Primary intraocular lymphoma.
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Adolescent↗
Biomedical subjects
C S Foster
Publications and source records attributed to C S Foster.
In vivo and in vitro hepatic 31P magnetic resonance spectroscopy and electron microscopy of the cirrhotic liver.
In vivo 31P magnetic resonance spectroscopy (MRS) provides direct biochemical information on hepatic metabolic processes. To assess in vivo changes in hepatic 31P MRS in liver transplant candidates, we studied 31 patients with cirrhosis of varying aetiology; 14 with compensated cirrhosis (Pugh's score < or = 7) and 17 with decompensated cirrhosis (Pugh's score > or = 8). Underlying cellular abnormalities were characterised using in vitro 31P MRS and electron microscopy. In vitro spectra were obtained from liver extracts, freeze-clamped at recipient hepatectomy, from all subjects. Electron microscopy of liver tissue was also performed in 17 cases. Relative to nucleotide triphosphates, elevations in phosphomonoesters and reductions in phosphodiesters were observed in vivo with worsening liver function. In vitro spectra showed elevated phosphoethanolamine and phosphocholine, and reduced glycerophosphorylethanolamine and glycerophosphorylcholine, mirroring the in vivo changes, but no distinction was noted between compensated and decompensated cirrhosis. With electron microscopy, functional decompensation was associated with reduced endoplasmic reticulum in parenchymal liver disease, but elevated levels in biliary cirrhosis. We conclude that in vivo spectral abnormalities in cirrhosis are consistent with alterations in phospholipid metabolism and quantity of endoplasmic reticulum. However, in individual patients the biopsy results do not always mirror in vivo findings.
Adult↗
Recurrent uveitis in a patient with adult onset cyclic neutropenia associated with increased large granular lymphocytes.
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Adult↗
Tetrandrine potently inhibits herpes simplex virus type-1-induced keratitis in BALB/c mice.
This study investigated the effect of tetrandrine (TDR) on experimental herpes simplex keratitis (HSK) in mice. BALB/c mice were divided as follows: Group 1, untreated; Group 2, acyclovir (ACV)-treated from day 0 postinfection; Group 3, ACV-treated from day 7; Group 4, TDR-treated from day 0; and Group 5, TDR-treated from day 7. All mice were infected in the right cornea with herpes simplex virus (HSV) type I. TDR 30 mg/kg and ACV 120 mg/kg were administered intraperitoneally daily. The mice were observed for 14 days postinfection. Clinical inflammatory reactions and ocular histopathology were analyzed. The herpes specific antibody response and the delayed type hypersensitivity (DTH) response were studied. Of the 22 untreated mice, 16 developed HSK (incidence, 72.7%). TDR given from day 7 reduced the HSK incidence to 8.5% (p < 0.01); the incidence of HSK was 45.4% in mice treated with TDR from day 0 (p > 0.05). Systemic ACV given from day 0 inhibited HSK development (p < 0.01); ACV given from day 7 resulted in an HSK incidence of 50% (p > 0.05). The specific anti-HSV antibody response in the serum of mice treated with TDR or ACV either from day 0 or day 7 was significantly less than that of untreated mice (p < 0.01 and p < 0.05, respectively), and TDR treatment suppressed DTH responses to HSV (p < 0.05). Systemic TDR administered after HSV inoculation of the cornea significantly modulates murine HSK development at least partly by modifying the host immune/inflammatory response to the virus.
Alkaloids↗
Cataract surgery in patients with uveitis.
Although cataract surgery for senile cataract is routine and easily performed, the decision to remove the cataract in a patient with a history of uveitis is considerably more complex and usually involves multiple considerations, related not only to the cause of the uveitis but also to the appropriate surgical procedures. The problems confronting the ophthalmologist caring for the patient with uveitis begin with the first visit. Establishing a diagnosis and controlling the inflammation are the critical elements in the treatment of the patient; these two factors will determine the incidence of cataract formation and other complications, the appropriate time for cataract removal, and the surgical strategy, as well as determine the visual outcome long before surgery occurs. Diagnosis, control of inflammation, preoperative management, particularities of the surgical techniques, and postoperative complications in patients with a history of uveitis have been reviewed previously in this section. Our aims in this article are to review the literature on this subject over the past year and to reemphasize the idea of a model of zero tolerance for inflammation to minimize the incidence of cataract and irreversible damage of ocular structures essential to good vision.
