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Biomedical subjects

J Chodosh

Publications and source records attributed to J Chodosh.

At least 19 recordsLinked to original sources

Photorefractive keratectomy for myopia in the setting of Thygeson's superficial punctate keratitis.

PURPOSE: To describe a patient with Thygeson's superficial punctate keratitis who underwent photorefractive keratectomy for the correction of myopia. METHODS: A 49-year-old woman with unilateral Thygeson's keratitis was examined before and after photorefractive keratectomy. RESULTS: A myopic patient underwent photorefractive keratectomy in the left eye and gained 20/20 uncorrected visual acuity. Seventeen months after surgery, symptomatic Thygeson's keratitis lesions recurred in the peripheral but not the central cornea. CONCLUSION: Photorefractive keratectomy reliably corrected myopia in a patient with previous Thygeson's keratitis. The recurrence of lesions only in the peripheral untreated cornea suggests that the inflammatory signal in Thygeson's keratitis may reside in the superficial corneal stroma.

Cornea↗

Cat's tooth keratitis: human corneal infection with Capnocytophaga canimorsus.

PURPOSE: To describe a patient with keratitis caused by Capnocytophaga canimorsus after traumatic injury with a cat's tooth. METHODS: Case report and review of the literature. RESULTS: Sixteen months after onset of infection, the patient regained 20/30 vision in the affected eye. However, he required 7 months of antibiotic therapy to eliminate the infection. CONCLUSION: C. canimorsus keratitis may follow penetrating corneal injury and wound contamination with cat saliva and may be recalcitrant to topical antibiotic therapy.

Adult↗

Patterned entry and egress by Epstein-Barr virus in polarized CR2-positive epithelial cells.

In polarized epithelium direction of viral entry and release correlates with proclivity of a virus to establish local versus systemic infection. The Epstein-Barr virus (EBV), whose principal tissue reservoir is B lymphocytes, also has disease manifestations in epithelium, suggesting intertissue spread potentially influenced by epithelial cell polarity. We stably transfected the B lymphocyte EBV receptor (CR2/CD21) into Madin-Darby canine kidney (MDCK) epithelial cells used extensively to study effects of cell polarity on infection by both DNA and RNA viruses. CR2/CD21 was detected on both apical and basolateral surfaces of polarized MDCK cells, with predominant expression basolaterally. However, infectivity was up to four-fold greater apically, suggesting that endogenous cell surface molecules, sorted asymmetrically onto polarized plasma membranes, may be involved in EBV entry into MDCK cells. EBV gp350/220, a replicative cycle glycoprotein added to the virus envelope on egress through the cell membrane, was immunolocalized by confocal microscopy to basolateral cell surfaces only. Apical entry of EBV with subsequent basolateral release of newly replicated virus favors systemic infection by viral dissemination to underlying lymphocytic aggregations. Under conditions of long-term culture, latent EBV was not stably maintained in these cells, suggesting that the epithelial phase of acute EBV infection may be transient.

Animals↗

Adenovirus keratitis: a role for interleukin-8.

PURPOSE: Adenovirus type 19 (Ad19) infection of the human cornea results in a chronic, multifocal, subepithelial keratitis. Existing evidence suggests that early subepithelial corneal infiltrates are composed of polymorphonuclear neutrophils. In this study, the capacity of Ad19-infected human corneal stromal fibroblasts (HCFs) to produce neutrophil chemotactants (chemokines) was tested. METHODS: HCFs grown from human donor corneas and passaged thrice were infected with a corneal isolate of Ad19 or mock-infected with virus-free media. Bioactivity of the cell supernatants was tested by a neutrophil chemotaxis assay. Supernatants were assayed by enzyme-linked immunosorbent assay for the neutrophil chemotactants interleukin-8 (IL-8) and GRO-alpha. Corneal facsimiles were generated with HCFs and collagen type I, infected with Ad19, and assayed by immunohistochemistry. RESULTS: Ad19 infection of HCFs increased neutrophil chemotaxis from a baseline of 0.4+/-0.7 cells/high-powered field (hpf; mock-infected) to 21.8+/-2.3 cells/hpf (Ad19-infected). Chemotaxis was reduced by the addition of neutralizing antibodies against IL-8 and GRO-alpha. Infection of HCFs induced quantities of IL-8 protein 300- and 1000-fold over mock-infected controls at 4 and 24 hours, respectively (33 versus 11,813 pg/mL at 4 hours, and 57 versus 76,376 pg/mL at 24 hours, P< or = 0.001 for both). In contrast, GRO-alpha protein levels were only sevenfold higher at 24 hours postinfection (118 pg/mL in mock-infected controls versus 880 pg/mL in Ad19-infected cell supernatants). Neither chemokine was induced by infection of an immortalized human corneal epithelial cell line. Immunohistochemistry of infected corneal facsimiles demonstrated IL-8 in the extracellular matrix within 3 days after infection. CONCLUSIONS: Production of chemokines in infected tissues facilitates an early innate immune response to infection, and in the infected corneal stroma represents an elementary defense mechanism. Interleukin-8 may play a role in the development of subepithelial infiltrates in adenovirus keratitis.

