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Biomedical subjects

J Sugar

Publications and source records attributed to J Sugar.

At least 19 recordsLinked to original sources
PubMed2001

Eye banking and screening for Creutzfeldt-Jakob disease.

OBJECTIVES: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. METHODS: Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. RESULTS: Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. CONCLUSIONS: Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.

Adolescent↗
PubMed2001

Cell density regulated expression of transcription factor Sp1 in corneal stromal cultures.

Sp1, a ubiquitously expressed transcription factor, has been implicated to have a role in cell differentiation and cell proliferation. In keratoconus, a corneal disease characterized by thinning and scarring of the central cornea, Sp1 is found up-regulated. In the present study, we examined the expression of Sp1 in stromal cells cultured from normal human and keratoconus-afflicted corneas and evaluated the influence of varying cell densities. Immunohistochemical staining, Western blotting and electrophoretic mobility shift assays indicated that in both normal human and keratoconus cultures, Sp1 protein levels and binding activities increased with the density of cells. The basal level of Sp1 in keratoconus cultures was higher than that in normals. These results demonstrate a marked density mediated up-regulation of Sp1 in corneal stromal cells, suggesting that the Sp1 expression may be regulated by differentiation states of the cells in the cornea. In addition, cells from keratoconus corneas in vitro appear to carry and retain the Sp1 abnormality as in vivo. The Sp1 defect may be an inborn error in keratoconus.

Adult↗
PubMed2000

Normal expression levels of cathepsins, protease inhibitors, and Sp1 in conjunctival tissues from patients with keratoconus.

PURPOSE: In keratoconus corneas, it has been shown that levels of degradative enzymes and transcription factor Sp1 are elevated and those of inhibitors are reduced, especially in the epithelial layer. This study is to determine whether the biochemical abnormalities identified in corneas also exist in conjunctival tissues. METHODS: Conjunctival tissues were collected from normal subjects and from patients with keratoconus, senile cataract, and other corneal diseases. Immunohistochemical staining for cathepsins B and G, alpha 1-proteinase inhibitor, alpha 2-macro-globulin and Sp1 was performed. RESULTS: The epithelium of all conjunctival specimens showed immunoreactivity toward the antibodies. The staining for cathepsins B and G, and the inhibitors was mostly cytoplasmic, while that for Sp1 was nuclear. The staining intensity in keratoconus specimens was all within normal range. CONCLUSIONS: These results suggest that the abnormalities in cathepsins B and G, protease inhibitors and Sp1 identified in keratoconus corneas are not manifested in the conjunctiva. Keratoconus appears to be a disease localized to the cornea.

Adolescent↗
PubMed2000

Medical management of Beauveria bassiana keratitis.

PURPOSE: To describe a case of Beauveria bassiana keratitis and to discuss the management of this rare condition. METHODS: An 82-year-old woman underwent surgical repair of a graft wound dehiscence. Seven months later, shortly after the removal of sutures, the patient developed a fungal keratitis. B. bassiana was identified as the infecting organism. The patient was treated with topical natamycin and oral fluconazole. RESULTS: Following antifungal therapy, the corneal ulcer was eradicated, but the patient underwent repeat penetrating keratoplasty for decreased vision due to corneal edema. The graft remains clear and visual acuity is substantially improved. CONCLUSION: The medical management of B. bassiana keratitis has previously been unsuccessful. The use of topical natamycin combined with oral fluconazole in the management of this case is discussed.

Aged↗
PubMed1999

Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in the tear film of patients with keratoconus.

PURPOSE: Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in the tear film of patients with keratoconus were measured to elucidate their possible roles in the pathogenesis of keratoconus. METHODS: Tear samples were collected from 15 keratoconus patients and 14 age-similar human control subjects. Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in each tear sample were quantified and compared between the two groups. RESULTS: Mean values for alpha1-proteinase inhibitor were 101.0+/-35.5 and 106.1+/-41.7 ng/microg protein for the keratoconus and control groups, respectively. The corresponding mean values for alpha2-macroglobulin were 13.5+/-6.8 and 14.8+/-7.5 ng/microg protein. Neither inhibitor showed a statistically significant difference between the keratoconus and control specimens. Subset analysis to evaluate the effects of contact lens wear and the presence of a graft in the fellow eye did not reveal a statistically significant difference. CONCLUSION: The tear film of patients with keratoconus contains normal levels of protease inhibitors. Therefore, the tear film may not be a source of the reduced inhibitor levels shown in the corneas of patients with keratoconus.

Adolescent↗
PubMed1999

Discordance for keratoconus in two pairs of monozygotic twins.

PURPOSE: We present two pairs of monozygotic twins discordant for keratoconus. METHODS: Two pairs of twins, each with one twin with keratoconus, and available family members were examined clinically and with computer-assisted videokeratography. Polymerase chain reaction-based zygosity assays using between nine and 11 unique, anonymous DNA markers were performed on blood obtained from the twins and surviving parents to assess the probability of genetic monozygosity. RESULTS: DNA probes showed a >99% probability that each of the two sets of twins was monozygotic. One twin from each pair had clinically diagnosed keratoconus. The remaining twins were normal by clinical examination and corneal topography. Clinical results for all family members examined were normal except that five of 13 from one family and one of six from the other family demonstrated "suspicious" corneal topography. CONCLUSION: Recent advances in knowledge and understanding of the twinning process suggest that monozygotic twins discordant for keratoconus does not preclude the possibility of a significant genetic component.

