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Biomedical subjects

M A Bach

Publications and source records attributed to M A Bach.

At least 73 records · Page 4Linked to original sources
PubMed1986

M. leprae and PPD-triggered T cell lines in tuberculoid and lepromatous leprosy.

Proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and bacillus Calmette Guerin-derived purified protein derivative (PPD) were studied in the presence or absence of interleukin 2 (IL 2) in high M. leprae responders (tuberculoid leprosy patients and healthy subjects) and low M. leprae responders (lepromatous leprosy patients). High responders in most cases developed a strong proliferative response to both antigens in the absence of IL 2. Additional IL 2 and restimulation with antigen plus autologous antigen-presenting cells (APC) allowed the derivation of antigen-specific T cell lines. The lines were assayed for proliferative responses to several mycobacterial antigens. Both PPD and M. leprae-triggered T cell lines exhibited a good proliferative response to either antigen and showed in addition a broad cross-reactivity with other mycobacteria, suggesting a preferential T cell response to epitopes shared by several mycobacterial species. Within the lepromatous group, 50% of the patients studied could mount a proliferative response to PPD antigen in the absence of IL 2, but none of them was able to do so with M. leprae antigen. The addition of IL 2 increased the number of positive responders to PPD in this group, and in some patients IL 2 was able to restore M. leprae reactivity as well, suggesting that IL 2 had overcome a suppressor mechanism. PPD and M. leprae-triggered T cell lines were obtained from these subjects (with IL 2 added from the beginning of the culture when required). M. leprae lines exhibited variable and unstable pattern of specificity, most lines exhibiting, at least transiently, a cross-reactive response to other mycobacteria, but some displaying only M. leprae-specific response. In contrast, PPD lines from these subjects consistently exhibited a good response to PPD, a lesser response to various other mycobacteria and no response to M. leprae, a pattern differing from that obtained with PPD lines of high M. leprae responders. Co-cultures of irradiated lepromatous PPD triggered T cell lines with fresh autologous PBMC non-specifically reduced the proliferative response of the latter to PPD, as well as to unrelated antigens. A similar suppression was also observed when PPD lines from one of the tuberculoid patients were assayed. PPD and M. leprae T cell lines from both high and low responders initially exhibited the same CD4+ CD8- phenotype. In all cases, antigenic specificity declined and could not be maintained after 5 to 8 wk of continuous culture, a change associated with the progressive appearance of CD8+ and Leu8+ cells.

Antigens, Surface↗
PubMed1986

Monoclonal anti-actin antibody recognizes a surface molecule on normal and transformed human B lymphocytes: expression varies with phase of cell cycle.

A monoclonal anti-actin antibody, 2C9, was used to study the distribution of an actin-like cell-surface antigen (hereafter termed actin) on a lymphoblastoid cell line LA350 and on human peripheral blood lymphocytes. It was determined that 8-40% of LA350 cells and 3-15% of peripheral blood lymphocytes from healthy donors stain specifically with 2C9, almost exclusively on IgM-positive cells. Treatment of cells with 2C9 prior to incubation caused cell-surface actin to first patch and then to cap. Treatment of cells with nonspecific protease caused a loss of surface actin, with reexpression of the marker after 8-12 hr. The expression of LA350 surface actin also increased with DNA synthesis and was demonstrated to be maximal during late G1/early S phase. Thus, this antigen may be a sensitive marker for activated lymphocytes. These studies contribute to our understanding of the expression and distribution of actin-like membrane proteins that may participate in regulatory signals mediated by anti-actin antibody.

Actins↗
PubMed1986

T-cell subsets and natural killer activity in Plasmodium falciparum-infected children.

Thirty children acutely infected by Plasmodium falciparum and suffering either benign uncomplicated malaria (17 cases), or cerebral malaria (13 cases), were investigated for T-cell number and subset distribution among peripheral blood mononuclear cells using OKT3, OKT4, and OKT8 monoclonal antibodies, and for natural killer (NK) activity using K562 cells as targets. They were compared to a group of 16 age- and sex-matched healthy Senegalese children. OKT8 cell percentage was found increased in both groups of patients with a decrease of OKT4 cell percentage in cerebral malaria patients only. Both groups thus exhibited a decreased OKT4/OKT8 ratio, which was slightly lower in cerebral malaria cases than in benign cases. NK activity was found elevated in uncomplicated cases of malaria, in contrast to patients suffering cerebral malaria, who exhibited a profound depression of NK activity.

Adolescent↗
PubMed1986

Comparison of the response to phytohemagglutinin, of peripheral blood mononuclear cells and cerebrospinal fluid lymphocytes in multiple sclerosis and other neurological diseases. Determination of the frequency of the precursor cells by a limiting dilution analysis.

