Biomedical subjects
Publications and source records attributed to C C Nelson.
The management of eyelid trauma presents some frustrating challenges to the general ophthalmologist. Because each case is unique, adaptation of general principles is essential for optimal ophthalmic treatment. This review includes the essentials of approaches to the evaluation and treatment of eyelid margin and canalicular lacerations. Specific attention is directed towards avoidance of complications.
Products encoded in the E1a oncogene of adenoviruses are required to activate transcription of all viral early genes and some cellular genes. A current interpretation of experimental data supports the hypothesis that this "trans-activation" is mediated solely by a block of amino acids known as conserved domain 3, which is unique to the largest E1a protein, while the remaining E1a protein sequences contain discrete domains required for functions other than trans-activation. However, there is also considerable evidence inconsistent with this simple model of E1a structure and function. Both of the major E1a proteins appear to participate in trans-activation by three different types of interaction with cellular transcription factors and other regulatory proteins. In this review we attempt to rationalize the experimental data and provide a more integrated view of E1a structure and function.
We show using mild extraction procedures that the p53 proto-oncogene forms a complex with adenovirus 5 E1b-58 kD during infection. These complexes are detected as coimmunoprecipitates from radiolabeled extracts of adenovirus infected cells on SDS-PAGE. Furthermore, adenovirus mutants with defects in E1b-58 kD fail to form complexes, whereas mutants in other early region genes still show evidence of complex. Using a panel of monoclonal antibodies to mouse p53, we show that antibodies reacting with N-terminal epitopes on p53, displace E1b-58 kD. This result suggests that E1b-58 kD binds to an N-terminal region of mouse p53. In addition, in a transient transfection assay in monkey COS cells, we show that an N-terminal deletion mutant of mouse p53 does not bind to E1b-58 kD but wild-type mouse p53 does bind. This result again suggests that E1b-58 kD binds an N-terminal determinant on p53.
This is the first study devoted to the histologic and histochemical characteristics of the orbicularis oculi muscle in children to the authors' knowledge. The orbicularis muscle was compared with extraocular, facial, and limb striated muscle. Light microscopy showed the orbicularis oculi muscle to be much smaller and more loosely packed than skeletal limb muscles. It further showed these muscle fibers to have greater variation in fiber size and shape and more endomysial and perimysial connective tissue. Finally, analysis of the histochemical reactions showed the orbicularis oculi had a higher percentage of fast-contracting fibers (Type II). This study establishes the histologic and histochemical standard characteristics for the orbicularis oculi muscle in children. It was found that orbicularis oculi muscles have some histologic and histochemical features in common with other facial muscles and other features in common with extraocular muscles.
We developed a patient eye shield consisting of a sandwich of polymethylmethacrylate and tinfoil to provide corneal and retinal protection from inadvertent injury during argon, neodymium:YAG, or dye laser treatment. The shield was tested with argon, dye, neodymium:YAG and CO2 lasers. This new eye shield is safe, comfortable, and easy to clean and use.
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Some undifferentiated F9 embryonal carcinoma cells allow adenovirus genes to be expressed independently of the E1a oncogene normally required for their activation; this has been attributed to a cellular equivalent of E1a in F9 cells. However, transcription of all early genes was low in undifferentiated OTF963 embryonic carcinoma cells during the first 48 hr after infection with adenovirus type 5 (Ad5). Transcription then increased to about the level seen 16 hr after infection of cells induced to differentiate by retinoic acid (RA) (referred to as RA-dF9 cells), but this increase did not occur in cells infected by the E1a deletion mutant dl312. Addition of E1a in trans, or of RA, had no immediate effect on viral transcription in OTF963 cells, but viral transcription increased about 48 hr after these additions. Ad5 induced transcription of several differentiation-specific genes in OTF963 cells with about the same kinetics as their induction by RA. These genes were superinduced in RA-dF9 cells by cAMP or infection by adenovirus. We suggest the small amount of E1a produced early in infection of OTF963 cells activates cellular genes, some of which are differentiation specific and required for efficient transcription of viral genes, so that E1a both induces and is induced by differentiation. The simple hypothesis of a cellular equivalent to E1a does not adequately explain the complex interactions between viral and cellular genes in OTF963 embryonic carcinoma cells.
