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H E Grossniklaus

Publications and source records attributed to H E Grossniklaus.

At least 19 recordsLinked to original sources
PubMed2002

[HLA class I antigen expression correlates with histological cell type in uveal melanoma].

PURPOSE: The prognosis of uveal melanoma is correlated with its histologic cell type. The epithelioid cell type is associated with a higher metastatic rate than the spindle cell type. The Human Leucocyte Antigen Class I (HLA-I) expression of the melanoma also correlates with the prognosis. In this study, we analyzed HLA-I antigen expression of uveal melanomas to determine whether a relationship exist between antigenic expression and melanoma cell type. METHODS: Formalin-fixed, paraffin-embedded spindle cell type (n = 11) and epithelioid cell type (n = 11) uveal melanomas were immunostained with the HC10 antibody (1:80) for HLA-I antigen expression with appropriate positive and negative controls. Sections were assessed semiquantitatively according to the percentage of stained cells. RESULTS: Among the spindle cell type melanomas, 2 out of 11 (18%) stained with HC10 antibodies. The staining intensity was less than 25% of the cells in these two melanomas. Among the epithelioid cell type melanomas, 9 out of 11 (82%) stained with HC10. The staining intensity was more than 25% of the cells in 5 of these 9 melanomas. CONCLUSIONS: It is unknown why spindle and epithelioid cell type uveal melanomas have different prognoses. Human uveal melanoma cell lines with low HLA-I expression are susceptible to NK cell-mediated lysis in vitro and in murine studies. The prognostically more favorable spindle cell type melanoma expresses less HLA-I than the epithelioid cell type melanoma. These results stress the role of NK cells in the rejection of uveal melanoma.

Histocompatibility Antigens Class I↗
PubMed2001

Murine high-fat diet and laser photochemical model of basal deposits in Bruch membrane.

OBJECTIVE: To examine the histologic, histochemical, and ultrastructural changes in Bruch membrane in mice on a high-fat diet with and without laser photochemical injury. METHODS: Five groups of C57BL/6 mice were studied. Group 1 included 2-month-old mice on a normal diet; group 2 included 8-month-old mice on a normal diet; group 3 included 8-month-old mice on a high-fat diet; groups 4 and 5 included 8-month-old mice on a normal diet or high-fat diet, respectively, that underwent laser application of one eye with argon blue laser (488 nm). The mice were killed and plasma lipid levels were measured. The eyes were examined by standard electron microscopy, filipin histochemistry for unesterified cholesterol (UC) and esterified cholesterol (EC), and the osmium-tannic acid-phenylenediamine method for preserving extracellular lipid particles. RESULTS: The plasma cholesterol level was significantly higher in the mice on the high-fat diet than the controls (P<.001). Bruch membrane was thicker in group 2 than group 1 (P =.04) and group 3 had a thicker Bruch membrane than group 2 (P =.003). All eyes in group 3 exhibited accumulation of electron-lucent debris. There was no histochemical and ultrastructural evidence that this material represented accumulated UC or EC. Seven of 9 laser-injured eyes in group 5 accumulated basal laminar deposit (BlamD)-like material in Bruch membrane (P =.02). CONCLUSIONS: Electron-lucent debris accumulates in murine Bruch membrane, and the amount correlates with age and high-fat diet. This debris has some similarities with basal linear deposits, although the debris does not form a discrete layer external to the basement membrane of the retinal pigment epithelium as occurs in basal linear deposits. These deposits do not appear to be UC or EC. Laser photochemical injury of the retinal pigment epithelium may result in the appearance of BlamD-like deposits in eyes with electron-lucent debris. The BlamD-like deposits in this model are similar to the basal laminar deposits that occur in age-related macular degeneration. CLINICAL RELEVANCE: This is an animal model of ultrastructural BlamD-like material in Bruch membrane that is very similar to the deposits that occur in age-related macular degeneration.

Animals↗
PubMed2001

Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey.

