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Biomedical subjects

H K Soong

Publications and source records attributed to H K Soong.

At least 19 recordsLinked to original sources

Non-tuberculous mycobacterial keratitis: a study of 22 cases.

AIM: To investigate causes and clinical findings of non-tuberculous mycobacterial keratitis, and to study its response to topical antibiotic therapy and surgical extirpative keratectomy. METHOD: A single centre, retrospective review of 22 patients with non-tuberculous mycobacterial keratitis seen in a 3 year period. Laboratory diagnoses were established with Ziehl-Nielsen acid fast staining and Löwenstein-Jensen cultures. RESULTS: In 20 patients (91%), there was an antecedent history of foreign body eye trauma (18 patients) or elective surgery (two patients). There were 19 cases of Mycobacterium chelonei, and three of M fortuitum. Clinical signs included epithelial defects, satellite or ring stromal infiltrates, crystalline keratopathy, and hypopyon. For topical antibiotic therapy, 20 patients received amikacin, while one patient received rifampin and another received ciprofloxacin, each in accordance with the results of the in vitro drug sensitivities. An extirpative keratectomy was performed in 15 cases; four of these cases additionally required a temporary conjunctival flap in order to finally eradicate the infection. At the end of the follow up period (median 18 months; range 3 months to 3 years) all eyes were stable and free of infection, with 19 (86%) having final visual acuities of 20/200 or better. CONCLUSION: Early clinical recognition and prompt laboratory diagnosis, together with aggressive topical antibiotic therapy and early keratectomy, may shorten morbidity and improve the clinical outcome of non-tuberculous mycobacterial keratitis.

Adult

Galvanotropic and galvanotaxic responses of corneal endothelial cells.

The effects of weak electric fields (E-fields) on cultured rabbit corneal endothelial cells were studied. The cells responded to steady E-fields (2-6 V/cm) by elongating their somata 90 degrees to the field (galvanotropism) and by migrating (galvanotaxis) towards the anode. During these directional movements, pseudopodia and ruffled membranes formed preferentially on the anodal side of the cells, while they retracted on the cathodal side. Fluorescent labelling for actin showed many stress fibers aligned parallel to the long axes of the elongated cells and few aligned toward the anodal direction. Fluorescent labelling for vinculin showed the abundance of cell-to-substratum adhesion foci at the termini of the stress fibers. Galvanotropic and galvanotaxic cellular movements were inhibited by cytochalasin D (0.1-0.5 microgram/mL) and the calmodulin antagonist, W-7 (80 mumol/L). These results suggest that E-field induced directional movements of corneal endothelial cells constitute a calmodulin-dependent, active (not passive) process.

Animals

Immune-mediated subepithelial blistering diseases of mucous membranes. Pure ocular cicatricial pemphigoid is a unique clinical and immunopathological entity distinct from bullous pemphigoid and other subsets identified by antigenic specificity of autoantibodies.

BACKGROUND AND DESIGN: There is much confusion in the clinical classification of immune-mediated subepithelial blistering diseases of mucous membranes. We conducted a 6-year comprehensive study to better classify this heterogeneous disease group. Indirect immunofluorescence was performed on a salt-split-skin substrate to detect circulating antibasement membrane antibodies (n = 47). Serologic reactivity against cultured keratinocyte antigens was examined by immunoblots (n = 38) and immunoprecipitation (n = 15). The results were correlated with the clinical features and direct immunofluorescence data of the entire patient group (n = 87) without preassignment of clinical diagnoses. chi 2 Statistical analyses compared these results with those of the classic bullous pemphigoid group (n = 36). RESULTS: When compared with the bullous pemphigoid patients, a subset of patients with combined oral mucosal and skin lesions demonstrated marked similarity in direct and indirect immunofluorescence findings and in serologic reactivity to bullous pemphigoid antigens. By contrast, a subset of patients with only ocular lesions exhibited significantly lower in vivo deposits of IgG and C3, higher deposits of fibrin, virtual absence of circulating antibodies, and negative serologic reactivity to bullous pemphigoid antigens. CONCLUSIONS: Ocular patients without skin or mouth lesions, in particular those with negative indirect immunofluorescence, should be distinctively classified as ocular cicatricial pemphigoid, a unique clinical and immunopathologic entity. Patients with mucous membrane involvement who also demonstrate skin lesions and antibodies to the root of salt-split-skin substrate should be classified as anti-BP Ag mucosal pemphigoid, even though they may exhibit severe oral and/or ocular diseases. The remaining mucous membrane patients are heterogeneous. Some can be classified on the basis of autoantibodies to other basement membrane determinants, or if serum autoantibody negative, on the basis of clinical features (ie, pure oral mucosal pemphigoid or overlapping mucosal involvement).

