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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 127 records · Page 7Linked to original sources

Proliferation of parenchymal epithelial cells enhanced in chronic pancreatitis.

This study was performed to determine whether pancreatic parenchymal epithelial cells in human chronic pancreatitis tissues retain a biologically significant capability to proliferate and, if so, within which epithelial compartment proliferation occurs. The techniques of immediate per-operative in vitro labelling with bromodeoxyuridine (BrdU) and conventional immunohistochemistry for Ki-67 antigen expression were used to identify proliferating cells. Concordance between the two techniques was confirmed in all tissues examined. In normal pancreas, proliferation was restricted to acinar epithelial cells, with no activity in the ductules. In chronic pancreatitis of both chronic obstructive and chronic calcifying types, the number of proliferating cells in the acini was significantly increased. A small population of proliferating cells was also apparent within ductules in chronic calcifying pancreatitis, but not in chronic obstructive pancreatitis. This investigation has shown that loss of parenchymal epithelium occurring in chronic pancreatitis is not caused by a primary failure of pancreatic 'stem-cell' proliferation, but is due to disproportionate attrition of differentiated parenchymal epithelial cells by a mechanism, possibly stromal in origin, which remains hitherto unidentified. The presence of proliferating ductular cells in chronic calcifying pancreatitis, but not chronic obstructive pancreatitis, suggests that distinct pathogenic processes may be operating in the former condition, which is classically regarded as secondary to ductal obstruction by stones, and in this single respect might be considered to be identical to chronic obstructive pancreatitis. Preservation of 'stem-cell' function supports the belief that regeneration of pancreatic parenchymal tissue could be a feasible proposition if biologically appropriate management strategies were developed to treat chronic calcifying pancreatitis.

Adult↗

Lepromatous uveitis diagnosed by iris biopsy.

Ocular leprosy is rarely seen in developed countries. We report the long-term follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin, iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy must be considered in the differential diagnosis of keratitis and uveitis.

Adult↗

Generation of a monoclonal antibody to P-glycoprotein peptides using tuberculin-PPD as a carrier.

A novel immunization protocol together with stringent selection criteria have been employed to generate a new murine monoclonal antibody ("D8", isotype IgG1, kappa) which specifically recognizes the human p170 drug resistance glycoprotein. This antibody is directed towards a defined peptide sequence located in the -COOH terminal region of the first external loop of the molecule. It is reactive with its epitope within the intact native glycoprotein in formalin-fixed and conventionally processed histological tissues, in flow-cytometric preparations and by Western blotting. The antibody precipitates its target peptide sequence from solution, and thus may be a useful reagent with which to establish an ELISA, RIMA or other similar assay. The peptide epitope recognized by this monoclonal antibody is restricted to the human MDR1 gene product and is not contained within the rodent homologue of the P-170 molecule. Immunohistochemistry has consistently failed to detect this epitope in rodent tissues, thus confirming that it does not exhibit the cross-reactivity of other currently available anti-P-glycoprotein monoclonal antibodies. The experience of this study emphasizes the value of the tuberculin-PPD (purified protein derivative) immunization protocol as a powerful strategy when generating monoclonal antibodies to small synthetic peptides. The resulting monoclonal antibody (D8) will be an invaluable reagent with which to analyse P-170 glycoprotein expression when assessing the role of multidrug resistance in human cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Recurrent nodular scleritis associated with varicella zoster virus.

PURPOSE: To describe a case of recurrent nodular scleritis that was apparently caused by reactivation of a varicella zoster virus infection. METHODS: Case report. Immunohistochemistry and polymerase chain reaction were used to detect viral antigen and DNA in the biopsy specimen of inflamed sclera of a patient with a history of recurrent nodular scleritis.

2-Aminopurine↗

Prostatic stromal cell phenotype is directly modulated by norepinephrine.

