Search PubMed⌕ Search

Biomedical subjects

R Folberg

Publications and source records attributed to R Folberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Distribution of prognostically important vascular patterns across multiple levels in ciliary body and choroidal melanomas.

PURPOSE: To investigate the validity of assigning patients whose eyes have been removed for ciliary body or choroidal melanoma to risk groups for metastasis based on the identification of microcirculatory patterns in one cross-section taken from the center of the tumor. METHODS: Multiple levels were cut through the blocks of 15 ciliary body or choroidal melanomas until the tumor was exhausted. Each level was examined for the presence of microvascular networks and parallel vessels with cross-linking histologic features strongly associated with death from metastatic melanoma. RESULTS: The central histologic section did not contain either microvascular networks or parallel vessels with cross-linking in eight tumors, nor were these patterns encountered in any of the more peripheral levels of the tumor. Seven tumors contained at least one focus of either microvascular networks or parallel vessels with cross-linking in the central histologic section. In two tumors, at least one of these patterns appeared in all histologic levels; in five tumors, at least one of these patterns appeared through multiple levels until just before the tumor was exhausted from the block (0.24 to 0.85 mm from the edge of the tumor). CONCLUSIONS: This study suggests that the prognostic classification of uveal melanoma based on the histologic profile of the microcirculation may be consistent throughout the tumor depth.

Choroid Neoplasms↗
PubMed1998

Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas.

PURPOSE: To describe the microcirculation architecture of metastatic choroidal and ciliary body melanoma. METHOD: Histologic sections of 35 metastases from 19 primary melanomas were stained to demonstrate microcirculation. RESULT: The appearance of microcirculatory networks in metastases is independent of the target organ but associated with the size of the metastatic deposit (estimated coefficient = 0.5959; SE = 0.3024; P = .0488). CONCLUSION: The microcirculatory patterns of primary uveal melanomas that are associated with metastatic behavior appear in foci of metastasis, regardless of the site of dissemination.

Choroid Neoplasms↗
PubMed1998

Vascular endothelial growth factor upregulation in human central retinal vein occlusion.

BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF), a key mediator of intraocular neovascularization, is triggered by hypoxia and has been shown in the eyes of animal models of central retinal vein occlusion (CRVO). However, there is little information on CRVO in humans, in particular, the identity of VEGF-producing cells. STUDY DESIGN: The study design was molecular localization of the site of VEGF production in the eyes of patients with CRVO. PARTICIPANTS: Ten formaldehyde solution-fixed and paraffin-embedded eyes removed surgically from patients with CRVO and neovascular glaucoma were studied. Five eyes with uveal melanoma and no neovascularization served as control specimens. METHODS: Thin whole-eye sections were hybridized in situ with a VEGF-specific probe to identify cells producing VEGF messenger RNA (mRNA). RESULTS: All ten eyes with CRVO showed evidence of intraretinal expression of VEGF mRNA. In all eyes, the inner nuclear layer showed VEGF-upregulated expression. Upregulation of VEGF mRNA was identified in four eyes in the ganglion cell layer and in two eyes with retinal detachment in the outer nuclear layer as well. CONCLUSIONS: The population of VEGF-producing retinal cells in each eye is likely to represent cells residing in ischemic regions of the retina. Hypoxia-induced VEGF is, most likely, the linking factor between retinal ischemia and iris and retinal neovascularization in CRVO.

Aged↗
PubMed1998

Correlation between surface water contamination with amoeba and the onset of symptoms and diagnosis of amoeba-like keratitis.

AIM: A seasonal variation was noted in the incidence of amoeba-like keratitis in Iowa. The level of contamination of amoeba in surface water has been found previously to vary on a monthly basis for Tulsa, Oklahoma, a region with a similar climate. It was hypothesised that this seasonal variation in amoeba-like keratitis correlated with the concentration of amoeba in surface water. METHODS: The monthly variation in the onset of symptoms was determined and date of diagnosis in 137 cases of amoeba-like keratitis, in Iowa, from January 1993 to the end of December 1996. RESULTS: Over a 4 year period a significant variation was found, on a monthly basis, in the onset of symptoms as reported by the patient. There were two peak periods per year when the onset of symptoms was most frequent: June and November. This corresponded closely with the concentration of amoeba in the ground water reported for a similar region in the mid-west (Tulsa, Oklahoma). A yearly increase was found in the number of cases diagnosed from January 1993 to the end of December 1996. CONCLUSIONS: This study supports the hypothesis that the concentration of amoeba in surface water may influence the rate of an amoeba-like keratitis infection.

Acanthamoeba↗
PubMed1998

MIB-1 and PC-10 immunostaining for the assessment of proliferative activity in primary acquired melanosis without and with atypia.