Autoantibodies

Secondary localized amyloidosis in interstitial keratitis. Clinicopathologic findings.

Cases of secondary localized corneal amyloidosis have been described in various corneal and ocular inflammations but are believed to occur uncommonly. The authors examined histopathologic specimens from 33 consecutive patients with interstitial keratitis who underwent penetrating keratoplasty for visual rehabilitation. In 11 cases (33%), multiple fusiform deposits of amyloid were identified and confirmed in middle and deep corneal stroma using histochemical staining. Characteristic electron microscopic findings were present in two cases. These results indicate that secondary localized corneal amyloidosis occurs frequently in interstitial keratitis and displays a distinct pattern of deposition.

Aged

FGF promotes corneal stromal fibroblast motility.

It is well-known that growth factors accelerate wound healing by stimulating mitosis. Growth factors may also directly stimulate the motility of individual cells. We employed two different experimental methods to determine if fibroblast growth factor (FGF) enhances the individual motility of corneal stromal fibroblasts (independent of mitogenic effects). The effects of FGF on the motility of tissue-cultured rabbit corneal stromal fibroblasts were investigated in a modified Boyden chamber and by the agarose drop motility assay. Both assays showed a significant enhancement of stromal fibroblast motility by FGF at 100 ng/ml. It appears, therefore, that FGF may promote corneal stromal wound healing not only by increased cellular proliferation, but also by increased cellular motility.

Animals

Effects of steady electric fields on human retinal pigment epithelial cell orientation and migration in culture.

Low-level, steady electric fields of 6-10 volts/cm stimulated directional orientation and translocation of cultured human retinal pigment epithelial cells. The orientative movements (galvanotropism) consisted of somatic elongation of the cells into spindle shapes, followed by pivotal alignment orthogonal to the field. The anodal edges of the cells underwent retraction of their plasmalemmal extensions, while the cathode edges and the longitudinal ends developed lamellipodia and ruffled membranes. These tropic movements were followed by a translocational movement (galvanotaxis) of the cells towards the cathode. Staining of these migrating cells for actin showed the accumulation of stress fibers at the leading (cathodal) edge, as well as at the longitudinal ends of the elongated somata. These results suggest that endogenous, biologically-generated electric fields (eg., injury currents) may play a role in the guidance and migration of retinal pigment epithelial cells after retinal injury.

Actins

Ocular cicatricial pemphigoid occurring as a sequela of Stevens-Johnson syndrome.

Ocular cicatricial pemphigoid is a chronic scarring inflammation of the ocular mucosae that can lead to blindness. Although cicatricial pemphigoid has been classified clinically, histopathologically, and immunopathologically, no definite initiating factor or precipitating factor has been identified. In this report, we describe five cases of ocular cicatricial pemphigoid that developed following an acute episode of severe ocular inflammatory injury secondary to Stevens-Johnson syndrome. The time lag between the onset of Stevens-Johnson syndrome and cicatricial pemphigoid ranged from a few months to 31 years. All five patients had linear immune deposits characteristic of cicatricial pemphigoid along the basement membrane zone of mucosal biopsy specimens as detected by either direct immunofluorescence microscopy or direct immunoperoxidase staining. In two patients whose serum was tested, a Western blot assay taken of keratinocyte antigens that had undergone electrophoresis reacted with the serum and identified a 120-kd epidermal antigen detected by the IgG class antibodies. All five patients were treated with systemic immunosuppressive therapy for cicatricial pemphigoid, and we obtained objective responses. Severe ocular mucosal injury such as that which occurs in Stevens-Johnson syndrome may be a precipitating factor in the development of ocular cicatricial pemphigoid.

