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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 217 records · Page 12Linked to original sources

T cell receptor V beta gene expression in experimental herpes stromal keratitis.

Our study examined T cell receptor (TCR) V beta mRNA expression in a murine model of experimental herpes simplex keratitis (HSK). We employed a polymerase chain reaction (PCR) technique to detect TCR V beta mRNA expression in the inoculated eyes of both HSK-susceptible and HSK-resistant mice at different time points after corneal inoculation with herpes simplex virus type 1 (HSV-1), followed by Southern blotting and densitometry analysis. In eyes from HSK-susceptible C.AL-20 mice, a more diverse TCR V beta transcript usage pattern was detected as compared with that seen in HSK-resistant C.B-17 mice. V beta 8 family members were expressed in both strains of mice at days 11, 14 and 21 post-inoculation. By densitometry, at day 11, the intensity of expression of V beta 8.2 and V beta 8.3 message was significantly greater in the eyes of C.AL-20 mice; V beta 8.1 was expressed only in C.B-17 mice. There were obvious differences in the TCR V beta expression between HSK-susceptible and HSK-resistant mice. The differences in the intensity of the message expressed by V beta 8 family members between the two strains could be correlated to previous experiments that showed V beta 8.1,2+ T cells as the main infiltrating cells in the corneas of HSK-susceptible mice by day 11 and 14 after challenge with HSV-1.

Animals↗

Destructive corneal and scleral disease associated with rheumatoid arthritis. Medical and surgical management.

The onset of necrotizing scleritis (NS) and peripheral ulcerative keratitis (PUK) in the clinical course of rheumatoid arthritis (RA) may reflect the presence of systemic, potentially lethal vasculitis. In an effort to better characterize this subset of patients with severe RA-associated corneal and/or scleral inflammation and to analyze the efficacy of therapy, we reviewed our experience in the medical and surgical management of 16 tertiary referral cases (25 eyes) unresponsive to aggressive conventional therapy with topical and systemic steroids as well as with systemic nonsteroidal drugs. Cytotoxic immunosuppressive therapy was instituted in all patients with NS and/or PUK. Cyclophosphamide and methotrexate were the most successful agents used. Cytotoxic immunosuppressive drugs in conjunction with early aggressive surgical treatment halted the relentlessly progressive inflammation and preserved the integrity of the globe in 92% of eyes. Visual acuity could be stabilized or improved in 83% of patients with NS and in 68% of patients with PUK.

Aged↗

Variable region usage in B cell deficient mice in a model of experimental herpes simplex virus retinitis.

By using PCR, we have found previously that differences in T cell receptor alpha/beta chain variable region (TCR alpha/beta) gene expression in lymph nodes (LN) existed between susceptible and resistant mice following anterior chamber (AC) inoculation with herpes simplex virus (HSV). We now report and compare the immunoglobulin gene variable region (Ig VH) and the TCR V beta mRNA expression in normal congenic mice (BALB/c and C.B-17) and also in B cell modulated C.B-17 mice (B-). RNA prepared from spleen and LN of these mice before and after HSV-AC inoculation was analysed by PCR using oligoprimers specific for 11 VH gene families and 19 V beta gene families. Densitometry analysis revealed that VH family mRNA expression levels in spleen and lymph nodes did not correlate with HSV susceptibility or resistance patterns in B-, BALB/c and C.B-17 mice. Analysis of TCR V beta chain genes showed that spleen of resistant C.B-17 and B-Ab transferred mice showed a preference for V beta 11 gene expression not seen in susceptible mice. In contrast, LN of BALB/c and B-, both susceptible mice, made TCR V beta transcripts that were indistinguishable from those generated by resistant C.B-17 mice, following HSV-AC inoculation. Finally, TCR V beta gene family repertoire appears to be severely diminished in uninfected B- mice (50% in LN and 45% in spleen) by anti-mu treatment.

Animals↗

The pathophysiology of ocular allergy: current thinking.

