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Biomedical subjects

D S Ridley

Publications and source records attributed to D S Ridley.

At least 19 recordsLinked to original sources

Mycobacterium leprae reactive T cell clones from lepromatous leprosy patients after prolonged dapsone chemotherapy.

The proliferative responses of peripheral blood mononuclear cells (PBMC) to Mycobacterium leprae and BCG were studied in two groups of leprosy patients: a group of 8 lepromatous patients who had been on treatment for more than 20 years (TLL) and a group of 8 untreated lepromatous leprosy patients (ULL). The mean response to M. leprae of the TLL group was 6195 cpm with 5 of the 8 patients responding positively. The mean response to M. leprae of the ULL group was 617 cpm, with only 1 patient showing a positive response. The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group. Thirteen M. leprae reactive clones were established from 2 TLL patients and 5 M. leprae reactive clones were established from 2 tuberculoid leprosy patients. Seven of these clones, 4 from the TLL patients and 3 from the tuberculoid (TT) patients could be studied further. Three of the TLL clones responded specifically to M. leprae, while one of the clones exhibited a broad cross-reactivity to other mycobacteria. All of these clones were of the CD4+CD8- phenotype. Our findings suggest that responsiveness to M. leprae can be detected in vitro in a proportion of LL patients who have undergone prolonged chemotherapy, and that this response involves M. leprae reactive CD8+CD8- T cells, of which some appear to be specific to M. leprae.

Antigens, Bacterial

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

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

Histological analysis and the pathogenesis of mucocutaneous leishmaniasis.

A series of over 400 well-documented biopsies of mucocutaneous leishmaniasis was evaluated to elucidate the histological processes associated with the elimination of parasites, and their correlation with the course of the disease. Non-specific inflammation was the most frequent and least effective response; its onset might be delayed, and in this event particularly the incidence of metastasis from skin to mucosa was high. Lysis of parasite-laden macrophages appeared to be the basic mechanism of parasite reduction, even when it was not overt. When it was acute the onset was usually rapid, and though it resulted in much tissue destruction the prognosis was generally better and mucosal metastasis rare. Lysis and non-specific inflammation both led to the formation of a post-necrotic type of granuloma, but reversion of the process was almost as common as progression. Ultimately a tuberculoid granuloma evolved and proceeded to resolution. In about 5 per cent of cases, macrophage activation appeared to bring about early resolution; neither reversion nor mucosal metastasis was seen.

Biopsy

An evaluation of the ELISA for schistosomiasis in a hospital population.

In order to evaluate the ELISA for schistosomiasis under the conditions of clinical practice, 1576 hospital patients were tested using a crude soluble Schistosoma mansoni egg antigen. Test sensitivity in detection of S. mansoni was found to be 96.2% and in S. haematobium 92.3%. The predictive value of positive results was high, reaching 88% at antibody levels three or more times the screening level. The test was considered by clinicians to be valuable for diagnosis and patient management, though it did not distinguish active from recently treated infections. Of 37 apparently false positive schistosome ELISA results only seven could be attributed to other helminth infections. Another nine patients had hepatitis. It is suggested that the antigens and antibodies of the two diseases are mutually cross-reactive, since reports have suggested a high increase of HBsAg patients with schistosomiasis.

Antibody Formation

Lucio's phenomenon: a comparative histological study.

To study further the pathogenesis of Lucio's phenomenon, we have made a comparative histological study of 11 patients with Lucio's phenomenon and 12 with ENL. Confirming the findings of others, Lucio's reaction could be distinguished from ENL by epidermal necrosis and by necrotizing vasculitis manifesting necrosis in the walls of superficial vessels and severe, focal endothelial proliferation of mid-dermal vessels. Furthermore, in Lucio's phenomenon large numbers of AFB were found in evidently normal and in swollen or proliferating endothelial cells. We hypothesize that patients with Lucio's phenomenon have an exceptionally deficient defense mechanism, allowing unrestricted proliferation of AFB in endothelial cells, facilitating contact between bacterial antigen and circulating antibody and leading to infarction; also, this nadir of resistance allows unimpeded dissemination of AFB, accounting for the clinical features of diffuse non-nodular leprosy. Thus, an explanation is offered for the restriction of Lucio's phenomenon to patients with diffuse non-nodular lepromatous leprosy.