AIMS: To compare the proliferative activity of intraepithelial melanocytes in primary acquired melanosis (PAM) without atypia and PAM with atypia by immunohistochemical staining for the Ki-67 antigen and the proliferating cell nuclear antigen (PCNA). METHODS: Formalin fixed, paraffin embedded sections from 35 archival specimens of PAM without atypia (n = 19) and with atypia (n = 16) were studied by immunostaining with MIB-1 and PC-10 monoclonal antibodies that react with the Ki-67 antigen and PCNA respectively. The results were calculated as the mean number of positive cells per eyepiece grid. All specimens were evaluated by two masked observers, and the interobserver reproducibility was assessed. RESULTS: The means of the positive cell count in PAM with atypia were significantly higher compared with PAM without atypia for both observers, in both the PC-10 and the MIB-1 stained sections. In a linear least square model that estimated the interobserver and between group variation, the difference of MIB-1 and PC-10 positive cell count between PAM without and with atypia remained highly significant. The difference between the observers was not significant. CONCLUSIONS: Immunostaining with MIB-1 and PC-10 demonstrated that PAM with atypia has higher proliferative activity than PAM without atypia. This method was found to be reproducible between different observers.

Antigens, Nuclear↗
PubMed1998

Biologic determinants of uveal melanoma metastatic phenotype: role of intermediate filaments as predictive markers.

The long-range goal of our research is to develop intervention strategies based on newly discovered biologic mechanisms responsible for the invasive dissemination of metastatic uveal melanoma. To accomplish this goal, we have focused on the biologic relevance of novel marker proteins contributing to the uveal melanoma metastatic phenotype. The expression of vimentin intermediate filaments (IFs), a mesenchymal marker, is typical of melanomas, whereas carcinomas typically express keratin IFs, which are markers for epithelia. Thus, cells that coexpress both IFs are regarded as "interconverted" in that they display both mesenchymal and epithelial phenotypes. Although the biologic functions of IFs have remained enigmatic, there is substantial support to suggest that the significance of vimentin/keratin coexpression is linked with poor patient outcome in cutaneous melanoma. Our data demonstrate that human uveal melanoma cell lines (isolated from primary choroidal or ciliary body melanomas and from foci of metastatic uveal melanoma to the liver), which contain predominant populations of cells that coexpress vimentin/keratins 8 and 18 (keratins 8,18) IFs, were 6-fold more invasive through collagenous extracellular matrices in vitro, compared with uveal melanoma cells expressing vimentin only, and were 8- to 13-fold more invasive than normal uveal melanocytes. Colocalization of vimentin/keratins 8,18 in cell cultures was corroborated by immunohistochemistry in histologic sections of tumors from which the cell lines were derived. Minor populations of these cells also coexpressed keratins 13 and 17. Experimental down-regulation of the predominant keratins 8,18 in the interconverted cells, using 16-mer antisense oligonucleotides, resulted in a significant decrease in the migratory ability of the cells-similar to levels achieved by cells positive only for vimentin. These findings provide justification for additional studies of the association between coexpression of IFs vimentin/keratins 8,18 and uveal melanoma metastasis.

Antisense Elements (Genetics)↗
PubMed1998

Regulation of uveal melanoma interconverted phenotype by hepatocyte growth factor/scatter factor (HGF/SF).

Human uveal melanoma disseminates initially and preferentially to the liver. This study describes the relationship between the expression of the c-met proto-oncogene (receptor for hepatocyte growth factor/scatter factor (HGF/SF)) in interconverted uveal melanoma cells (co-expressing vimentin and keratin intermediate filaments) and the regulation of their motogenic response to HGF/SF, a key step in local invasion and targeted dissemination to the liver. Expression of c-met in uveal melanoma cell lines correlates with both the appearance of an interconverted phenotype and invasive ability (measured in vitro). Using chemotactic checkerboard analysis, the greatest motogenic response to HGF/SF was achieved by invasive, interconverted, c-met-positive uveal melanoma cells. C-met was observed histologically in a uveal melanoma containing interconverted cells but was absent in a tumor composed of non-interconverted cells (vimentin positive/keratin negative). The c-met ligand, HGF/SF, although not expressed by uveal melanoma cell lines, was localized in tissue sections of primary uveal melanomas and metastatic melanoma to the liver. In the primary tumor, staining for HGF/SF was most intense at the level of the choriocapillaris, a finding that is significant because 1) highly remodeled neovascular loops and networks, which appear in tumors likely to disseminate, can be traced to the choriocapillaris and the draining vortex veins and 2) HGF/SF plays a role in tumor angiogenesis. Foci of metastatic melanoma to the liver stain diffusely for HGF/SF. Regulation of the uveal melanoma interconverted phenotype by HGF/SF may play an important role in the dissemination of this tumor.

Blotting, Northern↗
PubMed1997

Coexistent Acanthamoeba keratitis and herpetic keratitis.

