ether and some calibrated filaments. These three tests are collated and compared with the results of electromyographic examination of the nerve. The filament calibrated to 0.2 grams gives optimum sensitivity (0.79) and excellent specificity (0.95) in relation to the electromyographic test. Its routine use in the field is simple and reproducible and should result in a greater number of patients receiving the treatment they need.

Academies and Institutes↗
PubMed1992

[Epidemiological study of HIV seroprevalence in a leprosy patient population in Senegal].

We report the findings of an epidemiological study conducted between June 1989 and February 1990 on a population of leprosy patients in southern Senegal (Bignona major endemic disease sector). Two types of population were studied: patients living in urban areas and inmates of leprosaria. The global HIV seroprevalence (HIV 2 in all cases) of the leprosy-patient population was 1.15% (3/257): 0.8% (1/130) for the urban group and 1.5% (2/127) for the leprosaria. The seroprevalence rate does not differ significantly from that for the control group studied and for blood donors (1/221). The diagnosis of leprosy in the seropositive subjects had been established before 1980. None of them showed any sign of relapse. The immunodepression associated with the presence of HIV was only moderate: it was reflected in a lowering of the CD4 count and of the CD4/CD8 ratio, but with no clinical sign of AIDS.

Adolescent↗
PubMed1992

Human phagocyte respiratory burst by Mycobacterium bovis BCG and M. leprae: functional activation by BCG is mediated by complement and its receptors on monocytes.

We have measured the role of serum components on two parameters of the phagocytosis reaction: a) the chemiluminescence (CL) response associated with the oxidative respiratory burst in response to Mycobacterium bovis BCG and M. leprae, and b) the uptake of these two mycobacteria by healthy human monocytes. Pre-incubations of fresh or heat-inactivated serum or serum containing EGTA or EDTA indicate that these two mycobacteria activate the alternative complement pathway. Monoclonal antibodies against CR1 and CR3 inhibit the responses of M. bovis BCG and M. leprae, demonstrating that complement receptors mediate the phagocytosis of these two mycobacteria. Thus, complement and its receptors on the surface of the monocytes (CR1 and CR3) are important in the functional activation of phagocytosis of M. bovis BCG and M. leprae.

Antibodies, Monoclonal↗
PubMed1991

Endoneurial proliferation of perineurial cells in leprosy.

In leprous neuropathy the perineurium has very often an abnormal multilayered appearance and is infiltrated by many different types of inflammatory cells. We report here 13 cases characterized by an abnormal endoneurial proliferation of fibroblasts which seems to differentiate in perineurial cells. In several instances there is formation of many intrafascicular microcompartments. Such aspects have been described in various, but infrequent, cases of experimental and human neuropathies. It seems that severe Wallerian degeneration, diffuse endoneurial macrophage infiltration and lesion of the perineurium might lead to such a process.

Cell Division↗
PubMed1991

Role of growth hormone-releasing hormone on pentagastrin-induced growth hormone release in normal subjects.

In order to investigate the mechanisms by which gastrin cause GH release in humans we measured the GH response to pentagastrin alone (1.5 micrograms/kg/hour from 120 to 210 min) and following pretreatment with GHRH (GHRH 1-29,250 micrograms, iv at 0 min) in normal male subjects. Prior GHRH administration abolished the GH response to the second bolus of GHRH (1 micrograms/kg) administered two hours later. Pentagastrin infusion induced a rise in GH levels maximal at 60 min (9.1 + 0.6 ng/ml, mean + SE), but this rise was abolished by pretreatment with GHRH. Finally, we found that gastrin did not modify basal GH release or GH responses to GHRH by rat anterior pituitary cells in monolayer culture. Taken together, these data suggest that gastrin regulates GH secretion by acting at hypothalamic level.

Adult↗
PubMed1991

T cell response to purified filtrate antigen 85 from Mycobacterium bovis Bacilli Calmette-Guérin (BCG) in leprosy patients.

T cell proliferation and IFN-gamma production of peripheral blood mononuclear cells from 25 healthy controls and 39 leprosy patients were tested against BCG-bacilli and culture filtrate. Mycobacterium leprae and purified antigen 85 (the major secreted 30-32 kD protein antigen) from M. bovis strain BCG. In lepromin negative healthy controls, blastogenesis was low to M. leprae and completely negative to antigen 85. IFN-gamma levels were very low, close to detection limits. In all lepromin positive controls, significant proliferation and IFN-gamma secretion was found in response to M. leprae and antigen 85. In the group of lepromatous leprosy (LL) patients, 25/29 of patients (with either positive (13) or negative (12) lymphoproliferative response to BCG) were unreactive to M. leprae or to antigen 85. Four LL patients with positive T cell response to BCG responded with detectable lymphoproliferative response and IFN-gamma secretion to antigen 85. All tuberculoid (TT) leprosy patients responded to BCG, M. leprae and antigen 85. Hence, T cells from leprosy patients and controls demonstrate a marked parallelism of responsiveness towards whole M. leprae and purified antigen 85 from M. bovis BCG, suggesting strong cross-reactivity between the two species and underlining the biological importance of such secreted antigens.

Antigens, Bacterial↗
PubMed1991

M. leprae- and BCG-induced chemiluminescence response of monocytes from leprosy patients and healthy subjects: effects of gamma-interferon and GM-CSF.

Mycobacterium leprae, in contrast to BCG, failed to trigger any chemiluminescence (CL) response in mononuclear cells from either leprosy patients or healthy subjects, a deficit not reversed by either interferon-gamma or GM-CSF. Chemiluminescence responses induced without mycobacteria or with BCG were found to be lower in leprosy patients than in controls. M. leprae were also less well phagocytosed than BCG. However, there was a significant difference in phagocytosis between healthy and tuberculoid leprosy subjects. Phagocytosis was not altered by the addition of either lymphokine, and no major differences between healthy subjects and patients were observed. Preincubating mononuclear cells with anti-mycobacteria antibodies (lepromatous patients' sera) did not increase the CL response nor the phagocytosis of M. leprae or BCG.

Antibodies, Bacterial↗
PubMed1989

Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers.

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

ABO Blood-Group System↗