Seasonal allergic conjunctivitis is the only ocular disease to involve solely Type-1 hypersensitivity, the other main forms of ocular allergy--perennial allergic conjunctivitis, vernal and atopic keratoconjunctivitis and giant papillary conjunctivitis--each having a more complex immunological basis and a chronic inflammatory component. Involvement of secondary inflammatory cells, particularly eosinophils, in addition to the mast cells resident in the conjunctival substantia propria, can lead to more serious corneal damage with vision-threatening potential. Thoughtful management of allergic conjunctivitis is needed in order to control the ocular inflammation without incurring steroid-induced side-effects, and patient education is also an important factor in maintaining optimal allergen avoidance, especially in the more severe and chronic cases. Laboratory models can be helpful in assessing the potential of new drugs, and SWR mice (topically sensitised and challenged with short ragweed) show clinical signs of allergic conjunctivitis, together with mast cell and eosinophil involvement, remarkably similar to the human pathophysiology. The antiinflammatory activity of both steroids and nedocromil sodium observed in this animal model supports therapeutic evidence of the usefulness of second-generation mast cell stabilising drugs in the treatment of ocular allergy.

Animals↗

Expression of transforming growth factor-beta 1 in chronic pancreatitis.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine which modifies tissue stromal matrix synthesis, cell proliferation and immune function. In the present study, we have used a mouse monoclonal antibody to the latent (intracytoplasmic) form of TGF-beta 1 to compare its expression in 144 cases of human chronic pancreatitis (both obstructive and chronic calcifying) with that of 10 control pancreatic specimens. In all the control specimens, and most of those with chronic pancreatitis, cytoplasmic immunoreactivity was identified in pancreatic duct and ductular epithelium, in islet cells and in vascular smooth muscle and endothelium. Two distinct patterns of ductular epithelial staining emerged: in morphologically normal tissues, only individual distal ductular/centroacinar cells stained but in chronic pancreatitis (whether chronic calcifying or chronic obstructive) the staining was panductular. Positive cytoplasmic immunostaining of acinar epithelial cells was found in 3% of pancreatitis specimens but in none of the normal controls. There was no staining of fibroblasts. Synthesis of TGF-beta 1 appears to be normally restricted to a population of epithelial cells located in terminal/centroacinar regions of the ductules (together with occasional ductal cells) whereas in chronic pancreatitis, TGF-beta 1 is expressed in most ductular and ductal epithelial cells.

Case-Control Studies↗

Expression of collagens I, III, IV and V mRNA in excimer wounded rat cornea: analysis by semi-quantitative PCR.

A semi-quantitative polymerase chain reaction (PCR) methodology was used to evaluate the kinetic changes occurring in collagens I, III, IV and V mRNA in rat cornea following excimer laser keratectomy. cDNA was synthesized from RNA extracted from rat cornea at various times following excimer laser photoablative keratectomy. Collagen cDNA sequences were subsequently amplified using specific sets of oligonucleotide primers. Competitive PCR amplification was carried out using an internal standard so that a semi-quantitative analysis of message for synthesis of collagen types I, III, IV and V could be performed and time course dynamics of message for these collagens studied. There was a biphasic increase in the levels of collagens III, IV and V mRNA following excimer laser keratectomy. Collagen I mRNA levels demonstrated a more sustained increase and were still elevated at 6 weeks following wounding. Collagens IV and V mRNA showed the largest increase with an approximate three fold increase over controls between 4 days and 1 week. Our results demonstrate that upregulation of stromal collagens I, III, and V mRNA and basement membrane collagen IV mRNA occurs in rat cornea following excimer laser keratectomy.

Animals↗

Experimental model of allergic conjunctivitis to ragweed in guinea pig.

An experimental model of ocular allergy was developed in the guinea pig by exposing these animals to ragweed through topical contact on nasal and conjunctival mucosae, followed by subsequent challenge with ragweed contact on the conjunctiva. Animals developed clinical and histological signs of allergy with and without the use of interleukin 4 as adjuvant. This model mimics human hay fever conjunctivitis more naturally than do animal models previously reported, and it may be subsequently more valuable in the study of the response of allergic conjunctivitis to different therapeutic approaches.

Adjuvants, Immunologic↗

[Glycoprotein D (5-23) specific Th2-T-cell line induces HSV-1 keratitis].