Cataract↗
Expression of heat shock proteins in chronic pancreatitis: protective or pathogenic roles?
The tissue-distributions of heat shock proteins (HSP) identified by monoclonal antibodies ML-30, TB-78, CA-Str7-1, and MAB 72/73 have been examined in formalin-fixed and paraffin wax-embedded tissues from 10 normal pancreatic specimens and 92 cases of chronic pancreatitis. The chronic pancreatitis cases were divided by probable etiology into alcohol-related, postacute pancreatitis, or idiopathic. The HSP identified by ML-30 and CA-Str7-1 were constitutively expressed, with a regional distribution, by duct and ductular epithelial cells in all normal pancreatic tissues. The HSP detected by ML-30 were expressed uniformly throughout the cytoplasm of the majority of ductular epithelial cells in all cases of chronic pancreatitis, irrespective of suspected etiology, and in the ducts of all but two cases of alcohol-associated chronic pancreatitis. The HSP defined by CA-Str7-1 were identified in the majority of duct or ductular epithelial cells in most of the cases of chronic pancreatitis, although possible differential expression was observed with respect to etiology (ie, there seemed to be less HSP in cases of postalcohol pancreatitis). The HSP identified by TB-78 were not constitutively expressed by normal pancreatic tissues but were found in a few scattered epithelial cells in two of these cases. However, significant expression of these HSP were observed in most epithelial cells in a population of cases regarded as either alcohol-associated (0.05 > p > 0.02) or postacute chronic pancreatitis (0.01 > p > 0.001). The HSP identified by monoclonal antibody MAB 72/73 were either not demonstrable or were expressed at very low levels in both the normal and inflamed pancreatic tissues. Expression of the four groups of HSP molecules appeared to be differentially regulated both in normal pancreatic and in chronic pancreatitis tissues. These differences in expression may indicate different functions in normal tissues, with either a protective or a pathogenic role for these proteins in the diseased state. Our current findings support the hypothesis that expression of certain HSP, particularly those identified by TB-78, may be involved in the pathogenesis of distinct subtypes of chronic pancreatitis. Our data do not suggest that HSP are the primary targets of immune-mediated cytotoxic activity; nevertheless, enhanced expression of these molecules by pancreatic ductular epithelial cells does provide an environment in which increased amounts of endogenous intracellular peptides may be transported to the cell surface, thereby becoming potential targets of immune-surveillance and cell-mediated cytotoxicity. Conversely, HSP may play a protective role in such a manner that selected groups of pancreatic ductular epithelial cells withstand cytotoxic damage of chemical, metabolic, or immune origin, and for significantly increased periods of time than they would otherwise; HSP thereby conserve a population of "reserve" epithelial cells from which pancreatic regeneration might occur. Identification of distinct pathogenic groups, defined according to precise immunohistochemical criteria, might provide the basis of a functional assessment and hence allow development of biologically appropriate strategies for managing individual patients with chronic pancreatitis.
Adult↗
Ocular rosacea: patient characteristics and follow-up.
PURPOSE: The purpose of this report is to review the presenting symptoms and signs, treatment regimens used, complications encountered, and outcome in a cohort of patients with ocular rosacea. METHODS: The medical records of 131 patients with a diagnosis of ocular rosacea were reviewed retrospectively. Data were entered in a tabulated form, and a descriptive analysis was performed. RESULTS: The age range at presentation was between 23 and 85 years (mean, 56 years). Cutaneous manifestations of rosacea were present in 112 of the patients at their first visit. The most common presenting symptoms were foreign body sensation and burning, and the most common signs were telangiectasia and irregularity of lid margins, and meibomian gland dysfunction. Thirteen patients had decreased visual acuity at the time of presentation due to corneal complications. Six of these patients required penetrating keratoplasty during the course of their disease. Seven patients had severe cicatrizing conjunctivitis at the time of referral. One hundred thirteen patients were treated with oral tetracycline derivatives. Seven patients were left with visual acuity less than 20/400, and one patient underwent enucleation for corneal perforation and endophthalmitis. CONCLUSIONS: Ocular rosacea is a common disease involving the skin and the eyes. It is widely underdiagnosed by many ophthalmologists despite the blinding potential. Successful therapy requires a multidisciplinary approach.
