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Biomedical subjects

M F Waters

Publications and source records attributed to M F Waters.

At least 37 records · Page 2Linked to original sources
PubMed1990

Positive Mitsuda lepromin reactions in long-term treated lepromatous leprosy.

Twenty-four lepromatous (LL) patients, treated for 22 to 40 years with chemotherapy, including sulphones and with multidrug therapy, were tested with standard Wade-Mitsuda lepromin. Thirteen gave weak positive (3-4 mm) Mitsuda reactions, confirmed histologically in the ten whose reactions were biopsied. Six of the eleven negative reactors were partly accounted for by a history of relapse, and two others had probably taken dapsone irregularly. Eleven control LL patients, treated for less than 20 years, were uniformly lepromin negative. Spontaneous lepromin conversion appears to occur around 24 years after commencing successful chemotherapy. The late Mitsuda conversions are attributed to delayed clearance of the reservoir of bacterial antigen, but a poor correlation between Mitsuda and Fernandez positivity is not explained.

Humans↗
PubMed1990

Tuberculoid relapse in lepromatous leprosy.

It is commonly accepted that the attainment of bacteriological negativity fails to restore the immune state of leprosy patients who have downgraded to lepromatous. We report six patients who had been lepromatous (LLs), and who, after many years of chemotherapy and bacteriological negativity, were found upon relapse to have upgraded to borderline-tuberculoid (BT). Five had become Mitsuda lepromin positive. The relapses could be accounted for by proven or suspected dapsone resistance. The upgrading was associated with minimal signs of reaction, which was attributed to the low level of antigen in the almost resolved lesions. The manner of development of the new high immune lesions resembled the onset of a primary infection, clinically and histologically. The development of a positive Mitsuda reaction in longstanding LL leprosy is not necessarily an indication of cure.

Adult↗
PubMed1987

Events surrounding the recognition of Mycobacterium leprae in nerves.

Histological examination and immunocytochemistry of Schwann cells, macrophages, and mycobacterial antigen were used to study 48 nerves of untreated patients with leprosy. None of the patients was in reaction clinically, but microreactions, involving small clusters of Schwann cells and macrophages in all cases except LL, were marked by progressive degradation of acid-fast bacilli (AFB). This was thought to be the response to the recognition of mycobacterial antigen. In the first phase, the disintegration of one or more Schwann cells caused the release of AFB, accompanied by subacute inflammation. In the second phase, as edema and cellular infiltration subsided, the necrosis of Schwann cells was replaced by granuloma formation, mycobacterial antigen being in a soluble form. Myelinated cells harbored few degraded AFB, and there was evidence that antigen-associated myelin hastened the death of Schwann cells. Only then did antigen become immunologically detectable to induce an inflammatory response whose clearance and resolution was impeded by the restraint on cellular movement due to the structure of neural tissue. These developments were sporadic but continuous. AFB and antigen released by disintegrating Schwann cells were ingested by regenerating Schwann cells and by macrophages, producing a self-perpetuating cycle which might involve either small areas or the greater part of a fascicle, and could conceivably progress to a generalized reaction.

Antigens, Bacterial↗
PubMed1986

Prevalence and specificity of the enhancing effect of three types of interleukin 2 on T cell responsiveness in 97 lepromatous leprosy patients of mixed ethnic origin.