Adenoviridae↗

PCR assessment of HSV-1 corneal infection in animals treated with rose bengal and lissamine green B.

PURPOSE: In vivo, the ophthalmic dye rose bengal displays profound antiviral effects against herpes simplex virus (HSV)-1, thus limiting its utility in diagnosis of epithelial keratitis when used before viral culture is performed. In contrast, lissamine green B does not possess significant antiviral activity in vivo. To determine whether polymerase chain reaction (PCR) could successfully detect HSV-1 DNA in ocular samples that have been exposed to ophthalmic dyes, animal models were used to observe the presence of infectious HSV-1 and viral DNA in eyes treated with rose bengal or lissamine green B. METHODS: Animals were bilaterally infected with HSV-1 strain H129, and at daily intervals up to 16 days post infection (dpi) rose bengal or lissamine green B was instilled in the left eyes. The right eyes were not treated with dyes. Swabs of the dye-treated and untreated eyes were assayed by PCR for viral infectivity by culture and the presence of DNA specific for a fragment of the HSV-1 DNA polymerase gene. RESULTS: A statistically equivalent number of samples from lissamine green B-treated and untreated eyes were positive by both viral culture and PCR. In contrast, rose bengal significantly decreased the infectious virus present in ocular secretions. A total of 44% and 78% of the rose bengal-treated and untreated eye samples, respectively, were positive by culture from 1 through 16 dpi. PCR was more sensitive than culture for detection of HSV-1 in rose bengal-treated eyes, in that 74% of rose bengal-treated samples were positive by PCR compared with 44% that were positive by culture during the 16-day period studied. It was also noted that both rose bengal and lissamine green B treatments slightly prolonged the period during which viral DNA was detectable in ocular secretions by PCR, possibly because the singlet oxygen produced by these photoreactive dyes compromised ocular cellular, humoral, and nonspecific immune factors allowing viral DNA to persist for slightly longer periods. CONCLUSIONS: PCR can successfully detect HSV-1 DNA in ocular samples that are culture negative and contain rose bengal or lissamine green B. Visualization of ocular epithelial defects with lissamine green B does not interfere with detection of infectious virus or HSV-1 DNA.

Animals↗

Comparison and characterization of immunoglobulin G subclasses among primate species.

Little information is available on the immunoglobulin G (IgG) subclasses expressed in the sera of nonhuman primate species. To address this issue, we compared the IgG subclasses found in humans (IgG1, IgG2, IgG3, and IgG4) to those of nonhuman primates, such as baboons and macaques. Cross-reactive antihuman IgG subtype-specific reagents were identified and used to analyze purified IgG from sera by solid-phase enzyme-linked immunosorbent assay. Protein A-purified human IgG obtained from sera was composed of IgG1, IgG2, IgG3, and IgG4, whereas baboon and macaque IgG was composed of IgG1, IgG2, and IgG4. Protein G-purified human IgG was composed of IgG1, IgG2, IgG3, and IgG4, whereas baboon and macaque IgG was composed of IgG1, IgG2, and IgG4. To test the possibility that baboon and macaque IgG3 is actually present, but is outcompeted for binding to proteins A and G by the other more abundant IgG subclasses, we repurified the IgG from sera that did not bind either protein A or protein G. We found a baboon IgG3 population in the sera that did not bind protein A, but bound protein G. No IgG3 subtype was detectable in macaque sera. These data suggest that baboon sera, like human sera, contain four IgG subtypes, whereas macaque sera exhibit only three of the human subclass analogs. In addition, the IgG subtype-specific reagents were shown to be useful in determining the IgG subclass distribution following vaccination of baboons with hepatitis B surface antigen.