Adult↗
PubMed1999

Outcome of vitreoretinal surgery and penetrating keratoplasty using temporary keratoprosthesis.

PURPOSE: The use of a temporary keratoprosthesis has allowed earlier surgical intervention in eyes with coexisting vitreoretinal and corneal disease. We analyzed our experience with this type of surgery. METHODS: We retrospectively reviewed charts of patients in whom a temporary keratoprosthesis was used between 1987 and 1998. Analysis was focused on ocular history, indications for surgery, visual acuity (VA), intraocular pressure, anatomic results, and complications. RESULTS: A temporary keratoprosthesis was used in 31 eyes, 22 (71.0%) of which were for trauma-related indications. In 6 (19.4%) of the operated eyes, the fellow eye also had severely reduced VA. Retinal detachments were present in 30 (96.8%) eyes; most had evident proliferative vitreoretinopathy. Twelve (38.7%) eyes had vitreous hemorrhage, and 20 (64.5%) had corneal scars. Improvement in VA was seen initially in 45.1% of patients, and 51.6% maintained equal or better VA at their final visit as compared with before surgery. The common documented reasons for poor final VA were recurrent retinal detachments deemed inoperable (32.3%), phthisis (22.6%), and optic atrophy or macular scar (16.1%). Corneal grafts remained clear in 41.9%. Nine patients had further surgery. The most significant complication was one case of sympathetic ophthalmia. CONCLUSIONS: Combined vitreoretinal and corneal surgery using temporary keratoprostheses has been used in our institution to treat eyes with extreme abnormalities. Outcomes were less favorable than some reported in the literature, probably because of the severity of disease for which temporary keratoprostheses were reserved. Although results are probably better than the natural course of the disease, patients should be informed of realistic expectations for improvement and potential complications when offered this option.

Adolescent↗
PubMed1998

Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene.

PURPOSE: Because corneal tissue with familial subepithelial corneal amyloidosis (FSCA; gelatinous drop-like dystrophy of the cornea) contains lactoferrin the possibility that the FSCA gene was the human lactoferrin (hLF) gene was investigated. Due to contradictory published information we also mapped the hLF gene. METHODS: We mapped the hLF gene using a genomic clone of the entire hLF gene as a probe by fluorescence in situ hybridization (FISH). Utilizing PCR primers that are specific to the hLF gene, we also mapped the hLF via radiation somatic cell hybrid analysis. Linkage of the FSCA gene to the hLF gene was evaluated by genetic linkage analysis using polymorphic markers within and in the vicinity of the hLF gene. RESULTS: The hLF gene mapped to the short arm of chromosome 3 at 3p21. Linkage analysis using polymorphic markers for hLF and haplotype analysis of the 3p21 loci indicates that the FSCA gene is not linked to the 3p21 locus. CONCLUSIONS: The gene for FSCA is not the hLF gene in these families.

Amyloidosis↗
PubMed1998

Involvement of Sp1 elements in the promoter activity of the alpha1-proteinase inhibitor gene.

The transcripts of the alpha1-proteinase inhibitor in the cornea are different from those in hepatocytes and monocytes, suggesting that alpha1-proteinase inhibitor gene transcription may respond to different cell-specific regulatory mechanisms. Although information on alpha1-proteinase inhibitor gene structure has been obtained, little is known regarding the cis- and trans-acting factors that regulate its expression. In this study, we cloned and sequenced a 2. 7-kilobase 5'-flanking region upstream from the corneal transcription initiation site of the gene, demonstrated functional promoter activity, and identified the regulatory elements. Sequencing revealed that the 5'-flanking element was highly G/C-rich in regions proximal to the corneal transcription start site. DNase I footprinting located 10 potential Sp1-binding sites between nucleotides -1519 and +44. The putative promoter was functional in human corneal stromal cells, but not in human skin, scleral, and conjunctival fibroblasts, suggesting that the promoter may be corneal cell-specific. The promoter activity in the corneal cells was repressed when Sp1 was coexpressed. In the cornea-thinning disease keratoconus, down-regulation of the alpha1-proteinase inhibitor gene and increased Sp1 expression have both been demonstrated. The current results suggest that down-regulation of the inhibitor in keratoconus corneas may be related directly to overexpression of the Sp1 gene. This information may help elucidate the molecular pathways leading to the altered alpha1-proteinase inhibitor expression in keratoconus.

Base Sequence↗
PubMed1998

Three-dimensional scanning electron microscopic study of keratoconus corneas.

OBJECTIVE: To examine the 3-dimensional collagen fibril organization in the Bowman layer of keratoconus corneas. METHODS: Eight keratoconus corneas, 8 corneas with other diseases, and 5 normal human corneas were studied. A cell maceration method in combination with scanning electron microscopy was used to examine the collagen network in the Bowman layer. RESULTS: In normal corneas, the surface of the Bowman layer was smooth and collagen fibrils were regularly arranged. By contrast, sharply edged defects in the Bowman layer were found in keratoconus corneas. Lattice-like configurations of the ruptured Bowman layer and collagenous scar tissue were observed, to varying degrees, in all keratoconus corneas examined. None of the other diseased corneas exhibited the ruptures. CONCLUSIONS: Scanning electron microscopy demonstrated alterations in the Bowman layer specific to keratoconus. Fragmentation of the Bowman layer may be an early change leading to keratoconus conditions.

Adolescent↗
PubMed1998

The effect of propranolol versus placebo on resident surgical performance.

PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.

Adrenergic beta-Antagonists↗
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↗