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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 271 records · Page 15Linked to original sources

Biomicroscopic and histopathologic observations after corneal laser photocoagulation in a rabbit model of corneal neovascularization.

Corneal neovascularization complicates many anterior segment diseases. Corneal laser photocoagulation using yellow light (577 nm) has been shown to reduce corneal neovascularization. No histopathologic studies of the effects of this treatment on the eye have been reported, however. Target (cornea) and nontarget (iris, lens, retina, and choroid) ocular tissue were studied 1, 24, and 48 h and 5 days after yellow dye corneal laser photocoagulation in a rabbit model of corneal neovascularization. Biomicroscopic examination of the corneas revealed intracorneal hemorrhage in five of 24 (21%) eyes of nonpigmented rabbits. Faint lenticular opacities were observed in two eyes of pigmented rabbits 24 h after laser treatment. Histopathologic examination revealed increased cellularity (neutrophils) (p < 0.005) in the cornea, increasing from 1 h after treatment, peaking 24 h later, and persisting past 5 days. Distortion of the corneal lamellae by red blood cells occurred in eyes in which intracorneal hemorrhage developed. These results indicate that corneal laser photocoagulation using yellow light is a relatively safe procedure for reducing corneal neovascularization.

Animals↗

Atopic ocular disease.

Atopy arises from a complex interplay between immunogenetic controls and complex environmental allergens. Family studies of atopic patients indicate a polygenic control of IgE production overlayed with exposure to certain ubiquitous environmental antigens. Ultrapurified antigen studies in families indicate that HLA-D immune response genes, notably HLA-DR/Dw2, are implicated in some atopic responses. IgE-binding factors and gene regulation of proteins controlling glycosylation of them also influence the serum levels of IgE, as do the levels of at least two cytokines, IL-4 and gamma interferon.

Allergens↗

Evaluation of Ki-67 monoclonal antibody as prognostic indicator for prostatic carcinoma.

Prostate tissue containing either primary adenocarcinoma (45 patients) or benign hyperplasia (15 patients) was immunostained with the monoclonal antibody Ki-67, which recognises a human nuclear antigen expressed by human cycling cells. The percentage of cells staining positive was considered a measure of proliferation. This derived Ki-67 index was higher for carcinomas than for hyperplastic glands. Within the group of carcinomas, Ki-67 indices in patients with metastatic disease were significantly higher than in those without and there was a trend towards increasing Ki-67 indices with increasing Gleason grade. When patients with prostate cancer were prospectively followed up, the Ki-67 index did not predict either disease progression or hormone responsiveness. Ki-67 immunostaining may define a group of patients with prostate cancer of poor prognosis.

Adenocarcinoma↗

Expression of major histocompatibility antigens in human chronic pancreatitis.

T-lymphocytic infiltration of the exocrine pancreas and liver in patients with chronic pancreatitis has suggested that cell mediated immune mechanisms may play a part in the pathogenesis of this disease. As expression of major histocompatibility (MHC) antigens is a prerequisite for organ specific autoimmunity, the expression of HLA class I (beta 2-microglobulin) and class II (HLA-DR) determinants have been analysed, together with the presence of T-lymphocytes, in 93 patients (64 men and 29 women, mean age 40.6 years) having an operation for chronic pancreatitis. Ethanol (63 patients), recurrent acute pancreatitis (12), congenital lesions (2), and unknown (16) were suggested to be the causes of the disease. Immunohistochemical staining of formalin fixed and paraffin wax embedded tissue sections used conventional immunohistochemical techniques with specific anti-serum samples. No MHC expression was identified in 10 histologically normal pancreatic control specimens or in four cases of chronic pancreatitis secondary to obstruction by neuroendocrine tumours within the head of the pancreas. beta 2-microglobulin expression by pancreatic exocrine epithelial cells was seen in 76 chronic pancreatitis specimens (82%) while HLA-DR was present in 61 (66%). Simultaneous expression of both class I and II determinants was seen in 53 (57%) of cases. MHC determinant expression was not found in 10 cases (11%) of chronic pancreatitis. In the positive specimens, expression was confined to ductal and ductular (interlobular and intralobular) epithelium with no staining of acinar cells. Staining was not related to the suspected cause of the disease or age. T-lymphocytes were more prominent in chronic pancreatitis mean (SEM) (131 (15) cells per high powered field) than controls (5 (1), p < 0.01). Aberrant MHC expression by exocrine pancreatic epithelial cells occurring in the presence of an appreciable T-cell infiltration confirmed that the appropriate cellular conditions were present for cell mediated cytotoxicity to contribute to the pathogenesis of chronic pancreatitis.

Adult↗

Detection and partial characterization of ocular cicatricial pemphigoid antigens on COLO and SCaBER tumor cell lines.

Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune inflammatory disease which affects the conjunctiva and other squamous epithelial mucous membranes resulting in a scarring process. It is characterized by the deposition of an anti-basement membrane zone (BMZ) antibody in vivo. Sera from 11 patients with active OCP were studied. Using monkey esophagus and normal skin as substrate, weak staining of the BMZ was observed in conventional indirect immunofluorescence (IIF) assay. Using salt split human skin as substrate, the OCP sera demonstrated binding to the epidermal side of the split, in low titers with weak staining. Ten of the 11 sera were positive on an immunoblot assay using COLO and SCaBER tumor cell lysates demonstrating 230, 205, 160, and 85 kD proteins. Sera from six bullous pemphigoid (BP) patients, with only cutaneous involvement and high titer of anti-BMZ antibody, as detected by IIF, also bound to 230, 160, and 85 kD proteins on both lysates in comigration experiments. Serum from five normal individuals and two patients each with severe atopic conjunctival disease, erythema multiforme with chronic conjunctivitis and systemic lupus erythematosus (SLE), did not demonstrate those bands. When the two lysates were first absorbed with BP sera and then the same lysates were immunoblotted with OCP sera, in all ten OCP sera the 230, 160, and 85 kD bands were eliminated and only a single 205 kD band was uniformly present. These results indicate that OCP sera recognize peptide(s) present in 230, 205 and 160 kD proteins in lysates from COLO and SCaBER tumor cells. These proteins contain the immunodominant region of the BMZ molecule(s) in which the OCP antigen(s) reside. The OCP antigen(s) appears to be distinct from the BP antigen(s).

Animals↗

The role of Igh-1 disparate congenic mouse T lymphocytes in the pathogenesis of herpetic stromal keratitis.

The corneal destruction associated with herpes simplex keratitis (HSK) is primarily the result of the host's immune response to herpes simplex virus type-1 (HSV-1) infection. We examined the role of T cells and T cell subsets in the pathogenesis of HSK. Naive and immune T cells and HSV-1 immune CD4+ and CD8+ subsets from Igh-1 disparate BALB/c congenic mice were adoptively transferred into athymic BALB/c nude mice, which normally do not develop HSK. The results demonstrated that while the transfer of naive T cells from either HSK-susceptible C.AL-20 (Igh-1d) or HSK-resistant C.B-17 (Igh-1b) mice had little influence on HSK development, transfer of either CD3+ or CD4+ HSV-1 immune T cells from C.AL-20 mice resulted in the development of severe HSK in all of the recipients. Transfer of the same cell populations from C.B-17 mice resulted in the development of only a mild keratitis in 50% of the recipients. Transfer of CD8+ cells from either donor strain did not result in stromal disease in any recipient mouse. These results clearly demonstrate the pivotal role of CD4+ T cells in the development of necrotizing herpes stromal keratitis, and further demonstrate that CD8+ T cells are not essential in HSK development in the BALB/c system.

Animals↗

Antibody-dependent cellular cytotoxicity against cells infected with herpes simplex virus type 1 in Igh-1 disparate congenic mice.

The mouse Igh-1 locus on chromosome 12 influences herpetic stromal keratitis (HSK) patterns following corneal challenge with herpes simplex virus type 1 (HSV-1). Both cellular and humoral immune mechanisms appear to be important in modulating responses to HSV-1 infections, but the role of antibody-dependent cellular cytotoxicity (ADCC) is unclear. We studied the effector-cell function and antibody in an ADCC assay in Igh-1-disparate mice. Splenocytes from both HSK-susceptible C.AL-20 (Igh-1d) and HSK-resistant C.B-17 (Igh-1b) mice mediated equal amounts of ADCC to HSV-infected cell targets using monoclonal antibodies against HSV-1 glycoprotein D. Natural killer cell activity was significantly greater in C.AL-20 than in C.B-17 splenocytes. IgG2a was less efficient than both IgG1 and IgG2b in mediating ADCC to HSV-1-infected cell targets. The Igh-1 phenotype of the antibody source had no influence on ADCC activity. Our results suggest that the susceptibility of HSK observed in these Igh-1-disparate congenics cannot be explained by qualitative differences in the ADCC activity of effector cells and antibody produced in response to HSV-1 infection.

Animals↗

Serum levels of tumor necrosis factor-alpha and interleukin-6 in ocular cicatricial pemphigoid.

