Primary intraocular lymphoma with a low interleukin 10 to interleukin 6 ratio and heterogeneous IgH gene arrangement.
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DNA, Neoplasm↗
Biomedical subjects
C S Foster
Publications and source records attributed to C S Foster.
Systematic differential display: A strategy for a complete assessment of differential gene expression.
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DNA, Complementary↗
Influence of the alpha1-adrenergic antagonist, doxazosin, on noradrenaline-induced modulation of cytoskeletal proteins in cultured hyperplastic prostatic stromal cells.
BACKGROUND: Doxazosin, an alpha1-adrenergic antagonist, inhibits sympathetic contraction of prostatic stromal smooth muscle cells and is used in the relief of obstructive benign prostatic hyperplasia (BPH). In vitro application of noradrenaline stimulates expression of cytoskeletal filaments, particularly actin and myosin, by prostatic stromal cells, thus enhancing their differentiation towards smooth muscle cells. This study examined the possible role of doxazosin in reversing this phenotypic modulation as well as in inhibiting smooth muscle cell contraction. METHODS: Stromal cell tissue cultures derived from 10 human hyperplastic prostates were rendered quiescent by reduction of stripped fetal calf serum (FCS) to 1% (v/v) in the medium followed by treatment with 20 microM noradrenaline and/or 1 microM doxazosin for 10 days. Doxazosin, in 10-fold increments of concentration, was also added, separately, to two of these cell cultures, which were either quiescent or growing in 10% normal (unstripped) FCS. Harvested cells were labelled with fluorescein-labelled antisera to smooth muscle cytoskeletal filaments, and their individual fluorescence levels were analyzed flow-cytometrically. RESULTS: Noradrenaline increased expression of all cytoskeletal filaments studied. This effect was greatest for actin and myosin in proliferating cell cultures. Doxazosin largely reversed the increase in filament expression. This effect was most significant for actin and myosin and greatest in quiescent cultures. However, inhibition of the agonist effect of noradrenaline by doxazosin showed no clear dose-related response, in that expression of cytoskeletal filaments was differentially inhibited. CONCLUSIONS: The data suggest that doxazosin may inhibit not only stromal contraction of differentiated smooth muscle cells in BPH but also the phenotypic modulation of stromal smooth muscle cell differentiation induced by noradrenaline. These actions, together, may render prostatic stroma less contractile, and hence less able to respond to sympathetic stimulation, in patients with BPH. While effects on isolated stromal cells are of undoubted importance, failure to demonstrate a consistent dose-response relationship between expression of smooth muscle cell phenotype and inhibition by doxazosin suggests that additional influences, including humoral factors as well as the proximity of differentiated epithelium, are also likely to be involved in this interaction in the intact tissue.
Adrenergic alpha-1 Receptor Antagonists↗
Systematic comparison of gene expression through analysis of cDNA fragments within or near to the protein-coding region.
Life is controlled by the timely and ordered expression of genes. Identification of important genes involved in specific physiological and pathological conditions requires efficient methods to analyse differential gene expression. We describe a novel strategy, namely complete comparison of gene expression (CCGE), for a systematic assessment of differentially expressed genes. Using the CCGE method, double-stranded cDNA is digested with two restriction enzymes that cut with different frequencies, the representative cDNA fragments are generated within or near to the protein-coding region. After being flanked by two different types of adapters, and amplified by a nested suppression PCR, the selected cDNA fragments, representing entire cDNA population, can be divided into 256 subsets; amplified and compared in a systematic manner.
Animals↗
Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line.
Voltage-gated Na+ channels are expressed by highly metastatic MAT-LyLu cells, but not by poorly metastatic AT-2 cells, derived from the rodent Dunning model of prostatic cancer. We have investigated the possible involvement of these channels in the morphological development of the cells. Incubation of both the MAT-LyLu and the AT-2 cell line for 24 h with the Na+ channel blocker tetrodotoxin (TTX) at 6 microM altered the morphology only of the MAT-LyLu cell line. TTX produced significant decreases in: (a) cell process length and (b) field diameter, and increases in (c) cell body diameter and (d) process thickness. Importantly, 6 microM TTX had no significant effects on proliferation rates or cellular toxicity. The results suggest that Na+ channel activity plays a significant role in determining the morphological development of MAT-LyLu cells in such a way as to enhance their metastatic potential.
Animals↗
Bilateral acute retinal necrosis caused by cytomegalovirus in an immunocompromised patient.
