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Biomedical subjects

D S Ridley

Publications and source records attributed to D S Ridley.

At least 37 records · Page 2Linked to original sources
PubMed1984

C-reactive protein and apoB containing lipoproteins are associated with Mycobacterium leprae in lesions of human leprosy.

Skin biopsies from patients with leprosy across the spectrum from tuberculoid (TT) to lepromatous (LL), including histoid lepromas and erythema nodosum leprosum (ENL) reactions, were stained immunohistochemically for the presence of C-reactive protein (CRP) and the apolipoprotein, apoB. Mycobacterium leprae bacillary material comprising cell walls, cytoplasmic and soluble components was present with increasing abundance towards the lepromatous end of the spectrum and always stained positively with anti-CRP. M. leprae from armadillos did not stain with anti-human CRP indicating that the staining of M. leprae in human tissues was not due to a cross-reaction between anti-CRP and the organism itself. When CRP was present in large amounts apoB was also demonstrated in the same distribution. CRP was detected on bacilli and their degradation products within the cytoplasm of macrophages even in the absence of a raised serum CRP level in some ENL patients and also in two cases of advanced resolving lepromas. These findings demonstrate remarkable persistence of CRP in association with M. leprae in vivo, and raise intriguing questions about the possible role of CRP in relation to the handling of leprosy bacilli.

Animals↗
PubMed1984

Erythema nodosum leprosum (ENL). Ultrastructure of the connective tissue response.

In ENL lesions of the type associated with severe damage to the connective tissue of the dermis, large quantities of bacterial debris were demonstrated by electron microscopy, although not by light microscopy. The debris, in an advanced stage of degeneration, was present in the phagosomes of decrepit macrophages, in the extracellular compartment and, in particular, bound to degenerate collagen and elastic where immunoglobulin, complement, and inflammatory mediators had been demonstrated previously. It is suggested that the complexing of mycobacterial antigen is a major factor in the causation of connective tissue damage, as well as other aspects of ENL. The reason why connective tissue involvement is so variable has not been explained.

Antigen-Antibody Complex↗
PubMed1984

Exacerbation reactions in hyperactive lepromatous leprosy.

Exacerbation reactions (ER) are acute reactions occurring locally in histoid or other highly active lepromatous lesions with an exceptionally heavy bacterial load. Clinically, they are almost silent although they may cause ulceration and the release of viable bacilli. Histologically, the influx of polymorph neutrophils and coincident macrophage degeneration mimic erythema nodosum leprosum (ENL). Later, the signs of increased permeability or necrosis of small blood vessels and mast cell degranulation are differential features. The predominant immunoglobulin is IgE, and the main complement component is C1q, C3 being mostly undetectable. The reactions appear to be mediated in part by reagins (although eosinophils are not seen). Immune complexes probably form at antigen excess. Of equal importance may be the release from highly activated macrophages and neutrophils of hydrolases and proteases, which are capable of degrading connective tissue and other cell surfaces. This report is based on a histopathological and an immunocytological study of 13 exacerbation reactions in comparison with nonreacting hyperactive lesions and with ENL. The results support the view that the essential feature of histoid lesions is their hyperactivity.

Complement C1↗
PubMed1983

The long-term evolution of mycobacterial BCG and preformed immune complex BCG/anti-BCG granulomas in rats.

In previous studies it was found that infections with BCG or complexed BCG/anti-BCG in rat skin produced granulomas that appeared to resolve at 8 months. In this follow-up study 1 year later, it appeared that while lesions due to performed complexes had resolved, those due to BCG alone had undergone a massive reactivation. Nevertheless despite the loss of CMI the infection was restricted. The bacilli, present in enormously increased numbers, were dead; the host macrophages were large and activated. Epithelioid cells and dendritic cells were common. The granuloma was confluent, with patchy necrosis and inconspicuous polymorph infiltration. Although preformed complexes with viable bacilli formed at equivalence had produced a resolving lesion, the outcome of the natural infection was complicated by an imponderable balance of immunological responses. CMI does not appear to have been a determinant during the crucial phases of the infection.

Animals↗
PubMed1983

The evolution of the lesion in cutaneous leishmaniasis.

