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Biomedical subjects

C E Thirkill

Publications and source records attributed to C E Thirkill.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cancer-induced retinal hypersensitivity.

What are the earliest indications of cancer? What prompts an apparently healthy person to suspect that 'something may be wrong'? The first manifestations may involve a growing awareness of neuronal dysfunction, such as headaches, dizziness, physical degeneration or vision abnormalities. While denial may extend the time between the patient's appreciation of the health hazard, particularly if the indications are subtle, a sudden decline in vision may be one of the most readily perceived, and provide the strongest stimulation to seek medical help. Cancer-induced neuropathies are rare but provide much information on the genesis of a defined group of autoimmune reactions, and the biological mechanisms involved. The secondary effects of neoplasia, collectively termed paraneoplasia, are often the first indication of cancer. Sudden weight loss is one of the most recognised early signs, and is known to result from biochemical effects on tissues distant from the site of the growth. More recently, immunologic phenomena have been implicated in a series of different paraneoplasia. Examples, such as Lambert-Eaton myasthenic syndrome (LEMS), paraneoplastic cerebellar degenerations (PCD) and cancer-associated retinopathy (CAR) can be identified immunologically through the detection of autoantibody reactions with defined proteins. Interest in the clinical significance of paraneoplastic-associated immunologic reactions increased following the recognition of their strong disease association; PCD patients produce autoantibodies reactive with brain proteins, LEMS patients with muscle components and CAR patients with ocular antigens. Blood tests designed to detect these unusual autoantibody reactions are now in commercial use to identify different forms of paraneoplasia, sometimes before the neoplasm responsible has been identified. The cause of paraneoplasia-related autoimmune reactions has, in some cases, been traced to the patient's cancer, an immunologic connection based upon research findings and published reports of biopsies and cultures that actively express the key proteins involved in cancer-associated organ-specific hypersensitivity.

Autoimmune Diseases↗
PubMed1993

Antibody reactions with retina and cancer-associated antigens in 10 patients with cancer-associated retinopathy.

OBJECTIVE: Our objectives were to determine what clinical characteristics are common to the form of cancer-associated retinopathy (CAR) encountered in patients with small-cell carcinoma of the lung (SCCL). Is the 23-kd retinal CAR antigen/antibody reaction present in other forms of retinopathy? Can an antigen identical or similar to the 23-kd retinal CAR antigen be identified in an established culture of SCCL? METHODS: Ten patients with CAR who had SCCL were identified by their antibody reactivity with the 23-kd retinal CAR antigen. We inquired into common clinical characteristics by means of questionnaires to the referring physicians. We looked for antigen/antibody reactions with the 23-kd retinal CAR antigen in patients with diabetic and age-related macular degenerations and in a continuous, in vitro propagated culture of SCCL (HTB 119) obtained from the American Type Culture Collection. RESULTS: We encountered many similar signs and symptoms in our patient population. These included rapid vision loss, night blindness, color loss, vitreous cells, and either flat or greatly reduced electroretinograms. No corollary to the 23-kd CAR antigen/antibody could be identified in unrelated retinopathies or cultured SCCL. CONCLUSIONS: We conclude that patients with SCCL-related CAR consistently produce antibodies against the 23-kd retinal CAR antigen. This immunologic reaction was not found in patients with unrelated retinopathies and may possibly represent a cancer marker for SCCL.

Aged↗
PubMed1993

Intraperitoneal cultivation of small-cell carcinoma induces expression of the retinal cancer-associated retinopathy antigen.

OBJECTIVE: We have inquired into the reason why patients with cancer-associated retinopathy (CAR) produce antibody reactions with the 23-kd retinal CAR antigen. Possible reasons include the expression of this antigen in the related carcinoma. Previous studies have failed to identify any antigenic counterpart expressed by in vitro cultivated small-cell carcinoma of the lung. We, therefore, inquired into the effects of in vivo cultivation of the cancer cells and its influence on protein expression, with specific reference to the appearance of the 23-kd retinal CAR antigen. DESIGN: A complementary DNA library was prepared from small-cell carcinoma of the lung cells propagated intraperitoneally in Lewis rats and probed with antibodies reactive with the 23-kd retinal CAR antigen. RESULTS: We found evidence of the expression of a cancer-associated gene in ascites-propagated small-cell carcinoma of the lung that encodes for a protein antigenically similar to the 23-kd retinal CAR antigen. A complementary DNA encoding this protein revealed complete DNA sequence homology with the retinal CAR antigen showing the cancer cells are expressing this photoreceptor protein. CONCLUSIONS: We hypothesize that the carcinoma-retina immunologic cross-reaction is responsible for the induction of the unique antibody response encountered in patients with CAR with vision loss developing as a cancer-evoked autoimmune retinopathy.

