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Biomedical subjects

J Sugar

Publications and source records attributed to J Sugar.

At least 37 records · Page 2Linked to original sources
PubMed1998

Expression of degradative enzymes and protease inhibitors in corneas with keratoconus.

PURPOSE: Keratoconus is characterized by thinning and scarring of the central region of the cornea. Previous research showed that, in corneas obtained from patients with keratoconus, lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha1-proteinase inhibitor are reduced. This study was undertaken to examine further the expression of a spectrum of proteolytic enzymes and protease inhibitors. METHODS: Corneal buttons were collected from patients with keratoconus, healthy subjects, and patients with other corneal diseases. Immunohistochemical staining was performed on paraffin sections. Enzymatic assays and western blot analysis were carried out for cathepsins B and G. In addition, an in situ zymography procedure was used to examine the gelatin- and casein-digesting activities in corneas with keratoconus. RESULTS: An enhanced staining was found with antibodies to cathepsins B and G. Enzymatic assays and western blotting confirmed that the levels of these two enzymes were elevated in corneas with keratoconus. No alteration was noted with any of the matrix metalloproteinase (MMP) family members and other enzymes and inhibitors examined, although in situ zymography did indicate an increase in net gelatin- and casein-digesting activities in corneas with keratoconus. These activities were mostly abolished by inhibitors for serine and cysteine proteinases, but not by those for MMPs and aspartic proteinases. CONCLUSIONS: Levels of cathepsins B and G are increased in corneas with keratoconus. These enzymes may contribute to the heightened in situ gelatin- and casein-digesting activities, leading to abnormalities in keratoconus.

Adolescent↗
PubMed1997

Expression of transcription factors in keratoconus, a cornea-thinning disease.

Transcription factors are known to regulate gene transcription through the recognition and binding of specific DNA sequences in the promoter or enhancer regions of many genes. Keratoconus is a cornea-thinning disease in which upregulated expression of degradative enzymes and downregulated expression of protease inhibitors have been demonstrated. In view of the alteration in gene expression for multiple proteins, five common transcription factors, AP1, AP2, CREB, Sp1, and NF-kappa B were examined for their possible roles in keratoconus. Immunostaining experiments and Western blotting showed that Sp1 exhibited enhanced expression in keratoconus corneas. Increased binding of Sp1 consensus sequence oligonucleotides with nuclear extracts from the epithelium of keratoconus corneas was also seen by gel mobility shift assays. This is believed to be a first demonstration connecting Sp1 alteration to a human disease. The elevated Sp1 expression may contribute to the enzyme and inhibitor abnormalities found in keratoconus corneas.

Adolescent↗
PubMed1997

Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience.

OBJECTIVE: The purpose of the study is to evaluate the efficacy and risks of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). DESIGN: The study design was a clinical case series of CCIN. PARTICIPANTS: Seventeen patients, 16 with biopsy-confirmed CCIN and 1 with invasive squamous cell carcinoma (SCC), were included in the study. INTERVENTION: Patients received topical drops of MMC 0.02% to 0.04% four times daily from 7 to 28 days. Retreatment was done in cases of lesion recurrence. MAIN OUTCOME MEASURES: The size of the CCIN before and after the treatment and ocular complications post-MMC application were evaluated. RESULTS: Ten patients remained disease-free after one course of MMC application. In one case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in five patients with CCIN, regrowth occurred within 6 months of the first treatment. After retreatment, invasive SCC and CCIN in an additional two patients were eradicated. In two cases, although the size of the lesions decreased after two and three applications of MMC, regrowth occurred, and the CCIN returned to its original size. In the final case, limited recurrence has occurred and no retreatment has been done. The complications of MMC use included mild-to-moderate conjunctival hyperemia and mild allergy, which resolved after discontinuation of the treatment. Severe pain manifested when treatment was longer than 14 days. CONCLUSIONS: Application of topical MMC is an efficient treatment for most but not all cases of CCIN.

Administration, Topical↗
PubMed1997

Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas.