OBJECTIVE: To quantify the amount of optic nerve axonal loss associated with the presence of a mild relative afferent pupillary defect (RAPD) in an experimental monkey model. METHODS: The right macula of 5 rhesus monkeys (Macaca mulatta) was treated with concentrically enlarging diode laser burns until an RAPD was detected using a transilluminator light and measured with neutral density filters. Intervals between treatments were 3 to 7 days over a period of 2 months. Pupillary responses to light stimulation were recorded with a monocular infrared television pupillometer. Two months after detection of an RAPD, 5 treated and 4 control monkeys underwent euthanasia and enucleation. Histopathologic analysis and quantification of optic nerve axon counts using an image analysis system were performed. RESULTS: No RAPD was observed despite an estimated ganglion cell loss of up to 26%. A 0.6 log unit RAPD was present in 5 monkeys when the laser scar incorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 log units without further laser treatment. Histopathologic evaluation disclosed complete loss of the normal retinal architecture within the macula. The average fiber loss for the 4 treated eyes with 0.6 log unit RAPDs compared with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). The average difference in axon counts between untreated pairs of optic nerves was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of experimental and control eyes was statistically significant (P<.001). CONCLUSION: In rhesus monkeys, an RAPD develops after an approximate unilateral loss between 25% and 50% of retinal ganglion cells. CLINICAL RELEVANCE: Owing to redundancy in the anterior visual pathways, unilateral retinal ganglion cell loss may occur prior to the observation of an RAPD. The presence of an RAPD measuring 0.6 log units implies that significant retinal ganglion cell injury has occurred.

Animals↗
PubMed2001

[Metastatic uveal melanoma. Development of neoadjuvant treatment in animal experiments].

BACKGROUND: Up to 50% of patients with uveal melanoma develop metastases but none of the existing treatments of the primary tumor has been able to reduce the metastatic rate. Probably, micrometatases have already developed before treatment of the uveal melanoma and dormant micrometastases can persist for years before they start growing. This long time-span provides the possibility to treat micrometastases. METHODS: In order to develop an animal model for metastatic uveal melanoma, B16 melanoma cells were injected into the posterior ocular compartment of C57BL6 mice. These cells grew and metastasised to the lungs and liver. Immunological factors for the metastatic process and possible neoadjuvant treatments were investigated. RESULTS: Natural killer cells (NK) are of significance in the rejection of metastases and HLA-I expression of uveal melanomas correlates with the melanoma cell type. Interferon-alpha-2b increases the activity of NK cells and reduces the metastatic rate in the animal model. CONCLUSION: Treatment with interferon-alpha-2b results in decreased metastases from intraocular melanoma in a murine model.

Animals↗
PubMed2001

Indocyanine green effect on cultured human retinal pigment epithelial cells: implication for macular hole surgery.

PURPOSE: To evaluate potential toxic effects of indocyanine green dye on cultured human retinal pigment epithelial cells. METHODS: Controlled laboratory experiment. Cultured human retinal pigment epithelial cells were exposed to balanced saline solution, balanced saline solution with endoillumination, indocyanine green or indocyanine green with endoillumination. Cells were evaluated by light microscopy, electron microscopy, and a mitochondrial dehydrogenase assay. RESULTS: Retinal pigment epithelial cells exposed to indocyanine green showed no histologic or ultrastructural changes. Those exposed to indocyanine green alone or indocyanine green plus light demonstrated a significant decrease in mitochondrial enzyme activity (P = 0.0002 and 0.005, respectively). CONCLUSION: Brief exposure of cultured human retinal pigment epithelial cells to indocyanine green results in decreased mitochondrial enzyme activity but does not appear to influence cellular morphology or ultrastructure.

Cells, Cultured↗
PubMed2001

Pseudoadenomatous hyperplasia of the conjunctiva.

PURPOSE: To describe the clinical and pathologic features of three patients with pseudoadenomatous hyperplasia of the conjunctiva. DESIGN: Observational case series with clinicopathologic correlation. METHODS: Case reports and clinical histories and examination of three biopsy specimens. MAIN OUTCOME MEASURES AND RESULTS: Pseudoglandular hyperplasia of the conjunctiva was associated with chronic inflammation, including eosinophils, in two patients, and squamous epithelial hyperplasia in a third. The pseudoglands are lined by varying proportions of squamous epithelium and goblet cells. CONCLUSIONS: Pseudoglandular hyperplasia of the conjunctiva can mimic a well-differentiated mucoepidermoid carcinoma. Awareness of this entity may help to prevent misdiagnosis and unnecessary surgery.