Animals↗

Anatomy of mammalian conjunctival lymphoepithelium.

Ocular surface immune mechanisms are subservient to the fine function of the eye. A clear cornea with a smooth, well-lubricated facade is prerequisite to lucid vision. Hence, corneal inflammation and post-inflammatory scarring are intolerable, and the cornea contains a minimum of lymphoid elements. Although conjunctival dysfunction and consequent tear film deficiency can malign the corneal surface, conjunctival inflammation is tolerated to a considerable degree. In contrast to the human cornea, human conjunctiva contains an abundance of lymphoid tissue. Certain aspects of human conjunctival immunology elicit little debate. Langerhans cells are abundant in conjunctival epithelium. Isolated CD8+ suppressor/cytotoxic T cells predominate in conjunctival epithelium, while T cells in the substantia propria distribute equally between CD4+ T helper cells and CD8+ cells. Yet the presence of plasma cells in human conjunctiva, the expression of secretory component by human conjunctival epithelium, and the function of human conjunctival lymphoid follicles are in dispute. Confusion may derive in part from the use of inappropriate animal models; rodent conjunctiva does not appear to be a worthy facsimile for human conjunctiva. Discrepancies between different human studies likely result from variance in subject age, biopsy site and extent, histologic or histochemical technique, and perhaps the degree of inflammation present at the time of biopsy. Careful immunohistochemical and in situ molecular assays on well-defined loci within the conjunctiva of comparable human subjects may resolve such questions in the future. Organized mucosa-associated lymphoid tissue is rigorously defined as mucosal lymphoid follicles with an ultrastructurally distinct overlying lymphoepithelium. Based on available evidence, the epithelium overlying mammalian conjunctival lymphoid follicles does not contain distinct M cells. Whether zonal differences in morphology reflect real differences in the capacity to sample tear film antigens for presentation to the mucosal immune system remains to be established.

Animals↗

Photorefractive keratectomy for myopia in the setting of adenoviral subepithelial infiltrates.

PURPOSE: To report a patient with persistent subepithelial corneal opacities 18 months after adenoviral keratoconjunctivitis who underwent photorefractive keratectomy for the correction of myopia. METHODS: Case report, review of medical literature, and slit-lamp photography. RESULTS: The patient underwent photorefractive keratectomy in each eye, 1 week apart, with ablation of central corneal opacities and resultant best-corrected visual acuity of BE, 20/20. Symptomatic subepithelial stromal infiltrates recurred in the peripheral but not the central cornea of each eye 3 months after laser treatment. CONCLUSIONS: Photorefractive keratectomy was successful in the correction of myopia and prevented the recurrence of adenoviral subepithelial corneal infiltrates within the laser-treated central cornea.

Adenovirus Infections, Human↗

Postoperative Rhizopus scleritis in a diabetic man.

A 50-year-old diabetic man developed necrotizing scleritis with adjacent keratitis 4 weeks after uncomplicated cataract extraction and intraocular lens implantation through a scleral tunnel incision. Cultures of the necrotic sclera grew Rizopus species. Severe destruction of the globe ensued despite topical, subconjunctival, and intravenous amphotericin B, in combination with hyperbaric oxygen therapy. Histopathological examination of the enucleated globe was consistent with Rhizopus infection. One year later, the patient was well without signs of recurrence.

Antifungal Agents↗

Eradication of latent Epstein-Barr virus by hydroxyurea alters the growth-transformed cell phenotype.