Animals↗
PubMed1992

Management and monitoring of cancer-associated retinopathy.

Cancer-associated retinopathy is a rare paraneoplastic event that can involve allergic reactions and result in retinal degradation. A patient, who had a 35-year smoking history, complained of visual loss and was found to have serum antibodies that reacted with an extract of retina, including the previously described retinal cancer-associated retinopathy antigen. Prednisone treatment appeared to reduce the patient's antibody titers to normal levels. Visual fields stabilized, and the patient was able to maintain useful vision throughout the course of treatment until his death 1 year following initial diagnosis. To our knowledge, this is the first reported case in which monitoring of antibody responses to retinal antigens appeared to be useful in the decision whether to initiate prednisone therapy. Rising antibody titers to the cancer-associated retinopathy antigen probably occurs before progressive visual field loss and may be considered an indication for prompt steroid therapy.

Aged↗
PubMed1992

Circulating and localized immune complexes in experimental mycoplasma-induced arthritis-associated ocular inflammation.

Ocular deposits of immune complexes are believed to contribute to the anterior segment inflammations observed in association with the human arthritides. Arthritis-related ocular inflammations may be reproduced in animals by infection with certain species of mycoplasma. To evaluate the role of immune complexes in the production of ocular lesions, we studied their involvement in the rodent model of experimental arthritis-associated ocular inflammation induced by Mycoplasma arthritidis. Sprague-Dawley rats were infected with viable concentrates of M. arthritidis and monitored for the production of related circulating and intraocular immune complexes. Circulating immune complexes were monitored by antigen capture systems, and localized intraocular complexes were identified by indirect immunohistochemistry. Polyacrylamide gel immunoblot analysis of captured complexes confirmed the antigen(s) involved as proteins derived from M. arthritidis. Indirect immunofluorescence revealed localized complexes containing mycoplasma antigens within the ciliary-iris vasculature. Concentrations of the generated complexes diminished rapidly over a 30-day period. While complex deposits within ocular tissues could represent a contributing cause to the localized anterior segment inflammation reported in this rodent model, secondary challenge with viable M. arthritidis, which reproduced high concentrations of intraocular and circulating immune complexes, failed to elicit any ocular response.

Animals↗
PubMed1992

The cancer-associated retinopathy antigen is a recoverin-like protein.

Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration that occurs in association with certain forms of cancer. CAR patients typically possess high titers of autoantibodies against a specific photoreceptor protein--the 23 kD retinal CAR antigen. The mechanisms involved in the vision loss experienced by CAR patients are not understood, but serologic studies indicate the process could include a series of autoimmune reactions directed at specific components of the retina. Because the retinal CAR antigen is the principal ocular autoantigen involved in the antibody response of CAR patients, characterizing it would contribute to the understanding of putative autoimmune involvement. Serum antibodies from CAR patients have been used to isolate the gene encoding the CAR antigen from a cDNA library of human retina. Nucleotide sequence analysis suggests that the CAR antigen shows approximately 90% homology to the published amino acid sequence of bovine recoverin.

Amino Acid Sequence↗
PubMed1991

Antibody indications of secondary and superimposed retinal hypersensitivity in retinitis pigmentosa.

Antibody reactions with recognized retinopathy-inducing retinal antigens may be interpreted to reflect ongoing autoimmune events responsible for some forms of vision loss. We sought evidence of secondary and superimposed retinal hypersensitivity indicated by such antibody reactivity in a random group of patients with retinitis pigmentosa. We identified patterns of immunologic reactivity within members of a group of 52 patients with retinitis pigmentosa, which suggests some patients with retinitis pigmentosa may experience consequential superimposed retinal hypersensitivity. Identifying subgroups of patients with retinitis pigmentosa who exhibit indications of retinal hypersensitivity to known uveitopathogenic retinal proteins may permit the reduction of their rate of retinal degradation by immunomodulation.

Adult↗
PubMed1990

A clinical triad to diagnose paraneoplastic retinopathy.

Two elderly men developed photosensitivity and light-induced glare, transient visual symptoms, and progressive visual loss several months before small cell carcinoma of the lung was discovered. Both patients had impaired visual acuity and color vision, ring scotomas, and attenuated retinal arteriole caliber. Electroretinography demonstrated abnormal cone and rod-mediated responses. Antiretinal antibodies were identified in their serum. Their visual sensory function improved following therapy with immunosuppressive agents. The triad of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arteriole caliber should alert one to a paraneoplastic disorder affecting the retina.

