Biomedical subjects
Publications and source records attributed to J Sugar.
We report three patients undergoing keratoepithelioplasty using donor limbal tissue. All three had significant vascularization of the recipient bed and all three had inflammatory reactions with apparent partial replacement of the donor epithelium with host epithelium. Limbal transplantation, which is likely to include significant numbers of donor Langerhans' cells, may well increase the risk of graft failure in keratoepithelioplasty.
Topical cyclosporin A was used in the management of 43 patients with a variety of anterior segment inflammatory disorders that had failed corticosteroid treatment. Treatment with topical cyclosporin A ranged from 1 week to 43 months, with a mean treatment period of 13 months. Thirty-five patients (81%) with disorders including high-risk keratoplasty, atopic and vernal keratoconjunctivitis, ligneous conjunctivitis, ulcerative keratitis, and Mooren's ulcer had a beneficial result, with resolution, reduction, or prevention of inflammation. Six patients (14%) with scleritis, ocular cicatricial pemphigoid, or endothelitis showed no clinical improvement. Two patients (5%) had significant ocular discomfort, and the drug had to be discontinued in them. None of the other patients developed local side effects. Twenty-seven of these patients were followed with serial cyclosporin A blood levels and serum creatinine. None of these patients developed measurable drug blood levels or renal toxicity.
PURPOSE: This study was performed to examine the gelatinolytic and caseinolytic activities and the levels of two proteinase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin) and alpha 2-macroglobulin, in the human aqueous humor. METHODS: Aqueous humor samples were collected during elective surgery in patients with cataracts. Zymography with gelatin- and casein-containing gels was performed. The inhibitors were examined by Western blot analyses, enzyme-linked immunosorbent assay, and dot blot assays. RESULTS: The aqueous humor contained a major band of gelatinolytic activity at a molecular weight of 66 kD and minor bands at 125, 95, and 62 kD. These gelatinases were inhibited by 10 mM ethylenediaminetetraacetic acid (EDTA) or 1,10-phenanthroline. After extended incubation (48 hours), zymography on casein-containing gels showed proteinase bands with molecular weights in the 80- to 84-kD range. Additional bands at 68 and 48 kD also were observed. All the caseinase activities were inhibited by 10 mM phenylmethylsulfonyl fluoride and 1 microgram/ml aprotinin. No inhibition was observed with 5 mM EDTA, 5 microM E-64, or 1 microM pepstatin. These results indicated that the caseinases are serine proteinases. Western blot analysis showed a 53-kD alpha 1-proteinase inhibitor band in the aqueous humor. The concentration was 32.2 +/- 9.9 micrograms/ml, constituting approximately 15% of the total protein. A 360-kD protein band immunoreactive to anti-alpha 2-macroglobulin also was detected. Its level in the aqueous humor was 3.2 +/- 1.3 micrograms/ml. CONCLUSIONS: The gelatinases, serine-like proteinases, and proteinase inhibitors found in the aqueous humor may participate in the remodeling of extracellular matrices in the trabecular meshwork and other tissues bordering the anterior chamber.
Multivariate statistical methods have been used in several studies to increase the diagnostic reliability of TV image analyser systems. In recent years some algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both non-linear, were developed. This paper reports on preliminary results obtained with these methods in quantitative cytology and compares them to the traditional classifiers. A total of 21 normal, 15 dysplastic and 23 malignant, gastric imprint smears were Feulgen stained and analysed on a Leitz Miamed DNA cytophotometer system. Mean DNA content, the 2c deviation index (2cDI), 5c exceeding rate (5cER), G1, S, G2 phase fraction ratios, cell nucleus area and form factor were determined. Diagnostic accuracy of the discriminant analysis was 96% for the malignant cases, 87% for dysplasias and 81% for normal cases. Cluster analysis gave no significant result. Our diagnostic system utilizing fuzzy logic has made the diagnostic borders adjustable and reliable. The back-propagation neural net correctly classified the normal and malignant cases (100%) and all but one of the dysplasias (98%). The non-linear mathematical methods improved the reliability of the diagnostic system. These new algorithms gave results comparable to traditional classifiers. The application of these methods to clinical samples is encouraging.
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PURPOSE: Surgery is indicated for keratoconus when management with contact lenses fails. The authors sought to determine the relative contribution of various preoperative patient and ocular factors to the ultimate causes of contact lens failure. METHODS: The records of unoperated eyes of keratoconus patients whose contact lenses were managed intensively before undergoing penetrating keratoplasty (PK) at the authors' institution between 1981 and 1990 were selected for study. Univariate and multivariate analyses were performed to identify risk factors for early contact lens failure. RESULTS: The records of 99 keratoconic eyes of 75 patients with an average age of 34 years and average keratometry readings of 57.5 diopters at presentation were studied. Cases had been followed for an average of 27 months before PK. The primary reasons for PK were a best-corrected visual acuity of under 20/40 (despite good contact lens fit) causing disability for the patient (43%), contact lens intolerance (32%), frequent lens displacement (13%), and significant peripheral thinning of the cornea (12%). The referral source of the patient, sex, a history of PK in the fellow eye, or of contact lens wear in either eye did not alter the relative contributions of these parameters to surgery. CONCLUSION: Poor best-corrected visual acuity at presentation, higher keratometry readings (greater than or equal to 55 D), age (greater than or equal to 40 years), and duration of disease (greater than 5 years) were significantly associated with failure due to poor functional acuity and peripheral thinning, frequently leading to surgery within the first 12 months after presentation.
