Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Not all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens, we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells, and is a leading cause of human blindness. Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes, possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.
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PMID:Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide. 763 Apr 19

Interleukin-8 (IL-8) is a proinflammatory cytokine released at sites of tissue damage by various cell types. One important function of IL-8 is to recruit neutrophils into sites of inflammation and to activate their biological activity. Stromal keratitis induced by herpes simplex virus type 1 (HSV-1) is characterized by an initial infiltration of neutrophils. This study was carried out to determine whether cells resident in the cornea synthesize IL-8 after virus infection. Pure cultures of epithelial cells and keratocytes established from human corneas were infected with HSV-1, and the medium overlying the cells was subsequently assayed for IL-8 by an enzyme-linked immunosorbent assay. Cytokine mRNA levels in cell lysates were monitored by Northern (RNA) blot analysis. It was found that virus infection of keratocyte cultures led to the synthesis of IL-8-specific mRNA with more than 30 ng of IL-8 made per 10(6) cells. Neither UV-inactivated virus nor virus-free filtrates collected from HSV-1-infected keratocytes could induce IL-8 protein or mRNA, suggesting that viral gene expression was needed for induction of IL-8 gene expression. Unlike keratocytes, HSV-1-infected epithelial cells failed to synthesize IL-8 protein or mRNA. However, these cells readily produced both molecules following tumor necrosis factor alpha stimulation. HSV-1 had similar titers in both cell types. Thus, the failure to induce IL-8 synthesis was not due to an inability of the virus to replicate in epithelial cells. The capacity of HSV-1-infected corneal keratocytes to synthesize IL-8 suggests that these cells can contribute to the induction of the acute inflammatory response seen in herpes stromal keratitis.
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PMID:Induction of interleukin-8 gene expression is associated with herpes simplex virus infection of human corneal keratocytes but not human corneal epithelial cells. 768 2

The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were immunised subcutaneously with a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system. Low dosages (31 micrograms) of gD(5-23) protected against encephalitis and HSK. Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemocyanin (KLH) and was emulsified with adjuvant. Latent infection was found in all control mice but in only 50-75% of immunised mice. The most potent protection was correlated with anti-HSV-1 neutralising antibodies of IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1 antibodies. Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis.
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PMID:Immunisation against HSV-1 keratitis with a synthetic gD peptide. 771 56

This overview describes the development of interferon therapy in four different types of viral diseases. (1) Upper respiratory infections: despite extensive efforts interferons have not found a place in the treatment of these very common diseases. (2) Herpes keratitis: alpha interferons are highly active in combination therapy, but have gained only very limited clinical use. (3) Papillomavirus infections: alpha interferons have been approved for the treatment of papillomavirus infections of skin and mucous membranes and are in fairly wide clinical use. (4) Chronic hepatitis B, C and D: alpha interferons have become the treatment of choice and are used very extensively worldwide. The four examples illustrate both the clinical potentials and the limitations of alpha interferons and give some guidelines for future work. The overall conclusion is that chronic viral diseases lend themselves to interferon therapy more readily than acute viral infections. The general trend is toward the use of interferons in combination therapy.
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PMID:Development of antiviral therapy with alpha interferons: promises, false hopes and accomplishments. 774 94

In the case reported, herpes virus I after having caused relapsing keratitis in an eye promoted the formation of a severe corneal ulcer caused by Scopulariopsis brevicaulis, a saprophytic mycete found in soil, which only once has been described as the cause of keratitis in man. Scopulariopsis was identified microscopically after culturing the conjunctival secretion on Sabouraud dextrose agar medium, while DNA probe tests confirmed the absence of herpes virus I. Topical and oral administration of miconazole and scraping of the corneal infiltrate dispersed the infection. Subsequently local steroids were given to reduce the neovascularization, and a therapeutic contact lens was applied because of intercurrent corneal thinning. Three months after beginning antifungal therapy, the visual acuity had increased from 1/120 to 1/10. The case described confirms that S. brevicaulis can cause opportunist infections in a cornea previously damaged by a different agent.
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PMID:Fungal keratitis due to Scopulariopsis brevicaulis in an eye previously suffering from herpetic keratitis. 784 51