PURPOSE: Keratoconus is characterized by thinning and scarring of the central region of the cornea. The authors have shown, in corneas obtained from patients with keratoconus, that lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha 1-proteinase inhibitor (alpha 1-PI) are reduced. This study was undertaken to examine further the gene expression of cathepsin G, acid phosphatase, and alpha 1-PI in keratoconus corneas. METHODS: Corneal buttons were collected from patients with keratoconus, normal subjects, and patients with other corneal diseases. In situ hybridization was performed on paraffin sections using a tritium-labeled probe for cathepsin G or alpha 1-PI. Competitive polymerase chain reaction (PCR) was used to determine the messenger RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and stromal cells of keratoconus corneas. RESULTS: Silver grains, indicative of positive in situ hybridization products, were observed in all three cell types of normal corneas for both DNA probes. Compared with normal and other diseased controls, the labeling was enhanced for cathepsin G but was diminished for alpha 1-PI in the epithelium of keratoconus corneas. Competitive PCR showed that the mRNA level for acid phosphatase was higher and that the mRNA level for alpha 1-PI was lower in keratoconus corneas. CONCLUSIONS: These results indicate that the mRNA level for degradative enzymes in increased and that for alpha 1-PI it is reduced in keratoconus corneas. This study provides the first evidence that the altered expression of multiple enzymes and inhibitors in keratoconus occurs at the gene level. Furthermore, it implicates a possible role of coordinated transcriptional regulation of gene expressions in keratoconus.

Acid Phosphatase↗
PubMed1996

Discrete nuclear sclerosis in young patients with myopia.

OBJECTIVE: To review a series of young patients with myopia who had a visually disabling cataract. DESIGN: A retrospective review of 12 consecutive patients who had a visually disabling cataract and who were examined at the Cornea Service of the University of Illinois at Chicago. RESULTS: The mean age of the patients was 44 years (range, 34-54 years). The mean best-corrected visual acuity of the patients was 20/50, and the ocular history of the patients included a progressive decrease in vision. Six patients experienced disabling monocular polyopia. Their presumed diagnoses ranged from keratoconus to myopic degeneration. All of the patients noted resolution of their symptoms after cataract extraction. CONCLUSIONS: These patients are a select group that tends not to follow the established associations between visually significant lens opacities, age, and myopia. Cataract extraction is therapeutic, and prompt diagnosis can obviate unnecessary testing and repeated office visits.

Adult↗
PubMed1996

Normal lysosomal enzyme staining in skin tissues of patients with keratoconus.

Keratoconus is a disease characterized by thinning and scarring of the central portion of the cornea. We have shown, in corneas and conjunctival tissues obtained from patients with keratoconus, that lysosomal enzyme staining is enhanced in the epithelial layer. In this study, we examined the lysosomal enzyme staining in skin-biopsy specimens of patients with keratoconus. Tissues collected from four patients with keratoconus and six normal subjects were fixed and processed for histochemical staining. Results showed that the epidermal and dermal layers of all skin specimens stained positively for two lysosomal hydrolases, acid esterase and acid phosphatase. The enzyme staining in the skin epidermal and dermal cells of the keratoconus patients was within the normal range. The staining in the corneal and conjunctival epithelia of the same patients was more prominent than that of normal controls. It appears that the biochemical abnormality identified in keratoconus is not manifested in the skin.

Acetylesterase↗
PubMed1996

Risk factors for herpes simplex virus epithelial keratitis recurring during treatment of stromal keratitis or iridocyclitis. Herpetic Eye Disease Study Group.

AIMS: Possible risk factors were evaluated for herpes simplex virus (HSV) epithelial keratitis in patients with stromal keratouveitis. METHODS: The study population included 260 patients who had active stromal keratitis and/or iridocyclitis without epithelial disease and who were enrolled in one of three clinical trials of the Herpetic Eye Disease Study. Study treatment involved a 10 week course of topical placebo, topical prednisolone phosphate, or topical prednisolone phosphate with oral acyclovir. All groups received topical trifluridine four times daily for 3 weeks then twice daily for another 7 weeks. Patients were examined for HSV epithelial keratitis for 16 weeks. RESULTS: Dendritic or geographic epithelial keratitis occurred in 12 (4.6%) study patients. Adverse effects attributable to trifluridine prophylaxis were acute allergic blepharoconjunctivitis in 10 (3.8%) study patients and corneal epithelial erosions in 11 (4.2%) study patients. No significant difference in the occurrence of HSV epithelial keratitis was found among the study treatment groups: one (2.0%) of 49 topical placebo treated patients, nine (6.5%) of 138 patients treated with topical corticosteroids without acyclovir, and two (2.7%) of 73 patients treated with topical corticosteroids and oral acyclovir. Univariate exponential models suggested that patients with a history of previous HSV epithelial keratitis and non-white patients were more likely to develop HSV epithelial keratitis during treatment of stromal keratouveitis. CONCLUSION: Individuals with prior HSV epithelial keratitis and certain ethnic groups may have a higher rate of recurrent epithelial keratitis during the acute treatment of HSV stromal keratouveitis.