Peripheral blood mononuclear cells from 97 predominantly lepromatous leprosy patients and 11 control subjects were tested in a lymphoproliferative assay for response to Mycobacterium leprae (whole and sonicated), and sonicated M. vaccae, M. tuberculosis, and M. scrofulaceum, in the presence and absence of three types of interleukin 2 (IL-2) (crude, purified, and recombinant). IL-2 enhanced the response to sonicated M. tuberculosis and M. leprae organisms more often in patients than in control subjects, but not significantly so and only in a minority of patients. This effect was significantly more common (though still only found in a minority of 46%) using M. leprae organisms as antigen, than when using sonicates of M. leprae (19%) or M. vaccae (19%). However it was nearly as frequent using sonicated M. tuberculosis, or M. scrofulaceum. Thus in only nine patients was the effect specific to M. leprae. Enhancement by IL-2 could not be related to the type of IL-2 used, the dose of antigen, or the amount of endogenous IL-2 released by the cells tested. Similarly it was not related to the extent to which IL-2 caused increased background proliferation in control wells, which occurred to an equal extent using cells from control subjects, nor was it related to the extent of antigen-driven proliferation. The data have also been analysed in relation to duration of disease (50 years to a few weeks) and ethnic origin. No correlations have been revealed. Thus enhancement by IL-2 of the lymphoproliferative response to mycobacterial antigens does occur using cells from lepromatous leprosy patients, but it is found in a minority of patients, it is not specific to M. leprae, and can occur with cells from normal donors.

Antigens, Bacterial↗
PubMed1985

The involvement of dendritic cells in the cutaneous lesions associated with tuberculoid and lepromatous leprosy.

Full thickness skin biopsies were examined from 12 untreated leprosy patients and included five borderline tuberculoid (BT leprosy), five borderline lepromatous (BL leprosy) and two subpolar lepromatous leprosy cases. The non-lymphoid mononuclear cells present in the dermal infiltrates were analysed with immunohistological techniques using monoclonal antibodies (MoAb) which in normal tissues identify subpopulations of macrophage-like cells in tissue sections; RFD2 (recognizing all and monocytes/macrophages), RFD1 (recognizing interdigitating cells), NA1/34 (recognizing Langerhans cells) and RFD7 (recognizing only mature tissue macrophages). It was observed that using these MoAb no single cell type was unique to a particular state of the disease but that major differences in the proportions of these non-lymphoid mononuclear cells existed between BT leprosy and BL and LL leprosy. In BL leprosy lesions RFD2+ macrophages were the major cell type although a significant number (15-30%) of RFD1+ macrophage-like cells were also present. In contrast, in the dermal infiltrates of BT leprosy, RFD1+ cells were the predominant cell type (45-55%). The distribution of NA1/34+ Langerhans cells and the expression of Class II major histocompatibility (MHC) antigens was characteristically different in BT, BL and LL leprosy. The relationship between the presence and phenotype of cells considered to be involved in antigen presentation is discussed in relationship to the different clinical states in leprosy.

HLA-DR Antigens↗
PubMed1985

Lysozyme as a measure of cellular dynamics in the lesions of leprosy.

The levels and distribution of lysozyme-positive cells and exudate were studied in leprosy lesions through the spectrum, in untreated and treated patients, in relapse and in reactions. Altogether 124 skin biopsies were examined by the immunoperoxidase technique. Monocytes, neutrophil-polymorphs and mast cells were the most conspicuous cells seen. Lysozyme proved to be a useful means of indexing renewal of these cells in the lesions. Peak numbers of monocytes were seen in lesions of active lepromatous leprosy (LL) and of tuberculoid leprosy (TT), at poles of opposite immunological performance. In TT the stimulus for recruitment was delayed hypersensitivity (DH). A decline in DH from TT towards the middle of the spectrum, mid-borderline, was accompanied by a fall in monocyte level. Furthermore, reacting lesions due to enhanced DH also had increased numbers of monocytes. On the other hand reactions associated with immunological deterioration were similar to active lepromatous leprosy (LL) and monocyte influx was raised in response to the stimulus of free multiplication of bacilli in both cases. In TT delayed hypersensitivity acted also to promote the rapid transformation of monocytes to epithelioid and giant cells all of which were strongly positive for lysozyme. This was in contrast to much lower levels in histologically similar macrophage-epithelioid cells of BT granulomas. Lysozyme synthesis was not seen in macrophages after ingestion of M. leprae. Early foamy change was made conspicuous by lysozyme deposited in phagocytic vacuoles, but old foam cells in regressing lepromas were negative. Lysozyme bound to dead extracellular M. leprae but not to viable or intracellular organisms. Dead bacilli or immune complexes appeared to be the stimulus for neutrophil-polymorph recruitment, mainly in reactions.

