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Biomedical subjects

W R Lee

Publications and source records attributed to W R Lee.

At least 145 records · Page 8Linked to original sources
PubMed1994

Pathology of hereditary retinal degeneration associated with hypobetalipoproteinemia.

BACKGROUND: The clinical features and previously unreported ocular pathology in a case of heterozygous hypobetalipoproteinemia (HBL) associated with a pigment epitheliopathy are documented. Night blindness developed in a white woman with familial heterozygous HBL (cholesterol and low-density lipoprotein levels < 5% of normal) at 51 years of age. Ophthalmoscopy showed bilateral symmetric depigmentation at the posterior pole with pigment clumping and pavingstone configuration in the periphery. By the time the patient died, at 75 years of age, vision had deteriorated to hand motions. METHODS: One eye was removed 2 hours postmortem for light and electron microscopic study. RESULTS: The photoreceptors were absent, and the outer nuclear layer was replaced by glial cells throughout most of the retina, but there was some focal photoreceptor preservation in isolated regions. The outstanding feature was a massive deposition of basal linear deposit which was calcified in segments and which contained macrophages and the processes of glial cells: trilaminar bodies and melanin granules were identified in the macrophages. The remaining retinal pigment epithelial cells contained melanin but very little lipofuscin: intraretinal migration was minimal. CONCLUSIONS: The authors postulate that the pigment epitheliopathy associated with HBL is an abiotrophy in which photoreceptor discs are unable to regenerate due to locally disordered metabolism resulting from or acting in concert with the pigment epitheliopathy.

Aged↗
PubMed1994

Immunogold study of non-collagenous matrix components in normal and exfoliative iris.

The present investigation was undertaken to determine if some of the components of exfoliation material in iris tissue were unique to exfoliation or were part of normal iris architecture. Eleven normal iris specimens and 10 exfoliative iris specimens were processed for cryoultramicrotomy and London resin white embedding. Immunogold electron microscopy was used to investigate the fine structural distribution of amyloid P component, elastin, entactin, fibronectin, gp115, and vitronectin in normal iris and their association with exfoliation material. Exfoliation material was positive for amyloid P component and possibly gp115, neither of which were present in normal iris tissue. Elastin and fibronectin were present in the normal iris stroma but were not associated with exfoliation material. The distribution of amyloid P component in the vessel lumen and wall led to the conclusion that amyloid P is a serum contaminant. The presence of gp115 in exfoliation material represents the synthesis of a component novel to the iris vascular cell synthetic repertoire.

Adult↗
PubMed1994

Corneal endothelial cell abnormalities in an early stage of the iridocorneal endothelial syndrome.

A corneal disc, obtained from a 52-year-old woman suffering from an early stage of the iridocorneal endothelial syndrome (ICE), was investigated by various morphological techniques to analyse the structural variations in the endothelial cells and to identify the collagen types within the abnormal layer of Descemet's membrane. Scanning electron microscopy of the posterior corneal surface revealed a mosaic of (a) flat hexagonal cells resembling irregular but normal endothelial cells, and (b) rounded hexagonal (ICE) cells with numerous surface microvilli. Degenerative changes were present in each cell type, but were more common in the flat hexagonal cells which contained intracytoplasmic spaces. By transmission electron microscopy the flat hexagonal cells exhibited many of the features of normal endothelial cells in terms of organelles and intercellular attachments, but lateral invaginations were absent. The ICE cells differed in that the apical surface was covered by microvilli and the cytoplasm contained tonofilaments, which were also observed by light microscopic immunocytochemical staining. Most commonly, intercellular attachments were rudimentary in both types of cell and intercellular spaces were dilated, but desmosomes were sometimes prominent in the ICE cells where interdigitations were pronounced. In some sectors, the basal surface of the ICE cells was indented by deposition of clumps of fibrillar collagenous material. An immunocytochemical study of the abnormal posterior deposits localised type IV collagen to the amorphous matrix and collagen types III and V, but not type I, to the collagen fibril bundles. Mononuclear inflammatory cells were identified between the ICE cells in the monolayer. The evidence suggests that some of the flat hexagonal cells were undergoing a degenerative change while others were transforming into ICE cells.

Collagen↗
PubMed1994

Value of laryngeal cartilage sclerosis as a predictor of outcome in patients with stage T3 glottic cancer treated with radiation therapy.

