Functional aspects of glycoprotein N-linked oligosaccharide processing by human tumours.
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Antibodies, Monoclonal↗
Biomedical subjects
C S Foster
Publications and source records attributed to C S Foster.
An analysis of therapeutic decision making regarding immunosuppressive chemotherapy for peripheral ulcerative keratitis.
We reviewed our experience in the management of 47 patients (61 eyes) with peripheral ulcerative keratitis (PUK) to establish guidelines for appropriate indications to consider institution of systemic chemotherapy. Fifty-three percent of patients had a systemic disease as the etiology of PUK; one fourth of these were newly diagnosed as a result of meticulous history taking. The histologic demonstration of vasculitis in ocular tissue was the crucial step in deciding on chemotherapy in more than half of our patients. The presence of scleritis was highly associated with active vasculitis. Twelve of 14 patients with bilateral PUK required chemotherapy. Recommendations for an approach to therapy of PUK are presented.
Adult↗
Keratoconjunctivitis sicca and corneal ulcers.
We reviewed the records of 56 patients (109 eyes) who satisfied our criteria for keratoconjunctivitis sicca (KCS) to determine factors associated with the development of sterile corneal ulcers. The patient's age, sex, and associated local ocular surface and/or systemic disease were studied. We found a statistically significant association between the development of corneal ulceration and the presence of an underlying condition or disease state, especially chronic rheumatoid arthritis. Patient sex and age were not significantly associated with the development of corneal ulceration. We present three case histories that illustrate the complications that arise in managing KCS plus an associated disease and methods of management.
Adult↗
Plasma exchange in the therapy of Behçet's disease.
Present therapies for Behçet's disease are unsatisfactory in many cases. We investigated the role of plasma exchange in four patients with severe Behçet's retinitis who were unresponsive to standard medical therapies. Plasma exchange induced a rapid reduction of ocular inflammation with improved visual acuity in all cases. In patients with severe Behçet's retinitis, plasma exchange is able to interrupt the acute inflammatory activity, but relapses may occur.
Adolescent↗
Oncogene expression in cholangiocarcinoma and in normal hepatic development.
The expression of the proteins encoded by the ras, myc, and erb B-2 oncogenes was examined in 63 paraffin-embedded human cholangiocarcinomas of Thai and English origin using immunohistochemistry. The observed distributions were compared with oncogene expression in a series of human hepatocellular carcinomas. In an attempt to relate expression of these three oncogenes to specific stages of normal tissue differentiation, tissue sections of normal fetal, infant, and adult human livers were also examined. Of 63 cholangiocarcinomas, 59 (95%) expressed p62 c-myc, 47 (75%) expressed p21 c-ras, and 46 (73%) expressed p190 c-erbB-2. The expression of c-myc and c-ras but not of c-erb B-2 correlated directly with tumor differentiation as judged by morphologic criteria. No difference was observed in oncogene expression between intrahepatic and extrahepatic cholangiocarcinomas. Twelve of 14 hepatocellular carcinomas (86%) stained positively for all three oncoproteins. During normal liver development, expression of c-myc and c-ras was shown to occur from 18 weeks' gestation until 5 years of age, but not thereafter. Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation.
Adenoma, Bile Duct↗
Mast cells in conjunctiva affected by cicatricial pemphigoid.
Ocular cicatricial pemphigoid (OCP) is characterized by progressive conjunctival subepithelial fibrosis often leading ultimately to corneal blindness. Mast cells have been shown to play a role in several fibrotic disorders, but the role of mast cells in OCP is unknown. The authors compared the mast cell population in conjunctival biopsy specimens from 14 OCP patients and from six controls by using specific histochemical stains for mast cell subsets. The total mast cell number and the ratio of connective tissue mast cells to mucosal mast cells (MMCs) were significantly higher in OCP than in normal conjunctiva (P less than 0.05). This report is the first analysis of mast cell subsets in human ocular tissue. The results suggest that connective tissue mast cells (CTMCs) may play an important role in OCP and that therapy directed toward mast cells and their mediators may be an appropriate avenue for further exploration.
Adult↗
Scleral grafting for necrotizing scleritis.