Adult

Implantation of Kelman-style, open-loop anterior chamber lenses during keratoplasty for aphakic and pseudophakic bullous keratopathy. A comparison with iris-sutured posterior chamber lenses.

The clinical and specular microscopic results of 40 cases (39 patients) of penetrating keratoplasty during which a Kelman-style anterior chamber intraocular lens was implanted were reviewed retrospectively. Thirty-one pseudophakic eyes received an intraocular lens exchange and nine aphakic eyes received a secondary intraocular lens. Postoperative follow-up averaged 24.5 months (range, 3 to 51 months). At 1, 2, and 3 years after keratoplasty, 39.3%, 63.2%, and 63.6% of eyes, respectively, had visual acuities of 20/40 or better. Ninety-five percent of the grafts remained clear. Causes of poor postoperative visual acuity included cystoid macular edema (32.5%), new glaucoma (22.5%), and age-related macular degeneration (10.0%). Other causes were endothelial rejection leading to graft failure, corneal ulceration, and retinal detachment. Corneal endothelial cell loss by specular microscopy was 11.5% at 1 years, 21.3% at 2 years, and 25.0% at 3 years. These results were compared with cell loss associated with iris-sutured posterior chamber lenses in penetrating keratoplasty. Visual outcomes and complication rates were similar between these two methods; however, the endothelial attrition at 1 and 2 years for the sutured posterior chamber lens was greater than that of the Kelman anterior chamber lens.

Adult

Microfilaments, microtubules, and intermediate filaments in cultured corneal fibroblasts.

Corneal stromal fibroblasts play an important role in wound healing. Proteins from all three cytoskeletal classes (microfilament, microtubule, and intermediate filament) are involved in the control of various cellular events, such as motility, cell adhesion, shape changes, intracellular transport, and mitosis. By epifluorescent light microscopy, we studied the intracellular distributions of actin (microfilament), tubulin (microtubule), and vimentin (intermediate filament), as well as vinculin (a junctional protein connecting microfilaments to the cell membrane), in cultured corneal fibroblasts. Mutual positional relationships between actin and the other cytoskeletal proteins were investigated by double-labeling. Particular attention was paid to the leading edge of spreading or migrating fibroblasts and to their cell-to-cell contacts.

Actins

Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts.

The authors investigated effects of two antimetabolites, 5-fluorouracil (5-FU) and mitomycin C (MMC), on proliferation and motility of cultured rabbit subconjunctival fibroblasts. Both drugs caused dose-dependent inhibition of fibroblast proliferation. These effects were reversible at lower doses (0.33 mg/l of 5-FU, 1.0 X 10(-3) mg/l of MMC) and at an early stage of treatment, but became irreversible at higher doses or after longer treatment times. The degree of growth inhibition reached a plateau after 7 days of treatment. Neither drug altered fibroblast migration in the agarose droplet motility assay or on the intra-cytoplasmic actin distribution by epifluorescent-light microscopy. These results indicate that 5-FU and MMC inhibit subconjunctival fibroblast function predominantly by their effect on cell proliferation rather than on cell motility. The clinical implications of these results may possibly support the use of a much lower total dose of subconjunctival antimetabolite than used in the 5-FU clinical trial.

Actins

Effects of cytochalasin D on actin and vinculin in cultured corneal epithelial cells.