OBJECTIVES: To evaluate the response of prostatic stromal cells in vitro to the action of the agonist norepinephrine and to examine the role of cell density in this response. METHODS: Stromal cells isolated from transurethral chippings of patients with benign prostatic hyperplasia (BPH) were seeded onto tissue culture dishes either at high density (9 x 10(3) cells/cm2) or at low density (1.5 x 10(3) cells/cm2). Norepinephrine was added at concentrations in the range of 2.5 to 50 microM. Cells were harvested at the moment of confluence, labeled with monoclonal antibodies to four cytoskeletal proteins, and analyzed by flow cytometry. RESULTS: Sparsely plated stromal cells showed a consistent biphasic response in which a small fall in immunofluorescence occurred in the range of 5 to 15 microM norepinephrine but was thereafter followed by a progressive rise in fluorescence to 50 microM, indicating increased expression of smooth-muscle-associated cytoskeletal proteins. The shape of flow-cytometric frequency-distribution histograms for smooth-muscle myosin, desmin, and talin suggested that all mesenchymal cells in the stromal cultures were similarly modulated by norepinephrine. However, the effect on smooth-muscle actin was different in that a subpopulation of hyperreactive cells was identified. Densely plated stromal cells did not show a similar biphasic response to norepinephrine but instead demonstrated an overall downward trend, indicating a progressively diminished expression of these cytoskeletal proteins. CONCLUSIONS: Norepinephrine stimulation directly modulates BPH-derived prostatic stromal cells toward a differentiated smooth-muscle phenotype as evidenced by increased expression of cytoskeletal proteins. The effect of norepinephrine on cultures is cell-density-dependent, suggesting that intercellular communication is an important factor in coordinating the differentiation responses. This study has revealed a specific interaction between physical and humoral stimuli, which influences in part the phenotype of prostatic stromal cells. Such interaction is likely to determine the development of clinical BPH, and also the response of any individuals following therapeutic intervention using selective alpha-adrenergic blockade.

Cell Count↗

Characteristics of uveitis presenting for the first time in the elderly.

OBJECTIVE: This study aimed to describe the clinical characteristics of uveitis presenting de novo in the elderly. DESIGN: The study design was a description of a retrospectively identified case series. PARTICIPANTS: A population of 138 patients (209 eyes) with uveitis beginning after age 60 was analyzed. RESULTS: Uveitis in the elderly accounted for 10.4% of the authors' uveitis population. The localization of uveitis was anterior in 56.5% of patients, intermediate uveitis was diagnosed in two patients (1.4%), posterior uveitis was found in 25.4%, while 16.7% of patients presented with panuveitis. Idiopathic uveitis accounted for the majority of cases (31.2%), whereas herpes zoster ophthalmicus (11.6%), herpes simplex virus (6.5%), presumed sarcoidosis (5.8%), syphilis (4.3%) ankylosing spondylitis (4.3%), and birdshot chorioretinopathy (3.6%) were the most frequent specific diagnostic entities. Secondary elevation of intraocular pressure was common (67 eyes, or 32%). The development of macular edema complicated 28.7% of cases (60 eyes). Two cases of intraocular lymphoma were identified in 19 diagnostic vitreous biopsy specimens. Fifty-two percent of eyes retained visual acuity of 20/40 or more; 32.6% had final visual acuity worse than 20/100. CONCLUSIONS: Uveitis presenting for the first time in the elderly is not uncommon. Idiopathic uveitis accounts for the majority of cases, and herpes zoster ophthalmicus and herpes simplex virus are particularly prevalent. Intraocular lymphoma does not predominate in this age group. With adequate control of intraocular inflammation and its sequelae, the visual prognosis in patients in this age group with uveitis is relatively good.

Aged↗

Long-term follow-up of patients with atopic keratoconjunctivitis.

OBJECTIVE: This study aimed to review the presenting features, treatment administered to, histopathologic findings, and complications encountered in a cohort of patients with atopic keratoconjunctivitis. DESIGN: The study design was a retrospective cohort series. PARTICIPANTS: The medical records of 20 patients with atopic keratoconjunctivitis and a minimum follow-up of 3 years were reviewed. MAIN OUTCOME MEASURES: Conjunctival and corneal complications, visual acuity before and after surgery, and histopathologic features on conjunctival biopsy were measured. RESULTS: Significant keratopathy developed in 70% of patients, corneal neovascularization in 60%, fornix foreshortening in 25%, and symblepharon in 20% during the course of their disease. Eleven patients (12 eyes) required penetrating keratoplasty (3 for tectonic purposes and 8 for visual rehabilitation). Vision improved by four or more lines of Snellen acuity in four eyes, improved by two lines in two eyes, remained the same in five eyes, and worsened by two lines in one eye after keratoplasty. Cataract surgery was performed in seven patients (nine eyes) with vision improving by four or more lines in six patients (eight eyes). CONCLUSION: Atopic keratoconjunctivitis is a potentially blinding disease that may result in a poor visual outcome as a result of corneal complications. Elective surgical intervention may be of benefit and can be considered in those patients whose inflammation is well controlled.

Adolescent↗

Chronic keratoconjunctivitis associated with congenital dyskeratosis and erythrokeratodermia variablis. Two rare genodermatoses.

