Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gradual corneal thinning seen in keratoconus may be due to altered degradation of the corneal extracellular matrix. Studies have shown that human keratocytes produce matrix metalloproteinase-2 (MMP-2) and two proteins (28 kDa and 21 kDa) that are capable of inhibiting the activity of MMP-2. In the present study, the 28 kDa inhibitor from keratoconus keratocyte cultures has been characterized as it may be important to the elevated MMP-2 activity seen in these cultures. Biochemical analyses indicated that this keratoconus corneal inhibitor was similar to TIMP-1 from other sources. Oligonucleotides to the reported sequence of human tumor cell TIMP-1 were used for reverse-transcriptase PCR to generate a 700 bp clone of the 28 kDa inhibitor from keratoconus keratocyte cytoplasmic RNA. Sequence analysis verified that the clone was nearly identical to the reported human TIMP-1 with a single base substitution that did not affect the predicted amino acid sequence. In addition, protein translated from the clone corresponded to the expected size. This data suggests that the elevated levels of gelatinolytic activity in these keratoconus keratocyte cultures is not due to a primary alteration of the TIMP-1 molecule. Protein expression studies of the TIMP-1 clone are currently underway.
 ...
PMID:Characterization of a human corneal metalloproteinase inhibitor (TIMP-1). 750 19

A 30-year-old man with keratoconus in the right eye had radial keratotomy in the left eye. Two pairs of corneal relaxing incisions (CRIs) were made in the right eye to flatten the central cornea and reduce high astigmatism. The right eye required an enhancement, and two additional arcuate CRIs were made. A corneal ulcer developed in the right eye, with infiltrates in the incision and corneal thinning. Although the second set of CRIs resulted in more regular astigmatism, the corneal thinning and ulcer caused regression at two months postoperatively. A wedge resection was performed to even the irregular astigmatism. The results are presented.
 ...
PMID:Wedge resection in the cone after failed refractive surgery in a patient with keratoconus. 855 30

Keratoconus is characterized by the presence of corneal distortion (secondary to thinning of the apex) and either Fleischer's ring (found in 57% of patients) or Vogt's striae (found in 44% of patients). Often the only presenting symptom is decreased visual acuity. Steep keratometric readings are not usually diagnostic; 18% of patients with keratoconus have readings flatter than 45.00 D. Treatment requires correction of acuity with spectacles or contact lenses. More advanced cases are generally managed with rigid gas-permeable contact lenses. Corneal scarring occurs in approximately 43% of cases; 10% to 20% of patients require penetrating keratoplasty to restore acuity.
 ...
PMID:Keratoconus. 776 20

Keratoconus is a noninflammatory corneal disorder characterized by gradual stromal thinning and astigmatism. Altered degradation of corneal extracellular matrix is a suggested etiology for this disorder. In the present study we established keratocyte cultures from normal and keratoconus corneas and investigated the roles that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP, TIMP-2) may play. After chemical modification (reduction and alkylation) to remove the inhibitor and activation of enzyme with p-aminophenylmercuric acetate (APMA), keratoconus-conditioned media displayed a significant increase (p < 0.05) in the total potential gelatinolytic activity when compared with normal culture media treated in a similar manner. Basal levels of gelatinolytic activity in keratoconus culture media (no reduction, alkylation, or APMA treatment), determined by two different assay methods, tended to be about twice that of normal cell cultures. By zymography, both keratoconus and normal cultures showed identical enzyme patterns, which represented MMP-2 (72 kDa) in its proform and, depending on the treatment of the media, varying amounts of activated MMP-2 (65 kDa). This suggests that the increased gelatinolytic activity in keratoconus was not correlated with an increased appearance of either the 65-kDa-activated form of MMP-2 or a new MMP species. In addition, no differences in the amount of MMP-2 were detected that could account for the increased activities in keratoconus cultures. However, a relative decline in the detectable TIMP levels in keratoconus cultures resulted in an apparent three-fold increase in the ratio of MMP-2/TIMP. Northern blots showed no significant changes in mRNA levels for MMP-1, MMP-2, MMP-3, TIMP, or TIMP-2. These data suggest that a possible alteration in the interaction between MMP-2 and TIMP may play a role in the increased gelatinolytic activity seen in keratoconus tissues.
 ...
PMID:Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio. 815 82

Keratoconus is characterized by stromal thinning and conical deformity of the cornea that affects a small but significant portion of the population. Although keratoconus has been well studied, endothelial changes have not been extensively investigated. We studied the endothelium of 14 keratoconus corneal buttons obtained over the past 6 years by penetrating keratoplasty using light microscopy, scanning electron microscopy and transmission electron microscopy. Observations were correlated with patient history. Corneas demonstrated: endothelial cell pleomorphism and polymegathism (6 corneas); endothelial cell degeneration (13), and evidence of anterior chamber inflammation (4). Patterns of endothelial damage were variable ranging from isolated cell membranolysis to denudement of Descemet's membrane. Less damage was present at the apex of the cones than that observed in a circumferential pattern at the bases. In general the damage observed correlated with the severity and duration of the keratoconus with 9 years being the dividing time between mild and severe endothelial cell damage. These observations support other studies that implicate contact lens wear as a cause of pleomorphism and polymegathism in these patients. Endothelial cell alterations are likely a secondary event occurring due to mechanical stresses.
 ...
PMID:Pathology of corneal endothelium in keratoconus. 827 66

