Optical coherence tomography (OCT) abnormalities in rhodopsin mutant transgenic swine with retinal degeneration.
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Animals↗
Biomedical subjects
N A Syed
Publications and source records attributed to N A Syed.
Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive changes.
OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. METHODS: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.
Adaptation, Physiological↗
Cancer-associated retinopathy.
Patients with systemic cancer may have a variety of ocular complaints. Most commonly these are metastases or adverse effects of therapy. Paraneoplastic syndromes, like cancer-associated retinopathy, rarely cause ophthalmic symptoms. We describe a patient with a malignant mixed mullerian tumor and cancer-associated retinopathy who had circulating serum antibodies to recoverin and cells positive for recoverin in the tumor. We discuss the typical clinical symptoms as well as the pathophysiology of this uncommon disorder.
Antigens, Neoplasm↗
Mechanisms underlying spinal motor neuron excitability during the cutaneous silent period in humans.
The transient suppression of muscle contraction during the cutaneous silent period (CSP) could be produced either through postsynaptic inhibition of motoneurons or through presynaptic inhibition of the excitatory inputs to motoneurons that sustain voluntary contraction. We sought to delineate the mechanisms underlying the CSP in hand muscles by measuring changes in H-reflexes and motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) during the CSP in 10 healthy volunteers. H-reflexes and MEPs both measure the excitability of the motoneuron pool and activate similar subpopulations of motoneurons through different pathways. Inhibition of H-reflexes and MEPs of similar size was maximal at the midpoint of the CSP and gradually returned to baseline. The similar time course of recovery suggests that the H-reflex and MEP are affected by inhibition at a common site, most likely postsynaptic inhibition of the motoneurons.
Adult↗
SPARC deficiency leads to early-onset cataractogenesis.
PURPOSE: To determine the role of SPARC (secreted protein, acidic, and rich in cysteine) in cataractogenesis by examining mice deficient in a matricellular protein SPARC. METHODS: Mice were rendered SPARC-deficient by a targeted disruption of the gene. Slit-lamp microscopy and histology were used to examine the eyes of SPARC-null and wild-type mice from birth to 14 months of age. RESULTS: SPARC-null mice developed opacities in the posterior cortex of the eye as early as 1.5 months after birth. The diffuse cataracts appeared to progress toward the anterior cortex and reached maturity in many animals by 3.5 months of age. Early stages of cataractogenesis in SPARC-null mice included inhibition of normal lens fiber cell differentiation, degeneration of fiber cells, vacuole formation at the equator, and liquefaction of the cortex. No cataracts were detected in wild-type mice up to the age of 8 months. CONCLUSIONS: The early onset of cataracts in SPARC-null mice establishes that the gene is essential to the maintenance of lens transparency.
Animals↗
Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.
PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.
Animals↗
Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant.
The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.
Animals↗
Invasive spindle cell carcinoma of the conjunctiva.
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Aged↗
Retinoblastoma in a dog.
OBJECTIVE: To describe and classify a retinal tumor found in a dog that histologically resembles human retinoblastoma and to discuss the molecular mechanisms of retinal oncogenesis. METHODS: A dog eye with a retinal tumor was examined histologically. Studies including immunocytochemical analysis for retinal S-antigen and glial fibrillary acidic protein, enzyme histochemical analysis for carbonic anhydrase, and nick-end DNA labeling were used to characterize the tumor. Normal retina from another dog and other tumors from dogs, including 2 ciliary body medulloepitheliomas and a brain medulloepithelioma, were examined as controls. RESULTS: The retinal tumor disclosed characteristics typical of human retinoblastoma, including Flexner-Wintersteiner rosettes. It showed strong immunoreactivity with S-antigen and glial fibrillary acidic protein. Carbonic anhydrase activity also could be shown in the tumor. Apoptosis was found to be the predominant method of cell death as shown by nick-end DNA labeling. In contrast to the other tumors examined, this tumor contained areas with retinal photoreceptor and glial differentiation. CONCLUSIONS: The histopathologic findings and differential staining characteristics in this retinal tumor are compatible with retinoblastoma, making this, to our knowledge, the first documented case of spontaneous retinoblastoma in an animal.
Animals↗
The herpes simplex virus type 1 ribonucleotide reductase is required for acute retinal disease.
We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR) null mutant (ICP6 delta) to determine if the HSV-1 RR is required for acute retinal disease. Injection of the ICP6 delta mutant into the vitreous induced mild transient signs of infection (vitreal infiltrate, retinal inflammation, and changes in retinal cytology). In contrast, the parental KOS and a revertant virus (ICP6 delta + 3.1) in which the RR gene had been restored, caused severe retinitis. Injection of media alone also induced mild transient signs of disease. Two months after infection, ICP6 delta injected eyes could not be distinguished from normal eyes. Repeated injection of ICP6 delta (3 times, 2 weeks apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6 delta, grew to peak titers 1 x 10(3) to 1 x 10(5)-fold lower and cleared faster than KOS or ICP6 delta + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These results show that the viral RR is required for acute retinal disease.
