Histologic study of a torn inferior oblique muscle.
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Aged↗
Biomedical subjects
W R Green
Publications and source records attributed to W R Green.
A single amino acid variation within an immunodominant AKR/Gross MuLV cytotoxic T-lymphocyte epitope leads to a loss in immunogenicity.
C57BL/6 mice characteristically generate vigorous H-2K(b)-restricted cytotoxic T lymphocytes (CTL) directed against an immunodominant CTL epitope (KSPWFTTL) expressed by endogenous AKR/Gross murine leukemia viruses (MuLV). These AKR/Gross MuLV-specific CTL do not efficiently recognize tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, which express the highly homologous peptide RSPWFTTL. In this report, we not only confirm the inefficient recognition of FMR tumors by AKR/Gross MuLV-specific CTL, but also demonstrate that RSPWFTTL is poorly immunogenic in C57BL/6 mice. To gain insight into the mechanism(s) contributing to the inefficient recognition of FMR MuLV-induced tumors, we examined the RSPWFTTL dissociation rate from H-2K(b) as well as the ability for RSPWFTTL to diminish CTL effector functions by T-cell antagonism. In contrast to immunogenic peptides, which form stable MHC class I-peptide complexes having slow dissociation rates, poorly immunogenic peptides characteristically have faster dissociation rates. On the basis of a cell-surface MHC class I peptide stabilization assay, the dissociation rate of RSP-WFTTL from H-2K(b) is characterized by a half-life that is nearly identical to the half-life of KSPWFTTL. In addition, we could find no evidence for antagonistic inhibition of AKR/Gross MuLV-specific CTL over a wide concentration range of RSPWFTTL. Analysis of the role of the transporter associated with antigen processing (TAP), by use of recombinant vaccinia and Sindbis viruses expressing a hydrophobic amino-terminal endoplasmic reticulum (ER) targeting sequence coupled to RSPWFTTL, indicated that RSPWFTTL cell-surface presentation can be dramatically enhanced when directly targeted into the ER.
AKR murine leukemia virus↗
Photocoagulation of well-defined choroidal neovascularization in age-related macular degeneration: clinicopathologic correlation.
PURPOSE: To present the clinicopathologic features of the eyes of a patient with age-related macular degeneration (ARMD): the right eye was treated for well-defined extrafoveal choroidal neovascularization (CNV), and the left eye had an untreated disciform scar. METHODS: The patient was studied ophthalmoscopically and by fluorescein angiography at the time of presentation and on follow-up examinations up to 54 days after laser treatment, when he died. The posterior portions of both eyes (obtained postmortem), including the macula and optic nerve head, were sectioned serially for light microscopy. Tissue sections from both eyes were removed from glass slides and studied by transmission electron microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin layer of basal laminar deposit throughout the posterior pole. Two defects in Bruch's membrane without CNV were present within the area of laser photocoagulation located superior to the fovea. No CNV was present in the scar. Eleven areas of early CNV were present in the posterior pole. Histopathologic study of the left eye showed a prominent basal laminar deposit throughout the posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The clinicopathologic features of a treated eye with well-defined extrafoveal CNV, and the fellow eye with a disciform scar, both associated with ARMD, are presented. Although laser treatment obliterated a choroidal neovascular membrane, 11 additional areas of early, subclinical CNV were present.
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HIV-1-associated Kaposi's sarcoma in a predominantly black population at an inner city hospital.
BACKGROUND: Kaposi's sarcoma (KS) associated with human immunodeficiency virus type 1 (HIV-1) is the most common malignancy in patients with AIDS. It has been most commonly reported in white homosexual men, though a few cases have been reported in blacks. METHODS: We conducted a retrospective analysis of all HIV-1 seropositive patients with biopsy-proven KS seen at Howard University Hospital between February 1985 and June 1995. RESULTS: Of the 73 patients identified, 66 (90%), 4 were white, 2 were Hispanic, and 1 was of unidentified race. The median age was 32 years. Forty-eight (66%) were homosexual or bisexual men, and 10 (14%) were homosexual or bisexual with a history of intravenous drug use (IDU). A history of IDU or blood transfusion was the only risk factor in 7 (9%) and 2 (3%), respectively. The other 6 (8)% were heterosexual. The median survival was 2.2 years. A CD4 count <200 and the presence of an opportunistic infection were associated with shortened survival. CONCLUSIONS: The predominant risk factor for HIV-1-associated KS was homosexual or bisexual activity. Only a few women with KS were identified, and they also reported sexual transmission from male bisexuals and/or drug users. Poor survival was associated with CD4 <200, stage III and IV KS at presentation, and opportunistic infections.