Although systemic immunosuppressive chemotherapy is effective in halting progressive necrotizing scleritis, the onset of its action may be too slow to prevent profound scleral thinning and/or traumatic or spontaneous perforation. Scleral homografts may be used to maintain the integrity of the globe until immunosuppressive drugs can take effect. The authors reviewed their experience with scleral homografts in 12 patients with progressive necrotizing scleritis; eight (all with autoimmune disease) had concomitant chemotherapy and four (two with autoimmune disease) did not. Grafts remained stable in patients receiving both surgical and drug therapy over a mean follow-up of 12 months. One graft melted after discontinuation of chemotherapy, but regrafting and renewed immunosuppression salvaged the eye. Grafts in two of the patients not initially given chemotherapy melted rapidly (within 14 and 45 days, respectively). Both eyes were salvaged by regrafting and/or addition of chemotherapy. Though rarely successful by itself against necrotizing scleritis, scleral grafting is a useful adjunct to chemotherapy.
Aged↗
Cataract surgery and intraocular lens implantation in patients with uveitis.
The authors reviewed the outcome of extracapsular cataract extraction (ECCE) in 44 eyes of 38 patients with uveitis. Thirty-two of the 44 eyes received a posterior chamber lens implant; 87% of these achieved a stable visual acuity of 20/40 or better. Sixty-seven percent (8 of the 12 eyes) not receiving an implant achieved this level. The authors' results and current literature suggest that absolute control, preoperatively and postoperatively, of all uveitis inflammation and careful selection of patients as lens implant candidates are crucial for successful cataract surgery in uveitis patients. Complete removal of lens cortex and placement of an all-PMMA posterior chamber lens within the capsular bag are also believed to be important.
Adult↗
Glaucoma in patients with ocular cicatricial pemphigoid.
This retrospective review of 111 patients with ocular cicatricial pemphigoid (CP) identifies 29 patients (26%) with glaucoma. Twenty-seven of these patients had a history of glaucoma for a mean of 11.3 years before the diagnosis of CP was made. Most had advanced glaucoma, with a long history of medication use, optic nerve damage, and visual field loss. Patients with CP and glaucoma were more likely to manifest continued high-grade conjunctival inflammation than those with CP alone despite treatment for CP (P less than 0.05). Possible mechanisms including genetic susceptibility to both diseases, drug-induced conjunctival cicatrization, and CP-induced alterations in aqueous outflow are discussed. Physicians who care for patients with CP should remain mindful of the possible coexistence or development of glaucoma in this group of patients. Patients with glaucoma and chronic conjunctivitis of uncertain etiology should be referred for evaluation by physicians experienced in the detection and management of CP.
Age Factors↗
Herpes simplex virus--induced destructive corneal disease.
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Animals↗
Evidence for the potential influence of cyclic nucleotides on maintenance of or reactivation from latency of herpes simplex virus in trigeminal ganglionic neurons.
Herpes simplex virus infections are epidemic throughout developed countries, and recurrent herpes simplex keratitis is the most common cause of corneal blindness in these countries, NIH (1973). No available antiviral agent is capable of eradicating the state of viral ganglionic latency, and hence no effective treatment currently exists for prevention of viral re-activation from latency, with resultant recurrent infectious viral clinical manifestations. Putative triggers of re-activation include stress, sunburn, menses, trauma, and fever. These 'triggers' seem to share at least one common characteristic: the potential ability to influence intracellular cyclic nucleotide levels through the action of such first order messengers as catacolamines (stress, trauma) and/or arachadonic acid metabolites (sunburn, fever, trauma, and menses). We exploited an in vitro model of HSV ganglionic latency, and developed a model of in vitro organ culture ganglionic viral reactivation from latency. We then examined the effect of a variety of agents on this model. We found that agents which have been shown to elevate cyclic AMP levels consistently produce increased viral shedding (compared to control, spontaneous reactivation rate) in our model of viral reactivation from latency. In contrast, agents which have been shown to depress c-AMP levels and/or to elevate c-GMP levels inhibit viral reactivation from latency in this in vitro model. We conclude that intracellular cyclic nucleotide levels may influence events which control herpes simplex genome transcription.
Animals↗
Association of HLA-DR4 with ocular cicatricial pemphigoid.