Acute Disease↗
Refractory giant cell arteritis with spinal cord infarction.
We report an elderly patient with aggressive steroid-refractory giant cell arteritis manifesting as myelopathy and bilateral visual loss while on treatment. Pathologically, spinal cord infarction was observed and was due to extensive necrotizing granulomatous arteritis of spinal arteries. Spinal cord damage in giant cell arteritis is rare. One prior autopsy report of spinal cord infarction in giant cell arteritis did not identify vasculitic changes in the spinal arteries.
Aged↗
Primary orbital myxoid liposarcoma presenting as orbital pain.
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Exophthalmos↗
Melanocytes and iris color. Light microscopic findings.
OBJECTIVE: To systematically evaluate morphologic differences in iris stroma that contribute to clinically perceptible differences in iris color, using immunohistochemical identification of stromal melanocytes and fluorescence microscopy. METHODS: Paraffin-embedded sections from 51 human irides were stained with S100a and fluorescein isothiocyanate. Cells were counted and scored as melanocytes or other. Melanocyte number, proportion, and density were determined for light-colored (blue), medium-colored (hazel) and dark-colored (brown) irides and compared. RESULTS: No statistically significant difference was observed for mean total cellularity or mean melanocyte number among the three color groups. Mean total stromal cell count was 1177 +/- 259 (mean +/- SEM), and mean melanocyte number was 778 +/- 196 per 5-micrometer section. In human irides, 65.9% of the iris stroma is composed of melanocytes. Melanocyte density (number of cells per square millimeter) is not related to iris color. CONCLUSION: The number of melanocytes, the proportion of melanocytes, and iris stromal cellularity are not major contributors to iris color.
Aged↗
Infectious conjunctivitis.
This article is designed to aid the clinician in the diagnosis of bacterial and viral conjunctivitis by evaluating a wide variety of infectious causes of conjunctivitis. The work-up, including techniques of examination and pertinent laboratory studies, is discussed. Clinical features of each type are covered at length and specific therapy for each is included.
AIDS-Related Opportunistic Infections↗
Radical hysterectomy and tailored postoperative radiation therapy in the management of bulky stage 1B cervical cancer.
Ninety-two patients with Stage IB cervical cancers having a diameter equal to or greater than 4.0 cm were treated with radical surgery. Thirty-two patients received postoperative radiotherapy because of operative findings suggestive of high risk of pelvic recurrence. All 32 irradiated patients were treated with a standard pelvic field. Four patients also received paraaortic radiotherapy, and ten received intravaginal brachytherapy. Postoperative complications were seen in five patients (two nonirradiated, three irradiated). Projected 5-year survival is 79% (71% 5-year survival in irradiated patients, and 83% 5-year survival in nonirradiated patients). Preoperative evaluation of tumor volume was not found to reliably predict histologic high risk factors such as depth of stromal invasion, risk of lymph node metastases, or presence of extracervical/uterine involvement. A primary surgical approach in this group of patients with large-diameter Stage IB cervical cancers allows definition of those patients who might benefit from a combined surgical and radiotherapeutic approach to treatment based on findings at operation.
Adenocarcinoma↗
Treatment of advanced and recurrent squamous carcinoma of the uterine cervix with constant intraarterial infusion of cisplatin.
Twelve patients with primary or locally recurrent squamous carcinoma of the cervix were treated with constant internal iliac artery infusion of cisplatin (CDDP) via a totally implantable chemotherapy pump. Seven previously untreated patients received standard external and interstitial radiotherapy (RT) in conjunction with CDDP infusion. Five patients with isolated pelvic recurrences received CDDP therapy only. The chemotherapy pump was refilled weekly on an outpatient basis. All nine evaluable patients developed unilateral or bilateral lower extremity pain which responded to dosage reduction. No renal or marrow toxicity was seen. Both of the evaluable patients treated for recurrent tumor died 32 and 60 weeks after initiation of treatment. The seven patients treated primarily with RT + CDDP infusion include one who expired with persistent tumor and one with no evidence of disease (NED) after exenteration for a pelvic recurrence at 48 and 85 weeks respectively. The five remaining patients are NED at 12 to 60 weeks. Constant internal iliac artery infusion of CDDP via an implantable chemotherapy pump can be performed with acceptable toxicity. The preliminary results suggest that further study in previously untreated undergoing concurrent radiotherapy is warranted.
Carcinoma, Squamous Cell↗