Adult↗
Analysis of T cell receptor V beta gene expression in B cell deficient mice after experimental herpes simplex virus keratitis.
To examine the importance of B cells in the regulation of the T cell response to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B. mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR V beta transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p < 0.0001). Passive transfer of anti-HSV Ab into B. mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. AT the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR V beta gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a single TCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in spleen, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B. mice is manifested by dramatic changes in TCR V beta usage at the molecular level.
Animals↗
Mooren's ulcer: current concepts in management.
Mooren's ulcer is strictly a peripheral ulcerative keratitis (PUK) with no associated scleritis. It occurs completely in absence of any diagnosable systemic disorder that could be responsible for the progressive destruction of the cornea. The aetiology of Mooren's ulcer remains uncertain. However, recent studies indicate that it is an autoimmune disease directed against a specific target molecule in the corneal stroma, probably triggered in genetically susceptible individuals by one of several possible provocateurs. Advances have been made in the management of this disease. Immunosuppressive therapy has been shown increasingly successful in patients unresponsive to conventional treatment and in bilateral progressive destructive ocular disease.
Autoimmune Diseases↗
Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization.
Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of beta 4-integrin. The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as beta 4-integrin by its reaction with polyclonal and monoclonal antibodies to human beta 4-integrin. Sera from patients with bullous pemphigoid, pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding. These data strongly implicate a role for human beta 4-integrin in the pathogenesis of OCP. It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases. Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of cicatricial pemphigoid and help distinguishing them from bullous pemphigoid. This study highlights the function and importance of beta 4-integrin in maintaining the attachment of epithelial cells to the basement membrane.
Amino Acid Sequence↗
Referral patterns of uveitis in a tertiary eye care center.
OBJECTIVE: To analyze the referral patterns and diagnosis of uveitis during the past decade in a large tertiary eye center. DESIGN: The records of 1237 patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary from 1982 to 1992 were classified and analyzed. Data regarding sex, race, nationality, referral site, ages at presentation and onset of uveitis, ocular involvement, clinical characteristics, ocular condition, and systemic disease associations were obtained. RESULTS: The mean age at onset of uveitis was 37.2 years; the male-to-female ratio was 1:1.4. Most patients were white (85.8%), born in the United States (83.1%), and referred from within New England (84.7%). Anterior uveitis was most common (51.6%), followed by posterior uveitis (19.4%), panuveitis (16.0%), and intermediate uveitis (13.0%). Chronic (58.3%), nongranulomatous (77.7%), and noninfectious (83.1%) were the most frequent types of uveitis. The most common entities included idiopathic (34.9%), seronegative spondyloarthropathies (10.4%), sarcoidosis (9.6%), juvenile rheumatoid arthritis (5.6%), systemic lupus erythematosus (4.8%), Behçet's disease (2.5%), and the acquired immunodeficiency syndrome (2.4%). CONCLUSION: The appearance of new uveitic entities, such as the acute retinal necrosis syndrome, multifocal choroiditis and panuveitis, birdshot retinochoroidopathy, and acquired immunodeficiency syndrome-related uveitis, and the reemergence of the classic infectious causes of uveitis, tuberculosis and syphilis, have changed the way we approach the diagnosis and management of posterior and panuveitis at the Massachusetts Eye and Ear Infirmary.
Adolescent↗
T-cell subsets and T-cell receptor V beta utilization by Igh-1-congenic mice in herpetic retinal necrosis.