Administration, Topical↗
PubMed2001

Microphthalmia transcription factor immunohistochemistry: a useful diagnostic marker in the diagnosis and detection of cutaneous melanoma, sentinel lymph node metastases, and extracutaneous melanocytic neoplasms.

BACKGROUND: Melanoma is the most lethal form of skin cancer. Diagnosis of amelanotic melanoma and detection of micrometastases in sentinel lymph nodes pose diagnostic and therapeutic dilemmas for the dermatopathologist and clinician. OBJECTIVE: The purpose of this article is to determine the utility of immunohistochemistry using antibodies specific for microphthalmia in the identification of melanocytic lesions in the skin, eye, central nervous system, and sentinel lymph nodes. METHODS: Paraffin-embedded, formalin-fixed specimens of cutaneous melanoma, including amelanotic melanoma and lentigo maligna melanoma, were stained with antibodies specific for microphthalmia. In addition, paraffin sections of extracutaneous lesions, including sentinel lymph nodes, uveal melanoma, and central nervous system melanocytomas, were stained with the specific microphthalmia antibody. RESULTS: All cutaneous melanomas stained positively with microphthalmia, as did uveal melanomas and central nervous system melanocytomas. These findings confirm the melanocytic origin of melanocytomas and uveal melanomas and demonstrate that microphthalmia staining can be used to establish melanocytic origin of neoplasms. In addition, micrometastases were easily detected in sentinel lymph nodes. CONCLUSION: Microphthalmia transcription factor immunohistochemistry is a valuable tool in the identification of melanocytic lesions in numerous sites. Use of this stain may facilitate detection of micrometastases in sentinel lymph nodes.

Antibodies, Neoplasm↗
PubMed2001

Sinonasal undifferentiated carcinoma with orbital invasion: report of three cases.

PURPOSE: To report three patients with sinonasal undifferentiated carcinoma (SNUC) that invaded the orbit. METHODS: Retrospective small case series. The clinical, radiographic, and pathologic features of three patients with SNUC were reviewed. RESULTS: Three patients with SNUC that invaded the orbit were evaluated. A biopsy was performed on the tumors, which were composed of small, hyperchromatic cells with numerous mitoses and areas of necrosis. Immunohistochemical staining was positive for cytokeratins AE1.3, epithelial membrane antigen, and neuron-specific enolase in all three tumors. Electron microscopic examination showed absence of neurosecretory granules and presence of basement membrane production. Two patients were treated with surgical resection and postoperative chemotherapy and/or radiation. One patient was treated with preoperative radiation and chemotherapy. CONCLUSIONS: Sinonasal undifferentiated carcinoma is a high-grade tumor that arises in the nasal and paranasal sinuses and may invade the orbit. SNUC should be distinguished from other small, round, blue cell tumors, in particular, esthesioneuroblastoma.

Adult↗
PubMed2001

Ocular pathology in mitochondrial superoxide dismutase (Sod2)-deficient mice.

PURPOSE: To characterize the pathologic features in retina, optic nerve, and extraocular muscle of mitochondrial superoxide dismutase (Sod2)-deficient mice, a model of increased mitochondrial production of reactive oxygen species. METHODS: Morphometric and ultrastructural study of eyes of 43 homozygous sod2(tm1Cje-/-) mice and wild-type control animals. For retinal morphometric analysis, 32 manganese 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP)-treated animals aged either 9 to 10 days or 20 to 21 days were studied. Ultrastructural examination was performed on tissue from the treated animals, and 11 additional untreated mutant and control animals. RESULTS: In treated Sod2-deficient animals, the photoreceptor layer was thinner centrally at 9 to 10 days than in control animals (mean 8.8 vs. 14.7 microm). By 20 to 21 days, all retinal layers apart from the outer nuclear layer and retinal pigment epithelium (RPE) were thinner centrally in mutant animals (total retinal thickness, 233.2 vs. 272.6 microm; combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, 86.2 vs. 103.4 microm; inner nuclear layer, 51.8 vs. 60.3 microm; photoreceptors, 26.7 vs. 35.6 microm). Optic nerve cross-sectional area was less in 20- to 21-day-old treated Sod2-deficient animals than in control animals. Mitochondrial morphologic abnormalities (swelling, pale matrix, and disorganized cristae) were found predominantly in older mutant animals' (16 and 20 to 21 days) RPE and in extraocular muscle of a 16-day-old untreated mutant. CONCLUSIONS: In sod2(tm1Cje-/-) mice, there is relative progressive retinal thinning, with particular involvement of the inner retinal layers and an early effect on the photoreceptor layer, as well as mitochondrial morphologic abnormalities, all consistent with mitochondrial disease.