In order to elucidate the mechanisms for the elimination of Leishmania, the histological evolution of the lesions of cutaneous leishmaniasis was studied in 118 biopsies from four geographical areas known to be associated with different species or sub-species of Leishmania. Basically there were 3 types of response: A, parasites were eliminated within intact macrophages which later evolved as epithelioid cells; B, they were eliminated as a result of the lysis of the macrophages either individually or in small clusters, but the process was incomplete; C, there was necrosis proceeding to completion at the centre of a focalised mass of macrophages. In B and C the release of parasites caused tissue destruction; epithelioid cells were immature and often sparse, though giant cells were seen in C. A more definite tuberculoid response was found in draining lymph nodes. The response (A, B or C) depended partly on the parasite load, partly on geographical factors. The relative proportions of macrophages, plasma cells and lymphocytes in the lesions varied with the parasite index, but the relationship was the same in all 3 types of response. This suggested that the 3 responses might be the outcome of a common immunological mechanism operating at different antigen levels or antigen-antibody ratios.

Belize↗
PubMed1983

Extravascular immune complexes in experimental mycobacterial BCG granulomas.

Quantitative results of Mycobacterial BCG antigen, immunoglobulin and complement in rat skin lesions during the evolution of the granuloma reveal peak values of these factors at 49 days. The combination of antigen, Ig and complement, present extracellularly and in polymorphs at this time, indicates immune complex formation at an antigen-antibody ratio which may approximate to equivalence. This development coincides with mass lysis of host macrophages, and is followed by a sharp reduction in the antigen load. At 8 mth, surviving bacilli are coated with antibody and complement, and sequestrated in activated macrophages. It is possible that this antibody is non-specific and protective to the bacilli, leading to a second multiplication of organisms. But by 1 yr and 8 mth all the bacilli are dead, and immunoglobulins and complement are at very low levels. Although immune complex deposition and macrophage lysis was not associated with complete elimination of bacilli, it marked a turning point in the infection when the bacterial load was high and cell mediated immunity (CMI) was lacking. CMI may be important, especially at low antigen levels, but the crucial role here appears to have been played by complexed antibody. These experimental findings parallel those in human cutaneous leishmaniasis. They may explain some forms of necrosis in this condition and in tuberculosis.

Animals↗
PubMed1983

An outbreak of cutaneous leishmaniasis in Guyana: epidemiology, clinical and laboratory aspects.

An outbreak of cutaneous leishmaniasis reached epidemic proportions among military personnel in Guyana during the period from November, 1977 to March, 1980. As the patients presented from widely separated areas of the hinterland it is likely that cutaneous leishmaniasis is endemic throughout the virgin tropical rain forest of Guyana, although infection is normally sporadic. A striking clinical feature was the 'spirotrichoid' involvement of the draining lymphatics and nodes in half the cases, which histologically all came from the middle region of the spectrum (groups II, III or IV of Ridley's 1980 classification). All the cases tested were serologically positive to a Leishmania braziliensis antigen. One hundred and ten patients were successfully treated with pentamidine, with minimal side-effects, but some required a second course. Four relapsed patients all belonged to the same histological group.

Adolescent↗
PubMed1982

The specificity of serum antibodies to Giardia lamblia and to enterobacteria in gastrointestinal disease.

A comparative evaluation was made of immunofluorescent serum antibodies against Giardia lamblia and enterobacteria isolated from the upper intestine of patients with severe giardiasis. The study was carried out on sera from 51 patients belonging to seven intestinal disease groups. Antibodies against Giardia and against some enterobacteria were present in all eight cases of giardiasis with malabsorption, and absent in all five cases of invasive amoebiasis and in six normal control sera. Bacterial antibodies were found in the other five groups of intestinal disease, in 29 out of 38 cases. Giardia antibodies were found in only two of the other groups, tropical sprue (two cases) and coeliac disease (two cases). Thus Giardia antibodies may not signify active giardiasis but they were of restricted distribution and were sometimes present at relatively high titre. Bacterial antibodies were widely distributed but always at low titre. Absorption experiments indicated that the two types of antibody did not cross-react.

Antibodies↗
PubMed1982

Pregnancy and leprosy: the consequences of alterations of cell-mediated and humoral immunity during pregnancy and lactation.