Proliferative response to phytohemagglutinin (PHA) of cerebrospinal fluid lymphocytes (CSF-L) and peripheral blood mononuclear cells (PMBC) from patients with multiple sclerosis (MS) and other neurological diseases (OND) was tested using either bulk culture conditions or limiting dilution techniques in the presence of additional exogenous IL2. CSF-L response to PHA was found significantly lower than that of PBMC in both MS and OND patients. There was no significant difference in the response of CSF-L between the two groups. The limiting dilution analysis of the frequency of the precursors of PHA-responsive cells showed a strikingly decreased frequency of these precursors among CSF-L.

Adolescent↗
PubMed1986

Interleukin-1 released by blood-monocyte-derived macrophages from patients with leprosy.

In highly purified blood-monocyte-derived macrophages collected from patients with leprosy and from healthy individuals and cultured in vitro with mycobacterial antigens such as Mycobacterium bovis BCG or Mycobacterium leprae, we nonspecifically induced the synthesis of interleukin-1. Normally, all supernatants from cultured macrophages of all subjects tested produced similar amounts of interleukin-1. However, only in patients with lepromatous leprosy, M. leprae, but not BCG, induced high-level synthesis of prostaglandin E2, which acted as a suppressor factor in the mouse thymocyte proliferative assay used to measure the interleukin-1 content of the supernatants. Normal interleukin-1 content of those supernatants was demonstrated by blocking the prostaglandin E2 synthesis by the addition of indomethacin to the medium throughout the experimental procedure. We also tested the efficiency of a combination of BCG and M. leprae in reducing the prostaglandin E2 synthesis, but with the methodology used, we did not observe any beneficial effect of such a combination. These results demonstrate the possible role of M. leprae in the induction of at least one of the suppressive monokines and are additional arguments for the involvement of macrophages in the suppression of the specific cell-mediated immunity to M. leprae observed in lepromatous leprosy.

Adolescent↗
PubMed1986

[Double-blind treatment of 49 cases of chronic multiple sclerosis using hyperbaric oxygen].

Forty nine patients with a chronic form of multiple sclerosis (MS) [progressive or stable] were treated with hyperbaric oxygen (HO) in a double blind trial. Patients were divided in three groups: the first group (group I) received a course of 2.3 ATA HO with diazepam (5 mg); the second group (group II) received a course of 2 ATA HO; the third group (group III) was the control group. Each patient breathed an adapted gaseous mixture in high pressure. Each patient received 20 sessions of this procedure during 4 weeks. Patients were evaluated with clinical, neurophysiological and immunological parameters. Clinical examination consisted in the evaluation of the Kurtzke's Disability Status Scale (DSS) and Functional Status Scale (FSS). This evaluation was done in the week before the procedure, the week following the treatment, then in the third and sixth month. The neurophysiological study was a comparative analysis from the variations of visual, somesthesic and brain stem auditory potentials. The immunological study was the analysis of the lymphocyte populations (OKT4/OKT8 ratio). Each examination was carried out the week before, then the week following the procedure. We found no amelioration into three groups. Subjectively, some patients thought to be better, but this was true in the two treated groups (I, II) and in the control group (III). There was not an FSS significant variation. We also found no significant variation of evoked potentials and OKT4/OKT8 ratio. We observed some incidental effects of the treatment, particularly in group I, in which patients were treated with a higher pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1986

A follow up of T-cell subsets and of anti-M. leprae antibody titer as measured by the FLA-ABS test in Melanesian leprosy patients under polychemotherapy.

Melanesian leprosy patients from New Caledonia were studied for the following parameters during the course of polychemotherapy: peripheral blood T-cell subsets, as identified in an immunofluorescence assay with monoclonal antibodies OKT3 ("pan-T"), OKT4 ("helper/inducer"), and OKT8 ("cytotoxic-suppressor"), and anti-Mycobacterium leprae antibodies in the serum, as measured by the fluorescent leprosy antibody absorption test. A group of Melanesian healthy subjects with no known exposure to M. leprae served as controls. Healthy contacts of leprosy patients were also studied for the presence of anti-M. leprae antibodies. Untreated, nonreactional lepromatous patients displayed moderate but significant T-cell abnormalities, consisting of a decrease in the percentage of OKT3+ and OKT4+ cells with a decrease in the OKT4:OKT8 ratio. These abnormalities disappeared within nine months of treatment. A transient decrease in the percentage of OKT8+ cells with an increase in the OKT4:OKT8 ratio was seen in patients suffering erythema nodosum leprosum (ENL). Tuberculoid patients, whether treated or not, did not show any T-cell marker disturbances. Positive serological tests for anti-M. leprae antibodies were found in 100% of lepromatous patients, 92% of tuberculoid patients, and 56% of healthy contacts. No significant decline in the antibody titer was observed with treatment during the survey period.