PURPOSE: To determine whether sclerosis of the laryngeal cartilages was a predictor of a poor outcome in patients with stage T3 glottic cancer treated with radiation therapy. MATERIALS AND METHODS: Thirty-three patients with stage T3 glottic cancer underwent computed tomography (CT) before radiation therapy. Twenty-two patients underwent posttreatment CT. The presence of cartilage sclerosis, cartilage erosion, marrow invasion, and cartilage necrosis was determined. RESULTS: Nineteen of the 33 patients had cartilage sclerosis at CT. Seventeen patients had sclerosis of a single laryngeal cartilage (14 arytenoid, two cricoid, and one thyroid), and two had sclerosis of adjacent laryngeal cartilages (arytenoid and cricoid in both cases). Of the 17 patients with isolated laryngeal cartilage sclerosis, disease was controlled with radiation therapy alone in 15 and with salvage laryngectomy in two. Both patients with cricoid and arytenoid sclerosis died of their original cancer despite undergoing early salvage laryngectomy. Of the 14 patients without sclerosis, eight had no evidence of disease, two died of their disease, and four died of intercurrent disease. CONCLUSION: T3 glottic cancer with isolated laryngeal cartilage sclerosis can be cured with radiation therapy.

Glottis↗
PubMed1994

Radiologic appearance of the irradiated larynx. Part I. Expected changes.

PURPOSE: To present the expected appearance of the irradiated larynx and neck as seen at computed tomography (CT). MATERIALS AND METHODS: Sixty-one patients with primary squamous cell carcinoma of the larynx or hypopharynx were treated with radiation therapy. All patients underwent CT before and after treatment. RESULTS: Expected changes include symmetric thickening of the epiglottis, aryepiglottic folds, and false cords and increased attenuation of the paralaryngeal fat. The posterior pharyngeal wall tends to thicken and its mucosa enhances; retropharyngeal space edema is common. Glottic changes include increased attenuation of the paraglottic fat planes and thickening of the anterior and posterior commissures. Subglottic changes include thickening of the mucosa and submucosa. Soft-tissue changes include skin and platysmal thickening, as well as reticulation and increased attenuation of the subcutaneous and deeper fat. CONCLUSION: Familiarization with expected radiologic changes is essential for interpretation of CT images of the irradiated larynx so that such changes are not mistaken for signs of persistent or recurrent tumor.

Carcinoma, Squamous Cell↗
PubMed1994

Radiologic appearance of the irradiated larynx. Part II. Primary site response.

PURPOSE: To evaluate the computed tomographic (CT) appearance of laryngeal tumors treated with radiation therapy and the ability of CT to depict persistent or residual tumor. MATERIALS AND METHODS: Sixty-one patients with primary squamous cell carcinoma of the larynx or hypopharynx were treated with definitive radiation therapy. CT was performed in all patients before and after treatment. RESULTS: In 32 of 41 patients with cancer controlled at the primary site, CT showed complete resolution of tumor, whereas in 10 of 14 patients in whom radiation therapy failed, there was minimal or no reduction in tumor. In a subpopulation of patients who underwent repeat imaging, 18 of 19 with tumor controlled at the primary site had complete resolution of tumor. Overall, in four of 13 patients with 50%-75% reduction in tumor size or persistent substantial asymmetry at CT, therapy eventually failed at the primary site. CONCLUSION: Lesions that are reduced by 50% or less at 4-month follow-up CT are highly suspicious for treatment failure. Repeat CT studies every 4 months is recommended in addition to careful clinical follow-up.

Carcinoma, Squamous Cell↗
PubMed1994

Bilateral uveal melanoma presenting simultaneously.

A case of bilateral uveal melanoma in a 54-year-old man is described. On admission of the patient for a choroidal melanoma of the left eye, an asymptomatic ciliary-body tumour was detected in his right eye. A thorough general examination did not reveal any metastases. The left eye was enucleated and local excision of the tumour in the right eye was performed 2 months later. Histology confirmed the presence of malignant melanomas in both eyes. The tumours were of similar A/B spindle-cell type. The patient remained healthy, showing no sign of metastasis or local recurrence of melanoma 9 months after the date of diagnosis. The visual acuity in his remaining eye remained 6/6. Immunological assessment of the blood serum revealed abnormally high interleukin 1 beta (IL-1 beta) and IL-2 levels. Possible implications of these findings are discussed.

Choroid Neoplasms↗
PubMed1994

Multirecurrence of corneal posterior polymorphous dystrophy. An ultrastructural study.

