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)

A diagnostic hybridization assay for detecting herpes simplex virus type 1 (HSV-1) in ocular specimens was developed using cloned viral DNA as a probe. This hybridization assay is based on visualizing a biotinylated probe that is hybridized to the target DNA by a streptavidin/alkaline phosphatase system. The time required for performing this assay system is only two days. This assay system could detect a probe which had been hybridized to as little as 1 pg of homologous DNA and did not cross-react with DNA of other human herpes viruses except that of herpes simplex virus type 2 (HSV-2) which showed weak cross-reactivity. The assay system was applied to experimental keratitis in albino rabbits and clinical specimens. In experimental keratitis in rabbits it was possible to detect HSV-1 DNA in the eye swab samples at least until the ninth day after virus inoculation. Five clinical specimens collected from patients with corneal ulcer or blepharitis contained HSV-1 DNA in spite of the failure of demonstration of viral antigen and/or virus isolation in two cases.
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PMID:Detection of herpes simplex virus type 1 in herpetic ocular diseases by DNA-DNA hybridization using a biotinylated DNA probe. 284 77

This study evaluated the continued presence of herpes simplex virus (HSV) nucleic acid sequences after resolution of acute herpetic stromal keratitis in the rabbit ocular model. Forty-four rabbits were inoculated bilaterally with 10(5) plaque-forming units of RE strain HSV-1 by intrastromal injection. All eyes were cultured for the presence of HSV during acute disease and immediately before the animals were killed. Full-thickness corneal buttons were then removed and processed for in situ hybridization with a 3H-labelled HSV DNA probe representing the full-length HSV genome. HSV nucleic acid sequences were detected autoradiographically at all time intervals examined. HSV nucleic acid sequences were localized in the epithelium and the anterior stromal keratocytes during acute disease and in all corneal layers during latent infection. Retention of HSV nucleic acid sequences, either HSV DNA or HSV RNA, or both, in corneal tissues (epithelium, stroma, and endothelium) may be a contributing factor in the development of HSV-induced stromal keratitis.
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PMID:Detection of HSV nucleic acid sequences in the cornea during acute and latent ocular disease. 284 36

Hematoporphyrin (HP), at concentrations as low as 0.5 microgram/ml, was found to inhibit the in vitro replication of influenza A and herpes simplex viruses, but not of several other viruses. The effect required exposure of the viruses or cells to visible light and was demonstrable when HP was administered shortly before virus inoculation or during the infection. In studies on the mechanism of action of HP, we found that in the presence of light, HP caused decomposition of GMP but not of various other nucleosides. It caused breakdown of yeast tRNA and inhibited polymerization of RNA and DNA by influenza virus and HSV-1-specific polymerases as well as some other polymerases isolated from bacterial and mammalian sources. Protective effects of HP and light were demonstrable in embryonated eggs infected with the WSN and PR8 strains of influenza A virus and in mice infected with the WSN strain. HSV-1-induced keratitis in rabbits and HSV-2-induced dermatitis in mice were not responsive to HP treatment.
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PMID:Photodynamic inactivation of influenza and herpes viruses by hematoporphyrin. 302 46

Primary inoculation of mice and rabbits with an avirulent HSV-1 thymidine kinase negative (TK-) mutant reduced keratitis, mortality, and superinfection of the trigeminal ganglion (TG) as measured by cocultivation and iontophoresis-induced ocular shedding following ocular challenge with HSV-1 McKrae and W strains. However species differences were demonstrated; with complete protection in rabbits, and incomplete protection in mice. In mice, BUDR/autoradiography and restriction enzyme analysis identified both HSV-1 McKrae and W strains as having superinfected the TG, established latency and reactivated. Also, the avirulent TK negative inoculating strain was altered to a virulent TK positive strain through possible in vivo selection, mutation &/or host-modification, and possible in vivo recombination with the virulent challenge strains. We conclude that lower species differences require that potential HSV-1 vaccines be tested in non-human primates prior to clinical trials, and that a DNA-free subunit herpes vaccine represents a safer alternative to a live virus vaccine.
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PMID:HSV-1 thymidine kinase negative vaccine: pathogenicity, protection, and perils. 303 Jun 39

