Biomedical subjects
Publications and source records attributed to R H Cormane.
Human skin allografts cultured for approximately 6 weeks on a solid medium were transplanted to non-related human recipients with skin defects of various etiology. Although based on this study no answer could be given to the question whether these grafts survived or were replaced by cells of the recipient, it was observed that in most cases the grafts were not rejected and remained in situ several months up to over a year.
A simplified method is described to demonstrate Y chromosome fluorescence in interphase nuclei of epithelial cells in human buccal smears using Quinacrine Mustard. This technique turned out to be efficient in our hands and would be of value in determining the sex chromosomes in the epithelial cells of the skin in cases of allogeneic transplantations from females to males and vice versa to determine the peroid during which the grafts survived.
Twenty-three biopsies of skin lesions of patients with various types of leprosy, showing a recent reaction, were examined by means of immunofluorescence (IF) methods. The patients were divided into two groups according to the number of inflammatory cells, staining with various FTC-labelled anti-immunoglobulin antisera, in representative areas of the biopsies. It was found that the presence of these cells was correlated with a good response to thalidomide treatment.
An electron microscopic study of Mendes da Costa's disease (MCD) has been undertaken to determine whether this disease is a variant of epidermolysis bullosa dystrophica, or should be classified as a separate disease entity. It was shown that in MCD lacunae occur in the lower layers of the epidermis, in the presence of normal anchoring fibrils. In the recessive form of epidermolysis bullosa dystrophica (EBD), however, no lacunae were found in the epidermis, and anchoring fibrils were absent. These findings support the concept that MCD should not be considered as a special form of epidermolysis bullosa dystrophica.
Congenital hypomelanotic and hypermelanotic macules traced in three generations of a family suggested autosomal dominant inheritance. Some affected membbers also showed retarded growth and mental deficiency. Light microscopic findings of "splitdopa" preparations of lesional and normal skin were comparable, except that background staining of keratinocytes in dark macules was higher than in control skin. In light macules it was lower. Ultrastructurally, hypomelanotic skin showed small melanosomes (0.3 mu) that occurred in keratinocytes in melanosome complexes. Hypermelanotic skin revealed large melanosomes (0.6 mu) that were singly distributed in keratinocytes. Melanosome size in normal skin averaged 0.4 mu; distribution pattern was mixed. Melanin granules inside keratinocytes were fully melanized. Hyperpigmented, normal and hypopigmented skin of one person had histological features of black oriental and white skin. This clinical picture could well represent a new neurocutaneous syndrome different from tuberous sclerosis.
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Oral retinoic acid successfully and rapidly helped two patients with erythrokeratoderma variabilis. Treatment had to be maintained to prevent recurrence and no side effects have been observed so far.
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Human plasma kallikreins (EC 3.4.21.8) were purified as three distinct enzyme entities which hydrolyzed arginine esters and were active in releasing kinin from heated human plasma as measured by guinea pig ileum contraction bio-assay. The three enzymatically active fractions were termed as 19 S, 7 S-I and 7 S-II kallikreins. They represented purifications of 262- 2200- and 110-fold, respectively. These enzyme activities showed differences in physicochemical and biochemical properties as it appears from their elution profile on Sephadex G-200 and DEAE-cellulose columns, affinity for substrates and susceptibility of inhibition by various protease inhibitors such as trasylol and soya bean trypsin inhibitor. The data suggest that all these three enzyme preparations were most likely kallikreins. All these three enzymes (19 S, 7 S-I and 7 S-II) were inhibited by a series of amidino compounds competitively. Diamidines consisting of two amidinophenyl residues linked in para position by molecular bridge were comparatively stronger inhibitors of all of three enzymes than those linked in meta position and those having single ring structure. The possibility that some of these amidino compounds might prove to be useful for treatment of disease states where the kallikrein-kinin system plays a role, is discussed.
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The extracts of granules of human polymorphonuclear leukocytes hydrolyzed a variety of proteins including human and bovine hemoglobin, human fibrinogen, human and bovine serum albumin, bovine elastin, and casein. The hydrolysis of all the proteins except fibrinogen and elastin was increased by addition of urea. Various inhibitors of trypsin, kallikrein, plasmin, Clr, Cls, and other proteolytic enzymes had no inhibitory effect. Slight inhibition was observed with polyanethol sulfonate and strong inhibition with normal human serum. Serum of patients with hereditary angioneurotic edema having no functional C1-esterase inhibitor was as effective in inhibiting the proteolysis as normal serum. The inhibitor was localized in 4S fractions of normal serum fractionated on Sephadex G-200. Fractionation of normal serum by ammonium sulfate precipitation, Sephadex G-200 filtration, and CM-Sephadex chromatography did not result in appearance of inhibitory activity in more than one protein peak, suggesting the possibility that only one inhibitor might be responsible. Since all fractions which contained the inhibitor of proteolysis also contained alpha1-antitrypsin, since sera of patients having low alpha1-antitrypsin levels contained less inhibitory activity, and since antibodies against alpha1-antitrypsin reversed the inhibition obtained from normal serum, the inhibition of proteolysis may be attributed to alpha1-antitrypsin.