Adult↗
Ocular explosion during cataract surgery: a clinical, histopathological, experimental, and biophysical study.
INTRODUCTION: An increasing number of cases are being recognized in which a peribulbar anesthetic for cataract surgery has been inadvertently injected directly into the globe under high pressure until the globe ruptures or explodes. We reviewed the records of 6 such cases (one of which was reported previously by us), and one additional case has been reported in the literature. Surprisingly, 2 of these 7 cases went unrecognized at the time, and the surgeons proceeded with the cataract operation; all of the patients ultimately developed severe visual loss and/or loss of the eye. OBJECTIVES: To reproduce this eye explosion in a live anesthetized rabbit model and to perform a clinical, histopathological, experimental, biophysical, and mathematical analysis of this injury. METHODS: Eyes of live anesthetized rabbits were ruptured by means of the injection of saline directly into the globe under high pressure. The clinical and pathological findings of the ruptured human and animal eyes were documented photographically and/or histopathologically. An experimental, biophysical, and mathematical analysis of the pressures and forces required to rupture the globe via direct injection using human cadavers, human eye-bank eyes, and classic physics and ophthalmic formulas was performed. The laws of Bernoulli, LaPlace, Friedenwald, and Pascal were applied to the theoretical and experimental models of this phenomenon. RESULTS: The clinical and pathological findings of scleral rupture, retinal detachment, vitreous hemorrhage, and lens extrusion were observed. In the exploded human and rabbit eyes, the scleral ruptures appeared at the equator, the limbal area, or the posterior pole. In 2 of the 7 human eyes, the anterior segments appeared entirely normal despite the rupture, and cataract surgery was completed; surgery was canceled in the other 4 cases. In 4 of the 5 injected and ruptured rabbit eyes, the anterior segments appeared essentially normal. The experiments with human eye-bank eyes and the theoretical analyses of this entity show that the pressure required to produce such an injury is much more easily obtained with a 3- or 5-mL syringe than with a syringe 10 mL or larger. CONCLUSIONS: Explosion of an eyeball during the injection of anesthesia for ocular surgery is a devastating injury that may go unrecognized. The probability of an ocular explosion can be minimized by careful use of a syringe 10 mL or larger with a blunt needle, by discontinuing the injection if resistance is met, and by inspecting the globe prior to ocular massage or placement of a Honan balloon. When ocular explosion occurs, immediate referral to and intervention by a vitreoretinal surgeon is optimal. Practicing ophthalmologists should be aware of this blinding but preventable complication of ocular surgery.
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The role of proximal and distal sequence variations in the presentation of an immunodominant CTL epitope encoded by the ecotropic AK7 MuLV.
An emv-14-derived, replication-competent ecotropic murine leukemia virus [MuLV], designated AK7, was previously cloned from the AKXL-5 recombinant inbred mouse strain and partially characterized. While genetically encoding for an envelope-derived immunodominant CTL epitope [KSPWFTTL] located in the transmembrane region of p15TM, this virus, unlike the emv-11-derived virus AKR623, fails to be efficiently recognized by AKR/Gross MuLV-specific cytotoxic T lymphocytes [CTL]. AK7 thus provides the opportunity to study the role of retroviral sequence variations that are located outside of the immunodominant epitope as a mechanism of escape from CTL-mediated immune surveillance. In an attempt to identify which region[s] of the AK7 genome could account for its ability to evade efficient recognition by AKR/Gross MuLV-specific CTL, we have constructed recombinant murine retroviruses. The direct influence of a sequence variation twelve amino acids N-terminal to KSPWFTTL was explored with the use of chimeric viruses and determined not to significantly impair the presentation of KSPWFTTL to AKR/Gross MuLV-specific CTL. The long terminal repeat [LTR] derived from the AK7 virus, which possesses only one copy of the 99-base pair transcriptional enhancer in the U3 region, in contrast to AKR623 that possesses two copies of the tandem direct repeat enhancers, was also analyzed for its influence on the presentation of KSPWFTTL. Interestingly, our data indicate that the enhancer region derived from AK7 negatively influences the presentation of KSPWFTTL in the context of a recombinant AKR623 virus.
AKR murine leukemia virus↗
CD3+ CD8+ CTL activity within the human female reproductive tract: influence of stage of the menstrual cycle and menopause.