An intertypic recombinant constructed from HSV-1 x HSV-2 parents was isolated which failed to induce any overt ocular pathology when inoculated onto the sacrificed cornea of four-week-old SJL/J mice. During the 24-48 hour post-infection period there was transient virus replication but by day 3 the infectious titer in the eye had dropped by greater than or equal to 10(4)-fold, and little or no virus could be recovered thereafter. When immunosuppressed (600 r) mice were infected corneally, virus clearance was delayed several days but again no obvious ocular pathology was seen, and no mice died. By contrast, infection of the cornea with either parent was followed by virus replication and development of clinically apparent pathology which could progress to blinding stromal keratitis. The genome of the intertypic recombinant was analyzed by agarose gel electrophoresis of restriction endonuclease digests and found to consist entirely of HSV-1 DNA except for HSV-2 DNA sequences located between map units 0.10-0.16, 0.41-0.43, and 0.77-1.0. Potential explanations for the loss of virulence are discussed.
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PMID:Failure of intertypic recombinant constructed from HSV-1 x HSV-2 virulent parents to induce ocular pathology. 303 Jun 49

Acyclovir, an oral antiviral agent that inhibits viral DNA replication, was used to treat 27 patients (16 males, 11 females) (mean age, 50 years) with vision-threatening herpes simplex virus (HSV) infections. Twenty patients had active stromal keratitis or keratouveitis, four had controlled nonnecrotizing stromal keratitis but could not taper topical medications, and four eczema patients with previous HSV infections had intraocular surgery (1 of these patients also is included in the 20 with active stromal keratitis). All 20 patients with active stromal keratitis or keratouveitis improved on acyclovir, all four patients using acyclovir postoperatively were disease-free while on the drug, but only two of the four patients using acyclovir to assist tapering topical medications were successful. There has been only one recurrence during a cumulative 194 months while on acyclovir. Thirteen patients have remained on acyclovir, and three who stopped acyclovir had prompt recurrences. Acyclovir seems to be a promising adjunct antiviral agent for the treatment of recalcitrant epithelial, stromal, or uveal disease secondary to HSV.
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PMID:Oral acyclovir in the management of herpes simplex ocular infections. 317 10

To understand how human corneal endothelium compensates for cell loss, nuclear DNA-cytofluorometry and cell morphometry were carried out on injured corneal endothelium. The examined corneas included two cases of keratoconus complicated with acute hydrops and one without acute hydrops, two cases of herpetic keratitis, one case of post-intracapsular cataract extraction (post-ICCE) and one case of luetic keratitis. The endothelial cell layer was separated from Descemet's membrane and double-stained with Rhodamine-labeled wheat germ agglutinin-lectin (WGA) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI). The area of each cell was measured with a color image analyser and compared with its cytofluorometric nuclear DNA content. The endothelium in apparently intact regions of the diseased corneas showed the same DNA-ploidy pattern and cell area as the physiological corneas. However, endothelial cells in injured regions had greater area, even in diploidy, than in presumably normal ones and showed a larger number of hyperploid cells ranging from 4C to 36C. Hyperploid cells consisted of many multinucleates and few polyploidies and had extremely large and bizarre cytoplasm. All injured corneas were accompanied by cells with numerous micronuclei. A few asymmetrical 4C-binucleates (with DNA values such as 1.3 plus 2.6C) appeared in the case of the post-ICCE. It is concluded that damage to human corneal endothelial cells in vivo results in cell enlargement with or without DNA synthesis. Those changes appear more severe in diseased corneas than in the situation of physiological aging which we have reported previously. In severe cases, micronuclei, polyploid cells and multinucleated giant cells are frequent, thereby suggesting a possible long-persistent metabolic impairment of the endothelium after severe damage to the cornea.
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PMID:Changes in nuclear DNA content and cell size of injured human corneal endothelium. 340 92