Animals↗
PubMed2000

Correlation of histologic 2-dimensional reconstruction and confocal scanning laser microscopic imaging of choroidal neovascularization in eyes with age-related maculopathy.

OBJECTIVE: To topographically localize vascular channels, macrophages, and retinal pigment epithelium and other components of choroidal neovascularization (CNV) associated with age-related maculopathy. METHODS: Two postmortem eyes with age-related maculopathy and CNV were evaluated. The formalin-fixed CNV complex was excised and processed for confocal scanning laser microscopy including immunostaining for factor VIII-related antigen and incubation with Ig fluorescein isothiocyanate. After confocal microscopy, the specimens were serial step sectioned, stained, and 2-dimensional topographic reconstructions were made. The confocal images were compared with the 2-dimensional reconstructions. RESULTS: Both specimens contained central disciform scars surrounded by areas of intact retinal pigment epithelium. The first specimen was more atrophic and contained fewer choroidal neovascular channels than the second specimen. The topographic arrangement of the CNV and retinal pigment epithelial changes in the confocal images corresponded with the 2-dimensional reconstructions. Macrophages were concentrated around areas of vascularization. CONCLUSION: Confocal scanning laser microscopy of excised CNV simulates fluorescein angiography and topographic localization of the components of CNV provides insight into the pathogenesis of CNV.

Aged↗
PubMed2000

Neoadjuvant interferon alfa-2b treatment in a murine model for metastatic ocular melanoma: a preliminary study.

OBJECTIVES: To investigate the treatment of metastasis from uveal melanoma and to test the effect of interferon (IFN) alfa-2b in a murine model. METHODS: The B16-LS9 tissue culture melanoma cells were inoculated into the posterior intraocular compartment of 3 groups of C57BL/6 mice. The inoculated eyes were enucleated at 9 days and the mice were euthanized at 26 days after inoculation; the site and number of metastases were determined using standard histologic techniques. Group 1 was the control group; group 2 was given 20,000 international units (IU) of IFN alfa-2b intramuscularly 12 hours before enucleation, and group 3 received daily injections of 20,000 IU of IFN alfa-2b intramuscularly starting 4 days before enucleation. RESULTS: Pulmonary metastases were detected in 57%, 33%, and 0% of groups 1, 2, and 3, respectively; hepatic micrometastases were detected only in group 1. These results showed a significant decrease in hepatic metastases in mice receiving IFN alfa-2b vs controls (P =.005). CONCLUSION: Treatment with IFN alfa-2b results in decreased hepatic metastases from intraocular melanoma in a murine model. Arch Ophthalmol. 2000;118:1085-1089

Animals↗
PubMed2000

Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses.

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.

Alkaloids↗
PubMed2000

[Morphometric changes in the choriocapillaris and choroid in eyes with advanced glaucoma damage].