BALB/c inbred Igh-1-disparate mice exhibit different susceptibility to the development of HSV-1 stromal keratitis (HSK), which may be due to the differential immune regulation. CD4+ T lymphocytes may be critical for the disease induction. A T-cell line (CD4+, T-cell receptor V beta 8+, interleukin-4+) specific for the N-terminal amino acids 5-23 of glycoprotein D from HSV-1 [gD(5-23)] was established from HSK susceptible C.AL-20 mice. HSK-resistant C.B-17 mice, and HSK-susceptible BALB/c mice were injected intraperitoneally with cells (5 x 10(5)/mouse) alone or combined with HSV-1 corneal inoculation (10(5) PFU, KOS strain). Control groups were injected with HSV-antigen-unrelated cells (PPD specific), or were only HSV-1 infected. Migration of the adoptively transferred gD(5-23) Th2 cells was analyzed by histology, by immunohistochemistry and by cell membrane labelling (PKH26). The transfer of gD(5-23) cells accelerated the disease onset (day 2, compared to day 7 without cells). The transfer of gD(5-23) cells increased the incidence of HSK (BALB/c 100%, C.B-17 20%) compared to mice that were only infected with HSV-1 (BALB/c 75%, C.B-17 0%). Keratitis was more severe in mice injected with gD(5-23) cells. In contrast, the transfer of PPD-specific cells did not influence the disease patterns. Mice injected with gD(5-23) cells and not inoculated with HSV-1 did not develop keratitis. The results suggest that CD4+ MHC class II, V beta 8+, IL-4 expressing T-cells (T helper 2) may be important for the induction of HSK.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Corticosteroid-sparing strategies in the treatment of retinal vasculitis in systemic lupus erythematosus.

BACKGROUND: Systemic corticosteroids have been traditionally used in the therapy of retinal vasculitis in patients with systemic lupus erythematosus. The high morbidity associated with long-term corticosteroid therapy has prompted the use of corticosteroid-sparing strategies with cytotoxic agents. METHODS: This retrospective study summarizes the authors' experience of the last 10 years including 9 systemic lupus erythematosus patients with retinal vasculitis who required treatment for longer than 6 months. RESULTS: Seven of these patients were treated with cytotoxic agents. Average follow-up was 39 months. Inflammation was controlled clinically and angiographically in all patients using the following therapeutic regimens: systemic corticosteroids and hydroxychloroquine (n = 1 patient); systemic corticosteroids and cytotoxic chemotherapy (n = 6); cytotoxic chemotherapy and hydroxychloroquine (n = 1); and hydroxychloroquine alone (n = 1). Visual acuity was preserved (> 20/30) or improved in all patients. All patients retained excellent control of their systemic disease during their follow-up. Side effects of cytotoxic drugs requiring discontinuation of all chemotherapy were not encountered in this group; Imuran therapy did result in substantial adverse effects necessitating its replacement with other drugs. CONCLUSION: These results suggest a valuable role for corticosteroid-sparing drugs in the therapy of retinal vasculitis associated with systemic lupus erythematosus.

Adolescent↗

Penetrating keratoplasty in atopic keratoconjunctivitis.

Penetrating keratoplasty (PK) may be required for visual rehabilitation or tectonic purposes in patients with severe keratopathy due to atopic keratoconjunctivitis (AKC). The outcome of PK is often poor in such patients because of adnexal and ocular surface abnormalities. We studied nine AKC patients requiring PK and evaluated the visual outcome and prognostic factors in 11 eyes. The mean follow-up was 87.2 months (range, 30-180 months). Preoperatively all patients had visual acuity of hand motion to 20/200. Eighteen grafts were performed. Final visual acuity was 20/40 or better in 46% of the eyes. Ten eyes retained clear grafts and improved an average of 4.5 Snellen acuity lines.

Adult↗

Treatment strategies for scleritis and uveitis associated with inflammatory bowel disease.

We treated 19 patients with anterior uveitis, episcleritis, or scleritis associated with inflammatory bowel disease. Adequate control of ocular inflammation was achieved in 16 patients (84%). Ocular inflammation was adequately controlled with corticosteroids alone, without systemic adverse effects, in only three patients, all of whom had anterior uveitis associated with ulcerative colitis. Systemic nonsteroidal anti-inflammatory drugs proved beneficial in six of seven patients, and one additional patient benefited from another anti-inflammatory drug (hydroxychloroquine sulfate). Systemic cytotoxic immunosuppressive therapy was used in the remaining seven patients, six of whom had bilateral disease. Ocular inflammation was controlled in six of these patients. Azathioprine was beneficial for scleritis but was less effective for anterior uveitis, especially in Crohn's disease, thus necessitating the use of another cytotoxic agent. HLA-B27-positive anterior uveitis was more refractory to corticosteroid therapy and was more likely to require systemic cytotoxic immunosuppressive therapy. With the medical and surgical strategies described, vision was improved or maintained in all patients in the study group.