PURPOSE: To report a case of bilateral acute retinal necrosis caused by cytomegalovirus. METHODS: A diagnostic vitrectomy was performed on a patient with non-Hodgkin lymphoma who presented with a bilateral, rapidly progressing necrotizing retinitis and uveitis. RESULTS: Immunohistochemical studies and polymerase chain reaction disclosed cytomegalovirus as the cause of retinitis. The patient was treated with intravitreal and intravenous ganciclovir. CONCLUSIONS: Although rare, cytomegalovirus may lead to an appearance identical to acute retinal necrosis and should be considered among the viral etiologies of this syndrome.
Antibodies, Viral↗
Infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a monocular patient with Stevens-Johnson syndrome.
PURPOSE: To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome. METHOD: Case report. A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates. RESULTS: Anterior chamber aspirate disclosed acid-fast bacilli. A repeat corneal transplant was performed and antibiotic therapy begun. Histopathology showed focal acute inflammation surrounding collections of acid-fast bacilli, which were speciated as M. abscessus. CONCLUSIONS: M. abscessus is a cause of infectious crystalline keratopathy and endophthalmitis. Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy.
Adult↗
Hypertrophic discoid lupus erythematosus of the conjunctiva.
PURPOSE: To report the ophthalmic manifestations of hypertrophic discoid lupus erythematosus of the conjunctiva. METHOD: Case report and review of biopsy results. RESULTS: A 58-year-old woman with a history of chronic blepharoconjunctivitis presented with an unusual raised conjunctival lesion. Previous biopsy slides were reviewed and interpreted as diagnostic of discoid lupus erythematosus, hypertrophic or verrucous type. Both blepharoconjunctivitis and the raised conjunctival lesion resolved with hydroxychloroquine therapy. CONCLUSIONS: A raised conjunctival mass in the context of refractory blepharoconjunctivitis should elicit suspicion for discoid lupus erythematosus. The hypertrophic variant of this disease can affect the conjunctiva.
Biopsy↗
Intraocular lens removal from [corrected] patients with uveitis.
PURPOSE: To report a series of patients with uveitis and cataract who had undergone cataract extraction with posterior chamber intraocular lens implantation and who subsequently had the intraocular lens removed because of progressive intraocular damage from inflammation. METHODS: Review of the records of 19 patients after removal of a posterior chamber intraocular lens. The decision to perform surgery was based on standard criteria after evaluation at a single uveitis referral center. RESULTS: The complications leading to intraocular lens removal were perilental membrane (eight eyes), chronic low-grade inflammation not responding to anti-inflammatory treatment (eight eyes), and cyclitic membrane resulting in hypotony and maculopathy (three eyes). After intraocular lens removal the inflammation subsided and the visual acuity improved or stabilized in 14 of the 19 eyes. The causes of further reduction in the visual acuity of the other five patients were macular edema (two patients), maculopathy resulting from hypotony (one patient), retinal detachment (one patient), and vitreous hemorrhage (one patient). CONCLUSIONS: Intraocular lens implantation can form part of a reasonable plan for visual rehabilitation of patients with uveitic cataract, but inclusion of an intraocular lens in the plan is not always in the overall long-term best interest of the patient. Intraocular lens removal may salvage useful vision for patients who continue to exhibit complications secondary to uveitis after cataract extraction and intraocular lens implantation, provided the intraocular lens is removed before irreparable damage has been done to macula or optic nerve.
Acute Disease↗
Protein kinase C isoenzyme patterns characteristically modulated in early prostate cancer.
Expression of protein kinase C (PKC) isoenzymes -alpha, -beta, -delta, -epsilon, -gamma, -iota, -lambda, -mu, -theta, and -zeta, and of their common receptor for activated C-kinase (RACK)-1, was determined immunohistochemically using specific antibodies in formalin-fixed and paraffin-embedded specimens of early prostatic adenocarcinomas (n = 23) obtained at radical prostatectomy. Expression of each isoenzyme by malignant tissues was compared with nonneoplastic prostate tissues removed at radical cystectomy (n = 10). The most significant findings were decreased PKC-beta expression in early neoplasia when compared to benign epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC-epsilon (P < 0.0001). Detectable levels of PKC-alpha and PKC-zeta were also significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but did not correlate with either PKC-beta or PKC-epsilon for individual cases. Alterations in the levels of the four PKC isoenzymes occurred specifically and consistently during the genesis and progression of human prostate cancer. PKC-delta, -gamma, and -theta were not expressed in the epithelium of either the benign prostates or the cancers. Levels of expression for PKC-A, -iota, -mu, and RACK-1 were not significantly different between the benign and malignant groups. Although changes in PKC isoenzyme expression may assist in explaining an altered balance between proliferation and apoptosis, it is likely that changes in activity or concentrations of these isoenzymes exert important modulating influences on particular pathways regulating cellular homeostasis. The findings of this study raise an exciting possibility of novel therapeutic intervention to regulate homeostatic mechanisms controlling proliferation and/or apoptosis, including expression of the p170 drug-resistance glycoprotein, intracellular Ca2+ concentrations, and enhanced cellular mobility resulting in the metastatic dissemination of human prostate cancer cells. Attenuation of PKC-beta expression is currently being assessed as a reliable objective adjunct to morphological appearance for the diagnosis of early progressive neoplasia in human prostatic tissues.