The aims of the Australian Corneal Graft Registry are to collect and collate statistical information on the practice of corneal transplantation around Australia, to identify risk factors for corneal graft failure, and to provide information on graft and visual outcome. The current report encompasses analyses performed on 3608 corneal grafts (96% penetrating and 4% lamellar) entered into the Registry between May 1985 and July 1991. Sixty-four per cent of grafts have undergone one or more rounds of follow-up by the 189 contributing surgeons and 110 additional referring practitioners: five-year Kaplan-Meier graft survival for penetrating and lamellar grafts is 72% and 84%, respectively. The main indications for penetrating keratoplasty were keratoconus (31%), bullous keratopathy (25%), history of failed previous graft (14%), corneal scars and opacities (11%), and corneal dystrophies (7%). The most common reasons listed for failure of penetrating grafts were rejection (33%), glaucoma (11%), non-viral infections (10%), endothelial cell failure (8%) and herpetic infection (7%). In 19% of cases, the reason for graft failure was unclear. The main indications for lamellar keratoplasty were pterygium (32%), thinning, necrosis or ulceration from old beta-radiation therapy for pterygium (17%), and scleral ulcers, necrosis, ectasia, perforations or melts (29%). The most common reasons for the failure of lamellar grafts were corneal melting (43%) and sloughing of the graft (29%). Among the factors that influenced the survival of penetrating corneal grafts to a significant extent (P < 0.05) in univariate analysis were: the centre effect, indication for graft, graft number, a history of pregnancy or blood transfusion, inflammation before or at the time of graft, corneal vascularisation at the time of graft, a history of raised intraocular pressure, the donor cornea procurement source, the death to donor cornea enucleation time, graft size and large degrees of oversizing, lens status and the type of intraocular lens in situ. In the postoperative period, risk factors for failure included early removal of graft sutures, neovascularisation of the graft, herpetic recurrences in the graft and the occurrence of rejection episodes. The variables that best predicted penetrating corneal graft failure in Cox proportional hazards regression analysis were aphakia or the presence of an anterior chamber of iris-clip intraocular lens, very small or very large grafts, a history of previous ipsilateral graft, an indication for graft that was neither keratoconus nor any of the corneal dystrophies, inflammation at the time of graft, and a postoperative rise in intraocular pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The Australian Corneal Graft Registry. 1990 to 1992 report. 833 42

Keratoconus, a bilateral corneal disease, is characterized by modifications in corneal shape and thinning of the stroma. It affects young people. From a biochemical point of view, a decrease in collagen content, probably due to the high collagenase activity, has been reported. In these experiments, we have studied the membrane receptors for interleukin 1 alpha, and the corresponding dissociation constant (KD). We also investigated synthesis of prostaglandin E2 (PGE2) and collagen, as well as kinetics of cyclooxygenase. Data from normal human corneas and from keratoconus were compared. Fibroblasts from keratoconus proved to bear four fold more IL1 binding sites than those from normal cornea, with similar KD. Both types of cells synthesize prostaglandin E2, even if IL1 is not added to the medium, but the keratoconus cells produce ten times more than the normal cornea cells. When the cells are stimulated with IL1, synthesis of PGE2 strongly increases and the amounts produced by keratoconus cells are always higher than those of the normal cornea cells. Kinetics of the cyclooxygenase show that Vmax. is 10 times higher in keratoconus than in normal cornea cells; Km's are the same. The amounts of collagen synthesized by keratoconus cells are slightly lower than those of normal cornea cells. Addition of IL1 to the cultures enhances synthesis of collagenase by the cells and decreases collagen found in the culture media. The drop of collagen is more important in keratoconus than in normal cornea cell cultures.
 ...
PMID:Modification of prostaglandin E2 and collagen synthesis in keratoconus fibroblasts, associated with an increase of interleukin 1 alpha receptor number. 840 71

Eleven patients with blue sclera, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents were examined between January 1983 and September 1991. The clinical diagnosis was consistent with the Ehlers-Danlos syndrome type VI phenotype in all patients. A "halo" sign at the limbus was present in all patients. Corneal rupture occurred in seven patients (nine eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in three patients. Bilateral microcornea was present in one patient and two patients had a unilateral increased corneal diameter as a result of secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in five patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus.
 ...
PMID:Corneal abnormalities in Ehlers-Danlos syndrome type VI. 845 32

We observed 6 cases of secondary keratoconus with Fleischer's ring pattern corneal epithelial iron ring. These 6 cases were 2 males and 4 females. The causes of secondary keratoconus were 2 cases of trachoma, 2 cases of trauma, 1 case of keratitis, and 1 case of unknown origin. All showed thinning of the cornea and Fleischer's ring pattern corneal epithelial iron ring. After penetrating keratoplasty of 1 case, the button of the recipient showed the deposition of hemosiderin in the corneal epithelium stained blue by Prussian blue. At the same time we confirmed the existence of iron in the corneal epithelium by the X-ray ultimate analysis. Fleischer's ring is considered to be characteristic of keratoconus, but we have found that Fleischer's ring is also seen in secondary keratoconus in which the cornea becomes thinner secondarily for some reason.
 ...
PMID:[Six cases of secondary keratoconus with Fleischer's ring pattern corneal epithelial iron ring]. 864 46

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.
 ...
PMID:Normal lysosomal enzyme staining in skin tissues of patients with keratoconus. 877 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>