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Biomedical subjects

J D Cameron

Publications and source records attributed to J D Cameron.

At least 19 recordsLinked to original sources

Avellino corneal dystrophy. Clinical manifestations and natural history.

PURPOSE: The pathologic features of a variant of granular corneal dystrophy has been described in which the presence of lattice changes in addition to characteristic granular lesions has been documented. The authors investigated the mode of inheritance, natural history, and clinical manifestations of this dystrophy. METHODS: A family with this condition was investigated, and a pedigree was established. Family members underwent ophthalmic examination, and ophthalmic history was obtained. In addition, pathologic examination of corneal tissue from affected patients was performed. RESULTS: Similar to the four previously described cases, this family also traced its origins to Avellino, Italy. This autosomal dominant condition affected 27 of 92 family members, ranging in age from 5 to 77 years. Granular deposits were the earliest and most common manifestations. Lattice lesions were present in some patients with granular lesions. Older patients had anterior stromal haze between deposits, which impaired visual acuity. Recurrent granular deposits were noted in donor corneal tissue after penetrating keratoplasty for this condition. Pathologic examination of corneal tissue from affected patients confirmed the presence of hyaline material seen in granular dystrophy as well as fusiform deposits of amyloid, similar to those seen in lattice dystrophy type I. CONCLUSION: This study establishes the natural history and clinical manifestations of this condition.

Adolescent

Rabbit corneal epithelial cells adhere to two distinct heparin-binding synthetic peptides derived from fibronectin.

Fibronectin plays an important role in corneal reepithelialization during corneal wound healing. In this study, rabbit corneal epithelial (RCE) cell adhesion to fibronectin was further defined using proteolytic fragments of fibronectin and chemically synthesized peptides derived from the amino acid sequence of fibronectin. RCE cells adhere to intact fibronectin, the 75 kD fragment containing the RGDS (Arg-Gly-Asp-Ser) cell adhesion-promoting sequence, and the 33/66 kD cell adhesion promoting/heparin-binding fragments of fibronectin. The 75 kD fragment and the 33/66 kD fragments partially inhibited RCE cell adhesion to intact fibronectin, suggesting that these fragments represent distinct sites used by RCE cells to adhere to intact fibronectin. Two chemically synthesized peptides derived from the amino acid sequence of the 33/66 kD fragments of fibronectin, FN-C/H-I (YEKPGSPPREVVPRPRPGV) and FN-C/H-III (YRVRVTPKEKTGPMKE), directly promoted the adhesion of RCE cells. As further evidence that FN-C/H-I and FN-C/H-III play a role in the adhesion of RCE cells to the 33/66 kD fragments of fibronectin, we have shown that soluble FN-C/H-I and FN-C/H-III inhibited RCE cell adhesion on surfaces coated with the 33/66 kD fragments. In addition, polyclonal IgG against FN-C/H-I and FN-C/H-III partially blocked RCE cell adhesion to the 33/66 kD fragments, confirming that these sequences represent adhesion-promoting sites within these fragments. In contrast, two previously described peptides from the 33/66 kD fragments of fibronectin, which promoted the adhesion of a variety of cell types, FN-C/H-II (KNNQKSEPLIGRKKT) and CS-1 (DELPQLVTLPHPNLHG-PEILDVPST), did not support RCE cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Esthesioneuroblastoma presenting as sudden unilateral blindness. Histopathologic confirmation of optic nerve demyelination.

We report here a case of esthesioneuroblastoma an 11-year-old girl presenting as acute loss of vision with minimal evidence of orbital, nasal, or paranasal sinus disease, a rare presenting symptom for this tumor. The initial diagnosis was postviral optic neuritis, a pattern of presentation not previously reported. When vision failed to improve, magnetic resonance imaging revealed a lesion in the posterior ethmoid and sphenoid sinuses. After a biopsy, the tumor was excised through the cranium and paranasal sinuses. A mass completely surrounding the optic nerve without invasion was found. Histochemical staining suggested demyelination secondary to compression, confirming the clinical impression of optic neuritis. Anti-Leu 7 monoclonal antibody is useful in characterizing of this tumor, since other immunochemical stains can be misleading. Radiation and chemotherapy were given after the tumor was removed. Two years later, the patient has had neither recurrence nor complications.