OBJECTIVE: To describe a series of patients with proved herpes simplex virus keratitis (herpetic keratitis) who also had documented Acanthamoeba keratitis. METHODS: Herpetic keratitis was documented with viral cultures, immunologic stains, or histopathologic examination for multinucleated giant cells in the corneal epithelium. Acanthamoeba organisms were identified using confocal microscopy and epithelial biopsy with hematoxylin-eosin staining. Biopsy of the stroma and epithelium was used to identify Acanthamoeba organisms in 1 case. RESULTS: Cultures for herpes simplex virus were positive in 6 of the 9 cases. Immunologic stains were positive in an additional 2 cases, and in 1 case multinucleated giant cells were present in the epithelium consistent with the diagnosis of herpes simplex virus keratitis. Tandem scanning confocal microscopic findings were positive for Acanthamoeba in 8 of the 9 cases, and all of them demonstrated Acanthamoeba organisms in epithelial scrape biopsy specimens. In 1 case, which was not evaluated with confocal microscopy, Acanthamoeba was detected using a stromal and epithelial biopsy. Two of the 9 patients had a history of contact lens use. CONCLUSION: Acanthamoeba keratitis may be present as a secondary or opportunistic infection in patients with herpetic keratitis.

Acanthamoeba↗
PubMed1997

Relative importance of quantifying area and vascular patterns in uveal melanomas.

PURPOSE: To test whether the cross-sectional area of choroidal and ciliary body melanomas and quantification of microcirculatory networks and parallel vessels with cross-linking are features associated with death from metastatic melanoma, and to compare new with conventional histologic prognostic features. METHODS: The cross-sectional area of 234 ciliary body or choroidal melanomas was measured from digitized images of histologic sections. The percentage of cross-sectional area occupied by two microcirculatory patterns-networks and parallel vessels with cross-linking-was calculated for the 152 tumors containing at least one focus of either pattern. Kaplan-Meier survival curves were generated based on cross-sectional and percentage of cross-sectional areas of these patterns. Cox proportional hazard regression methods related time to death from melanoma with sets of predictor variables. For each model, percent variation explained was computed. RESULTS: Patient survival differs significantly when tumors are classified based on cross-sectional area: small (<16 mm2), medium (> or =16 mm2 but <61.4 mm2), and large (> or =61.4 mm2). Patients with tumors containing networks and parallel vessels with cross-linking microcirculation patterns that occupy 2% of cross-sectional area have a significantly worse prognosis than do those patients with tumors containing a smaller percentage of these patterns. CONCLUSIONS: Quantifying cross-sectional tumor area and the percentage area occupied by networks and parallel vessels with cross-linking microcirculatory patterns in ciliary body and cho. roidal melanomas provides significant prognostic information. Compared with more conventional prognostic characteristics, the most dramatic increase in prognostic information is provided by determination of the presence or absence of microvascular patterns.

Choroid Neoplasms↗
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↗
PubMed1997

Correlation of ultrasound parameter imaging with microcirculatory patterns in uveal melanomas.

Previous studies demonstrated a correlation between acoustic backscatter parameters and survival in ocular melanoma. The histologic presence of microvascular networks in ocular melanoma is also associated with death from metastases. This study tests the hypothesis that melanomas grouped on the basis of these microvascular patterns are separable by ultrasound spectrum analysis. We scanned 40 melanomas using a 10-MHz ultrasound unit equipped for digitization of radio frequency data. After enucleation, tumors were sectioned in planes corresponding to the ultrasonographic examination and stained to demonstrate microcirculation. Acoustic spectral parameters were compared between 14 melanomas with a nevuslike microcirculation and 26 with foci of high-risk microvascular structures. Smaller scatterer size, lower acoustic concentration and greater spatial variability were found to correlate with high-risk microvascular patterns and areas of cystic degeneration. We suggest that nonvascular extracellular matrix components associated with microvessels may be responsible for the correlation of acoustic parameters with microvascular pattern and distribution.

Choroid Neoplasms↗
PubMed1997

The microcirculation of choroidal and ciliary body melanomas.

The microcirculation of ciliary body and choroidal melanomas is remodelled into patterns. The presence of microvascular networks, composed of back-to-back loops that encircle microdomains of tumour, and parallel vessels with cross-linking, are associated with death from metastatic melanoma. The formation of these complex vascular patterns may result from reciprocal interactions between the tumour cell and the extracellular matrix, and pattern formation may reflect an invasive tumour cell phenotype. Ciliary body and choroidal melanomas are among the few forms of cancer treated before a pathologist assigns a grade to indicate whether tumour is likely to follow a benign or aggressive course. There is evidence to suggest that prognostically significant microcirculatory patterns may be detectable by non-invasive imaging techniques that may provide a substitute for biopsy to guide the clinical management of patients with these sight- and life-threatening tumours.