BACKGROUND: After unilateral anterior chamber (AC) inoculation with herpes simplex virus type 1 (HSV-1), C.B-17 and BALB/c congenic mice, which differ only in a limited region around the lgh-1 locus on chromosome 12, show a striking difference in susceptibility to development of encephalitis and contralateral necrotizing chorioretinitis. METHODS: After AC inoculation with HSV-1 (KOS), C.B-17 and BALB/c mice were followed up for the clinical signs of encephalitis and chorioretinitis. At different time points following inoculation, lymphocytes isolated from the spleen were triple-stained with antibodies directed against CD4 or CD8, IL-2R, and various V beta T-cell receptor (TCR) subsets, and were analyzed by flow cytometry. RESULTS: These lgh-1-disparate congenic mice showed differences in the time course of splenic V beta T-cell receptor (TCR) usage in both CD4+, IL-2R+ and CD8+, IL-2R+ T cells. By day 1 post infection (p.i.), C.B-17 mice showed an increase of V beta 8 and V beta 9 TCR by both CD4+, IL-2R+ and CD8+, IL-2R+ splenic T cells. Susceptible BALB/c mice delayed the increase of splenic V beta 8 and V beta 9 TCR by CD4+, IL-2R+ T cells, which was noted by day 4 p.i. Furthermore, in BALB/c mice the usage of V beta 9 by CD8+ cells was increased by day 6 p.i. CONCLUSIONS: Our findings indicate that early preferential splenic usage of a restricted repertoire of TCR occurs after ocular inoculation with HSV-1 in resistant C.B-17 mice. Such preferential TCR usage by activated T cells may prevent viral replication in the brain and contralateral eye and may be linked to protection from development of encephalitis and destructive herpesmediated ocular inflammation.
Animals↗
Immunology of the skin and the eye.
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Autoimmune Diseases↗
Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis.
PURPOSE: Two multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). METHODS: Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled. Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days. Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28. A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. RESULTS: When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest difference observed between treatments was 0.5 score unit, not clinically significant. There were no statistically significant differences in cell scores in either study (P > .05). No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). CONCLUSION: Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis.
Acute Disease↗
Intermediate uveitis and retinal vasculitis as manifestations of cat scratch disease.
PURPOSE: To study the ocular manifestations of systemic Rochalimaea infection. METHODS: We examined a healthy 21-year old woman who had floaters in both eyes. A bilateral mild vitreitis and multiple foci of retinal vasculitis were found; during the ensuing two weeks, exudates appeared over the inferior pars plana. The patient owned five kittens but had no history of cat bites or scratches. Serum levels of antibodies to Rochalimaea were elevated. RESULT: The retinal vasculitis and vitreitis resolved after three weeks of therapy with ciprofloxacin hydrochloride without concomitant anti-inflammatory therapy. CONCLUSION: Rochalimaea infection should be considered in the differential diagnosis of intermediate uveitis and retinal vasculitis.
Adult↗
bcl-2: role in epithelial differentiation and oncogenesis.
The precise regulation and maintenance of balance between cell proliferation and cell death in multicellular organisms is critical for tissue homeostasis. bcl-2 initiates a new gene family involved in the regulation of cell death and survival without affecting cell proliferation. Expression of Bcl-2 has been reported in a wide range of hematopoietic cells, nonneoplastic epithelia (both hormone-responsive and nonresponsive), and epithelial malignancies. Although the major group of epithelial cells expressing Bcl-2 protein are in the proliferating zones, expression is not directly related to cell proliferation. Bcl-2 is also associated with stem cells committed to differentiation and morphogenesis. The survival advantage provided by Bcl-2 prolongs the life span of epithelial cells with differentiation potential and allows proliferation, differentiation, and morphogenesis to proceed. The gene expression in hormone-responsive organs may contribute to the sustained life of those terminally differentiated epithelial cells and a decrease in Bcl-2 levels leads to cell death by apoptosis. Overexpression of bcl-2 protects epithelial cells from death, but it is neither able to immortalize normal cells, nor to cause tumorigenic transformation of immortalized epithelial cells. Heterogeneous expression of Bcl-2 in epithelial malignancies suggests that the gene is differentially regulated. Furthermore, its expression in association with precancerous lesions suggests a role in the early stage of tumorigenesis. The effects of Bcl-2 expression on sensitivity of epithelial cells to drug, radiation, and hormone therapies vary depending on the typed of tumor. Expression of Bcl-2 is associated with resistance to hormone therapy and recurrence in prostate carcinomas, whereas in lung and breast carcinomas it is associated with a better prognosis. Studies now being performed should clarify the underlying mechanisms of differential gene regulation in different tissues and show the clinical significance of the expression of bcl-2 and other members of the bcl-2 gene family.
