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)

Athymic (nude) mice have played an important role in defining the function of the immune system and its role in infectious diseases. In the majority of these studies, heterozygous +/nu mice have been used as normal controls for the nu/nu mice, and it has been assumed that +/nu mice have essentially normal immune systems. We have compared the response of +/+, +/nu and nu/nu BALB/c mice following ocular infection with HSV-1 and have found that +/nu mice develop significantly more severe blepharitis, vascularization of the cornea, stromal keratitis and extraocular disease (herpetiform spread) than +/+ BALB/c mice. The extraocular disease was particularly severe in the +/nu mice, suggesting that factors regulating herpetiform spread of the virus are deficient in these mice. Susceptibility to lethal encephalitis did not differ between +/+ and +/nu mice. These results suggest that significant differences exist in the response to ocular HSV infection between +/+ and +/nu mice.
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PMID:Susceptibility of +/+, +/nu and nu/nu BALB/c mice to ocular herpes simplex virus infection. 128 12

Different manifestations on some ocular and adnexal structures may accompany ichthyosis. Some ophthalmological manifestations in the clinical course of ichthyosis may endanger the eye and even lead to the sight loss. The paper reports a case of a patient with congenital ichthyosiform erythrodermia and ophthalmological manifestations on the lids and cornea. In addition to ichthyosis of the lid skin, squamous blepharitis and cicatricial ectropium of the lower lids were also present, while signs of exposure keratitis on the right eye and corneal leucostaphyloma on the left eye were also noted. Presence of lagophthalmos and permanent exposure of both eyeballs led to deterioration of the condition which may result in the sight loss on the right eye, as well. Therefore, contracture release of both lower lids was performed followed by full-thickness skin graft. Surgical procedure and the postoperative course were uneventful. The operation successfully corrected position of the lower lids and enabled formation and reestablishment of the precorneal tears film which led to improvement of the condition of the cornea. The effect has been maintained for six postoperative years now.
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PMID:[Ophthalmologic manifestations in patients with ichthyosis]. 130 16

Previous studies to determine the efficacy of new antiviral compounds in treating HSV ocular infections have used rabbit models. However, rabbits are expensive to purchase and maintain, and require the use of substantial amounts of test compounds. We have used the currently licensed antiviral trifluorothymidine in a murine model of HSV-induced ocular infection to demonstrate that the less expensive murine model can be used for the in vivo evaluation of potentially useful antiviral compounds. Treatment with TFT reduced the severity of blepharitis, vascularization of the cornea, stromal keratitis, and the percentage of animals developing symptoms. TFT treatment did not reduce the peak titers of infectious virus in the eyes of the infected animals, but did enhance clearance of virus from the tissues in a dose-dependent manner. Treatment with 1.0% TFT prevented the establishment of reactivatable latent infections. However, treatment with 0.01% or 0.1% TFT did not affect latency. The ED50 values for blepharitis, vascularization, and stromal keratitis ranged between 0.007% and 0.023%. These results are very similar to results obtained in rabbits and establish baseline data for comparing rabbit and murine models. This murine model provides a potentially less expensive alternative for in vivo drug testing.
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PMID:A murine model of herpes simplex virus-induced ocular disease for antiviral drug testing. 156 Jan 5

Nine months after leaving the Lebanon, a four-year-old immigrant boy presented with a 5 months history of blepharitis. The lesion remained therapy-resistant for aminoglycoside antibiotics. Six months later, the patient presented with an indolent granulomatous necrotizing purulent blepharitis and follicular conjunctivitis. Diagnosis was made by Giemsa stain and histopathology, which revealed amastigotes in macrophages consistent with the diagnosis of oriental cutaneous leishmaniasis. Therapy with systemic recombinant gamma Interferon, which is described for the first time in this disease entity, resulted in a successful primary healing of the cutaneous lesion. Self-healing epithelial keratitis was the only side-effect observed. Ophthalmologists in Germany should be aware of the differential diagnosis of oriental cutaneous Leishmaniasis in patients suffering from chronic granulomatous lid lesions of patients from countries endemic/epidemic for Leishmaniasis. Laboratory diagnosis is simple. Insights into the immunology of infection have made possible novel therapeutic avenues using gamma-Interferon being effective without serve side-effects and allowing for a good primary healing of the cutaneous lesions.
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PMID:[Unilateral chronic granulomatous blepharitis as a leading symptom of Oriental cutaneous leishmaniasis in Germany. Giesma stain as rapid diagnosis and initial description of systemic therapy with gamma-interferon]. 157 80

