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Biomedical subjects

A M Roth

Publications and source records attributed to A M Roth.

At least 19 recordsLinked to original sources

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↗

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↗

Malignant fibrous histiocytoma of the ocular adnexa.

Malignant fibrous histiocytomas are common sarcomas of later life. They arise most commonly in the lower extremities and, only rarely, in the head and neck. Fibrous histiocytomas, mostly benign, have been reported in the orbit and conjunctiva, but only three benign lesions have been described in the eyelids. I present a case of malignant fibrous histiocytoma of the eyelid which recurred locally, but has shown no evidence of metastases.

Aged↗

Linear nevus sebaceous syndrome.

The pathologic terms hamartoma, choristoma, nevus, and phakoma often are confused. We discuss them in relation to a patient with the linear nevus sebaceous syndrome who had a large limbal mass that grew unusually rapidly and was excised. Histopathologic examination showed that it was a complex choristoma composed of lacrimal gland, adipose tissue, and myxomatous tissue. The latter has not been described previously in this disorder. This neuro-oculocutaneous syndrome has been considered one of the phakomatoses.

Adipose Tissue↗

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↗

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↗

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↗

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↗

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↗

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↗

Extensive squamous cell carcinoma of the conjunctiva presenting as orbital cellulitis: the hermit syndrome.

The authors present three cases of extensive squamous cell carcinoma of the conjunctiva invading the orbit and masquerading as orbital cellulitis. All cases were in elderly alcoholic men living in relative social isolation. Total exenteration of the orbit was required in all three cases. Only one patient has had long-term follow-up; he was well 5 years after presentation. The other two patients were well 15 and 5 months after surgery.

Aged↗

Acanthamoeba sclerokeratitis. Determining diagnostic criteria.

Acanthamoeba infection of the cornea is an entity now recognized with increasing frequency. We saw two cases of Acanthamoeba sclerokeratitis in contact lens wearers in whom scleritis (anterior and posterior) played a central role in the clinical course of the disease. Scleritis is probably a more common component of Acanthamoeba infection than has generally been acknowledged. Posterior scleritis has not, to our knowledge, been reported previously in this disorder. The clinical diagnosis of Acanthamoeba infection has often been missed due to lack of a definition of the historical and clinical criteria by which this disease is characterized. We reviewed the 26 previously reported cases and suggest a set of criteria that can be used to establish an early diagnosis. Historical criteria include minor corneal trauma, exposure to soil or standing water, or contact lens wear. Clinical characteristics include severe pain, infiltrative (often ring-shaped) stromal keratitis, variable anterior uveitis, epithelial erosion, scleritis, standard bacterial culture negativity, chronicity, and lack of response to antimicrobial agents.

Adolescent↗

Conjunctival transplantation. Autologous and homologous grafts.

Autologous conjunctival transplants have been used successfully for restoration of damaged ocular surfaces. Homologous (allogeneic) conjunctival grafts have been explored less systematically. We developed a nonhuman primate model for comparison of autologous and homologous conjunctival transplantation in order to assess the clinical viability and immunopathologic characteristics of these grafts. Autologous or homologous grafts were performed in nine adult rhesus monkeys. Both autologous and homologous grafts were compared for clinical viability and immunopathologic change. Clinical results suggest that, although homologous grafts incited a greater inflammatory and scarring response, there was minimal graft shrinkage and a normal surface epithelium. Immunopathologic studies using laminin, bullous pemphigoid antigen, and fibronectin indicate that, despite the increased inflammatory response seen in homografts, the epithelial surface is normal. With our increasing ability to modulate the immune response, conjunctival homografts may play a role in restoration of the ocular surface.

Animals↗

Cystic conjunctival masses as the presenting sign of disseminated lymphoma.

Systemic malignant lymphoma rarely presents as conjunctival masses. Biopsy of unusual cystic conjunctival masses from a 49-year-old woman showed malignant lymphoma. On subsequent examination, the patient was found to have disseminated systemic malignant lymphoma. Examination of possible predictive clinical features of the conjunctival lesions showed that these were of little value in diagnosing the systemic malignancy.

Antineoplastic Combined Chemotherapy Protocols↗

Malignant melanoma of the iris: recurrence after 19 years.

Late recurrences of malignant melanoma of the iris are rarely reported. The case of a patient who had apparently had a spindle and nevoid cell melanoma totally excised from his iris is presented. Two and a half years later he sustained blunt trauma and developed retinal detachment in the same eye. The eye became phthisic after two unsuccessful attempts to repair the detachment. Seventeen years later he was seen with discomfort in the eye and was found to have a ruptured globe with prolapse of dark jelly-like material. Pathologic study revealed this to be recurrent spindle-B melanoma. This case, along with two similar cases from the literature, emphasizes that iris melanomas can recur many years after the original excision and that long-term follow-up is indicated.

Humans↗

The ultimate diagnoses of patients undergoing temporal artery biopsies.

Patients with signs and symptoms of giant cell arteritis may have normal temporal artery biopsy specimens. To study the relationships between signs and symptoms of this disease and the ultimate clinical diagnosis, we reviewed 51 patients who had undergone temporal artery biopsy. The mean age of the patients with abnormal biopsy specimens was higher than that of patients with normal biopsy specimens. We found headache, fever, and jaw claudication were useful symptoms in predicting abnormal biopsy specimens. The ultimate diagnoses of patients with normal biopsy specimens and no response to treatment showed high incidence of malignant neoplasms and diabetes mellitus.

Aged↗