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Biomedical subjects

A H Rahi

Publications and source records attributed to A H Rahi.

At least 55 records · Page 3Linked to original sources

Immunoglobulins of normal aqueous humour.

Immunoglobulin levels have been measured in aqueous humour and blood from 79 patients undergoing cataract extraction. A linear relationship between serum and aqueous IgG was found, but this was not so for IgA, and IgM was not detected in any of the aqueous samples. The morphological features of both the blood-ocular and the blood-brain-cerebrospinal fluid barriers, and the influences governing the passage of immunoglobulins across these barriers are considered. The similarity between two theories of protein penetration, diffusion through the iris root into the eye, and via the "functional leak" into the cerebrospinal fluid, are considered. We feel that the discrepancy between IgG and IgA penetrations into aqueous, despite their similar molecular weights, may be due in part to the larger hydrodynamic volume and consequently increased frictional ration of IgA, although the existence of selective IgG transfer has not been excluded.

Aqueous Humor↗

Prospects for the immunodiagnosis of ocular tumours.

Amongst other properties, malignant neoplasms are characterized by having antigenic determinants not normally found in mature healthy tissue. Consequently an immune response is usual on the part of the host and in recent years interest has centred on the twin possibilities of putting this property to diagnostic and therapeutic use. In our own laboratory we have concentrated on the diagnostic potential of immunological techniques in the investigation of pigmented tumours of the uvea. We have found that not only malignant melanomata, but also many naevi, can provoke an immunological reaction and we have shown that this is directed largely against contractile elements in the cytoplasm. Such reactions, which are not strictly tumour-specific, may be a source of diagnostic confusion and need to be excluded if immunology is to be of value in distinguishing malignant lesions of the uveal melanocytes from innocuous naevi.

Antibodies↗

Contractile protein antigens in the cells of malignant melanoma of the choroid and their diagnostic significance.

Sera from patients with proved and suspected melanoma of the uvea and from patients with innocuous uveal naevi were found by immunohistological techniques to have an affinity for the cytoplasm of malignant choroidal melanoma cells in an appreciable proportion of cases. The responsible antibodies were subsequently shown to react with smooth muscle protein in a variety of tissues and not to be melanoma-specific. It was also shown by electron microscopy that microfilaments consistent with contractile protein are a feature of the cytoplasm of malignant choroidal melanoma cells. The latter observations, which do not appear to have been reported previously, mean that false positives are to be expected if immunodiagnostic techniques are used for the recognition of malignant disease of the uvea, especially as smooth muscle antibodies can occur in non-neoplastic ocular diseases.

Antibody Specificity↗

Immunological investigations in chronic simple glaucoma.

Serum immunoglobulins and antinuclear antibodies were estimated in 225 patients, including cases of chronic simple glaucoma, "low tension glaucoma", and ocular hypertension. The results showed that, while the mean levels of immunoglobulins Ig A and Ig M were not significantly higher in patients with glaucoma than a control series of normal adults, the mean level of Ig G was higher in those with chronic simple glaucoma. There was no clear relationship between Ig G levels and the severity of the disease as judged by the visual fields and optic disc changes. Antinuclear antibodies were found in a larger proportion of patients with chronic simple glaucoma and ocular hypertension as compared to the normal population, but there was no correlation with the severity of the disease. The incidence of other non-organ-specific and organ-specific autoantibodies was not significantly different from that of the control group. Although these results suggest an association of raised levels of Ig G and a higher incidence of antinuclear antibodies in patients with glaucoma, the evidence is insufficient to suggest that disorders of the immune system have an aetiological significance in chronic simple glaucoma.

Antibodies, Antinuclear↗

Immunopathology of the lens. I. Humoral and cellular immune responses to heterologous lens antigens and their roles in ocular inflammation.