Granuloma↗
PubMed1985

Giant reactions to tuberculin in lepromatous leprosy patients.

A detailed account and definition is given of the previously inadequately described "giant reactions" to tuberculin occasionally seen in leprosy patients. The reaction is an accelerated and exaggerated response to species-specific antigens of Mycobacterium tuberculosis found in both PPD and New tuberculin. Our studies were performed in Malaysia, Uganda, Spain, and England. There was a significantly higher incidence of the phenomenon in Malaysia than in the other centers, but this may have been because there alone previously untreated lepromatous (LL and BL) patients were serially tested for up to three years after starting chemotherapy. Of the 28 patients exhibiting giant reactions, 27 occurred among lepromatous patients (24 LL and 3 BL), of which only 3 (1 LL and 2 BL) were untreated. One treated BL patient had developed, and one untreated BL patient was a family contact of, active tuberculosis. Giant reactions are uncommon in untreated and in very long-term treated LL patients, but may occur in up to a fifth of those receiving their first 1-3 years of chemotherapy. Although the mechanism is not yet understood, it appears to be a coincidence of delayed hypersensitivity of the tuberculin type and a less-delayed phenomenon of excessive local edema associated with local lymphadenopathy and short-lasting symptoms of malaise and pyrexia. It is suggested that the majority of giant reactions occur during a period of temporary lack of immune regulation associated with changing levels of antigenic load.

Adult↗
PubMed1984

Reversal by interleukin-2 of the T cell unresponsiveness of lepromatous leprosy to Mycobacterium leprae.

In some subjects Mycobacterium leprae causes disseminated (lepromatous) disease. Such subjects show both in vivo and in vitro deficient T cell responses to M. leprae, but not to other antigens. We have recently shown that lepromatous peripheral blood mononuclear cells (PBMC) failed to produce interleukin 2 (IL-2) in response to M. leprae and that T cell-conditioned media (TCM) can reverse the T cell unresponsiveness in a majority of lepromatous leprosy patients (Haregewoin et al. 1983). Here we show that highly purified and recombinant IL-2 had effects similar to TCM. On the other hand, lepromatous PBMC produced IL-1, and IL-1 had no restorative effect. These findings provide further evidence that the unresponsiveness in lepromatous leprosy often results from a deficiency in IL-2 production. After initial stimulation with TCM + M. leprae, lepromatous PBMC could be restimulated with M. leprae alone, providing clear evidence that M. leprae-reactive lymphocytes were generated in the presence of TCM. The present findings are discussed in relation to the possible mechanisms involved in the failure of IL-2 production. If our findings can be reproduced in vivo, IL-2 may offer a novel approach to therapy in lepromatous leprosy.

Antigens, Bacterial↗
PubMed1984

Parasitism of antigen presenting cells in hyperbacillary leprosy.

Full thickness skin biopsies from four patients with borderline lepromatous leprosy (BL leprosy) have been examined. Immunohistological techniques have been employed to analyse the non-lymphoid mononuclear cells present in the dermal infiltrates associated with the BL lesions. This analysis was performed using three monoclonal antibodies, RFD2 (recognizing macrophages), RFD1 (recognizing interdigitating cells) and NA1/34 (recognizing Langerhans cells). It was found that the vast majority of non-lymphoid mononuclear cells in the lesions were RFD2+ macrophages. However, a significant number (15-30%) of macrophage like cells were RFD1+ interdigitating cells. A very small number of NA1/34+ Langerhans cells were also identified within the dermal infiltrates. Combination immunohistology and Ziehl Neelsen staining revealed that all these cell types could be found containing the Mycobacterium leprae organisms. The proportions of parasitized cells within each subpopulation was equivalent to the overall proportion of each cell type within the infiltrate. The significance of parasitism of cell types thought to be involved in antigen presentation and induction of immune responses is discussed.

Antibodies, Monoclonal↗