PURPOSE: These studies examined regulation of the cytokines interleukin-6 and tumor necrosis factor-alpha in ocular cicatricial pemphigoid (OCP), a systemic autoimmune disease. METHODS: Serum levels of interleukin-6 and tumor necrosis factor-alpha in sera collected from 35 patients with OCP, 29 normal persons and 17 patients with ocular inflammatory diseases were determined using an enzyme-linked immunosorbent assay. RESULTS: Levels of interleukin-6 were significantly decreased in sera of patients with OCP (median, 28.9; range, 7.5 to 136.7 pg/ml, P < 0.001) compared with sera from normal subjects (median, 65.2; range, 21.1 to 303.9 pg/ml). Sera from patients with non-OCP, extraocular inflammatory diseases and uveitis, showed no such decrease. In contrast, tumor necrosis factor-alpha levels were significantly elevated in OCP patients (median, 22.5; range, 8.3 to 44.4 pg/ml, P < 0.001), whereas no such increase was observed in sera from patients with extraocular inflammatory disease or uveitis, compared to normal sera controls (median, 17.4; range, 5 to 27.2 pg/ml). CONCLUSIONS: These results suggest that elevated serum tumor necrosis factor-alpha levels and decreased serum interleukin-6 levels can be added to the increasing list of systemic immunologic correlates of active OCP, again emphasizing that OCP is a systemic disease whose primary manifestation is ocular.

Adult↗

Alternatively spliced fibronectin molecules in the wounded cornea: analysis by PCR.

PURPOSE: To determine whether certain fibronectin isoforms participate in corneal epithelial wound healing, the authors used the polymerase chain reaction to detect different splicing patterns of the EIIIA segment of fibronectin mRNA in epithelial scrape-wounded cornea of rats. METHODS: Specific fibronectin cDNA sequences synthesized from rat cornea with total RNA were amplified with various sets of synthetic oligonucleotide primers. RESULTS: The authors detected both the EIIIA+ and EIIIA- fibronectin mRNA isoforms during corneal wound healing. The kinetics of corneal expression of both total fibronectin mRNA and the EIIIA- fibronectin mRNA isoform was polyphasic; an initial decrease was followed by an increase at 45 minutes, a second increase at 2 hours, and a third increase at 4 days after wounding. EIIIA+ fibronectin mRNA, not found in normal cornea, also was detected during healing. CONCLUSIONS: The expression of total fibronectin mRNA and both the EIIIA+ and EIIIA- fibronectin mRNA is upregulated during corneal epithelial wound healing. The expression of EIIIA+ fibronectin mRNA during wound healing, a fibronectin isoform that was highly expressed in embryonic tissue, suggests that this fibronectin isoform is involved functionally in corneal wound healing.

Alternative Splicing↗

Six cases of scleritis associated with systemic infection.

Isolated scleritis (without keratitis) associated with infections is uncommon, and correct diagnosis and appropriate therapy for it are often delayed. Six patients with infection-associated scleritis were seen at our institution between May 1983 and May 1990 (these patients represented 4.6% of all patients with scleritis [six of 130 patients] in that period). Three of these cases were associated with systemic infections. One was associated with syphilis, one was associated with tuberculosis, and one was associated with toxocariasis. Three cases resulted from local infections. One was associated with infection with Proteus mirabilis, one was associated with infection with herpes zoster virus, and one was associated with infection with Aspergillus. The Aspergillus infection developed after trauma and the P. mirabilis-induced infection developed after strabismus surgical procedures. Four of the six cases were initially misdiagnosed and inappropriately managed. Correct diagnosis was made seven days to four years after onset of symptoms. Review of systems, scleral biopsy, culture, and laboratory investigation were used to make the diagnosis. Differential diagnosis of scleritis must include infective agents.

Aged↗

Systemic acyclovir and penetrating keratoplasty for herpes simplex keratitis.

Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir following corneal transplantation for herpes simplex keratitis was compared to that in nine patients (9 eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without receiving postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared to a 44% (4/9) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2/14) of acyclovir treatment eyes and in 56% (5/9) of the grafts in patients not receiving acyclovir. Long term prophylactic oral acyclovir significantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients with a history of recurrent herpes simplex keratitis who underwent corneal transplantation.

Acyclovir↗

Long-term results of systemic chemotherapy for ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive, blinding, autoimmune disease that scars mucous membranes. We studied the long-term outcome in 104 consecutive patients (average follow-up: 4 years) to determine whether complete remission could be achieved following a course of treatment with immunosuppressive drugs. We found that prolonged periods of remission off therapy are maintained in about one third of OCP patients. Follow-up must be continued for life as relapse occurs in approximately one third of cases. Those who relapsed regained disease control readily upon reinstitution of therapy and did not deteriorate to more advanced cicatrization. Sex, age, initial degree of inflammation and the incidence of extraocular involvement did not bear a prognostic significance. The mechanism which underlies the differing responses to therapy is not yet known.

Adult↗

Markers of the metastatic phenotype in prostate cancer.

Metastatic malignant disease is the single most common cause of treatment failure and subsequent mortality of most human malignancies, including prostate cancer. Presently, cells expressing the metastatic phenotype cannot be identified within a primary tumor population. Hence, accurate assessment of the likely behavior of an individual primary malignancy cannot be made at the time of diagnosis. The studies now reported have been aimed at identifying some of the features that may be associated with the metastatic phenotype of prostatic cancer. Insight into those factors that may be involved in prostate cancer metastasis has been gained from a variety of experimental approaches as well as study of intact human prostate cancers.

Animals↗