Posterior polymorphous corneal dystrophy (PPD) is a rare bilateral, autosomal-dominant disease. The presence of the epitheliumlike endothelium and the thickening of Descemet's membrane by the posterior collagenous layer (PCL) has been reported in the majority of published cases. Reepithelialization of the posterior cornea in donor tissue has been reported only once. Therefore, to examine this process we examined, by light and electron microscopy, three corneal buttons (an original and two subsequent keratoplasties after 3 and 4 years, respectively) from the left eye of a patient with bilateral disease. Our study showed a repopulation of the posterior surface of the donor corneas by the host epitheliumlike endothelium, which was of identical morphology in each case. In contrast to the previously published work, a posterior collagenous layer in the failed grafts was absent from the axial cornea, where the epitheliumlike endothelium was in direct contact with donor Descemet's membrane. A PCL at the periphery in the failed transplants was of the fibrocellular type and differed from the fibrillar PCL in the first keratoplasty specimen. The fibroblastlike cells within the fibrocellular PCL were distinct from the underlying epithelial-like cells and contained numerous tertiary phagolysosomes. We suggest that the major contributor to the fibrocellular PCL in the repeat keratoplasties was a fibrous ingrowth from the host/graft junction and not the epitheliumlike endothelium. It appears that the synthetic capacity of the epitheliumlike endothelium was similar to that of the normal epithelium and was much lower than that of normal native endothelium.

Corneal Dystrophies, Hereditary↗
PubMed1993

Localized carcinoma of the prostate (stages T1B, T1C, T2, and T3). Review of management with external beam radiation therapy.

BACKGROUND: Optimal treatment for patients with localized carcinoma of the prostate is controversial. Radiation therapy is an established modality in the management of these patients, and several reports indicate the results are comparable to those achieved with radical prostatectomy. Recently effectiveness of therapy for carcinoma of the prostate is being evaluated in light of post-treatment prostate-specific antigen (PSA) determinations. METHODS: A review was performed of multiple publications and data from selected institutions with large experience in the management of carcinoma of the prostate. Survival and clinical incidence of local recurrence and distant metastases were analyzed as well as preliminary data on postirradiation PSA levels. Factors that affect the outcome of therapy and relevant clinical trials are discussed. RESULTS: Reported differences in the age of patients treated with radical prostatectomy (59-63 years), irradiation (63-69 years), or observation (69-75.5 years) were identified. The effect of surgical staging on outcome of irradiation was significant. In multiple series of patients clinically and radiographically staged, the 5-year disease-free survival (DFS) with external irradiation was 95-100% for clinical stage T1a, 80-90% for Stage T1b,c, and 50-70% for clinical Stage T3. A correlation has been identified between the initial PSA levels and the probability from freedom of chemical failure (PSA elevation) after definitive irradiation. In five series comprising 814 patients with Stage T1c and T2 tumors, the DFS (end point chemical failure) was 95%, with initial PSA of less than 4 ng/ml, 83-92% with 4.1-10 ng/ml, 35-85% with 10.1-20 ng/ml, and 10-63% with PSA higher than 20 ng/ml. In the various series, follow-up ranged from a median of 1.5 years to a minimum of 4 years. In two series of 225 and 201 patients receiving doses of 7500-8000 cGy, less morbidity has been observed with three-dimensional treatment planning conformal radiation therapy than with conventional irradiation. New directions for future clinical trials are discussed, including dose escalation studies; use of high linear energy transfer to improve locoregional tumor control; and combination of irradiation and androgen suppression to enhance local tumor control, decrease distant metastasis, and improve survival. Preliminary results of a randomized study recently reported by RTOG strongly suggest that the use of goserelin acetate and flutamide decreases the incidence of clinical local recurrence (12.4% in 225 patients) compared with a control group treated with irradiation alone (25.2% in 230 patients) and enhances disease-free survival. CONCLUSIONS: Although modern approaches to the management of patients with localized carcinoma of the prostate with irradiation are effective, investigators must continue to critically assess policies of treatment, develop appropriately designed prospective clinical trials, and define the optimal management of patients with localized carcinoma of the prostate.

Carcinoma↗
PubMed1993

Elective inguinal lymph node irradiation for pelvic carcinomas. The University of Florida experience.

