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I A Cree

Publications and source records attributed to I A Cree.

At least 109 records · Page 6Linked to original sources

Mast cells in leprosy skin lesions.

The variability of mast cell density within and between leprosy skin lesions was examined as a basis for future studies, and whether the number of mast cells in the lesion was determined by local or systemic factors was evaluated. The mast cell density in the granuloma, skin appendages, and intervening dermis was assessed by counting mast cells in glycol methacylate sections stained with Giemsa stain and relating these counts to area measurements obtained by planimetry. In biopsy specimens taken from the edge of established lesions the density of mast cells within the granulomata was considerably higher than that in the intervening dermis and was comparable with that found in the appendages. No major differences in mast cell density were found between unaffected skin and the centre or edge of individual lesions. Mast cell densities in biopsy specimens from the edge of different lesions on the same patient were also similar, suggesting that the mast cell density within the granulomata is independent of the site of the lesion and is determined systemically.

Adult↗

A quantitative study of the relationship between systemic and histological parameters of immunity in individual leprosy patients.

A group of 52 untreated leprosy patients were examined to determine the relationship between local and systemic immunological parameters across the clinico-pathological spectrum. The Ridley-Jopling classification, bacterial index (BI), and granuloma fraction (GF) were assessed in biopsies from 40 cases. The densities of apoptoses, mitoses, and plasma cells were also measured. Systemic immunity to mycobacteria was assessed by skin tests with leprosin A and PPD, and by measurement of the serum antibody responses to Mycobacterium leprae, M. tuberculosis, and M. scrofulaceum. The serum responses to phenolic glycolipid-I (PGL-I) of M. leprae was assessed using a glycoconjugate which mimics an immunodominant epitope. The serum antibody levels and skin test results showed the expected inverse relationship. The BI within lesions showed an inverse correlation with the skin test results, but none of the other histological parameters studied showed a significant relationship with the other measurements of systemic immunity. Our findings suggest that the inverse relationship between delayed-type hypersensitivity and humoral immunity in leprosy patients, which is strong in groups of patients across the leprosy spectrum, is less strong in individual patients than is often thought. The lack of correlation of many histological and systemic parameters suggests that local factors modulate systemic immunity in the pathogenesis of leprosy lesions.

Adolescent↗

Measurement of phagocyte chemiluminescence in a microtitre plate format.

Previously described assays of phagocyte chemiluminescence have required large numbers of cells and have not been able to follow responses from a large number of samples in single experiments. Recently, sensitive luminometers which employ a 96 well microtitre plate format have become available. We describe the application of this equipment to the measurement of phagocyte chemiluminescence using lucigenin to enhance the response and the estimation of the opsonic activity of serum. It was found that as few as 5 X 10(4) cells (polymorphonuclear leukocytes or monocytes) per well and a ratio of 10:1 zymosan particles to cells gave good results when opsonised with 10% whole serum. This method allows assays of opsonic activity to be performed in triplicate on large numbers of sera with a relatively small number of phagocytes and should aid the investigation of the role of opsonisation in infectious disease.

Humans↗

Blood flow velocity in cutaneous lesions of leprosy.

The velocity of blood flow in the cutaneous lesions of leprosy was measured by the noninvasive technique of laser-Doppler velocimetry in nine male patients, all under treatment with World Health Organization multidrug regimens. In three patients with stable borderline tuberculoid (BT) lesions, the blood-flow velocity was slightly faster over the lesion than that in adjacent uninvolved skin. There was no substantial difference between different sites at the center and edge of individual lesions in each patient, but there was some variation between subjects. In one other BT patient with a reversal reaction, blood-flow velocity was 20-fold greater than in adjacent uninvolved skin. In four patients with stable borderline lepromatous/lepromatous (BL/LL) disease, the blood-flow velocity was 3 to 9 times faster over the plaques than in adjacent skin. There was relatively little difference between measurements over comparable points at the edge and center of individual plaques, or between plaques in the same patient, but there were considerable differences between patients. A fifth BL patient in reversal reaction showed generally similar results to those found in the stable BL/LL patients. Histometric study of the biopsies taken immediately after blood-flow measurement from two different plaques on each of four BL patients showed a clear relationship between the granuloma fraction measured by planimetry and the blood-flow velocity. This finding suggests that laser-Doppler velocimetry might prove to be a useful, clinically acceptable, noninvasive technique for monitoring the severity of hyperemia as an early indication of reversal reaction during chemotherapy trials in leprosy patients.

Adult↗

Reproducibility of histology in leprosy lesions.

The variability of three commonly used histological parameters in leprosy histology was examined within and between lesions on individual patients by taking two biopsies, either from opposing edges of the same lesion or from the edge of two separate lesions. There was little variation in granuloma fraction (GF), bacterial index (BI), or histological classification on the Ridley-Jopling scale between biopsies from opposing edges of the same lesion, but there was considerable variation in the GF between biopsies from the edge of different lesions. A lesser degree of variation was seen in the BI between different lesions, and there was little difference in histological classification between established lesions. Thus, it appears that local factors influence the size of the leprosy granuloma, but its histological composition and bacterial load are determined systemically.

Adult↗

Cell death in granulomata: the role of apoptosis.

Unequivocal apoptosis were seen by light microscopy in examples of leprosy, sarcoidosis, tuberculosis, Crohn's disease and foreign body granulomata. A limited electron microscopic investigation showed typical apoptotic bodies in both sarcoid and leprosy granulomata. The number of apoptosis and mitoses in granulomata were counted and their densities calculated. The wide variation in the results between individual lesions may reflect differences in disease activity.

Cell Survival↗

The influence of killed Mycobacterium leprae and other mycobacteria on opsonized yeast phagocytosis.