Choroid Neoplasms↗
PubMed1996

Outbreak of keratitis presumed to be caused by Acanthamoeba.

PURPOSE: A sharp increase of Acanthamoeba keratitis from two cases per year to 30 cases per year at our institution prompted this study to determine whether there was a change in the clinical characteristics, basic epidemiology, and outcome of this disease. METHODS: We reviewed all cases of Acanthamoeba keratitis diagnosed at the University of Iowa Hospitals and Clinics from mid-1993 through 1994. RESULTS: We screened 217 patients with keratitis by tandem scanning confocal microscopy and suspected Acanthamoeba in 51 patients. Diagnosis was confirmed by cytology in 43 patients (48 eyes). There were no positive cultures. Patients examined within four weeks of onset of symptoms were younger (mean age, 32.6 +/- 15.4 years) and wore contact lenses (11 of 18 patients), and infrequently herpes simplex keratitis (four of 18 patients) was diagnosed. Patients examined after four weeks were older (mean age, 54.0 +/- 19.5 years), infrequently wore contact lenses (six of 25 patients), and often had herpes simplex keratitis (12 of 25 patients). CONCLUSIONS: Corneal examination with tandem scanning confocal microscopy was associated with a marked increase in the detection of Acanthamoeba, strongly suggesting that the disease is more prevalent than suspected. Acanthamoeba may account for many cases of clinically presumed herpes simplex keratitis, the leading cause of corneal blindness in the United States. Acanthamoeba should be considered in the differential diagnosis of any unexplained keratitis, even those of short duration.

Acanthamoeba↗
PubMed1996

Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.

AIMS/BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia induced angiogenic factor. Recent studies have shown that high levels of VEGF accumulate in the vitreous of patients with proliferative diabetic retinopathy (PDR). The purpose of the present study was to identify the retinal cells that upregulate VEGF expression in human PDR patients representing progressive stages of retina deterioration. METHODS: Thirteen formalin fixed and paraffin embedded enucleated eyes with PDR were used (eyes were enucleated because of being blind and painful as a result of neovascular glaucoma). Thin retina sections were hybridised in situ with a VEGF specific probe, to identify cells producing VEGF mRNA. RESULTS: All eyes with PDR showed upregulated expression of VEGF mRNA, specifically in the cells of the neurosensory retina. VEGF expression was upregulated in all three nuclear layers--namely, the ganglion cell layer, the inner nuclear layer, and the outer nuclear layer. However, in each patient, VEGF producing cells were mostly distributed in a different layer, or even confined to a specific region in that layer. For example, expression by the outer nuclear layer was mostly detected in detached (presumably hypoxic) regions of the retina. CONCLUSIONS: Progression of PDR is distinguished by a sustained, upregulated expression of VEGF by the neurosensory retina. Cells in all retina layers can potentially contribute to augmented VEGF production. The restricted population of VEGF producing cells in each case is likely to represent cells residing in ischaemic regions of the retina. Thus, VEGF may function as a linking factor between retinal ischaemia and PDR associated neovascularisation.

Adult↗
PubMed1996

Expression of type VI collagen in uveal melanoma: its role in pattern formation and tumor progression.

Choroidal and ciliary body melanomas disseminate exclusively by a hematogenous route because there are no lymphatics inside the eye. Although angiogenesis is an absolute precondition for metastasis in this tumor system, not all morphologic expressions of tumor angiogenesis are associated with metastasis from choroidal and ciliary body melanomas. Specifically, the remodeling of the microcirculation to form vascular networks is very strongly associated with metastasis. Type VI collagen is upregulated in tissue remodeling and the generation of tissue patterns and is either not present in the normal choroid or present at very low levels. This study was designed to investigate the possible expression of type VI collagen in the stroma of choroidal and ciliary body melanomas. Type VI collagen was detected in tissue sections from five primary choroidal melanomas and three melanomas involving the choroid and ciliary body in the subendothelial compartment of the microcirculation and in avascular areas by immunohistochemistry. Melanoma cell lines were established from each of these tumors. Cultured melanoma cells invaded into type I collagen gels and expressed type VI collagen by immunohistochemistry. Using specific primers for human type VI collagen, the expected band size (413 base pairs) was isolated from one of the cell lines by reverse transcriptase PCR. The presence of type VI collagen in the melanoma tumor stroma reflects active remodeling of the uveal extracellular matrix microenvironment by the melanoma cells themselves. Before the formation of the microvasculature, the expression of type VI collagen and of the other matrix components, such as hyaluronan, to which it binds, may erect a scaffold permitting the formation of higher order stromal patterns such as vascular networks. These stromal patterns, which are markers of tumor progression, may be detectable clinically by a specialized form of ultrasonography that detects backscatterers of the same dimension as tissue compartments encircled by vascular loops in networks.

Base Sequence↗