A new compound has been found, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA), that has potent and selective activity against a broad spectrum of DNA viruses, including herpes simplex virus (types 1 and 2); varicella zoster virus; thymidine kinase-deficient (TK-) mutants of herpes simplex and varicella zoster virus; human cytomegalovirus; phocid, simian, suid, bovid and equid herpesviruses; African swine fever virus; vaccinia virus; and human adenoviruses. It is also active against retroviruses. We also report that, in mice and rabbits in vivo, the compound is effective against both local and systemic infections with herpes simplex virus type 1, including herpetic keratitis caused by a TK- mutant which is resistant to the classical anti-herpes drugs.
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PMID:A novel selective broad-spectrum anti-DNA virus agent. 376 96

Virazole is a synthetic nucleoside active in tissue culture against at least 16 DNA and RNA viruses. Applied topically, it inhibits herpetic keratitis in rabbits and tail lesions induced by herpes, vaccinia, and vesicular stomatitis viruses in mice. Injected intraperitoneally into mice, it inhibits splenomegaly and hepatomegaly induced by Friend leukemia virus and respiratory infections caused by influenza A(O), A(2), and B viruses and parainfluenza 1 virus. infections is also effective.
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PMID:Broad-spectrum antiviral activity of Virazole: 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide. 434 Sep 49

Acyclovir (aciclovir) is a nucleoside analogue antiviral drug related to cytarabine, idoxuridine, trifluridine and vidarabine. In common with these earlier antivirals, acyclovir is active against some members of the herpesvirus group of DNA viruses. The efficacy of topical acyclovir has been convincingly demonstrated in ocular herpetic keratitis, and in initial and primary initial genital herpes infection, but little or no clinical benefit was seen when non-primary initial genital infections were assessed separately. Acyclovir ointment demonstrated little benefit in recurrent genital herpes but topical acyclovir cream decreased the course of the infection by 1 to 2 days. Orally and intravenously administered acyclovir were beneficial in initial genital herpes infections, and oral therapy shortened the duration of recurrent infections by 1 to 2 days but did not ameliorate pain. In non-immunocompromised patients with recurrent herpes simplex labialis, generally little clinical benefit was seen with the use of topical acyclovir ointment even when therapy was initiated during the prodromal phase, while topical acyclovir cream effected small but significant improvements in the clinical but not the symptomological course of the disease. However, in immunocompromised patients, both intravenous and topical acyclovir shortened the clinical course of herpes simplex virus infections occurring mainly on the lips, oral mucosa and face, and prophylaxis with either oral or intravenous acyclovir suppressed the appearance of recurrent lesions from latent virus for the period of drug administration, but acyclovir did not eradicate latent herpesviruses. In non-immunocompromised patients, intravenous acyclovir was shown to decrease the acute pain of zoster, especially in the elderly, but postherpetic neuralgia was not ameliorated. When immunocompromised patients were studied, intravenous acyclovir inhibited the progression of zoster infections and shortened the healing time and duration of viral shedding in patients with cutaneous disseminated zoster. However, acute and post-herpetic pain were not significantly affected. Well designed controlled studies are underway to establish the efficacy of acyclovir in herpes simplex encephalitis and cytomegalovirus infections in immunocompromised patients, infections due to Epstein-Barr virus, and neonatal herpesvirus infections. Despite some aspects of the drug's use which require further clarification, acyclovir will make a major impact on the treatment of herpesviral infections. Barring unexpected findings with wider clinical use, it will become the agent of choice in several conditions.
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PMID:Acyclovir. A review of its pharmacodynamic properties and therapeutic efficacy. 631 32


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