One hundred fourteen Ethiopian women with leprosy and 33 healthy women without leprosy were studied prospectively throughout 119 and 37 pregnancies, respectively, and followed up during lactation. Fifty-five women showed worsening of their leprosy status; in 31 (56%) this was observed during the third trimester of pregnancy. Forty women were diagnosed as having Type 1 lepra reaction; in 20 (50%) the first occurrence was during the first six months of lactation. Twenty-eight women had Type 2 lepra reaction, which in 19 (68%) first occurred during the third trimester of pregnancy or the first six months of lactation. These adverse effects of pregnancy on leprosy are thought to be associated with suppression of maternal cell-mediated immunity during gestation and recovery postpartum. Implications for the obstetrician, physician and leprosy health worker are discussed.

Antibody Formation↗
PubMed1982

An immunoperoxidase study of immunological factors in skin lesions across the spectrum of leprosy.

The immunoperoxidase technique was used to assess the quantity and situation of various immunological factors in 24 skin biopsies which represented the leprosy spectrum from TT to LL. The factors were immunoglobulins (IgG and IgM), complement components (C3, C3d and Clq), plasminogen, muramidase (lysozyme), C-reactive protein and alpha-1-antitrypsin. The results were compared with previous reports on the assessment of these factors in serum. The quantities of these factors in the lesions produced peaks at TT and LL, with a dip in the BT-BB region (C-reactive protein and alpha-1-antitrypsin excepted). The immunoglobulins, present mainly in plasma cells and lymphocytes, correlated in general with reports of serum levels. The complement components were present in appreciable amounts, though the serum levels are depressed; they were seen in young mononuclear cells with a low bacterial load. All factors produced an ascending gradient in active lesions from BT to BL or LL, which correlated with the bacterial load and its viability. In regression (studied only in LL) there was a decrease in all factors. In TT there was an increase in most factors which did not correlate with the antigen load, and which probably resulted in an excess of antibody over antigen. In active LL there is probably an antigen excess. The results suggest the possibility that there is a common defect from BT to LL, in which the generation of immunological factors within the lesion of immunological factors within the lesion is a secondary response to the antigenic load. In TT alone (a rare group) is there an enhanced immunological response unrelated to the antigen load. In support of this was the finding of Ia antigen only in TT lesions.

Complement System Proteins↗
PubMed1981

The cryopreservation of standard sera.

To determine the storage temperature needed for the preservation of standard sera for serodiagnostic tests, groups of sera were tested before and after storage at -70 degrees C and -20 degrees C for periods of up to five years. The temperature required depended on the nature of the test, but no definite advantage was found in storage at -70 degrees C. For complement fixation this temperature was inadequate and greatly inferior to liquid nitrogen. For immunofluorescence it had no apparent advantage over a temperature of -20 degrees C, and for some other tests it was no more than marginally superior.

Blood Preservation↗
PubMed1981

The histological course of reactions in borderline leprosy and their outcome.

The histological course and the outcome of reactions was followed in 12 patients who were all in the borderline (BT-BL) zone of the spectrum at some time during the reaction. In eight patients the reaction proved to be of the upgrading or reversal type with a shift in classification toward the tuberculoid pole. In two patients the reaction was of the opposite downgrading type, and in two there was no significant change in classification as a result of the reaction. Early reactions were characterized by edema and an increase in the number of lymphocytes which was more marked in upgrading than downgrading reactions, but at this stage the outcome could not be reliably predicted. In the acute stage necrosis was apparent in severe cases and was followed by giant cell formation and the evolution of the granuloma cells depending on the direction of the shift: organized clusters of mature epithelioid cells in upgrading, macrophages in downgrading. At all stages the collagen of the dermis might be involved in varying degree, which in extreme cases included fibrinoid necrosis and scarring in the late stage. The histology is compared to that of tuberculin reactions. All cases were bacteriologically positive at the onset of the reaction. The results were consistent with the view that these reactions are delayed type hypersensitivity phenomena associated with the unmasking of bacterial antigen in nerve or other protected sites, or with an increase of hypersensitivity as a result of treatment. They demonstrate the evolution of a granuloma in mycobacterial disease.

Biopsy↗