Acyclovir↗
PubMed1996

Expression of wound healing and stress-related proteins in keratoconus corneas.

PURPOSE: Keratoconus is characterized by thinning and scarring of the central portion of the cornea. This study was performed on keratoconus corneas to examine the expression of proteins related to wound healing including vimentin, an intermediate filament protein, and tenascin, and extracellular matrix protein. The expression of stress-related cytokines, heat shock proteins and ubiquitin was also investigated. METHODS: Corneal buttons were collected from patients with keratoconus, normal subjects and patients with other corneal diseases such as pseudophakic bullous keratopathy. Immunofluorescence staining was performed on frozen sections for vimentin and tenascin, and immunoperoxidase staining was carried out on paraffin sections for cytokines, heat shock proteins and ubiquitin. RESULTS: To varying degrees, all proteins examined, except tenascin and heat shock protein 90, were found to be expressed in normal human corneas. The expression of vimentin, tenascin, transforming growth factor-beta, interleukin-1, heat shock protein 27, and ubiquitin was enhanced in keratoconus corneas. A similar enhancement however was also observed in other diseased corneas. CONCLUSIONS: Altered expression of several wound healing or stress-related proteins was noted in keratoconus corneas. The alterations appear to be nonspecific injury or wound responses in association with corneal diseases.

Adolescent↗
PubMed1996

Effect of neodymium: YAG laser posterior capsulotomy on corneal grafts.

Patients undergoing neodymium: yttrium-aluminum-garnet (Nd: YAG) laser posterior capsulotomy for posterior capsular opacification after penetrating keratoplasty were reviewed retrospectively for incidence of graft rejection. All patients underwent extracapsular cataract extraction with posterior chamber intraocular lens implantation (PC-IOL) performed as a separate or combined procedure. Only one of 20 eyes (4.7%) of 20 patients developed corneal graft rejection over a follow-up period of 6 months to 6 years after capsulotomy. Nd: YAG laser capsulotomy does not appear to increase the risk of corneal graft rejection.

Cataract Extraction↗
PubMed1995

Primary corneal graft failure. A national reporting system. Medical Advisory Board of the Eye Bank Association of America.

OBJECTIVES: To describe a national eye banking registry and to assess the effects of donor age, cause of donor death, time from death to procurement, storage time, and distance between the points of recovery and transplantation on the reported occurrence of primary corneal graft failure. DESIGN: We performed a retrospective case-control study to estimate the odds ratios of five donor factors for cases of primary graft failure voluntarily reported to a national registry using controls from selected eye banks. We also performed a nested case-control cohort study to compare cases of primary graft failure that occurred in both corneas from the same donor with those of nonmated corneas in which primary graft failure was reported to assess odds ratios for the same donor factors. PATIENTS: One hundred forty-seven patients developed primary graft failure in penetrating keratoplasty transplantations performed between January 1, 1991, and December 31, 1993. These cases were reported to the Adverse Reaction Registry of the Eye Bank Association of America, Washington, DC. Controls included 7240 donor corneas distributed by nine eye banks during 1992. RESULTS: Of the 147 donor corneas that developed primary graft failure, 17 (12%) were obtained from donors who were aged 70 years and older, 39 (27%) came from donors who died of trauma, 13 (9%) had a cadaver time longer than 12 hours, 10 (7%) had a storage time longer than 7 days, and 38 (26%) were distributed outside the eye bank's region. Compared with controls, these donor corneas were more likely to have a storage time longer than 7 days (odds ratio, 2.4; 95% confidence limits, 1.2 and 4.6) and to come from donors aged 70 years and older (odds ratio, 2.4; 95% confidence limits, 1.4 and 4.0). The 22 corneas (15%) in which primary graft failure occurred in both recipients from the same donor were 8.5 times (95% confidence limits, 1.1 and 51.5) more likely to be preserved beyond 1 week than were nonmated corneas with primary failure but were not from significantly older donors. Logistic regression analysis showed that the association between prolonged storage time and primary graft failure in mated corneas remained significant even when the analysis was controlled for other donor factors. CONCLUSIONS: No clearly defined donor or eye banking factor accounted for most cases of primary graft failure, although prolonged corneal storage and advanced donor age may increase its risk. Ophthalmologists are urged to report to their eye bank all cases of primary graft failure and other adverse events that might be attributable to donor eye tissue.

Adult↗