BACKGROUND: There is little published information pertaining to elective inguinal lymph node irradiation for carcinomas originating in the pelvis that place the inguinal lymph nodes at risk. METHODS: Between October 1964 and October 1988, 164 patients with primary carcinomas originating in the pelvis that placed the inguinal lymph nodes at risk for subclinical disease received elective inguinal lymph node irradiation at the University of Florida. All patients had a minimum follow-up of 2 years from the start of radiation therapy. Primary sites included the penis, urethra, vulva, anal canal, distal rectum (within 4 cm of the verge), and the cervix or vagina when the tumor involved the distal one-third of the vagina. In 148 patients, both groins were clinically negative; in 16 patients, one groin was positive and the other negative by clinical examination. Treatment techniques were individualized according to the primary site. Tumor doses to the inguinal lymph nodes varied, although more than 70% of patients received 4500-5000 cGy (range, 2650-6780 cGy) over 5 weeks (range, 2-7 weeks) at 180-200 cGy per fraction. Patients were excluded from the analysis of disease control in the inguinal area if they died less than 2 years from treatment with the inguinal lymph nodes continuously disease free or if they experienced recurrence at the primary site with the inguinal lymph nodes clinically negative at the time of recurrence. RESULTS: The inguinal lymph node control rate was 96% (101 of 105). No patient in whom recurrent disease developed in the inguinal lymph nodes underwent salvage therapy. CONCLUSIONS: Elective irradiation of the inguinal lymph nodes is highly effective in controlling subclinical disease from carcinomas originating in the pelvis and can be accomplished with minimal acute or long-term complications.

Adult↗
PubMed1993

Erythropoietin structure-function relationships. Mutant proteins that test a model of tertiary structure.

On the basis of its primary sequence and the location of its disulfide bonds, we propose a structural model of the erythropoietic hormone erythropoietin (Epo) which predicts a four alpha-helical bundle motif, in common with other cytokines. In order to test this model, site-directed mutants were prepared by high level transient expression in Cos7 cells and analyzed by a radioimmuno assay and by bioassays utilizing mouse and human Epo-dependent cell lines. Deletions of 5 to 8 residues within predicted alpha-helices resulted in the failure of export of the mutant protein from the cell. In contrast, deletions at the NH2 terminus (delta 2-5), the COOH terminus (delta 163-166), or in predicted interhelical loops (AB: delta 32-36, delta 53-57; BC: delta 78-82; CD: delta 111-119) resulted in the export of immunologically detectable Epo muteins that were biologically active. The mutein delta 48-52 could be readily detected by radioimmunoassay but had markedly decreased biological activity. However, replacement of each of these deleted residues by serine resulted in Epo muteins with full biological activity. Replacement of Cys29 and Cys33 by tyrosine residues also resulted in the export of fully active Epo. Therefore, this small disulfide loop is not critical to Epo's stability or function. The properties of the muteins that we tested are consistent with our proposed model of tertiary structure.

Amino Acid Sequence↗
PubMed1993

Site-specific mutagenesis of Drosophila alcohol dehydrogenase: evidence for involvement of tyrosine-152 and lysine-156 in catalysis.

Amino acid sequence comparisons reveal that tyrosine-152 and lysine-156 of Drosophila alcohol dehydrogenase (ADH) are conserved in homologous dehydrogenases, suggesting that these residues are important in catalysis. To test this hypothesis, we used site-directed mutagenesis to substitute tyrosine-152 with phenylalanine, histidine, or glutamic acid or to substitute lysine-156 with isoleucine. All of these mutants are catalytically inactive. Two mutants were active: A cysteine mutation of tyrosine-152 has 0.25% of wild-type ADH activity, while an arginine substitution of lysine-156 retains 2.2% of wild-type ADH activity. Kinetic analysis shows that the cysteine mutant increases Km(ethanol) 56-fold and Km(propan-2-ol) 100-fold, while Km(NAD) values are essentially unaltered. The arginine mutant also shows the significant enlargement of Km(ethanol), but not of Km(NAD). Furthermore, the cysteine mutant and arginine mutant have different substrate specificity and behave differently on competitive inhibition than wild-type ADH. These results suggest that both tyrosine-152 and lysine-156 have essential roles in catalysis by Drosophila ADH.

1-Propanol↗
PubMed1993

Can pretreatment computed tomography findings predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone?

PURPOSE: To determine if pretreatment computed tomography findings can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with radiotherapy alone. METHODS AND MATERIALS: Twenty-nine patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with radiotherapy alone; all had a minimum 2-year follow-up. High-quality pretreatment computed tomography scans were retrospectively reviewed by a single head and neck radiologist for tumor involvement of various anatomic subsites within the larynx, and total tumor volumes were calculated for 18 of the most recent patients using a computer digitizer. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. RESULTS: A significant decrease in the local control rate was observed for cancers involving the face of the arytenoid (11 of 20 [55%] vs. 9 of 9 [100%]; p = .02), or the paraglottic space at the false vocal cord level (7 of 16 [44%] vs. 13 of 13 [100%]; p not equal to < .01). Tumors assigned a high tumor score (6, 7, or 8) had a significantly decreased rate of local control with radiation therapy when compared with tumors assigned a low tumor score (< or = 5): 1 of 7 (14%) vs. 19 of 22 (86%) (p = .01). Total tumor volume also significantly correlated with the rate of tumor control. For tumors measuring 3.5 cm3 or less, local control was achieved in 11 of 12 patients (92%), whereas for tumors greater than 3.5 cm3, local control was achieved in 2 of 6 patients (33%) (p = .02). CONCLUSION: Pretreatment computed tomography scans can contribute significantly to the treatment decision for patients with T3 glottic carcinoma and can define a subset of patients with an excellent chance of being cured with preservation of a functional larynx after treatment with radiotherapy alone.