OBJECTIVE: The purpose of the study was to report the ocular manifestations and immunohistopathologic description of two rare forms of genodermatosis: congenital dyskeratosis (CD) and erythrokeratodermia variabilis (EKV). DESIGN: Case reports. PARTICIPANTS: Two patients with CD and EKV presenting with chronic keratoconjunctivitis were studied. INTERVENTION: Clinical photography to show ocular manifestations and dermatologic findings was performed. Conjunctival biopsy was performed to determine the histopathology and immunohistopathology. RESULTS: In the patient with EKV, the eyelid skin was dry, erythematous, and thickened. The lid margins showed plugging of some of the Meibomian glands, madarosis, and occasional trichiasis. The epibulbar conjunctiva was injected and had a moderate papillary reaction. Both corneas had pronounced vascularization and stromal scarring. Conjunctival biopsy results disclosed a striking number of degranulating mast cells and moderate numbers of plasma cells. Immunohistopathology showed pronounced immunoglobulin G (IgG)-positive cells in the stroma and immunoglobulin A (IgA) positivity in the epithelium. There was scattered immunoglobulin M (IgM) and moderate C3 and C4 positivity in the stroma. In CD, the patient had keratinized lid margins, entropion formation, trichiasis, cicatrizing conjunctivitis, and symblephra formation. The corneal surface was keratinized, with deep and superficial vascularization. Conjunctival biopsy specimens showed pronounced epithelial keratinization and squamous metaplasia. Degranulating mast cells and eosinophils were prominent in the stroma. Immunohistopathology showed C4 and immunoglobulin D positivity on the keratinized epithelial surface with rare foci of immunoglobulin E-positive cells. Basal epithelial cells were positive for IgA and IgG, and a large number of IgA and IgG plasma cells were present in the substantia propria. CONCLUSION: To the authors' knowledge, these case reports represent the first clinical description of the ocular manifestation of EKV and the first immunohistopathologic description of the affected conjunctiva in EKV and CD, both of which should be considered in the differential diagnosis of genodermatosis associated with chronic keratoconjunctivitis.

Adolescent↗

Outcomes in anterior uveitis associated with the HLA-B27 haplotype.

OBJECTIVE: This study aimed to test the hypothesis that patients presenting with anterior uveitis who are HLA-B27 positive, either with or without associated systemic disease, have a less-favorable outcome than do patients with idiopathic anterior uveitis who are HLA-B27 negative. DESIGN: Retrospective case-controlled series. PARTICIPANTS: Ninety-seven patients who were HLA-B27 positive with no systemic disease, 94 patients who were HLA-B27 positive with systemic disease, and 72 patients who were HLA-B27 negative who presented with anterior uveitis were studied. MAIN OUTCOME MEASURES: Ocular complications (e.g., secondary glaucoma, cataract formation, pupillary synechiae, vitritis, cystoid macular edema, and optic disc edema), medical and surgical treatment, number of recurrent attacks, and final visual acuity were recorded for all patients. RESULTS: The patients who were HLA-B27 positive, either with or without systemic disease, experienced a greater number of complications than did the patients who were HLA-B27 negative. Periocular corticosteroids, systemic corticosteroids, and systemic immunosuppressive chemotherapy were required in a far greater number of HLA-B27-positive patients than in HLA-B27-negative patients (60% vs. 11%, 53% vs. 7%, and 18% vs. 1%, respectively; P < 0.001). The percentage of legally blind eyes was significantly greater in the HLA-B27-positive group, both with and without systemic disease, when compared with the HLA-B27-negative group (11% vs. 2%; P < 0.005). CONCLUSIONS: The prognosis of anterior uveitis associated with the HLA-B27 haplotype, either with or without associated systemic disease, is less favorable when compared with that of HLA-B27-negative patients with idiopathic anterior uveitis.

Adolescent↗

High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis.

OBJECTIVE: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. DESIGN: Case series. PARTICIPANTS: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. INTERVENTION: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. RESULTS: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). CONCLUSION: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs. inactive vs. control). These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response.

Aqueous Humor↗

Generation of metastatic variants by transfection of a rat non-metastatic epithelial cell line with genomic DNA from rat prostatic carcinoma cells.