Migrating corneal epithelial cells in culture elaborate lush arrays of actin filament bundles (stress fibers) which terminate peripherally at discrete cell-to-substratum adhesion complexes. These complexes contain several specific adhesion plaque proteins, of which vinculin is one. Vinculin, a 130 kD protein, putatively links the intracellular actin bundles in a transmembrane fashion (via integrin, a specific plasmalemmal junction protein) to focal attachment sites onto the underlying extracellular matrix substratum. Migrating rat corneal epithelial cells in tissue culture are treated with 0.1-1.0 microgram/ml cytochalasin D, an inhibitor of actin polymerization. This resulted in a generalized disruption of stress fibers, causing actin to the diffusely redistributed into discrete, round patches. Most, but not all, of these patches of actin appeared to colocalize with foci of vinculin. The focal patches of vinculin appeared to be larger and more diffuse in the cytochalasin-treated cells compared to the drug-free cells. These cytochalasin-induced cytoskeletal changes were associated with total cessation of cell migration and increased cellular detachment from the substratum.

Actins

Effects of electric fields on cytoskeleton of corneal stromal fibroblasts.

Low-level, steady electric fields (6-10 volts/cm) stimulated cultured corneal stromal fibroblasts to undergo directional orientation and translocation. The orientative movements (galvanotropism) consisted of somatic elongation of the cells into spindle shapes along an imaginary axis perpendicular to the field; the cathodal edge of the cell underwent retraction, while the anodal edge and the longitudinal ends developed ruffled membranes and lamellipodia. The translocational movements (galvanotaxis) consisted of directed migration of the cells towards the anode. While most actin-containing stress fibers became aligned along the long axes of the elongated fibroblasts (with distal ends of the stress fibers terminating at the longitudinal extremes of the cells), some were aligned towards the anodal direction (with distal terminations inside ruffled membranes and lamellipodia on the leading anodal edge of cells). The distal ends of stress fibers were associated with discrete foci of vinculin, ie, focal indicators of cell-to-substrate adhesion; these foci were abundant at the longitudinal ends and at the anodal edge of the elongated cells. The observed cytoskeletal changes are consistent with an active, rather than passive, directed migration of stromal fibroblasts in response to constant electric fields.

Actins

Endothelial rejection following penetrating keratoplasty using Healon or BSS.

In order to evaluate the effect of a commonly used sodium hyaluronate preparation (Healon, Pharmacia AB, Uppsala, Sweden) on the incidence of endothelial rejection, endothelial cell loss, intraocular pressure, and corneal thickness after penetrating keratoplasty, we conducted a randomized clinical trial. Patients were allocated to receive Healon (n = 41) or BSS (Alcon Laboratories, Inc., Fort Worth, TX, U.S.A.; n = 37) during surgery. At 1 year after surgery, the Kaplan-Meier estimate of the proportion remaining free of endothelial rejection was 78.1% (SE 6.5%) in the Healon group, and 70.6% (SE 7.9%) in the BSS group. Survival analysis showed no overall difference in endothelial rejection between groups. The percent loss in endothelial cell density showed substantial variability within each group, but for those followed 2 years after surgery, the amount of loss was significantly less in Healon-treated patients (17.3% versus 30.2%). Four Healon patients required medication for intraocular pressure rises in the early postoperative period, and the average intraocular pressure 1 day after surgery was greater in the Healon group (18.2 versus 13.7 mm Hg). Corneal thickness was slightly greater in patients receiving Healon, but no clinically important differences were noted.

Acetates

Effects of 5-fluorouracil on cultured rabbit lens epithelial cells.

The effects of 5-fluorouracil (5-FU) on growth and F-actin structure were investigated in cultured rabbit lens epithelial cells. A dose-inhibition study showed that for its antiproliferative effect on cells, the ID50 of 5-FU is 0.6 mg/l. This is similar to the value reported for subconjunctival fibroblasts and corneal epithelial cells. 5-FU does not affect the F-actin structure of the cells. Although cataract formation by 5-FU has not been reported, susceptibility of the lens epithelial cells to 5-FU should be considered when treating glaucoma patients with this drug.

Actins