In experimental rabbits heterologous soluble lens proteins consisting of alpha-, beta-, and gamma-crystallins were found to be antigenic; they stimulated a marked antibody response compared to a rather weak T-cell response. The serum antibodies to alpha-crystallins appeared first, to be followed by antibodies to beta- and gamma-crystallins in that order. The rabbits did not respond to heterologous gamma-crystallins unless these were injected with Freund's adjuvant containing mycobacteria. Incomplete Freund's adjuvant (i.e., without mycobacteria) was found to be an inferior immunoaccelerator so far as lens antigens are concerned. The response to lenticular antigens in both magnitude and duration varied in different rabbits, which suggested to us the important role played by a central control mechanism involving the immune response (Ir) genes. Some of the antibodies in potent lens antisera cross-reacted with mitochondria, endoplasmic reticulum (i.e., microsomes), contractile organelles, and cell nuclei. This explains for the first time at least in part the reasons for the widely observed phenomenon of the reactivity of lens antisera with ocular and extraocular structures. Antibodies to soluble lens proteins as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic heterologous immunisation followed by discission of the lens does not lead to the typical changes of phakoallergic endophthalmitis in the rabbit.

Animals↗

Immunopathology of the lens. II. Humoral and cellular immune responses to homologous lens antigens and their roles in ocular inflammation.

It has been possible for the first time to demonstrate antibodies to homologous lens proteins in rabbits without the addition of adjuvant. By means of immunofluorescence and immunoperoxidase methods it has been possible not only to show for the first time that homologous lens antibodies cross-react with extraocular tissues but that the cross-reacting antigens are related to the cell mitochondria, microsomes, and the proteins associated with contractile organelles. The rabbits did not produce antibodies to gamma-crystallins even when the whole lens homogenate was injected with Freund's complete adjuvant. This suggests that gamma-crystallins are non-antigenic in homologous situations, and this may be related to both B- and T-cell tolerance. Alternatively, the failure of gamma-crystallins to induce antibody production may be due to intermolecular antigenic competition with other crystallins. The presence of mycobacteria in an adjuvant is essential for an antibody response to be detectable by agar diffusion techniques. The response to homologous lens antigens, both in magnitude as well as in duration, varied in different rabbits, which suggested to us that a central control mechanism involving the immune response (Ir) genes may plan an important role. Antibodies to homologous lens proteins as detected by immunofluorescence and immunoperoxidase methods were shown to be of the IgG class. This is the first time that the kinetics of the immune response to the same homologous lens antigen in saline with or without incomplete or complete adjuvant has been examined and their relative merits compared. Systemic homologous immunisation followed by discission of the lens led to a marked Arthus type reaction in and around the lens, but a typical granulomatous phakoallergic endophthalmitis was not produced. It seems likely that the rabbit is not suitable for the production of an experimental model of this condition.

Adjuvants, Immunologic↗

Immunopathology of the lens. III. Humoral and cellular immune responses to autologous lens antigens and their roles in ocular inflammation.

In experimental rabbits it has been shown for the first time that autologous lens protein is antigenic when injected with Freund's complete adjuvant. Although lens haemagglutinins were detected in 6 out of 7 rabbits, in only 3 of the 6 animals did the titre reach a maximum of 1:640. A weak agar precipitation reaction was obtained with only 1 of the 3 sera. It would appear, therefore, that the passive haemagglutination test is superior for the detection of autologous lens antibodies. The response to autologous lens antigen both in magnitude as well as in duration varied in different rabbits, which suggested to us the possible role played by a central control mechanism involving the immune-response (Ir) and immune-associated (Ia) genes which are part of the major histocompatibility complex. Alternatively, this variation may be the result of an antigenic competition between various autologous crystallins. Antibodies to autologous lens protein as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic autologous immunisation produces only a mild uveitis and does not lead to a granulomatous intraocular inflammation. Intravitreal injections of autologous lens protein in pre-immunised animals, however, produced an Arthus type of acute endophthalmitis. Autologous lens antisera showed limited cross-reactivity with ocular and extraocular tissues, which could be detected only by such sensitive techniques as immunofluorescence and immunoperoxidase methods.

Animals↗

Immunoglobulins and antinuclear antibodies in aqueous humour from patients with juvenile "rheumatoid" arthritis (Still's disease).