The human female reproductive tract (RT) has been analyzed by others with respect to NK cell cytolytic activity, but not CD3+ T cell (CTL) cytolytic activity. Here, we describe the cytolytic capacity of mucosal CD3+ T cells both longitudinally within the RT (Fallopian tube, uterine endometrium, endocervix, ectocervix, and vaginal mucosa) and temporally throughout the menstrual cycle, using a redirected lysis assay system. Cytolysis by CD3+ CD8+ T cells is found throughout the RT and appears to be hormonally regulated, since in the uterine endometrium, the capacity for CD3+ T cell cytolytic activity is present during the proliferative phase of the menstrual cycle and absent during the subsequent secretory (postovulatory) phase. In contrast, in postmenopausal women the entire RT, including the uterus, retains the capacity for strong CD3+ T cell cytolytic activity. These findings suggest that the high levels of estradiol and progesterone present during days 14 to 28 of the menstrual cycle down-regulate CTL activity in the uterus. As a consequence, the absence of this activity may allow implantation of a semiallogeneic embryo that would otherwise be rejected. Further, these studies indicate that CTL activity is regulated differentially in different regions of the RT, persisting in the cervix and vagina throughout the menstrual cycle.
Adult↗
A shift in the requirement for CD4+ T cells in the generation of AKR/Gross MuLV-specific CTL in AKR.H-2b:Fv-1b mice occurs prior to the onset of age-dependent CTL nonresponsiveness.
In the current study, the elimination of CD4+ T cells from B6 mice, by treatment with anti-CD4 monoclonal antibody, had little effect on their ability to mount an AKR/Gross (MuLV)-specific CTL response. In contrast, for AKR.H-2b:Fv-1b mice, there was a shift as the mice aged from 5 to 7 weeks to a requirement for CD4+ T cells for AKR/Gross MuLV-specific CTL generation. When CD4+ T-cell-depleted AKR.H-2b:Fv-1b responder mice were immunized at 5 weeks of age they were able to elicit a strong anti-AKR/Gross MuLV CTL response. However, if the CD4+ T-cell depletion was done at 6 weeks and then the mice were primed in vivo, their antiviral CTL responsiveness was markedly decreased. Following CD4+ T-cell depletion at 7 weeks the mice were totally incapable of generating anti-AKR/Gross MuLV-specific CTL. AKR/Gross MuLV-specific CTL isolated from AKR.H-2b:Fv-1b mice recognized the class I-restricted immunodominant epitope (KSPWFTTL) and three subdominant epitopes, previously identified as CTL epitopes for B6 mice. Analysis of IL-2, IFN-gamma, IL-4, and IL-10 lymphokine profiles in supernates harvested from MLTC wells, and the results of supernate transfer experiments, suggested that the age-dependent shift to CD4+ T-cell dependence in AKR.H-2b:Fv-1b mice does not correlate with an obvious change in the in vitro lymphokine profiles. Experiments in which exogenous IL-2 was used to supplement in vitro cultures containing CD4+ T-cell-depleted 7-week responder mice suggested that the CD4+ T-cell requirement was at the in vivo priming stage of antiviral CTL generation. These data suggested a fundamental change in virus-specific CTL which correlates with slight aging in the AKR.H-2b:Fv-1b mouse strain. To our knowledge, this is the first report of a shift in the requirement for CD4+ T lymphocytes for the generation of virus-specific CTL over such a short period of time. Moreover, it is of interest that this shift in CD4+ T-cell-dependence by antiviral CTL occurs just prior to the onset of CTL nonresponsiveness in the AKR.H-2b:Fv-1b mouse strain.
AKR murine leukemia virus↗
Clinicopathologic study of the cornea in X-linked ichthyosis.
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Cornea↗
Comparison of transillumination and histologic slide measurements of choroidal melanoma.
OBJECTIVE: To compare transillumination and histologic slide measurements of choroidal melanomas in 479 eyes randomized to enucleation in the Collaborative Ocular Melanoma Study. DESIGN: Transillumination defects were measured during gross examination of enucleated eyes. Tumor basal diameter and height were measured on histologic slides and each tumor was assigned to 1 of 8 distinct shape categories. Comparison of the transillumination and histologic slide measurements revealed 3 categories of difference: underestimation (transillumination measurement more than 4 mm smaller than the histologic slide measurement), overestimation (transillumination measurement more than 4 mm larger than the histologic slide measurement), and agreement within 4 mm. RESULTS: There was good correlation between transillumination and histologic slide estimates of largest basal diameter, particularly when the basal diameter was 16 mm or less. Measurement discrepancies were related to the shape of the tumors but not to the presence of subretinal fluid or fixation. CONCLUSION: Agreement was high between measurements of transillumination defect and histologic sections.
Brachytherapy↗
Familial internal limiting membrane dystrophy. A new sheen retinal dystrophy.