Prostate cancer is the second leading cause of male death from malignant disease in Europe and in the USA. Failure to prevent or eliminate metastatic dissemination is a fundamental problem underlying the current inadequate treatment of prostate cancer, and novel therapeutic strategies are required if this disease is to be successfully managed. No independent markers are yet available to predict the behaviour of any individual prostate cancer, particularly its potential to metastasize, and there is now an urgent prerequisite to identify and characterize genes specifically involved in determining the metastatic phenotype of prostate cancer cells before any biologically appropriate treatment modality can be devised. To identify DNA sequences that trophically promote the metastatic phenotype, we have established a new transfection assay with which to monitor activity of prostate cancer genomic DNA. Rat prostatic G and AT6.1 cell lines derived from the same original Dunning R3327 rat prostatic carcinoma exhibit, respectively, low- and high-metastatic phenotypes when grown in syngeneic Copenhagen rats. Rat mammary epithelial cell line 'Rama 37' derived originally from Wistar-Furth rats yields benign non-metastasizing adenomas when inoculated subcutaneously into syngeneic animals. In this report, the Rama 37 cell line is successfully used as the recipient cell-line for transfected DNA fragments extracted from rat prostatic carcinoma G and AT6.1 cells. New metastatic variants of Rama 37 cells have been generated. Enzymatically fragmented genomic DNA from rat metastatic prostate carcinoma cell lines was co-transfected together with plasmid pSV2neo into parental Rama 37 cells, followed by culture in the presence of Geneticin-G418 to select for the transfected cells. To enable subsequent identification of metastasis-promoting DNA sequences, the fragmented genomic DNA sequences were covalently attached to specifically engineered linker DNA molecules to flank the genomic DNA before transfection. Thereafter, the resulting transfectants were pooled and inoculated into mammary fat pads of female Wistar-Furth rats. Metastases produced by the transfectant cells in vivo were reestablished from secondary tumours and probed for the presence of the specific synthetic oligonucleotide sequences that flanked, and hence identified, the presence of the transfected DNA. These new metastatic cells are shown to provide a sensitive assay system with which to detect DNA sequences responsible for conveying the metastatic phenotype of prostate cancer when inoculated into syngeneic rats.

Animals↗

Ciliary body melanoma masquerading as chronic uveitis.

PURPOSE: To report a case of ciliary body melanoma that masqueraded as chronic uveitis. METHODS: A patient experienced persistent unilateral panuveitis and elevated intraocular pressure. Inflammation and pressure worsened after cataract extraction and lens implantation. Diagnostic vitrectomy was non-revealing. RESULTS: Repeat vitrectomy and lens implant removal revealed a ciliary body mass, suggestive of melanoma. Ultrasonography and clinical evaluation by the retinal oncologists supported this diagnosis. The uveitis persisted despite aggressive medical treatments, including methotrexate. Proton beam irradiation of the melanoma led to resolution of uveitis and restoration of normal intraocular pressure. CONCLUSION: Ciliary body melanoma can present as chronic uveitis and refractory glaucoma.

Cataract Extraction↗

Comparative effectiveness and molecular pharmacological mechanisms of antiallergic agents on experimental conjunctivitis in mice.

The purpose of this study was to determine the effectiveness of antiallergic agents in the treatment of experimental murine ragweed conjunctivitis. SWR/J mice were divided into eight groups: 1; normal controls (unmanipulated); 2, untreated; 3, lodoxamide; 4, cromolyn; 5, livocarbastine; 6, nedocromil; 7, buffer solution (BS); and 8, tetrandine (TDR). Groups 2-8 were exposed to ragweed pollen through topical application to conjunctival and nasal mucosa, followed by conjunctival challenge with the allergen. Allergic conjunctivitis was evaluated by scoring of the clinical signs and histopathology. mRNA gene expression of interleukin 1beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha) in conjunctiva was analyzed by reverse transcription polymerase chain reaction techniques. Exposed mice developed allergic conjunctivitis clinically and histologically that was modulated by topical lodoxamide, cromolyn, livocarbastine, or nedocromil eye drops or TDR intraperitoneally injected. Histopathologic analysis demonstrated that the drugs and TDR significantly reduced conjunctival eosinophil infiltration and the number of intact and degranulating mast cells. IL-1beta and TNF-alpha mRNA gene expression in conjunctiva of treated mice was inhibited compared with untreated and BS-treated controls. No IL-6 mRNA expression was observed even on the conjunctiva of the untreated mice. The antiallergic drugs and TDR exerted a similar action on the murine model of allergic conjunctivitis and demonstrated pharmacologic effectiveness on the conjunctival mRNA expression of cytokines IL-1beta and TNF-alpha.

Alkaloids↗

Peripheral ulcerative keratitis after Salmonella gastroenteritis.

PURPOSE: To describe a case of bilateral peripheral ulcerative keratitis after Salmonella gastroenteritis. METHODS: Case report with description of treatment and outcome. RESULTS: The peripheral ulcerative keratitis gradually resolved in both eyes after appropriate systemic antibiotic therapy and local ocular care. CONCLUSION: Peripheral ulcerative keratitis can result as a consequence of infectious gastroenteritis.

Aged↗

The ocular manifestations of rheumatoid disease.

The inflammatory arthropathies that affect the eye most commonly are RA, JRA, and the seronegative spondyloarthropathies. These conditions not only cause devastating systemic findings but can be the source of damaging ocular disease. The inflammatory nature of these entities, with the accompanying liberation of mediators of inflammation, can result in a cycle of tissue destruction that culminates in blindness. The diseases reviewed can present first with systemic or ocular findings; thus, all physicians must be equipped with the appropriate knowledge to make accurate and timely diagnoses so that appropriate management strategies can be employed. The successful recognition and treatment of these conditions can prevent their associated systemic and ocular morbidity.

Adolescent↗