HLA typing for A, B, and C locus antigens was performed on 70 patients with ocular cicatricial pemphigoid (OCP) and on 1849 controls. Additionally, typing for DR and DQ antigens and for the complement proteins (C2, factor B, C4A, and C4B) was performed on 63 patients and on the same control population. A significantly higher incidence of the following antigens was found in the OCP patients when compared to the control population: DR4 (43% in patients compared to 18% in controls, p = 0.0001); DR5 (41% compared to 16%, p = 0.0001); DQw3 (57% compared to 31%, p = 0.0010); A2 (60% compared to 28%, p = 0.0001); B8 (24% compared to 13%, p = 0.0086); B35 (19% compared to 9%, p = 0.0097); and B49 (7% compared to 2%, p = 0.0052). The complement types SC01, SC30, SC32, SC41, and SC42 were also significantly increased in patients compared to controls. No significant differences were found based on ethnic background, involvement of multiple mucous membranes, history of glaucoma, or deposition of specific immunoreactants in conjunctival biopsy samples. These findings may provide further insights into the pathogenesis of OCP and may help to localize a susceptibility gene for this autoimmune disease.
Complement Fixation Tests↗
Preliminary serological studies comparing immunofluorescence assay with radioimmunoassay.
We assayed serum from 12 patients with untreated cicatricial pemphigoid affecting the conjunctiva for circulating autoantibodies directed against the epithelial basement membrane zone. We employed a conventional indirect immunofluorescence assay, with monkey esophagus and human conjunctiva as substrates, and compared the results with those obtained employing a radioimmunoassay measuring antibasement membrane zone antibody binding to COLO-16 and to SCaBER tumor cell lines. The indirect immunofluorescence assay on normal human conjunctival substrate detected circulating antibodies to conjunctival epithelium in 6 of 12 CP patient serum specimens. Monkey esophagus failed to detect antibodies to the epithelial basement membrane zone. In contrast, autoantibodies were detected in all 12 specimens by the radioimmunoassay. Specificity, as demonstrated by appropriate controls and assay of normal human serum, was 100%. These results demonstrate that radioimmunoassay employing COLO-16 or SCaBER cells is an exquisitely sensitive and specific assay for detection of circulating antibasement membrane antibodies in patients with cicatricial pemphigoid affecting the conjunctiva.
Aged↗
Effects of blood transfusion and cyclosporin on rabbit corneal graft survival.
Blood transfusion prolongs renal, cardiac, and skin allograft survival, but promotes rejection of bone marrow allografts. At present, it is unclear whether transfusion induces allograft tolerance or sensitization in corneal transplants. We performed eccentric penetrating keratoplasty on New Zealand albino rabbits, using Dutch rabbits as donors. Twenty-four recipient rabbits were randomly allocated into four groups. The control group received no pretreatment. The other three groups received a donor-specific whole-blood transfusion and/or cyclosporin seven days before the corneal transplants. A single blood transfusion accelerated allograft rejection by an average of 8.8 days (p = 0.0005). In contrast, a single cyclosporin pretreatment prolonged graft survival by an average of 5.3 days (p = 0.02). There was no evidence of interaction effects between transfusion and cyclosporin (p = NS). Therefore, unlike renal, cardiac, and skin allografts and similar to bone marrow allografts, prior blood transfusion accelerates corneal allograft rejection in our rabbit model. Although our data can not be extrapolated to human corneal transplants, our results raise the question whether blood transfusion can sensitize humans to corneal allografts.
Animals↗
Chorioretinal disease patterns in congenic mice following intraocular inoculation with HSV-1.
Disease patterns and immunologic parameters were studied employing inbred and Igh-1 disparate congenic mice to determine the role of host genetics and Igh-1-linked gene products in the von Szily model of viral chorioretinitis. Following intracameral inoculation of 1.5 x 10(4) PFU HSV-1 (KOS), 100% of BALB/c (Igh-1a), 62% of A/J (Igh-1e) and none of the C57BL/6J (Igh-1b) inbred mice developed contralateral necrotizing chorioretinitis. Multigenic differences between inbred mice prohibit conclusions about the specific role of Igh-1-linked immune regulation in this model. In order to more exactly define Igh-1-specific restriction of HSV-1-mediated chorioretinitis, Igh-1-disparate, congenic BALB/c mice were studied following both anterior chamber and intravitreal inoculation protocols. Anterior chamber inoculation resulted in contralateral retinal necrosis in 75% of BALB/c (Igh-1a) mice, 30% of C.AL-20 (Igh-1d) and 5% of the C.B-17 (Igh-1b) congenic mice; all strains showed ipsilateral retinal sparing. Following intravitreal inoculation of HSV-1 a similar restricted disease pattern was found in contralateral eyes. Contralateral chorioretinitis developed in 30% of BALB/c, 15% of C.AL-20 and 6% of C.B-17 mice. Ipsilateral disease, however, was found in all murine strains. These disease patterns developed despite equivalent suppression of systemic DTH and equivalent RPE permissivity to viral replication. These data demonstrate that host genetics strongly regulates contralateral HSV-1-mediated chorioretinal disease patterns by a mechanism unrelated to the development of systemic suppression of DTH and specifically support a dominant role for gene products linked to the Igh-1 locus in the immunomodulation of ocular disease.