OBJECTIVE: To describe the clinicopathologic features of a previously unreported retinal dystrophy. METHODS: Fourteen members of a single family were examined. The medical records of 2 additional family members were reviewed. Pathologic examination was performed on 2 eyes of 1 affected patient. RESULTS: Five individuals were identified with a retinal dystrophy characterized by a glistening inner retinal surface throughout the posterior pole. Visual loss occurred in 3 affected patients in later life owing to superficial polycystic retinal edema and retinal folds. Electroretinographic testing revealed a selective diminution of the b wave. Pathologic examination revealed an abnormal internal limiting membrane with schisis cavities in the inner retina. Endothelial cell swelling, pericyte degeneration, and basement membrane thickening were present in retinal capillaries. CONCLUSIONS: A previously unreported sheen retinal dystrophy is described. Pedigree analysis suggests an autosomal dominant mode of inheritance. A primary defect in Müller cells is the suspected, but unproved, cause. No effective treatment for the associated visual loss is known. The term familial internal limiting membrane dystrophy is proposed to describe this condition.
Adult↗
Clear cell differentiation in choroidal melanoma. COMS report no. 8. Collaborative Ocular Melanoma Study Group.
OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. RESULTS: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid.
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Central cloudy corneal dystrophy of Francois. A clinicopathologic study.
Central cloudy corneal dystrophy of Francois was first described in 1955 by J. Francois; its pathophysiology remains unknown. An 80-year-old woman with bilateral central cloudy corneal dystrophy of Francois was examined after having undergone a combined penetrating keratoplasty and cataract extraction. The corneal button was obtained. Light microscopy revealed stromal staining for acid mucopolysaccharide. Transmission electron microscopy revealed extracellular vacuoles, some of which had fibrillogranular material and electron-dense deposits. Fibrillogranular material was present in and around some keratocytes. Numerous endothelial vacuoles contained light-staining fibrillogranular material and round electron-dense granules. Our findings suggest that the opacities in patients with central cloudy corneal dystrophy of Francois are due to the extracellular accumulation of mucopolysaccharide and lipidlike material. Further studies are needed to elucidate the nature of these deposits.
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Clinicopathological correlation of technetium bone scan in vascularization of hydroxyapatite implants. A primate model.
OBJECTIVES: To report the histopathological and bone scan characteristics of the stages of hydroxyapatite fibrovascular integration and to consider the implications for the timing of peg drilling in a primate model. DESIGN: Three monkeys received hydroxyapatite implants covered only anteriorly with a fascia lata button to which the rectus muscles were sutured. Weekly bone scans were evaluated quantitatively and qualitatively. The orbits were harvested at 2, 4, and 8 weeks and examined histopathologically. RESULTS: Quantitatively, the implant's technetium uptake increased, then reached a plateau by 4 weeks. Peripheral uptake was present on the images and histologically at 2 weeks. When bone scan images suggested complete vascularization by the fourth week, the implant was 99% vascularized histologically. Completion of vascularization was ascertained at 8 weeks, without further discernible changes in the bone scans. CONCLUSIONS: The technetium bone scan is sensitive to the vascularization of the hydroxyapatite implant and discerns when complete vascularization is approached. This primate study models closely the clinical findings we have recently reported. We advocate at least a 4-week interval between the time the bone scan suggests full vascularization and peg drilling.
Animals↗
Ocular involvement in familial erythrophagocytic lymphohistiocytosis.
BACKGROUND: Familial erythrophagocytic lymphohistiocytosis (FEL), a rare, rapidly fatal childhood disorder, is characterized by intermittent fevers, hepatosplenomegaly, cytopenia, hypercytokinemia and lymphohistiocytic infiltration with erythrophagocytosis involving multiple organs. We report the clinical and histological features of two infants with FEL and emphasize the ocular findings. METHODS: Microscopic examination of formalin-fixed, paraffin-embedded autopsy material was performed. Immunohistochemical studies were performed in case 1. RESULTS: The first patient presented with clinical and laboratory features and a family history consistent with FEL, and a liver biopsy revealed a lymphohistiocytic infiltrate with erythrophagocytosis consistent with FEL. A deceased brother had been diagnosed with FEL. Autopsy showed widely disseminated lymphohistiocytic infiltrates affecting the liver, spleen, bone marrow, lungs, kidneys and brain. Histologic examination of both eyes disclosed a prominent lymphohistiocytic infiltrate of the optic nerve with destruction of nerve fiber bundles as well as milder infiltrates in the choroid, scleral canals, perineural areas in the orbit and the optic nerve head perivascularly. The second patient also had the typical clinical, laboratory and autopsy findings with similar involvement of most organs, including extensive infiltration of the spleen and bone marrow. Histologic examination of one eye revealed marked lymphohistiocytic infiltration of the entire choroid as well as milder infiltration in the trabecular meshwork, iris, ciliary body, optic nerve, meninges and around the central retinal vein in the optic nerve. CONCLUSION: The findings of this study further define the ocular pathologic features of FEL, which are a part of a generalized, multiorgan disseminated disease.