The hallmark of infection by human herpesviruses, life-long persistence in the host, is unaffected by current antiviral therapies effective against replication of virus. In vitro studies indicated that low concentrations of the ribonucleotide reductase inhibitor, hydroxyurea, completely eliminated Epstein-Barr virus (EBV) episomes from latently infected Burkitt's lymphoma (BL) cell subsets, providing the first example of chemotherapeutic eradication of a latent herpesvirus from any cell population. Unlike parental EBV-positive BL cells, virus-free cell progeny from one treated cell line no longer exhibited the malignant phenotype in tumorigenicity assays. Hydroxyurea-treated primary B lymphocytes immortalized by EBV ceased to proliferate as episomes were lost. The altered growth phenotype of both BL cells and immortalized primary B cells suggests that latent EBV is an appropriate and accessible therapeutic target for treatment of some EBV-induced lymphoproliferations.

Animals↗

Molecular epidemiology of Staphylococcus aureus and Enterococcus faecalis in endophthalmitis.

Genomic DNA fingerprint analysis was performed on 39 Staphylococcus aureus and 28 Enterococcus faecalis endophthalmitis isolates collected from multiple clinical centers. Among 21 S. aureus genomic DNA fingerprint patterns identified, five clonotypes were recovered from multiple unrelated patients and accounted for 58.9% (23 of 39) of the isolates analyzed. Compared with strains having unique genomic DNA fingerprint patterns, the S. aureus clonotypes occurring more than once were more likely to result in visual acuities of 20/200 or worse (P = 0.036 [chi2 test]). In contrast to the S. aureus isolates, the E. faecalis endophthalmitis isolates were a clonally diverse population, enriched for the expression of a known toxin, cytolysin, which is plasmid encoded.

Bacterial Typing Techniques↗

Purification and characterization of secretory IgA from baboon colostrum.

In this report, we describe a method for purifying secretory immunoglobulin A (sIgA) from baboon (Papio anubis) colostrum. The colostrum was first clarified by centrifugation and then analyzed with various anti-human Ig-specific immunologic reagents. Cross-reactive IgA in the baboon colostrum was identified by ELISA. Western blot analysis also demonstrated cross-reactive epitopes associated with human IgA1, IgA2, secretory component (SC), and joining (J) chain. To purify the sIgA, colostrum was separated into 4 distinct fractions by gel filtration chromatography. Analysis of the individual fractions by ELISA indicated that the IgA elutes over one peak. The IgA fraction was compared with purified human sIgA on SDS-PAGE, and exhibited heavy (H) chains, light (L) chains, SC, and J chain. The baboon colostrum was also analyzed by ELISA for specific IgG H and L chain epitopes utilizing monoclonal antibodies (MAbs). No significant quantity of IgG was detected in the baboon colostrum or in the individual 4 fractions, while L chain reactivity was observed in the sIgA fraction. The sIgA fraction was pooled, concentrated, and was found to contain approximately 7 mg/ml sIgA. To determine if the baboon sIgA was dimeric like human sIgA, the purified sIgA was sized by molecular sieve chromatography. The molecular size of the sIgA preparation (350 kDa) was determined empirically by comparison to known molecular species used to calibrate the column. In addition, native SDS-PAGE indicated that baboon sIgA, like human sIgA, migrates between IgG and IgM, suggesting it has a dimeric form. The purified baboon sIgA preparation should prove useful in the future study of mucosal immune responses induced in non-human primate species and for the generation of sIgA-specific immunological reagents.

Animals↗

Acanthamoeba infection after radial keratotomy.

PURPOSE: To describe a case of Acanthamoeba infection of the cornea after radial and astigmatic keratotomy. METHODS: A 29-year-old man developed ulcerative keratitis in the right eye 6 weeks after uncomplicated radial and astigmatic keratotomy. RESULTS: Three sets of corneal cultures for bacteria and fungi were negative. Culture on non-nutrient agar grew Acanthamoeba organisms. Clinical improvement occurred after topical antiamebic therapy was instituted. CONCLUSIONS: Incisional keratotomy may predispose the cornea to delayed-onset infectious keratitis. Acanthamoeba should be considered as a possible cause of infection and should be cultured for in refractory cases.

Acanthamoeba↗