Aqueous humour and blood from twenty cataractous patients with chronic anterior uveitis and the monopauciarticular form of juvenile rheumatoid arthritis were tested for immunoglobulins G, A, and M and for autoantibodies, particularly those against nuclear antigens. The aqueous immunoglobulins were raised in the majority of patients even when the eyes were normal biomicroscopically. Raised IgG antinuclear antibodies were found in 85% of the aqueous samples. Information obtained from the study of aqueous humour from fourteen patients with senile cataract was used for statistical analysis of these data. The presence of high molecular weight immunoglobulins in the aqueous humour from patients with Still's disease suggests an abnormal blood-ocular barrier which may be responsible for the recurrence which follows an ostensibly treated primary attack of uveitis. The presence of antinuclear antibody in a few aqueous samples without a concomitant rise in the blood levels is suggestive of local antibody synthesis.

Antibodies, Antinuclear↗

Practolol and ocular toxicity. Antibodies in serum and tears.

Serological studies in 22 patients presenting with ocular disease attributable to dosage with the beta-blocking agent practolol revealed a raised incidence of antinuclear antibodies. There was also a marginal increase in the incidence of antibodies to smooth muscle in the more severely affected individuals but the incidence of ther autoantibodies and levels of IgG, IgA, and IgM were within normal limits. Semi-quantitative analysis of tears from 14 of the patients showed absence or near absence in the more severely affected patients of secretory IgA, which is indicative of damage to the lacrimal gland. Other immunological parameters in the tears were normal.

Animals↗

Pathology of practolol-induced ocular toxicity.

The ocular side-effects of prolonged practolol administration concern the cornea and conjunctiva and are related to deficient tear secretion and the formation of an autoantibody which has an affinity for the intercellular zones of squanmous epithelium. Histopathological study of six cases, including a review of the necropsy findings in two, showed destruction of lacrimal gland tissue, epidermalization of the conjunctival epithelium, with epitheliolysis and stromal ulceration of the cornea leading to perforation in two patients. Immunoperoxidase studies showed fixation of specific antibody in the corneal and conjunctival epithelium but, in the one case in which the tissue could be adequately studied, complement fixation could not be demonstrated. Possibly, therefore, the immune response in patients with practolol-induced ocular damage is secondary to the epithelial disturbance rather than its cause.

Aged↗

Evaluation of macrophage electrophoretic mobility (MEM) test as an indicator of cellular immunity in ocular tumours.

The macrophage electrophoretic mobility (MEM) test of Field and Caspary did not clearly separate patients with ocular neoplastic disease from those with inflammatory disease, although there was some indication of discrimination between choroidal melanoma and ocular inflammation. In our hands the test failed to give a reproducible result for the immunodiagnosis of ocular malignancy. The technique, however, seems to provide some indication of delayed hypersensitivity in experimental inflammatory eye diseases when relatively pure antigens are used.

Animals↗

Experimental immune retinitis: induction by isolated photoreceptors.

An antigen prepared from the outer limbs of the photoreceptors failed to produce retinal lesions within 3 months by systemic immunisation alone in the rabbit. Intra-vitreal injection of the antigen in a pre-immunised rabbit resulted in an Arthus type response. Repeated systemic immunisation for over 1 year after an intravitreal injection produced retinal degeneration in the uninjected eyes of two rabbits. Anti-visual cell antibodies were not shown to be cytotoxic to organ cultures of retina. Possible reasons are discussed in relation to in vitro studies of thyroid, kidney and spinal cord.

Animals↗

Anatomy of passive arthus reaction in the cornea. A preliminary communication.

Corneal changes in passive Arthus reaction are essentially the same as that reported to occur in active Arthus reaction and consist of accumulation of polymorphonuclear leucocytes around the deposits of immune complexes, release of lysosomes and fragmentation and dissolution of collagen fibrils. In addition, degenerative changes were found in the corneal endothelium and Descemet's membrane.

Animals↗