Antineoplastic Combined Chemotherapy Protocols

Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant.

The stiffness of the thoracic aorta can be assessed non-invasively. If aortic stiffness can be shown to be related to coronary heart disease, perhaps it can be used to identify which patients with hypercholesterolaemia are most likely to have atheromatous changes and thus to be selected for intensive cholesterol-lowering treatment. Hence the distensibility of the transverse aortic arch was measured by echocardiography of the aortic arch in four groups of patients--symptom-free patients with normal serum cholesterol; symptom-free patients with raised serum cholesterol; patients with coronary heart disease (all with raised serum cholesterol), and post-heart-transplant patients. In all groups distensibility fell with age. The regression slope was steeper (p less than 0.05) for patients with known coronary disease than for either of the disease-free groups, and among cardiac transplant recipients there was also a segregation of distensibility values between those with and without atheroma in their native hearts. The results indicate that aortic distensibility might be an indicator of coronary heart disease and that it might be useful in identifying which symptom-free subjects with modest hypercholesterolaemia should be treated aggressively.

Aging

Type IV collagen and corneal epithelial adhesion and migration. Effects of type IV collagen fragments and synthetic peptides on rabbit corneal epithelial cell adhesion and migration in vitro.

Type IV collagen, a 500-kilodalton (alpha 1)2(alpha 2)1 heterotrimer with noncollagenous domains (NC1) is the major molecule in most basement membranes in the body. In addition to its structural role as scaffolding, type IV collagen is involved in promoting adhesion and migration of various cell types in vitro, including rabbit corneal epithelial cells. This study assessed the effect of purified proteolytic fragments of type IV collagen and selected synthetic peptides derived from the alpha 1 and alpha 2 chains that are related to the adhesion and directed migration of dissociated primary cultured rabbit epithelial cells. Two homologous peptides (HEP-1 and HEP-2) derived from alpha 1 and alpha 2 NC1 regions were found to promote epithelial cell adhesion. A peptide (HEP-3) derived from an interruption of the triple helix of type IV collagen was effective in promoting corneal epithelial cell migration in both chemotaxis and haptotaxis assays. The helical fragment of type IV collagen promoted both directed migration and ample adhesion, indicating that there may be at least another moiety in the helical region responsible for cell adhesion. The results with these peptides revealed to some extent how corneal epithelial cells react at the molecular level with type IV collagen. They could serve as the basis for therapeutic agents to modify corneal epithelial behavior in situations of perturbed wound healing.

Amino Acid Sequence

Posterior infectious crystalline keratopathy with Staphylococcus epidermidis.

Two cases of infectious crystalline keratopathy located in the posterior stroma after penetrating keratoplasty are presented. Topical steroids and suture removal were risk factors in both cases. In the first case, a moderate anterior chamber reaction was present. Crystalline infiltrates persisted on topical and systemic steroid therapy. In the second case, deep corneal ulceration, hypopyon, and vitreitis were noted. A vitreous aspirate showed rare gram-positive cocci in pairs. The corneal ulceration and crystalline keratopathy persisted despite intravitreal and topical antibiotics. Therapeutic penetrating keratoplasty was performed in both cases. Staphylococcus epidermidis sensitive to vancomycin was isolated from corneal tissue. Light microscopy documented aggregates of gram-positive bacteria anterior to Descemet's membrane, with an overlying keratitis. Electron microscopy in the second case showed all bacteria within stromal keratocytes. No clinical recurrence was seen using topical vancomycin. As demonstrated in the cases presented, infectious crystalline keratopathy can occur exclusively in the deeper layers of the cornea. Isolation of S. epidermidis, associated inflammation, and intraocular spread of organisms are rare findings.

Aged

Human tissue distribution of novel basement membrane collagen.