Administration, Topical↗

Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid.

Cicatricial pemphigoid (CP) is a chronic autoimmune blistering disease affecting multiple mucous membranes derived from stratified squamous epithelium and occasionally the skin. CP has a wide spectrum of disease manifestations. Patients with oral pemphigoid (OP) have a benign self-limited disease in which pathological changes are restricted to the oral mucosa. On the other hand, patients with ocular cicatricial pemphigoid (OCP), a chronic condition marked with relapses and remissions, have ocular involvement and also perhaps involvement of other mucous membranes. All clinical subsets are characterized by the presence of a similar anti-basement zone autoantibody. The factors that determine the development of one form of CP or the other are not known. In a previous study, we described the association between OCP and the DQB1*0301 allele (P = 0.006). In this study, we have analyzed 22 Caucasian patients with OP and their family members for major histocompatibility complex DRB generic, DQA1, and DQB1 allele associations by PCR-sequence-specific oligonucleotide probe hybridization. The results were compared to those obtained from 17 Caucasian patients with OCP and to control Caucasian alleles and haplotypes. The DQB1*0301 allele frequency was 38.6% in OP, 52.9% in OCP, and 17.8% in controls. Statistically significant associations were detected between the DQB1*0301 allele and both OP (P = 0.0047) and OCP (P < 0.0001). In addition, DRB1*04 showed a statistically significant association (P = 0.005) with OCP when compared to controls. Analysis of major histocompatibility complex class II haplotypes showed significant statistical associations between both OCP and OP and the HLA-DRB1*04, DRB4*0101, DQA1*03, DQB1*0301 haplotype (P < 0.0001 and P = 0.0012, respectively). Our results indicate that DQB1*0301 is a marker of both oral and ocular forms of CP. The analysis of the amino acid sequence of the DQB1 alleles present in both OP and OCP suggested that amino acid residues at position 57 and positions 71-77 may also be markers of CP.

DNA Probes↗

Establishment and in vivo characterization of multidrug-resistant dunning R3327 rat prostate-carcinoma cell-lines.

We describe the selection of 3 new multidrug-resistant cell lines derived from tumor cells of different metastatic phenotypes within the Dunning R3327 model of rat prostatic carcinoma. Cell lines of weak (AT2) and strong (AT3 and MAT-LyLu) metastatic behavior were cultured in vitro and challenged with doxorubicin at progressively increasing concentrations. Chemosensitivity was determined colorimetrically by release of precipitated formazan pigment (MTT assay). Expression of the multidrug-resistance glycoprotein (P-170) was monitored immunocytochemically and by Western blotting using monoclonal antibody C219. The behavior of the parental and resultant drug-resistant cells was assessed by their growth in syngeneic rats. Doxorubicin challenge of the initially drug-sensitive parental prostatic carcinoma cell lines resulted in the rapid development of multidrug resistance together with simultaneous expression of P-glycoprotein. While lung and lymph-node metastases developed in host animals inoculated with parental AT3 and MAT-LyLu cells, no metastases developed in the multidrug-resistant progeny of these cell lines. This study has shown that Dunning rat prostate-carcinoma cell lines, previously sensitive to different cytotoxic agents, rapidly become multidrug-resistant and express P-glycoprotein following exposure to doxorubicin. Furthermore, development of multidrug resistance is associated with a less aggressive tumor phenotype and loss of metastatic potential. Nevertheless, it is unlikely that the non-metastatic phenotype of Dunning rat prostatic carcinoma cells is solely associated with expression of P-glycoprotein. These new multidrug-resistant cell lines exhibiting an altered behavioral phenotype will provide a valuable model with which to analyze the relationship between expression of P-glycoprotein and the metastatic phenotype of prostatic carcinoma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Efficacy of lodoxamide 0.1% ophthalmic solution in resolving corneal epitheliopathy associated with vernal keratoconjunctivitis.