Adenocarcinoma↗
PubMed1990

Interactions of cultured rat synovial and ocular ciliary body cells with two strains of Mycoplasma arthritidis.

Strains of Mycoplasma arthritidis differ in their ability to cause joint and ocular inflammations. Although the reasons for this difference are not fully understood, pathogenic mycoplasmas commonly require close associations with the cells they damage. Using 3H-uridine labeled mycoplasma, we compared cellular interactions of in vitro cultivated rat synovial and ocular ciliary body epithelial cells with two American Type Culture Collection strains of M. arthriditis shown to differ in their virulence. Radiolabeling assays gave evidence of a stronger retention capability on cultured cells by the more pathogenic strain, 14152. Scanning electron microscopy demonstrated cellular associations with the two strains of mycoplasma, with more of the 14152 adhering to both cell types. Examination by transmission electron microscopy showed evidence of contact between the more virulent 14152 strain and both cell types, but no similar evidence with the comparatively less virulent strain, 19611. The pathogenicity of different strains of M. arthritidis may vary according to their ability to closely associate with specific target cells involved in the disease process.

Animals↗
PubMed1988

Arginine metabolism in wounds.

Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of [guanido-14C]arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis.

Amino Acids↗
PubMed1987

Cancer-associated retinopathy.

Antiretina antibodies have been found in the serum samples of four patients with cancer experiencing concomitant loss of vision (cancer-associated retinopathy [CAR] syndrome). These immunoglobulins bound an antigen from normal pooled retina having a molecular weight of 23,000 daltons, which we describe as the CAR antigen. No corresponding antibodies could be found in serum samples obtained from patients with cancer not experiencing vision loss, from patients having retinitis pigmentosa, or from normally sighted individuals who did not have cancer. The early detection of rising antibody titers against the CAR antigen could prove important in the identification of patients likely to suffer from CARs.

Aged↗
PubMed1983

Application of monoclonal antibodies to detect intraocular mycoplasma antigens in Mycoplasma arthritidis-infected Sprague-Dawley rats.

Sprague-Dawley rats infected with Mycoplasma arthritidis by tail vein inoculation develop extensive disseminated joint inflammation, frequently accompanied by conjunctivitis and anterior uveitis. The intraocular inflammation is apparently directed at mycoplasmas localized within the stroma of the ciliary body, which have been detected with monoclonal antibodies by indirect immunofluorescence. The monoclonal antibodies are directed against an antigenic determinant on the enzyme arginine deiminase isolated from M. arthritidis, but they do not react with the same enzyme derived from Mycoplasma hominis. The antigen bound by the monoclonal antibodies can also be detected by immunofluorescence in M. arthritidis-infected tissue cultures and is not lost after glutaraldehyde fixation or paraffin-embedding procedures. The value in the application of monoclonal antibodies reactive with arginine deiminase lies in the fact that although this enzyme may be found in mycoplasmas and several other species of bacteria it is not a normal constituent of mammalian tissues.

Animals↗
PubMed1982

Mycoplasma arthritidis-induced ocular inflammatory disease.

Mycoplasma arthritidis was demonstrated to incite experimental conjunctivitis and uveitis in Swiss Webster mice which have a known susceptibility to the arthritis customarily associated with infection by this mycoplasma. The initial symptom of ocular involvement was conjunctivitis, which appeared as early as 1 day after intravenous injection with viable culture concentrates of M. arthritidis. By day 2, histological analysis showed intraocular localized inflammatory reactions that were confined primarily to the anterior portion of the uvea and produced results which were compatible with those seen in iridocyclitis. Serological assays of the titer and the class of antibodies involved in the early humoral immune response to infection confirmed the predominance of immunoglobulin G (IgG) concentrations over IgM concentrations that was described by others (Cole et al., Infect. Immun. 4:431-440, 1971) and revealed significant titers of the IgG2a and IgG2b subclasses of complement-fixing antibodies. The rapid onset of acute conjunctivitis, together with the early appearance of immunoglobulins of the IgG class, suggests that the M. arthritidis-infected Swiss Webster mice may have experienced an anamnestic response to the mycoplasma antigens. These observations introduce a new animal model for the study of mycoplasma-induced experimental uveitis and conjunctivitis, which are demonstrated here to accompany a disseminated systemic disease process.

Animals↗