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Most immunologic diseases are caused by the derailment of the humoral or cellular pathways of the immunologic defense system. This derailment results from numerous factors such as the inability of the patient to remove the pathogen; the consumption, defect, or deficiency in any component of these pathways, and the overproduction of any of the components. To diagnose these immunologic disorders one has to detect the pathogen and the reactions caused by it and to determine the cause of its nonclearance. The immunofluorescence techniques has been invaluable in detecting both the antigen that causes the disease and the reactions initiated by the antigen, such as the production of antibodies and the activation of the complement system. The immunoperoxidase technique has also been used for these purposes in certain instances. For detecting the circulating immune complexes which occur as intermediates in the chain of reactions initiated by the antigen, various physiochemical and biologic techniques have been used. However, none of these tests seems to be totally reliable for determining whether circulating immune complexes are present. The consumption of complement was detected by hemolytic estimations and radial immunodiffusion or rocket electrphoresis. These techniques were also useful in detecting the hereditary deficiencies in immunoglobulins and components of classical and alternative pathways of complement activation. Since these techniques cannot be used to estimate IgE, the radioallergosorbent test was used to measure such levels in the atopic patients. Cellular hypersensitivity was detected with skin tests together with methods which assess the ability of lymphocytes to produce mediators in response to antigen. Many of these mediator assays, however, are not suitable for this purpose. A satisfactory substitute appears to be to determine the factor in antigen-stimulated, lymphocyte culture supernatants which activates macrophages to take up radiolabeled colloidal gold or radiolabeled glucosamine. In contact allergic dermatitis, an increase in the IgD-bearing lymphocytes and granulocytes has also been correlated with cellular hypersensitivity. Lymphocytes and polymorphonuclear leukocytes coated with antibodies mainly directed against nuclear antigens of the basal layer cells of the noninvolved epidermis have invariably been encountered in psoriasis. The use of these findings for diagnostic purposes and for understanding the mechanisms of certain diseases is being explored.
Immunofluorescence techniques were used to demonstrate the presence of immunoglobulin (Ig) and complement (C) bearing polymorphonuclear leukocytes (PMNL) in specimens of skin from the lesions of ten patients with allergic contact dermatitis and of ten with psoriasis vulgaris. The distribution patterns of these Ig- and C-coated cells in the peripheral blood of the twenty patients were also studied. Ten normal healthy controls were included. In cases of allergic contact dermatitis, IgD was the predominant class of Ig on the PMNL. The percentage of C-bearing PMNL were also significantly increased, suggesting that both molecules might be present on the cell memebrane of these cells at the same time. In psoriasis vulgaris, the predominant class of Ig on the PMNL was IgG. The percentage of PMNL coated with C were not signficantly raised. These results suggest that in allergic contact dermatitis the PMNL can be coated with both Ig and C which may render them cytophilic; they also show that in psoriasis vulgaris PMNL can bind Ig. In the ten healthy controls, it was possible to distinguish between those PMNL which are and those which are not bearing immunoglobulin.
The occurrence of ANA in eluates of lymphocytes and polymorphonuclear leucocytes obtained in five untreated psoriasis patients could be demonstrated by means of the indirect immunofloruescence technique. These antibodies appear to be mainly directed against the nuclei of the basal cell layer, however, ANA directed against the nuclei of epidermal and dermal cells have also been encountered. The immunological mechanisms in psoriasis may therefore be looked upon as the result of an alteration in the structure of nucleic acid or nuclear protein of the basal layer cells. Finally psoriasis may be the result of an interplay of various exogenous factors and a special genetical make-up leading to the release of certain nuclear proteins initiating a delayed type immune response at the onset and an Arthus type reaction located in the upper layers of the epidermis at a later stage of the disease, and as a secundary phenomenon the derailment of keratinization. Moreover a slightly decreased mean percentage of circulating lymphocytes forming rosettes with sheep erythrocytes have been found in the patients studied. This slight decrease suggests a diminution of the T-lymphocyte control facilitating the antibody production by B-lymphocytes. The course of events in psoriasis is a self perpetuating inflammatory process.
Peripheral blood lymphocytes of 28 untreated and 17 treated patients with different types of leprosy were investigated for the occurrence of immunoglobulin (Ig) bearing cells by means of a smear method. Seven healthy Africans served as controls. In a later stage a complementary study was performed on 6 tuberculoid and 6 lepromatous leprosy patients by means of a suspension method. The immunofluorescence technique was used for the detection of Ig-bearing cells, In tuberculoid leprosy an increase of Ig-bearing cells seems to occur during treatment, predominantly expressed by an increase in IgD-bearing cells. In lepromatous leprosy no increased percentages of Ig-bearing cells were observed.
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