A multicenter, randomized, double-masked, parallel-group study compared the long-term efficacy and safety of lodoxamide 0.1% ophthalmic solution and placebo in 118 patients with vernal keratoconjunctivitis. The test drugs were instilled four times daily for 90 days. Lodoxamide 0.1% ophthalmic solution was significantly (P < .05) more effective than placebo in lowering severity scores for epithelial disease and corneal staining, evidence of the superior efficacy of lodoxamide 0.1% ophthalmic solution in reversing the corneal complications commonly associated with moderate to severe vernal keratoconjunctivitis. Additionally, lodoxamide 0.1% ophthalmic solution ameliorated the other key signs of vernal keratoconjunctivitis, including upper tarsal papillae, limbal signs (papillae, hyperemia, and Trantas' dots), and conjunctival discharge. The between-group differences in the relief of symptoms (itching, tearing, and photophobia) were clinically significant but not always statistically significant. Treatment-related adverse events were reported with similar frequency in both treatment groups, and none were serious.

Adolescent↗

Histological and immunopathological analysis of T-cells mediating murine HSV-1 keratitis.

BACKGROUND: Thymus-derived lymphocytes play a critical role in the development of herpes simplex keratitis (HSK). T-cell subsets defined by their expression of various T-cell receptor (TCR) V beta segments were studied following corneal HSV-1 infection (p.i.). METHODS: Conjunctiva, corneal limbus and corneal stroma of two inbred BALB/c congenic mouse strains which differ only in the gene products closely linked to the Igh-1 locus on chromosome 12 were analyzed. RESULTS: While C.B-17 mice (Igh-1b) were resistant to HSK, C.AL-20 mice (Igh-1d) clinically developed severe necrotizing keratitis by day 11 p.i. The corneal stroma of C.B-17 mice remained clear, while it was increasingly infiltrated by mononuclear cells and neutrophils in C.AL-20 mice by day 11 p.i. In C.B-17 mice, Thy1.2+ cells were found in the conjunctiva between days 2 to 4 p.i., and subsequently decreased. Only a few Thy1.2+ cells were found in the limbus, and no such cells were found in the stroma. In contrast, in C.AL-20 mice the numbers of Thy1.2+ cells (activated CD4+, V beta 8+ T cells) profoundly increased in the conjunctiva by day 4 p.i. These cells infiltrated the limbus between days 7 and 11 p.i. and eventually entered the stromal tissue by day 11 p.i. CONCLUSIONS: Our data suggest that the HSV-1-induced corneal tissue destruction is mediated by mononuclear cells and neutrophils and that these cells are probably attracted into the cornea by cytokines elaborated by activated CD4+, V beta 8+ T cells.

Animals↗

Effect of fish oil on cancer cachexia and host liver metabolism in rats with prostate tumors.

The aim of this study was to investigate whether tumor-induced cachexia and aberrations in host liver metabolism, induced by the MAT-LyLu variant of the Dunning prostate tumor, could be prevented by omega 3 fatty acids from fish oil. On day 0, adult Copenhagen-Fisher rats fed normal chow ad libitum were inoculated with 10(6) MAT-LyLu cells (n = 14) or saline (n = 9). On day 7, when tumors were palpable, four tumor-bearing (TB) and four nontumor-bearing (NTB) rats were put on isocaloric diets with 50% of total energy as fish oil. The introduction of fish oil-enriched diets caused a reduction in energy intake to less than half of the energy intake by animals fed normal diets during days 7-14 (difference by dietary group: NTB, P < 0.001; TB, P < 0.001). During days 14-21, energy intake in fish oil-fed animals returned to approximately 75% of energy intake by animals fed normal diets (difference by dietary group: NTB, P < 0.003; TB, P = 0.001). Carcass weight of animals on day 21, when the study was terminated, was significantly related to initial weight (P = 0.05) and mean food intake during the study (P = 0.01). When data were adjusted for these variables using analysis of covariance, with NTB animals on normal diets being the reference group, significant loss of carcass weight was observed in TB animals on normal diets only (mean +/- SEM 58 +/- 10 g loss, P < 0.001), but not in TB animals on fish oil diets (8 +/- 18 g loss, P = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