Adult↗
PubMed1993

Uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis in the Lewis rat: an ultrastructural study.

The histopathological features of uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis (EAE) were investigated using light and electron microscopy. Lewis rats were immunized by spinal cord homogenate, complete Freund's adjuvant and Bordetella pertussis. The eyes of rats with EAE exhibited vasculitis in the iris, trabeculitis and endothelial abnormalities in the retinal vessels; vasculitis was observed in the optic nerve and brain. Endothelial cells in the vessels in the iris, retina, optic nerve and central nervous system were noted to be elevated (high endothelial-like venules, or HELV). Inflammatory cells in the vascular lumen were attached to the surface of endothelial cells in abnormal areas in the iris. By comparison with the findings in the iris and retina, there were no significant changes in the vessels of the ciliary body and choroid. The ultrastructural features indicated that anterior uveitis in acute EAE resulted from vasculitis in the iris due to changes of the endothelial cells and was not due to a reaction against the myelinated nerves or any other particular components of the iris. In addition, our results suggested that vasculitis in the iris was consequent upon specialized changes of the endothelial cells similar to HELV which were responsible for the transcellular emigration of lymphocytes in other inflammatory diseases or in experimental models. HELV change plays an important role in the perivascular inflammatory process in the iris, retina, optic nerve and central nervous system in EAE and possibly in multiple sclerosis.

Animals↗
PubMed1993

Prevalence, diagnostic features, and response to trabeculectomy in exfoliation glaucoma.

BACKGROUND: The "true" prevalence and clinical attributes of exfoliation glaucoma remain controversial. The authors studied these characteristics in glaucoma patients requiring trabeculectomy. METHODS: One hundred consecutive patients undergoing trabeculectomy for open-angle glaucoma were investigated by clinical examination (biomicroscopy and gonioscopy) and classified into three categories: exfoliation glaucoma, possible exfoliation glaucoma, and primary open-angle glaucoma (POAG). A definitive diagnosis of exfoliation glaucoma was provided by pathologic examination of iris tissue. RESULTS: All 22 patients with clinical evidence of exfoliation glaucoma and 4 of 18 patients with possible exfoliation glaucoma on clinical examination had ultrastructural evidence of exfoliation material. The prevalence of exfoliation glaucoma, therefore, was 26%. The clinical examination for the diagnosis of exfoliation glaucoma had an 85% sensitivity rate and a 100% specificity rate. In comparison with POAG, patients with exfoliation glaucoma had higher untreated intraocular pressure (IOP), higher IOP with medical therapy, and shorter duration of medical therapy. They were more often operated on for unacceptably high IOP. Exfoliation glaucoma patients exhibited significantly lower IOP after surgery. CONCLUSION: Exfoliation glaucoma is common in patients requiring trabeculectomy for open-angle glaucoma. This condition differs from POAG by a poorer response to medical therapy and a better response to trabeculectomy.

Aged↗
PubMed1993

Morphology of iris vasculopathy in exfoliation glaucoma.

Iris tissue obtained from 26 consecutive patients operated upon for exfoliation glaucoma and control iris tissue from 26 age-matched subjects operated upon for primary open angle glaucoma was used to investigate the iris vasculopathy associated with exfoliation glaucoma. By light microscopy exfoliation material was discerned by increased density of the perivascular matrix in affected vessels. By transmission electron microscopy exfoliation vasculopathy was divided into 4 grades. Grade I was characterized by focal accumulation of exfoliation material without evidence of cellular degeneration. In grade II, exfoliation material accumulation was accompanied by degeneration of vascular supporting cells; endothelial cells were unaffected. In grade III, endothelial cells exhibited degenerative changes and in grade IV, exfoliation material occupied an acellular vascular wall (ghost vessel). It is suggested that in iris vessels the synthesis of exfoliation material can be attributed primarily to the vascular supporting cells.

Arterioles↗