Disease Progression↗
Severity of episcleritis and systemic disease association.
OBJECTIVE: To analyze patient characteristics and correlate between the site and severity of the inflammation and ocular and/or systemic disease association in a cohort of patients with episcleritis. DESIGN: Retrospective case series. METHODS: Medical records of 100 patients with episcleritis were reviewed. Data were analyzed using a customized database software. RESULTS: The age range at presentation was 18 to 76 years (mean, 43; median, 44). Sixty-nine percent of the patients were female. Thirty-two (32%) patients had bilateral involvement. The episcleritis was nodular in 23 eyes (16%). Half of the patients had a concurrent eye disease. Associated systemic disease was found in 36 patients (36%). In two patients, episcleritis preceded a systemic vasculitic disease (Wegener granulomatosis and Cogan syndrome). Ocular complications included uveitis (11.4%), corneal involvement (15%), and glaucoma (7.8%). No significant correlation of the site and severity of inflammation to the presence of associated systemic or ocular diseases was found. The mean follow-up was 16.5 months. Twenty-eight patients experienced recurrence of episcleritis during the follow-up. Half of the patients required treatment with oral nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Episcleritis is usually a benign, self-limited disease, but it should not be trivialized since it may be associated with systemic disease and ocular complications. A careful review of systems should be performed in all patients presenting with episcleritis, and this should be repeated at least annually during the follow-up. A thorough eye examination is obviously essential to detect and treat ocular complications.
Adolescent↗
Conjunctival lymphoma masquerading as chronic conjunctivitis.
OBJECTIVE: Malignant lesions of the conjunctiva may present with slowly evolving signs resembling inflammation. The authors describe the clinical and histopathologic findings of two patients with bilateral conjunctival lymphoma who presented with a history of chronic conjunctivitis without clinically noticeable subconjunctival nodules. DESIGN: Case report. PARTICIPANTS: Two patients. INTERVENTION: Both patients underwent conjunctival biopsy for evaluation of persistent conjunctival inflammation that did not respond to various medical treatment methods. RESULTS: Histopathologic examination revealed extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in one patient and follicle center lymphoma in the other patient. Both patients subsequently received radiation therapy and achieved a complete remission with no evidence of recurrence in the follow-up period of 20 and 16 months, respectively. CONCLUSIONS: Conjunctival lymphoma should be included in the differential diagnoses of chronic conjunctivitis. Persisting signs and symptoms of conjunctivitis not responding to standard treatment should prompt biopsy.
Adult↗
Intraocular-central nervous system lymphoma: clinical features, diagnosis, and outcomes.
OBJECTIVE: To analyze the clinical features, laboratory investigations, and diagnosis of intraocular-central nervous system (CNS) lymphoma in a cohort of patients who underwent diagnostic vitrectomy. DESIGN: Retrospective case series. METHOD AND STUDY MATERIALS: Thirty-four vitreous biopsy specimens obtained from 26 patients with treatment-resistant or unusual uveitis were re-evaluated in a masked fashion. The specimens were classified into three groups: "negative," "suspicious of malignancy," and "positive" based on the cytologic features, immunomarkers, and flow cytometry. The medical records of the patients were reviewed retrospectively. MAIN OUTCOME MEASURES: The reliability of vitreous cytology in diagnosing intraocular-CNS lymphoma and the differences in clinical features of patients with intraocular-CNS lymphoma and uveitis. RESULTS: The two ocular pathologists concurred in their criteria for interpretation of all specimens. There was 100% concordance between the cytologic reports read independently by the two ocular pathologists over the 5-year period and the read-out done in a masked fashion at the time of the study. Ten patients were diagnosed with intraocular-CNS lymphoma based on the vitreous cytology and clinical features. The time interval between the initial presentation and vitreous biopsy was 1 week to 2 years, with 80% of the patients diagnosed within the first year. Retinal involvement in the form of lymphomatous subretinal pigment epithelial infiltrates, vasculitis, and apparent retinochoroiditis was present in six cases. Initial neuroimaging studies revealed concomitant CNS involvement in three patients, and an additional three developed CNS lymphoma following diagnosis by vitreous biopsy. Patients were treated with radiotherapy, chemotherapy, or both. Two of the four patients with a follow-up of greater than 12 months died due to CNS involvement. CONCLUSIONS: Vitreous cytology is a sensitive, reliable, and reproducible method of diagnosing intraocular-CNS lymphoma. A high index of suspicion based on the clinical findings and course of the uveitis is critically important in decision-making for diagnostic vitrectomy. Central nervous system involvement is frequent and associated with a high mortality rate. Ophthalmology 1999;106:1805-1810
Adult↗
Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: a preliminary study.