The influence of killed mycobacteria on the metabolic burst associated with phagocytosis of opsonized zymosan by normal human polymorphonuclear leucocytes (PMNL) or monocytes was studied by chemiluminescence (CL) measurements. M. leprae reproducibly reduced the peak and total CL of both types of phagocyte to a small, but highly significant extent. Electron microscopy showed that M. leprae were phagocytosed: cells with ingested or adherent M. leprae phagocytosed fewer zymosan particles. M. leprae did not cause aggregation of the phagocytes or quenching of CL. M. lepraemurium did not influence the CL response to zymosan. Addition of M. tuberculosis caused an increased response with PMNL but not with monocytes.

Cell Aggregation↗

Studies of cell death (apoptosis) and cell division in leprosy granulomas.

We have studied the histological changes across leprosy lesions by taking biopsies from the center and edge of the lesions and from the clinically uninvolved skin outside the lesions. A comparison of the granuloma fraction (GF) between biopsies from the center and edge of lesions and the adjacent unremarkable skin shows that the greatest GF is found at the edge of lesions, except in early tuberculoid (BT) cases when biopsies from the center have the greatest GF. Central healing of leprosy lesions occurs without tissue necrosis or appreciable fibrosis. Apoptosis, a form of individual cell death in living tissues, is known to be the mechanism of cell loss in a variety of situations, and we have found it to occur in leprosy lesions. Apoptotic activity is greatest at the edge of established tuberculoid lesions, but can be found in the center of the lesion in early cases. We, therefore, suggest that apoptosis is the mechanism by which epithelioid cells are lost during central healing in tuberculoid leprosy lesions. In the small number of multibacillary cases studied, apoptosis were found in biopsies from both the center and edge of the lesions. Mitoses can be found in biopsies from both lepromatous and tuberculoid lesions. However, the degree of mitotic activity does not appear to be related to the position of the biopsy within the lesion, and immigration of monocytes into the granulomas may be of greater importance than cell division in maintaining the numbers of epithelioid cells or macrophages present.

Cell Division↗

Osmosin and ileal ulceration: a case report.

A 78-year-old woman presented with an acute abdomen and was found to have a perforation of her terminal ileum. She did not survive the post-operative period and at necropsy was found to have numerous ulcers of the ileum. In the ulcerated areas there was a transmural chronic inflammatory infiltrate, but no evidence of granulomata. We believe that this ulceration was caused by ingestion of Osmosin tablets containing indomethacin and suggest a possible pathogenesis.

Aged↗

Quantitation of the granuloma fraction in leprosy skin biopsies by planimetry.

The proportion of the dermis occupied by granuloma in histological sections of skin biopsies from leprosy patients is known as the granuloma fraction. It can be estimated by direct microscopy on a scale of tenths using a low-power objective. We have compared this method with measurement of the granuloma fraction by planimetry, which gives comparable results but is much more accurate and precise. The implications of these findings for the objective assessment of the effects of treatment regimes on leprosy are discussed.

Biopsy↗

Prognostic value of measurement of elastosis in breast carcinoma.

The extent of elastosis in the stroma within the anatomical "tumour" in 80 patients with breast carcinoma was assessed by observational microscopy using a 4-point grading system, and measured by semiautomated histometry as an area percentage with a Quantimet 720 image-analysing computer. In this retrospective study, measurement of elastosis in tissue removed at time of initial diagnosis was shown to have little value for prediction of duration of survival.

Adult↗

A study of the histological basis of textural analysis.

In an attempt to quantitate histological structure by textural analysis, the characters of a stained microscopical field were recorded as a frequency polygon of the relative areas defined by successive increments of optical density: this is known as the optical density/area (OD/A) profile. In a study of lymph-nodes in Hodgkin's disease and of carcinoma of the female breast, each stained tissue section was found to have an OD/A profile of characteristic shape: moreover, in each of the lesions studied it was shown that the shape of the profile could be replicated by summing the profiles of each constituent cell type and intercellular matrix in proportions determined by differential cell counts and direct measurement of the degree of cell packing in the tissue. In an investigation of the influence of specimen preparation on OD/A profile, it was shown that density of staining and section thickness were important variables. Using the density of staining of tissue lymphocytes as an internal standard, a simple method was developed of compensating for differences in the density of Mayer's haemalum staining greater than those met with in practice. Attempts to compensate for intentionally large differences in section thickness were much less successful, but this was considered to be relatively unimportant since, in practice, the variation in thickness of sections cut on a modern microtome by a competent microtomist had been shown to be slight and to have a negligible effect on the OD/A profile.

Breast Neoplasms↗

Measurement of phagocyte chemiluminescence using a microtitre plate luminometer.

The use of chemiluminescence techniques to study the interaction between bacteria and phagocytes has been useful for examining the extent to which serum factors, such as opsonins, are important in internalization of the organisms and the response of the cell to phagocytosed bacteria. However, such methods have been limited by the number of experiments which can be performed at one time using most commercial luminometers. However, the recent introduction of the Amerlite microtitre plate luminometer allows the measurement of chemiluminescence responses in 96-well microtitre plates. Using this instrument, lucigenin-enhanced chemiluminescence can be detected from as few as 5000 cells (polymorphonuclear leukocytes or monocytes) per well with a 1:10 ratio of cells to zymosan particles opsonized with 10% serum. The opsonic capacity of up to 100 sera can be measured in triplicate wells in a single experiment using four microtitre plates and polymorphonuclear leukocytes prepared from less than 40 ml freshly obtained venous blood. We are currently using this technique to investigate the effect of serum opsonins on the interaction between normal human polymorphonuclear leukocytes and monocytes with mycobacteria of three species (Mycobacterium leprae, M. tuberculosis, and M. avium-intracellulare). Other possible applications of this method are discussed.

Humans↗