Animals↗
A new murine model of allergic conjunctivitis and effectiveness of nedocromil sodium.
BACKGROUND: Allergic conjunctivitis is the most common atopic disease affecting the eye. To study the pathophysiology and effectiveness of antiallergic drugs, it is necessary to develop animal models that closely mimic human allergic conjunctivitis. OBJECTIVE: The study was performed to develop an experimental murine model of ocular allergic conjunctivitis to an airborne allergen. METHODS: SWR/J mice were divided into the following groups: group 1, untreated, experimental; group 2, phosphate-buffered saline-treated; group 3, nedocromil sodium-treated; and group 4, unmanipulated controls. Groups 1, 2, and 3 were exposed to ragweed by topical contact with the nasal and conjunctival mucosae. Allergic conjunctivitis was evaluated by scoring of clinical signs, serum IgE levels, and histologic findings. RESULTS: Mice exposed to ragweed had clinicopathologic signs of allergic conjunctivitis and specific anti-ragweed IgE. Allergic conjunctivitis was modulated by nedocromil sodium. Treated mice had fewer clinical signs of allergy, lower levels of ragweed-specific IgE, reduction of conjunctival eosinophil infiltration, decrease in the number of intact and degranulating mast cells, and reduction of cytokine release. CONCLUSION: This is the first report of a murine model of allergic conjunctivitis to an airborne allergen that can be used to study the disease pathophysiology and its response to treatment.
Animals↗
Prognosticators for visual outcome in sarcoid uveitis.
PURPOSE: The purpose of the study is to delineate the visual prognosticators in sarcoid-associated uveitis given the current standards of care. METHODS: The records of 60 patients with sarcoid-associated uveitis who were observed for at least 6 months were studied retrospectively. Multivariate regression models using the generalized estimating equations approach to adjust for the correlation between fellow eyes were applied to determine disease, patient, and treatment characteristics that altered the odds of visual rehabilitation. RESULTS: One hundred twelve eyes of 43 women and 17 men who met the inclusion criteria were identified. Seventy-seven percent of patients were white, 15% black, and 8% of Hispanic origin. Uveitis developed in the patients at a mean age of 42 (range, 4-82) years. Of the 112 affected eyes, 81% had granulomatous and 15% nongranulomatous uveitis. Most patients (66%) had anterior or intermediate uveitis alone. Ninety-one percent had chronically smoldering disease; another 7% had recurrent flares, and only 1 patient had a monophasic acute course to her uveitis. Vision-threatening complications developed in many patients, including 58% in whom cystoid macular edema developed and 25% in whom media opacities developed, requiring cataract surgery or vitrectomy or both. Overall, 34% of treated eyes and 51% of patients had final visual acuities that were superior to their acuities at presentation. The factors most significantly associated with a final visual acuity of worse than 20/40 after controlling for potential confounders were as follows: delay in presentation to a subspecialist (odds ratio [OR] = 2.94, P = 0.05), total duration of uveitis (OR = 1.04, P = 0.09), development of cystoid macular edema (OR = 0.37, P = 0.07) or glaucoma (OR = 4.54, P = 0.02), presence of intermediate (OR = 5.00, P = 0.01) or posterior uveitis (OR = 8.33, P = 0.04), and systemic steroid use (OR = 0.30, P = 0.03) were the parameters most strongly correlated with a lack of visual acuity improvement. Delay in presentation to a subspecialist (OR = 20.00, P = 0.01), development of glaucoma (OR = 50.00, P = 0.005), presence of intermediate (OR = 25.00, P = 0.02) or posterior uveitis (OR = 50.00, P = 0.02), black race (OR = 11.11, P = 0.02), (log) visual acuity at presentation (OR = 0.05, P = 0.0001), and use of systemic steroids (OR = 0.07, P = 0.02). CONCLUSION: Multivariate outcomes analysis, particularly after correcting for the correlation between fellow eyes, is a useful analytic tool for optimization of standards of care and for disease risk stratification to aid both physicians and patients.
Adolescent↗