Adolescent↗
PubMed1986

Antibodies to phenolic glycolipid-1 and to whole Mycobacterium leprae in leprosy patients: evolution during therapy.

Sera from 92 patients were tested by the ELISA method for the presence of IgM antibodies to phenolic glycolipid-1 (PGL-1) of Mycobacterium leprae, and of both IgM and IgG antibodies to the whole M. leprae bacillus. All untreated lepromatous patients exhibited high antibody levels in all three assays. A sharp decline of IgM antibodies to PGL-1 and whole M. leprae was observed during the first two years of therapy, while IgG antibodies to whole M. leprae showed a progressive decrease only over a number of years. Low titers of IgM antibodies to PGL-1 and IgG antibodies to whole M. leprae could be detected in about 50% and 75% of patients, respectively, after more than ten years of treatment, with only 15% showing persisting IgM antibodies to the whole bacillus. Antibody levels as measured by the three assays used were correlated with the bacterial index in patients treated for less than four years. In patients treated longer than four years, only IgM antibodies, whether directed to PGL-1 or to whole M. leprae, remained correlated to the bacillary load. Tuberculoid patients exhibited a different antibody pattern, showing a lower frequency (and lower levels) of antibodies of PGL-1 and of IgG antibodies to whole M. leprae than lepromatous patients, and no detectable IgM antibodies to the whole bacillus. IgG antibodies to whole M. leprae were more frequently noted than antibodies to PGL-1, the latter declining more rapidly during therapy.

Antibodies, Bacterial↗
PubMed1985

Early expression in (NZB X DBA/2)F1 hybrids of thymus dysfunction and abnormal antibody production inherited from the NZB parent.

NZB mice, DBA/2 mice and reciprocal F1 hybrids between both strains were studied from birth to two months of age for the secretion of a serum thymic factor, thymulin (formerly named Facteur Thymique Sérique) and for spontaneous and antigen-induced immune responses: spontaneous splenic anti-2,4,6-trinitrophenyl (TNP) plaque-forming cells (PFC), spontaneous IgM serum levels, immune direct anti-sheep red blood cells (SRBC) PFC and immune serum antibody production to human gamma globulin (HGG) as well as susceptibility to tolerance induction by deaggregated HGG. An early decline of thymulin serum level was detected from two weeks of age both in NZB mice and F1 hybrids, the latter maintaining a level intermediate between that of both parental strains. Such a fall of circulating thymulin was associated to a decreased number of thymulin-secreting cells. F1 hybrids and NZB mice exhibited at two and three weeks of age spontaneous anti-TNP PFC in the spleen, and increased IgM serum levels as compared to DBA/2 mice. When immunized at birth with SRBC or at two weeks of age with HGG, NZB mice and F1 mice similarly exhibited a higher anti-SRBC antibody response, as measured 5 days later by PFC numbers, and a higher anti-HGG serum antibody production 2 weeks post-immunization, than age-matched DBA/2 mice. F1 hybrids tended to develop with age spontaneous and immune antibody responses lower than NZB mice but still much higher than DBA/2 mice. Conversely, after tolerization at birth with deaggregated HGG NZB mice but not the F1 hybrids produced higher titers of anti-HGG antibodies upon challenge than similarly tolerized DBA/2 mice. DBA/2 mothered and NZB mothered F1 hybrids did not differ for any parameter tested and no influence of the sex could be detected.

Animals↗
PubMed1985

Strain variation of lymphokine production and specific antibody secretion in mice infected with Mycobacterium lepraemurium.

Mice from strains showing either phenotypical expression of Bcg gene (C57BL/6, BALB/c, DBA/1, and (C57BL/6 X DBA/2)/F1, CBA, A/J, DBA/2) were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). The number of acid-fast bacilli (AFB) within the spleens, the ability of spleen cells to produce in vitro interleukin 1 and 2, and the serum levels of specific anti-MLM antibodies were assessed 3 months later. The number of AFB recovered from the spleens of various strains followed the strain distribution of genetically controlled innate resistance established for Mycobacterium bovis infection. A decrease of interleukin 2 production by spleen cells could be detected in C57BL/6, DBA/1, DBA/2 and (C57BL/6 X DBA/2)F1 mice only. The level of anti-MLM antibodies was found to be higher in C57BL/6, BALB/c and A/J mice than in the other strains tested. Thus no evidence appeared of a direct influence of the Bcg gene on lymphokine production and antibody secretion.

Animals↗
PubMed1985

Specificity study of PPD-reactive human T cell line and clones.