Choroid↗
Histopathologic and electron-microscopic features of corneal and scleral collagen fibers in osteogenesis imperfecta type III.
BACKGROUND: This report describes the histopathologic and electron-microscopic features of an eye from a patient with osteogenesis imperfecta type III. In particular, the diameters of corneal stromal and scleral collagen fibers were determined. METHODS: The eyes of an 18-year-old white male with osteogenesis imperfecta type III were examined by light and electron microscopy and the pathological features were compared with an age-matched control eye. RESULTS: The cornea was clear. The sclera had a blue color and was moderately thinned, especially at the equator. Light microscopy revealed absence of Bowman's layer. Transmission electron microscopy confirmed complete absence of Bowman's layer without evidence of scarring or inflammation. The collagen fibers of the corneal stromal lamellae were about 25% narrower than in the control, but the cornea was otherwise unremarkable ultrastructurally. The collagen fibers of the sclera were approximately 50% narrower than in the control and were much more uniform in size. Prominent portions of elastic fibers, which are usually only present in a small number in the inner portion of the sclera, were present throughout the sclera. CONCLUSION: We propose that it is the uniformity of the scleral collagen fibers which gives the sclera translucence, producing the blue color often observed clinically in osteogenesis imperfecta. Absence of Bowman's layer of the cornea did not interfere with the stability of the cornea in this case. This appears to be the first published pathological examination of the eye in osteogenesis imperfecta type III.
Adolescent↗
Ocular explosion after peribulbar anesthesia: case report and experimental study.
PURPOSE: A peribulbar anesthetic injection for cataract surgery produced a 10.5-mm scleral laceration and lens extrusion. This study sought to recreate this unfortunate clinical situation. METHODS: Twenty-one human eye bank eyes were ruptured by intraocular injection of saline through Atkinson needles. The hydrostatic pressure required for globe rupture was measured by three different techniques in seven globes. RESULTS: Forty-eight percent of the scleral lacerations were equatorial and 52% were perilimbal. Lens extrusion occurred with three of the perilimbal lacerations. Rupture pressures by each technique averaged 3065, 4972, and 5648 mmHg. CONCLUSION: Peribulbar injection can produce inadvertent ocular explosion.
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Morphometric analysis of pars plana development in humans.
BACKGROUND: Quantitative features of pars plana development in humans are not well characterized. Knowledge of the dimensions of this region is important for our understanding of the anatomy of infant eyes for the purposes of surgery. The purpose of this study was to provide a morphometric description of pars plana growth in relation to 1) postconceptional age and 2) axial length. METHODS: We reviewed histologic specimens from 204 human eyes of postconceptional ages ranging from 10 weeks to 5 years. Axial length and temporal pars plana width were measured directly with a reticule system. The relationships among pars plana width, axial length, and postconceptional age were examined. RESULTS: The most rapid phase of pars plana growth occurred between 26 weeks and 35 weeks gestation. A linear relationship between pars plana width and axial length existed once the axial length reached 12 mm (correlation coefficient = 0.918; P = 0.0001). In infants of 38-42 weeks postconceptional age, mean pars plana width was 1.87 mm (range, 0.9-2.8 mm; standard direction = 0.48 mm), and mean axial length was 17.7 mm (range, 15-23 mm; standard direction = 1.9 mm). After the age of 62 weeks postconception, all eyes had a temporal pars plana width > or = 3 mm and an axial length > or = 19 mm. The estimated age at which there was a 95% chance of the pars plana width being > or = 3 mm was 64.4 weeks (95% fiducial confidence limits, 60.8-86.2 weeks). CONCLUSIONS: The pars plana first develops during the second trimester of gestation. A rapid growth phase occurs between 26 weeks and 35 weeks postconception. The dimensions of the pars plana are correlated closely with axial length and postconceptional age. Assuming that a pars plana width of 3 mm is required for surgery to be performed via a pars plana approach, we estimate that pars plana vitreous surgery can be performed when the patient is at least 62 weeks old (postconception), which is a 6-month-old full-term infant.
Aging↗