An intertypic recombinant isolated from rabbit kidney cells following co-transfection of HSV-1(17) and HSV-2(186) DNA failed to induce overt ocular pathology when inoculated onto the murine sacrificed cornea at concentrations as high as 10(7) PFU per eye. In contrast, both parents induced corneal disease at a 1000-fold lower dose. The reason(s) for the failure of the intertypic recombinant, designated RO25X, to induce corneal pathology was investigated. It was found that the recombinant was 100-fold more sensitive to the inhibitory effects of interferon (IFN) alpha/beta than the parent strains in corneal button growth studies in vitro. R025X readily grew in cultured mouse corneal fibroblasts at a low multiplicity of infection. However, the peak titer was approximately 8-fold lower than that of strain 17. Addition of rabbit anti-IFN alpha/beta to the culture medium resulted in a 4 to 5-fold increase in infectious titer compared to its growth in the absence of antiserum. Most significantly, when mice were pre-treated in vivo with anti-IFN alpha/beta 24 hours prior to virus corneal infection, 67% of the recipients developed moderate to severe stromal keratitis, whereas none of the controls developed corneal pathology. Blepharitis was also significantly increased in incidence and severity in the antiserum treated hosts. We conclude that the inability of R025X to induce ocular disease was due, at least in part, to the inhibitory effects of interferon produced in response to infection.
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PMID:Evidence endogenous interferon production contributed to the lack of ocular virulence of an HSV intertypic recombinant. 165 Jun 72

We used a herpes simplex virus (HSV) type 1 ribonucleotide reductase (RR) null mutant (ICP6 delta) to study the role of HSV-1 RR in ocular HSV infections. We found that ICP6 delta was unable to induce vascularization of the cornea or stromal keratitis following inoculation into the cornea of BALB/c mice, but was able to induce a transient mild blepharitis. The parental strain (HSV-1 KOS) and a revertant of ICP6 delta, ICP6 delta+3.1, both caused severe ocular disease, indicating that HSV-1 RR is required for ocular virulence in mice. ICP6 delta grew poorly in vitro (Vero and BALB/c 3T3 fibroblasts) and in vivo (eye, trigeminal ganglia and brain) compared to ICP6 delta+3.1 and HSV-1 KOS, suggesting that the avirulence of ICP6 delta is due to poor growth in the host. ICP6 delta also grew less well in primary human corneal fibroblasts, suggesting that RR may be required for virulence in humans. These results indicate that drugs inhibiting the function of RR might be effective in treating ocular HSV infections.
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PMID:The herpes simplex virus ribonucleotide reductase is required for ocular virulence. 165 68

Seven monoclonal antibodies (mAb) specific for defined discontinuous and continuous epitopes on glycoprotein D of herpes simplex virus type 1 (HSV-1) were surveyed for their capacity to protect against virus-induced corneal disease in a murine ocular infection model. A known amount of purified mAb was transferred passively to BALB/c mice 24 hr after topical infection with HSV-1 on their scarified corneas. At high doses (50-136 micrograms), all seven mAbs protected against the development of persistent necrotizing stromal keratitis. Significant protection was also observed at low doses (20 micrograms) with two mAbs to discontinuous epitopes and two mAbs to continuous epitopes. Selected high-dose mAbs also were able to reduce the severity of blepharitis. These results indicated that at least seven different antigenic sites on glycoprotein D can serve as targets for effective antibody therapy in the murine model of HSV-1 ocular infection.
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PMID:Prevention of herpes keratitis by monoclonal antibodies specific for discontinuous and continuous epitopes on glycoprotein D. 171 18