Peripheral blood mononuclear cells from a PPD-sensitive human subject, in vitro stimulated by PPD, could be maintained for several weeks in interleukin 2-containing medium, with regular reactivation with PPD and irradiated autologous mononuclear cells used as antigen-presenting cells. The proliferative response of this T cell PPD-reactive bulk culture could be stimulated to proliferate by PPD itself as well as by BCG and other mycobacteria. This T cell line comprised a majority of T cells expressing the OKT4+, OKT8- phenotype, and a minor proportion of T cells (8%) showing the OKT4-, OKT8+ phenotype. Two PPD-reactive clones, both OKT4+, were obtained from this line by the limiting dilution technique. Clone C9 was found to be highly specific of PPD and BCG, whereas clone A9 could be activated by four other species of mycobacteria. These data demonstrate the existence of species-specific and cross-reactive epitopes within PPD and prompt for the use of PPD-reactive clones as a tool for identification and purification of the molecules bearing these epitopes.

Cell Line↗
PubMed1985

Selective improvement of thymus and some T cell dysfunctions in NZB mice by in utero thymulin treatment.

NZB mice were treated during gestation with thymulin, a thymus-secreted, zinc-associated nonapeptide. Control pregnant NZB mice received either zinc alone or saline alone. Offspring from all three groups of NZB mothers, and age-matched DBA/2 mice, were tested for the following immunologic parameters: thymulin serum levels at 2 and 5 wk of age; splenic anti-sheep red blood cell (anti-SRBC) plaque-forming cell (PFC) numbers after immunization at birth or at 2 wk of age; anti-human gamma-globulin (anti-HGG) antibody titers after immunization at 2 wk of age, with or without prior tolerance induction at birth with deaggregated HGG; spontaneous IgM serum levels at 2 and 5 wk of age; spontaneous splenic anti-trinitrophenyl (anti-TNP) PFC numbers at 2 wk of age. As compared with DBA/2 mice, young NZB mice exhibited low circulating thymulin titers, high antibody responses to SRBC and to HGG, resistance to tolerance induction by deaggregated HGG, increased spontaneous IgM serum levels, and increased spontaneous anti-TNP PFC numbers. However, marked reductions in anti-SRBC and anti-HGG antibody production, both thymus-dependent responses, were observed in the young NZB offspring of thymulin-treated mothers as compared with NZB controls born from zinc- or saline-treated mothers. A delay in the postnatal decrease of serum thymulin levels was also noted in the offspring of thymulin-treated mothers. Interestingly, these effects of in utero thymulin treatment tended to become more pronounced with advancing age during the postnatal period. Conversely, IgM serum levels, spontaneous anti-TNP PFC and sensitivity to tolerance induction were not affected by thymulin treatment during fetal life. Taken together, the data suggest that in utero exposure to pharmacologic concentrations of thymulin induces a persistent and selective improvement of some thymus and T cell dysfunctions but has no effect on intrinsic B cell abnormalities of NZB mice.

Animals↗
PubMed1985

In vivo polyclonal stimulation of antibody secretion by two types of bacteria.

We previously proposed that one benefit of early polyclonal antibody secretion after bacterial infection might be the formation of antibodies protective against infection by a second pathogen. In order to analyse this possibility, the polyclonal and anti-phosphorylcholine (PC) plaque-forming cell (PFC) response induced by Staphylococcus aureus Cowan I (SA) was compared with the same responses stimulated by unencapsulated Streptococcus pneumonia strain R36a. S. aureus stimulated significant anti-PC PFCs, despite an inability to detect immunoassay-reactive PC on the surface of SA (present on R36a). The induction of these antibodies appeared very similar to the mechanism for producing polyclonal responses. R36a also stimulated both anti-PC and polyclonal PFCs, but by different means. In summary, our data suggest that each type of bacteria induces polyclonal and anti-PC responses through different mechanisms, and that the polyclonal antibody response stimulated by one group of bacteria can contain antibodies directed towards a second and different genus of bacteria.

Animals↗
PubMed1984

Pneumococcal cell wall phosphorylcholine elicits polyclonal antibody secretion in mice.

Immunization of mice with phosphorylcholine (PC)-bearing Staphylococcus pneumoniae Type 2, strain 36a (R36a) results in both a PC-specific and a polyclonal increase in splenic plaque-forming cells. The polyclonal increase was observed in all strains tested, including those bearing an X-linked immune defect resulting in an undetectable anti-PC immune response. The magnitude of the polyclonal response is directly related to the amount of bacterial surface PC as detected by enzyme-linked immunosorbent assay. Congenitally athymic (nude) mice mount an anti-PC plaque-forming cell response after R36a immunization but fail to produce a significant polyclonal response. From our results it appears that PC on the cell wall of a bacterium acts both as a polyclonal activator and a specific antigen, stimulating each by different mechanisms.

Animals↗