The authors have defined the specificity of monoclonal antibodies to collagen fragments of basement membrane (BM) and have used these highly specific antibodies to study the human tissue distribution of two novel 28 kd noncollagenous (NC1) peptides (M28 , M28+) compared with those derived from type IV collagen (alpha 1[26 kd] and alpha 2[24 kd] NC1). A limited distribution of the 28 kd peptides was observed in specialized BM of the kidney, eye, cochlea, lung, and brain, whereas type IV collagen is found in all human BM. These novel peptides, which colocalize with each other, are found in BM that also contain type IV collagen but do not, in all cases, colocalize with type IV collagen. The presence of the 28 kd peptides in the BM of the kidney, cochlea, and eye is in keeping with abnormalities involving these components in BM of patients with Alport familial nephritis (FN), who frequently have hearing loss, anterior lenticonus and retinal flecks in addition to renal disease. These 28 kd peptides are distinct, biochemically and immunochemically, from the alpha 1 and alpha 2 chain NC1 peptides of type IV collagen, and represent either peptide fragments of genetically distinct BM collagen molecules or additional molecules originating from the same gene family as type IV collagen.

Antibodies, Monoclonal

The importance of intraocular lens inspection prior to implantation.

Open-loop, posterior chamber intraocular lenses were obtained from existing inventories of regional hospitals and surveyed for functional (optical) and structural defects. The majority of lenses (90%) were acceptable by industry optical grade standards. Most of the lenses (90%) varied by at least 0.5 diopter from the power stated on the packaging. Two lenses did not meet optical resolution standards. Most of the lenses (80%) had some surface or loop surface abnormality as judged by scanning electron microscopy. Four of the lenses had surface protrusions or burrs, either at the tip of the loop or at the lens-optic junction. These more serious defects could be seen easily at magnifications of the operating microscope. The lenses with serious structural defects tended to be the same as those lenses with functional (optical) defects. This study demonstrates the usefulness of careful intraoperative examination using the operating microscope prior to intraocular lens implantation to detect manufacturing defects which continue to exist in currently manufactured lenses. Lens inspection should be directed to the ends of the loops, the loop-optic junction, and the internal surface of the positioning holes.

Humans

Quantification of corneal organ culture migration: central and peripheral epithelium.

This report outlines a method for rapid quantification of corneal epithelial cell movement in a block organ culture system designed to model a penetrating or perforating wound of the cornea. Rabbit corneas were secured over a plastic conformer with a chalazion clamp. Two-millimeter, full-thickness corneal specimens were sampled from central and peripheral cornea and placed in tissue culture. The aim of the procedure was to produce full-thickness corneal specimens from well-defined geographic areas of the cornea of reproducible size and shape without undue trauma to the epithelium. The instruments used for measurements were simple, allowing for accumulation of a large number of observations which could be subjected to rigorous statistical evaluation. This method was used to determine if there was a detectable difference in the rate of epithelial cell movement over stromal cut surface of specimens from the periphery of the cornea, versus the rate over specimens from the central area of the cornea. In this block organ culture system the peripheral epithelial cells migrated more rapidly than samples of central epithelial cells (P less than 0.05). This study shows a simple, rapid method for producing and evaluating block corneal organ cultures and shows that the site of specimen sampling must be controlled in corneal epithelial cell studies employing block organ culture. This method will be useful for in vitro screening of novel pharmacologic agents which have the potential for influencing corneal wound healing prior to evaluating these agents in vivo.

Animals

Circumferential nodulocystic keratopathy. A case report.

An apparently unique type of corneal nodular keratopathy is presented. The keratopathy was characterized by large, circumferentially bilaterally located, cystic nodules just inside the limbus. No epithelial cell or collagenous degeneration nor evidence of chronic inflammatory process was found on histopathologic examination of a biopsy of a nodule. Proteinaceous material was present between the epithelial cell basement membrane and collagenous stroma. There was no antecedent history of keratitis or uveitis. The patient was known to have inflammatory bowel disease (regional ileitis) and rheumatoid arthritis with ankylosing spondylitis. However, the corneal lesions could not definitely be associated with any of these disorders. This case does not correspond with any previously described corneal disorders. We have termed it circumferential nodulocystic keratopathy, which best describes its clinical and histologic features.