Cells of keratoconus corneas have been reported to produce higher levels of collagenolytic/gelatinolytic enzymatic activities than do cells of normal corneas. The current study investigates the contribution of 1) specific enzyme gene products, and 2) the degree to which these proteins are present in the activated forms, to the increased enzymatic activities. We demonstrate that two neutral gelatinolytic enzymes, a 66/59 kD form and a 92 kD form, can be directly extracted from both normal and keratoconus corneas. These enzymes are identified as the pro- and activated forms of MMP-2 and as the pro-form of MMP-9, specific members of the matrix metalloproteinase family. Normal and keratoconus corneas show no significant differences in amounts or types of extractable neutral gelatinases, nor in the amounts or types that they synthesize in culture. Furthermore, in both the normal and keratoconus corneas, gelatinases are found primarily in the inactive form. These studies suggest the possible importance of changes in proteinase inhibitor levels to the characteristic biochemical features of keratoconus corneas.
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All three types of lattice corneal dystrophy are inherited and localized, and they largely involve linear corneal amyloid deposits. We encountered two white families with lattice corneal dystrophy which closely resembled type III. Four generations of one family and three of another family exhibited lattice corneal dystrophy. Because both families are from Caccamo, Sicily, Italy, we believe it is likely that both are from a single mutation. Thick, ropy lattice lines were seen to traverse the corneas almost from limbus to limbus and were easily detected with direct illumination. Histopathologic examination revealed accumulations of varying sized amyloid deposits in the stroma and ribbons of amyloid between the stroma and Bowman's layer typical of lattice corneal dystrophy type III. We have named the disease in this family lattice corneal dystrophy type IIIA, because of three differences from lattice corneal dystrophy type III: the presence of corneal erosions, the occurrence in whites, and the autosomal dominant inheritance pattern.
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The effect of cytosine arabinoside on adenosylmethionine synthesis in relation to its proliferation-inhibiting ability was investigated in HT/29 and SW 620 human colon-tumor cell lines. A significant decrease in adenosylmethionine synthetase (E. C.2.4.2.13) activity was found after 2.5 h incubation with the drug, suggesting that depletion of adenosylmethionine pools might occur. Both this possible loss of adenosylmethionine and the cytostatic effect of cytosine arabinoside could partly be reversed by the exogenous administration of the former drug. Our data show that the cytostatic effect of cytosine arabinoside may be due in part to a shortage of adenosylmethionine; this finding is important for the design of combination chemotherapy regimens.
The authors describe the nature of current social and economic forces impacting on the education and future practice of general psychiatry residents in child and adolescent psychiatry. They review theoretical and practical reasons for training in child and adolescent psychiatry, analyze the form and content of what is currently taught based on a national survey of general training programs, and suggest guidelines for the training and postgraduate practice of general psychiatrists in evaluating and treating children and adolescents. The authors conclude that while social and economic changes necessitate general psychiatrists' clinical involvement with children and adolescents, insufficient general training may necessitate postgraduate education and supervision. They pose ethical and professional dilemmas for the field in meeting the national shortage of child and adolescent psychiatrists and propose strategies to enhance recruitment into child and adolescent residency training.
Postmortem cortical tissues from Alzheimer's disease cases were found to contain significantly higher levels of the heat shock proteins hsp 72 and hsp 73 than control cortical tissues. This elevation was associated with the disease pathology in that it was not observed in Alzheimer's disease cerebella and was not correlated with perimortem characteristics such as age or cause of death of the patient or postmortem interval of the brain tissue. Examination of polysome translation products on two dimensional gels and by immunoprecipitation indicated that the syntheses of hsp 72/73 were increased in Alzheimer's disease tissues. In addition, immunoprecipitation of newly synthesized hsp 72 showed that numerous other nascent polypeptides were co-precipitated, which indicates an irreversible cotranslational association with the hsp 72. These results indicate that induction of specific heat shock proteins is associated with Alzheimer's disease and that cotranslational processes are affected by this induction.
Proteoglycan molecules in keratoconus corneas were studied by immunohistochemical and electron microscopic histochemical methods. Compared with normal human control subjects, the staining intensity with monoclonal antibody 9-A-2 was enhanced in the stroma of scarred keratoconus corneas, whereas the intensity with antibody J-19 was reduced. The 9-A-2 experiment showed an increased immunoreactivity of dermatan sulfate proteoglycan epitopes, and the J-19 experiment indicated a decreased immunoreactivity of sulfated keratan sulfate epitopes. Uronic acid analyses were consistent with the 9-A-2 data. Electron microscopy performed after cuprolinic blue staining showed apparent accumulation of abnormally thick, chondroitinase ABC-sensitive, dermatan sulfate proteoglycan filaments in keratoconus corneas. Such filaments were especially prominent in scarred areas. In addition, Keratan sulfate proteoglycan filaments appeared to be less abundant than those found in normal control corneas. Similar alterations of both types of proteoglycan molecules were also seen and reported in scarred corneas. The similarity suggests that the proteoglycan abnormalities found in keratoconus corneas may be secondary, at least in part, to scarring.
We reviewed the clinical files of 10 patients who had undergone excision of unilateral epibulbar limbal dermoids. Preoperatively, all of the affected eyes had worse visual acuity (P less than .02) and more astigmatism (P less than .01) than the contralateral eyes. Postoperatively, every patient was cosmetically improved. Of the eight patients for whom both preoperative and postoperative visual acuity measurements had been obtained, in six it had changed minimally (less than or equal to 1 line), and in two it had improved (less than or equal to 2 lines). Surgical complications included persistent epithelial defects (40%) and peripheral corneal vascularization and opacity (70%). These complications do not outweigh the cosmetic and visual benefits of dermoid excision in selected patients.
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