Adenovirus infection was compared in F9 (OTF963) cells and cells induced to differentiate with retinoic acid, in order to study expression of early genes under the control of the reported "E1a-like factor" in F9 cells. However, not only was transcription of the viral E1a gene defective in undifferentiated cells but expression of all the other early genes was found to be reduced in OTF963 cells in comparison to differentiated cells. The defect in early gene expression was detected at the level of transcriptional initiation during the first 48 h of infection and resulted in similarly low levels of viral cytoplasmic mRNA and viral protein synthesis. Viral DNA replication was delayed and reduced. After 48 h of infection, the defect in transcription in OTF963 cells of E1a and other early genes was relieved, so that by 72 h postinfection the level of transcription was similar to that 16 h after infection of differentiated cells. At no time did adenovirus early gene expression occur independently of viral E1a. These results suggest limits to the generality and explanatory power of the hypothesis that F9 embryonal carcinoma cells contain an E1a-like factor.
We performed punctal occlusion by thermal cautery on 23 patients (45 sides, 90 puncta). One punctum on the right side was randomly assigned to deep cauterization of the punctum and vertical canaliculus, and the other punctum assigned to cauterization of the punctum only. The two treatments were assigned to the opposite puncta on the left side. One month after cauterization, the puncta that received deep cauterization were significantly more likely to have remained closed than those that received superficial cauterization (P less than .01). Survival analysis over a period of follow-up that exceeded one year after surgery, using time to examination because of a reopened punctum as the endpoint, indicated a long-term advantageous effect of deep over superficial cauterization.
Xeroderma pigmentosum is an autosomal recessive, precancerous dermatosis caused by defective repair of ultraviolet-damaged DNA. Characterized clinically by progressive cutaneous pigmentary alterations and tumorigenesis, it serves as a model for ultraviolet carcinogenesis. We describe the clinical and histopathologic findings in a 31-year-old woman with xeroderma pigmentosum and a massive iris melanoma of the left eye. Histologic examination following enucleation revealed diffuse iris replacement by spindle and epithelioid cells with extension into the trabecular meshwork. Evidence of direct extraocular extension was absent, and a metastatic evaluation showed no abnormalities. To our knowledge, this is the first reported case of xeroderma pigmentosum complicated by melanoma of the iris. It provides further evidence suggesting a role for sunlight exposure in the pathogenesis of uveal melanoma.
We randomly selected 26 patients with essential blepharospasm to receive either botulinum toxin or saline injection in their lower eyelids to evaluate the necessity of lower eyelid injection to relieve blepharospasm. As diplopia may occur from botulinum toxin injections for blepharospasm, most commonly from injection of the lower eyelid, and surgical relief of blepharospasm is often achieved by excision of only the upper eyelid protractors, omission of toxin from the lower eyelid seemed both desirable and possible. All patients received botulinum toxin in the upper eyelids, above the eyebrows, across the glabella, and near the lateral canthus. Thirteen of 15 patients who received saline in their lower eyelids had relief of spasm, with the same spasm-free interval as those who received toxin. We recommend avoiding injection of toxin in the medial two thirds of the lower eyelid in order to diminish the likelihood of diplopia from inferior oblique muscle paresis.
This is the first reported study on accurate computerized measurements of lacrimal punctal size in normal adults. There was a wide variation found between patients. The lower lid puncta were consistently noted to be larger than those of the upper lids. This is clinically significant in dry-eye patients who may need to be treated with punctal plugs of various sizes.
Penetrating orbital injuries may involve intracranial structures as well. We report an unusual case of permanent visual loss, temporary complete ophthalmoplegia, and penetration of the internal carotid artery following penetrating nail injury. CT scanning and arteriography are important diagnostic tests to consider prior to removal of an orbital foreign body. This case also demonstrates the importance of delaying repair of traumatic ptosis and ophthalmoplegia.
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Atracurium is a relatively new neuromuscular blocking anesthetic with known histamine release effects which has become popular in ophthalmic anesthesia. This report describes the IV use of Atracurium causing an anaphylactic reaction manifested by localized edema of all four eyelids, conjunctival chemosis and mild laryngeal edema requiring scheduled ptosis and strabismus surgery to be cancelled.
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To determine the frequency of ocular metastases in the general population, we conducted a prospective histopathologic study of 716 eyes obtained from patients who had malignant neoplasms at the time of death. Fifty-two patients had ocular metastases; all of these individuals had widespread metastases that contributed to their deaths. The overall incidence of ocular metastases among all fatal cases of cancer was 9.3%. Thirty-three of the 117 patients with various types of leukemia and four of the 60 patients dying with lymphoma had ocular involvement. The total incidence of ocular metastases in patients dying of all types of carcinoma was 4.0%. In the nine patients dying of sarcoma, no ocular metastases were detected. We estimate that about 22,000 patients who will die of cancer in the United States during 1983 will have ocular metastases.