Animals↗
Herpes simplex virus type-1 strain influence on chorioretinal disease patterns following intracameral inoculation in Igh-1 disparate mice.
We have previously shown that the Igh-1 locus on chromosome 12 of the mouse influences contralateral disease patterns in the modified von-Szily model. Following intracameral injection with 1.5 X 10(4) PFU of HSV strain KOS (HSV-KOS), 75% of BALB/cByJ (Igh-1a), 30% of C.AL-20 (Igh-1d) and 5% of C.B-17 (Igh-1b) mice develop contralateral chorioretinal necrosis. In contrast, Igh-1 congenic mice do not develop contralateral chorioretinal necrosis following anterior chamber inoculation of the same dose of an HSV-KOS mutant lacking surface glycoprotein-C (HSV-GC-KOS). Similarly, injection of wild type HSV strain mP (HSV-mP) into the anterior chamber of susceptible BALB/cByJ mice induces destructive contralateral chorioretinitis whereas injection of the same dose of the mutant HSV strain MP (HSV-MP) lacking surface glycoprotein-C does not induce a destructive contralateral chorioretinitis. In addition, higher doses of HSV-mP inoculum abrogate the Igh-1-associated contralateral chorioretinal protection seen in C.B-17 mice; protection is restored in C.B-17 mice at lower HSV-mP doses that still cause contralateral chorioretinitis in BALB/cByJ mice. These data demonstrate the influence of the viral isolate on the modified von-Szily model and specifically the requirement for the presence of glycoprotein-C on the surface of HSV for the development of contralateral destructive chorioretinitis.
Animals↗
Cyclic nucleotide modulation of herpes simplex virus latency and reactivation.
Clinical observations and experimental studies suggested that the relative proportions of ganglionic neuronal intracellular cyclic adenosine monophosphate (c-AMP) and cyclic guanosine monophosphate (c-GMP) concentrations may influence the state or activity of herpes simplex viral DNA in its relationship with the host cell DNA. We studied the effects of putative modulators of intracellular cyclic nucleotide levels on herpes simplex virus (HSV) reactivation from latency in murine trigeminal ganglion cells. We also investigated the effects of these same mediators on the c-GMP and/or c-AMP concentrations in HSV-latently infected trigeminal ganglion cells and in acyclovir-suppressed, HSV-infected neuroblastoma cells. Cholera toxin and theophylline increased c-AMP levels (2-fold and 5-fold at 1 min and 30 sec, respectively for cholera toxin and 2-fold and 1.5-fold at 1 min and 30 sec for theophylline) and enhanced the rapidity of HSV reactivation from latency (P less than 0.005). Exogenous dibutyryl c-AMP also stimulated viral reactivation (P less than 0.005). Carbamylcholine increased c-GMP levels (7-fold and 6-fold at 15 sec and 30 sec, respectively), produced no significant change in c-AMP levels, and delayed HSV reactivation from latency (P less than 0.005). None of these mediators had a demonstrable effect on HSV replication.
Acyclovir↗
Factors influencing predilection and outcome in bacterial keratitis.
Complete records from 175 patients with 176 episodes of culture-proven bacterial keratitis treated over a 4-year period at the Massachusetts Eye and Ear Infirmary in Boston were analyzed. Sixty-three percent of the infections involved gram-positive organisms, and 40% involved gram-negative organisms; 15% were polymicrobial. There was a high incidence of infection with Staphylococcus aureus (28%), coagulase-negative staphylococci (14%), diphtheroids (14%), Pseudomonas aeruginosa (14%), and Streptococcus pneumoniae (12%). Gram stain correlation was achieved in 55%. Potential predisposing factors, usually multiple, were identified in 97% of the patients. Fifty percent of the ulcers were associated with such iatrogenic factors as prior topical corticosteroid therapy, penetrating keratoplasty, and contact lens use. Trauma occurred in only 16%. Several statistically significant associations of epidemiologic factors and outcome variables were revealed. Ninety-five percent of the ulcers resolved with therapy, but only 44% of the patients had visual acuity better than the level at admission, and 13% developed major complications.
Adolescent↗