Albumins

Clinico-histopathologic correlation of a successful glaucoma pump-shunt implant.

A 64-year-old diabetic man was treated for neovascular glaucoma with a pump-shunt implant (seton) after maximal medical therapy was unsuccessful. The seton, with supplemental agents, maintained the intraocular pressure (IOP) within a therapeutic range for 6 months, until the time of death from cardiac complications. Histopathologic evaluation of the eye showed the inlet of the seton in the periphery of the anterior chamber, not in contact with a coexisting anterior chamber intraocular lens (IOL). There was no fibrosis of the intracameral portion of the device. The tissue tract containing the silicon outlet tube extended from peripheral Descemet's membrane, through the sclera, to exit in the episcleral tissue over the posterior pars plana. Fibrous tissue originating from the episclera encased the external chambers of the seton. The internal contours of the fistulous tract, i.e., that portion adjacent to the seton, were smooth. There was no gross tissue hiatus at the exit port of the seton. The posterior wall of the fibrous capsule surrounding the seton in this region was diaphanous and immediately anterior to an area of cystic tissue comprising an equatorially placed bleb. The bleb was characterized by an irregular internal surface and a cystic cavity crossed by collagenous columns, suggesting it was the sub-Tenon's reservoir of aqueous. The success of the seton in this particular case may be due to a lack of fibrous reaction in the anterior chamber and the establishment of a stable filtering bleb in the equatorial region of the eye.

Anterior Chamber

An experimental model for uveal touch syndrome.

Posterior chamber intraocular lenses (IOLs) were implanted in cat eyes after extracapsular cataract extraction or phacoemulsification. Various degrees of iris and IOL contact occurred. In 52% of the eyes in which contact was present, there was associated fibrovascular membrane formation, which was statistically significant when compared to eyes in which there was no iris-IOL contact. The eyes were examined histopathologically; proliferation of anterior cuboidal cells, as well as a fibrous response within the stroma, was noted in eyes with the most extensive contact. Human clinical correlates are discussed. This study demonstrates experimentally that the iris will not tolerate significant prolonged IOL contact.

Animals

Clinical significance of hematic cyst of the orbit.

Hematic cyst is a rarely encountered orbital lesion consisting of encapsulated blood or blood breakdown products. The abnormality may be recognized by identifying the cystic structure by B-scan ultrasonography or computed tomography. Cysts located peripherally in the orbit tend to have histologic features suggesting hematoma formation. More centrally located orbital cysts are sometimes associated with vascular abnormalities. In other cases, the etiology is obscure, as in the case presented here. The visual prognosis is usually good, and associated systemic abnormalities are lacking.

Adult

Effects of matrix proteins on rabbit corneal epithelial cell adhesion and migration.

Extracellular matrix and basement membrane proteins are important in promoting the adhesion and migration of various cell types. Laminin and type IV collagen are found in basement membranes throughout the body while fibronectin is found associated with some basal lamina, in loose connective tissue, and in all body fluids. In the current study fibronectin, laminin, and type IV collagen were assessed to determine their effect on the adhesion and migration of dissociated rabbit epithelial cells. In a kinetic analysis fibronectin was found to be the most effective of the three proteins in promoting cell adhesion. Cell adhesion promoted by fibronectin could be modulated by an arg-gly-asp-ser (RGDS) peptide, a sequence which is found within the fibronectin molecule. In dose-response experiments type IV collagen effectively promoted cell adhesion at concentrations as low as 4 x 10(-16) moles per well in 96 well tissue culture plates. Type IV collagen was the most effective protein tested in promoting chemotactic and haptotactic migration. These proteins, proteolytic fragments, and peptides derived from them, could prove useful as therapeutic agents, modifying corneal epithelial phenotypic behavior in wound healing, corneal transplantation and following ocular surgery or trauma.

Animals