Sixty-seven patients undergoing allogenic bone marrow transplantation (BMT) were examined before and at regular intervals for up to 87 months (1-87 months, mean 18) after transplantation. Within a period of 1-39 months, 14 of these patients died (11 male, 3 female; age at BMT 16-46y). Five of these patients died within the first 100 days. They showed no eye involvement; three patients had intraretinal hemorrhage, in one case of squamous blepharitis and filiform keratitis developed during chronic graft-versus-host disease (GVHD). In contrast, 22 of 53 (41.5%) surviving patients (30 male, 23 female; age at BMT 1-47y) were found to have ocular involvement. Before BMT only two cases of retinal hemorrhage and central chorioretinal scars each were detected. During the stage of acute GVHD (up to day 100), nine patients were free of ocular manifestations. However, 16 of the 20 patients with chronic GVHD showed ocular involvement; 14 (70%) had reduced tearflow, ten had severe keratoconjunctivitis sicca, four suffered from sterile corneal ulcerations. Bilateral cataracts were detected in 11 patients, nine of whom only had minimal posterior subcapsular opacification, possibly resulting from highdose steroid medication. One additional case presented with bilateral multifocal recurrent chorioretinitis and panuveitis. The fundus lesions appeared some months after BMT (before cyclosporin-A treatment started) and recurred during systemic treatment. All patients undergoing allogenic BMT, especially when treated for severe chronic GVHD, require regular ocular observation to avoid complications such as keratoconjunctivitis sicca at an early stage, as late complications are often severe and hardly amenable to conservative or surgical treatment.
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PMID:Manifestations of graft-versus-host disease following allogenic bone marrow transplantation. 182 Nov 95

The authors used the method of mixed ocular infection and subsequent in vivo selection to isolate Herpes simplex virus type 1 intratypic recombinants with increased ocular virulence and neurovirulence. Four recombinants were studied in some detail (DRG1A3, DRG2A2, DRG3A3, and DRG4A1). The recombinants had lethal doses in 50% of animals tested (LD50) at least 2-3 log units lower than either parent virus (OD4 and CJ394) and caused significantly more severe stromal keratitis, vascularization of the cornea, and blepharitis than either parent. Studies on the ability of DRG1A3 and DRG4A1 to replicate in the eye, trigeminal ganglia, and brain showed that these recombinants replicated to higher titers (1-3.5 log units) than the parents in all three tissues. One of the parents, OD4, spread to the central nervous system with the same kinetics as CJ394, DRG1A3, and DRG4A1 but had a restricted ability to replicate in all tissues, which may account for its lack of virulence. The other parent, CJ394, was nonneurovirulent but replicated to titers which were only 1-1.5 log units lower than the neurovirulent recombinants. These recombinants should be useful in studying virulence determinants in herpetic ocular infections.
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PMID:Mixed infection with herpes simplex virus type 1 generates recombinants with increased ocular and neurovirulence. 217 82

Since July 1985, 23 patients have been entered into a phase I/II clinical trial using intraarterial 5-bromodeoxyuridine (BUdR) (400-600 mg/m2 daily for 8.5 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy daily in 6.5 weeks) in the treatment of malignant gliomas (Kernohan grades 3 and 4). The side effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Mucopurulent conjunctivitis and exposure keratitis developed in several patients and spontaneous corneal perforation developed in one. Eyes from two individuals examined at autopsy showed significant changes. Animal studies that predated clinical trials using rhesus monkeys did not predict the ophthalmologic complications seen in human subjects.
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PMID:The ocular effects of intracarotid bromodeoxyuridine and radiation therapy in the treatment of malignant glioma. 218 31


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