Blood Vessels

Surface markers on lymphocytes and cells of the mononuclear phagocyte series in skin sections in leprosy.

E, EA and EAC rosetting techniques and Ig fluorescence were used in a study of receptor sites in cryostat sections of lesions through the spectrum of leprosy, and for comparison in some other mycobacterial and granulomatous lesions. Anti-C3, and trypsin were used as blocking agents. Lymphocytes in borderline lepromatous leprosy produced EA adherence and IgG fluorescence indicating B type cells. Lymphocytes in tuberculoid leprosy produced neither E or EA adherence and no fluorescence; these cells were presumed to be T cells. EAC and EA adherence was more marked in areas of macrophage infiltration, where there were few lymphocytes, than over the lympocytes themselves. Two distinct patterns emerged: (i) EA binding together with IgG fluorescence was seen in active lepromatous leprosy and could be localised to the surface of individual macrophages, and (ii) EAC binding together with IgM fluorescence was seen in the granuloma of tuberculoid leprosy and sarcoidosis, but could not be definitely related to cell surface; rather it was diffusely spread over the whole granuloma; EAC adherence was diminished by anti-C3 serum. Trypsin removed EA binding completely, but only diminished EAC adherence. It is suggested that the EA pattern indicates immunoglobulin receptors on macrophage and lymphocyte surfaces: and that the EAC binding (which is stronger than EA) involves C3 and IgM receptors at extracellular sites as well as C3 receptor sites on epithelioid cell surfaces. EA and EAC binding were enhanced in borderline tuberculoid leprosy in reaction and erythema nodosum leprosum, suggesting that immunoglobulin and complement receptor sites increase in number with enhanced hypersensitivity.

Cell Membrane

Immunofluorescent reactions with microfilariae: 1. Diagnostic evaluation.

Microfilariae have been evaluated as antigen for the indirect immunofluorescent test in the diagnosis of filariasis. Sonicated, unlike whole, microfilariae present no problems in handling on a slide. The cytoplasmic antigen that is exposed by sonication, unlike the sheath or cuticular antigen, reacts with filariasis sera irrespective of whether or not there is a detectable microfilaraemia. The cytoplasmic antigen of microfilariae of various species was marginally superior to Dirofilaria adult worm as antigen for diagnostic immunofluorescence in respect of both sensitivity and specificity. The microfilariae extruded from the uterus of an adult D. immitis were a useful source. But the best results were obtained with the sonicated microfilariae of Brugia pahangi, with which it was possible to utilize both cytoplasmic and sheath antigens simultaneously, giving a positivity rate of 95% for filariasis infecions as a group. This test is thought to be the best available at present for the sero-diagnosis of filariasis, in spite of some lack of specificity. For individual filarial infections a homologous microfilarial antigen is probably the deal.

Antigens

Giardiasis: clinical and therapeutic aspects.

Malabsorption was present in 29 of 40 symptomatic patients with giardiasis. Twenty-three had impaired D-xylose absorption; in 20 vitamin B12 absorption was low, and 15 patients had steatorrhoea. More severe malabsorption was associated with more marked histological abnormalities. Metronidazole, 2-0 g as a single daily dose on three successive days, produced a parasitological cure rate of 91%. In contrast, the standard course of mepacrine, 100 mg thrice daily for 10 days, eradicated the parasite in only 63% of patients. Improvements in absorption and jejunal morphology followed anti-giardial treatment. Tetracycline in eight patients failed to eradicate the parasite, intestinal absorption was unaltered, and histological appearances of the jejunal mucosa often deteriorated.

Adult