OBJECTIVE: To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens. DESIGN: Noncomparative, interventional case series. PARTICIPANTS: Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens. INTERVENTION: Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks. MAIN OUTCOME MEASURES: Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions. RESULTS: Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient, Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients. CONCLUSIONS: Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid.
Age of Onset↗
Management of uveitic glaucoma with Ahmed glaucoma valve implantation.
OBJECTIVE: To evaluate the safety and efficacy of Ahmed glaucoma valve implantation for the management of glaucoma associated with chronic uveitis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nineteen patients (21 eyes) with chronic uveitis underwent Ahmed glaucoma valve implantation for uncontrolled glaucoma between 1995 and 1998. INTERVENTION: All patients had their uveitis controlled before surgery via immunomodulatory therapy. Ahmed glaucoma valve implantation was performed. Immunosuppression was continued in the early postoperative period for strict control of inflammation. MAIN OUTCOME MEASURES: Control of intraocular pressure (IOP). A secondary outcome measure was the number of antiglaucoma medications required to achieve the desired IOP. Visual acuity and complications associated with the surgery were monitored. RESULTS: The postoperative follow-up averaged 24.5 months. At the most recent visit, all 21 eyes had IOPs between 5 and 18 mmHg. The average pressure reduction after Ahmed glaucoma valve implantation was 23.7 mmHg. The average number of antiglaucoma medicines required to achieve the desired IOP was reduced from 3.5 before surgery to 0.6 after surgery. No eye lost even a single line of Snellen acuity at the most recent postoperative visit. Two eyes developed hypotony in the course of follow-up. One resolved without specific intervention, and the other eye required two autologous blood injections and tube ligature to correct the hypotony. One eye underwent Ahmed glaucoma valve replacement for abrupt valve failure. Two eyes underwent penetrating keratoplasty for reasons believed to be unrelated to the glaucoma surgery. Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 94% at 1 year. CONCLUSIONS: Ahmed glaucoma valve implantation can be an effective and safe method in the management of uveitic glaucoma. The authors hypothesize that control of the patients' uveitis, through preoperative and long-term postoperative immunomodulatory therapy, may have contributed to the success rate reported herein.
Adolescent↗
Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma.
OBJECTIVE: Diagnosis of intraocular-central nervous system (CNS) lymphoma is commonly made by identifying malignant lymphocytes in the vitreous. However, such cells are in the minority in the vitreous cellular infiltrate (most are reactive lymphocytes), and therefore lack of cytologic support from biopsied vitreous samples in patients suspected of having intraocular-CNS lymphoma may occur. Recent data suggest that interleukin-10 (IL-10) levels are elevated in the serum and vitreous of patients with non-Hodgkin's lymphoma, whereas IL-12 and IL-6 levels are elevated in patients with uveitis of non-neoplastic etiology. The authors evaluated the usefulness of measuring vitreous levels of IL-6, -10, and -12 in the diagnosis of intraocular-CNS lymphoma. DESIGN: Prospective case series. PARTICIPANTS: Seventeen patients with intraocular inflammation who underwent a diagnostic or therapeutic vitrectomy: 4 patients with intraocular-CNS lymphoma and 13 patients with uveitis unrelated to a neoplasm. INTERVENTION: Eighteen vitreous specimens were obtained prospectively. Concentrations of IL-6, -10, and -12 were measured by enzyme immunosorbent assay, and relative ratios of the interleukins were calculated. Cytopathologic examination and flow cytometry of vitreous cells were also performed. MAIN OUTCOME MEASURES: The ratio of IL-10/IL-12 and IL-10/IL-6 was calculated to assess any association of intraocular-CNS lymphoma and high vitreous IL-10 relative to IL-6 and IL-12 levels. RESULTS: The IL-10/IL-6 and IL-10/IL-12 ratio was greater than 1 in 8 of 14 vitreous specimens obtained from 13 patients with non-neoplastic uveitis. One of the four specimens from patients with cytologically proven intraocular-CNS lymphoma had vitreous IL-10/IL-6 and IL-10/IL-12 ratios of less than 1. CONCLUSION: Although a helpful diagnostic tool, an elevated vitreous IL-10 to IL-6 or IL-12 ratio is not always associated with intraocular-CNS lymphoma.
Central Nervous System Neoplasms↗