BACKGROUND: In addition to elevated intraocular pressure, a compromised ocular blood supply has been implicated in the pathogenesis of primary open-angle glaucoma (PCOG). METHODS AND MATERIALS: We analyzed 20 eyebank eyes with end-stage PCOG and compared these with 20 age-matched controls. The following variables were measured: density and diameter of large choroidal vessels in the macular and equatorial choroid; thickness of the choroid in the macular and equatorial region; and density and thickness of choriocapillaris in the macular, peripapillary, and equatorial choroid. RESULTS: Eyes with glaucoma displayed a lower density of the capillaries of the choriocapillaris than control eyes in the macular, temporal peripapillary, and equatorial choroid, with 0.50 vs. 0.55 (P = 0.018), 0.46 vs. 0.51 (P = 0.016), and 0.50 vs. 0.55 (P = 0.038), respectively. Assessment of large choroidal vessels in the macular choroid showed that eyes with glaucoma had less density of veins (11.7 vs. 38.9/mm2; P < 0.001) and arteries (7.7 vs. 12.4/mm2; P = 0.005) and arteries with a higher diameter (45.6 vs. 28.2 microns; P < 0.001) than control eyes. The large vessels in the equatorial choroid displayed no significant difference in diameter but a lower density (21.2 vs. 44.1/mm2; P = 0.017) in eyes with glaucomatous damage than controls. CONCLUSION: Eyes with advanced glaucomatous damage after long-standing PCOG exhibit many changes in the choroidal vasculature. We cannot conclude from our study whether the observed vascular changes in the choroid are primary pathogenic factors or secondary phenomena.

Capillaries↗
PubMed2000

Band-shaped and whorled microcystic dystrophy of the corneal epithelium.

OBJECTIVE: To report the clinical, histopathologic, and electron microscopic features of band-shaped and whorled microcystic corneal epithelial dystrophy. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients, two eyes. INTERVENTION: The involved area of corneal epithelium was scraped from each cornea. RESULTS: Histopathologic examination showed microscopic vacuoles in the epithelial cytoplasm in both cases. Electron microscopic examination revealed mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The process recurred clinically in one patient. Changes in corneal topography are documented in one patient. CONCLUSION: Clinical findings and pathologic studies seem nearly identical to those in the original report. No pattern of systemic disorder or medication use was found. The cause of this condition remains unknown.

Aged↗
PubMed2000

Pathologic findings in late endophthalmitis after glaucoma filtering surgery.

OBJECTIVE: To report the clinicopathologic features of four eyes enucleated for late-onset bleb-related endophthalmitis. STUDY DESIGN: Retrospective case series. MATERIALS: Four enucleated eyes. METHODS: The clinical and histopathologic features of four patients who underwent enucleation for late-onset endophthalmitis after glaucoma filtering surgery were reviewed. RESULTS: The eyes were enucleated for endophthalmitis one to five years after trabeculectomy. Two of the four eyes had trabeculectomy with adjunctive mitomycin-C. All four eyes had streptococci cultured from the aqueous and/or vitreous. Common pathologic features included inflammation involving the anterior segment, lens and choroid. One eye exhibited focal granulomatous uveitis. CONCLUSIONS: Late-onset endophthalmitis after glaucoma filtering surgery is often due to streptococcal species and rapidly progresses over a few days. Phacoanaphylaxis with associated granulomatous uveitis may contribute to the poor prognosis in this setting.

Aged↗
PubMed2000

Conjunctival lymphocytic infiltrates associated with Epstein-Barr virus.

PURPOSE: To describe the clinicopathologic features of two patients with Epstein-Barr virus (EBV) associated conjunctival lymphocytic infiltrates. DESIGN: Two case reports. METHODS: The clinical histories and pathologic findings of two patients with salmon-colored conjunctival infiltrates are described. MAIN OUTCOME MEASUREMENTS: Clinical observation and pathologic examination of conjunctival biopsy specimens with accompanying immunohistochemical staining, flow cytometric immunophenotyping, and polymerase chain reaction analysis when appropriate. RESULTS: One patient had ipsilateral preauricular lymphadenopathy, elevated serum EBV titers, and a unilateral reactive lymphocytic infiltrate resulting in a conjunctival mass. The other patient had bilateral conjunctival lymphocytic infiltrates causing conjunctival masses. There was an expanded clonal population of B lymphocytes in the conjunctival mass in the second patient. Both patients had EBV antigen in their conjunctival lymphocytic infiltrates. CONCLUSIONS: Conjunctival lymphocytic lesions associated with EBV represent a spectrum of reactive infiltrates to monoclonal populations.

Adult↗