Activities of four antioxidative enzymes (superoxide dismutase, glutathione reductase, catalase, and peroxidase) and of three transferases (serum glutamic oxaloacetic and pyruvic transaminases, gamma-glutamyl transpeptidase) were measured in the lacrimal fluid of patients with herpetic keratitis. Measurements of lacrimal enzymes in the course of the disease helps assess the efficacy of treatment and permits its correction. After the treatment of herpetic keratitis is over, activities of the lacrimal enzymes should be assessed together with clinical signs, this permitting a prediction of a recurrence of ophthalmic herpes and timely administration of anti-relapse treatment.
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PMID:[Enzymatic analysis of lacrimal fluid in viral keratitis]. 789 97

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.
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PMID:The role of Igh-1 disparate congenic mouse T lymphocytes in the pathogenesis of herpetic stromal keratitis. 790 69

Natural killer (NK) cells and acquired cell-mediated immunity effector cells (delayed type hypersensitivity (DTH) and cytotoxic T lymphocytes (CTL)) have been reported to play a vital role in the defence of the host against tumour and viral infections in locations other than the eye. A vigorous cellular inflammatory response to viral infections of the cornea, however, with the attendant damage to the corneal clarity, has obvious evolutionary disadvantages, and a substantial body of evidence indicates that in animals (e.g. mice) which are highly susceptible to inflammatory destruction of the cornea following corneal encounter with herpes simplex virus, it is the animal's immunological/inflammatory response which is responsible for the corneal damage. We examined the role of natural killer cells in the development of herpes stromal keratitis (HSK) in NK-deficient (C57BL/6J-bgj (beige)) mice and their NK-competent (C57BL/6J (black) relatives. The beige (NK-deficient) mice were just as resistant to HSK as were the black mice. We also studied the effects of NK cell depletion of BALB/c Igh-1 disparate congenic mice. C.AL-20 (Igh-1d) mice are ordinarily highly susceptible to necrotising HSK. In vivo NK-cell depletion in these mice significantly decreased the incidence and severity of HSK in these animals (p < 0.0005). Corneas from untreated C.AL-20 mice contained T cells, macrophages and NK cells. The corneal infiltrate from NK-depleted C.AL-20 mice consisted of T cells and macrophages but no NK cells. These data indicate that NK cells are participants in the development of HSK in the murine model of this disease.
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PMID:The role of natural killer cells in the development of herpes simplex virus type 1 induced stromal keratitis in mice. 795 34

Rabbit cornea (control or infected with herpes virus) was studied at different time periods after the infection. The change of both ultrastructure and topochemistry of lactate dehydrogenase, adenosine triphosphatase, 5'-nucleotidase is found. The alteration of phosphohydrolase ultracytochemistry is probably due to the enzyme mechanisms which are responsible for reproduction of the herpes simplex virus. Further study of herpetic keratitis enzymology will allow better understanding of the pathogenesis and improve the treatment of herpetic keratitis.
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PMID:[Ultrastructural and ultracytochemical analysis of herpes infected cornea]. 798 38

Tai-Ding-An (3-phthalimido-2-oxo-n-butyraldehyde bisthiosemicarbazone, TDA) is a synthetic antiviral drug developed by our institute. Because of its low water/lipid solubility. Tai-Ding-An is limited to topical treatment of herpes viruses infected skin diseases and of condylomata acuminata (ginital warts), one of sexual transmitted diseases (STD), caused by human papilloma virus (HPV). Ten TDA derivatives IIIb-e, Va, Vb, VIIa-e have been synthesized in order to search for compounds with higher antiviral activity and better solubility than the parent compound as well as to explore structure and activity relationship. Among the ten analogs, three compounds (IIIc, VIIa and VIIb) were found to be effective against herpes simplex virus. The most potent inhibitor was 3-phthalimido-2-oxo-n-butyraldehyde bis- N4- phenylthiosemicarbazone (IIIc, PTDA) which was approximately 10 times more active against HSV-2 as compared with TDA. Compound IIIc was also found to be effective on the topical treatment of herpetic epithelial keratitis in rabbits.
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PMID:[Studies on antiviral agents: synthesis of tai-ding-an analogs]. 799 23


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