Transgenic mice and age-related mutations.
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Aging↗
Biomedical subjects
G R Douglas
Publications and source records attributed to G R Douglas.
Application of galactose-sensitive E. coli strains as selective hosts for LacZ- plasmids.
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Cloning, Molecular↗
Induction of chromosomal aberrations in Chinese hamster ovary cells by triethyllead acetate.
Organolead compounds enter the environment primarily through the combustion of leaded gasoline and industrial discharge. Lead and lead-containing compounds have been shown to induce a broad spectrum of toxic effects, including hematopoietic, renal, neurologic, and carcinogenic effects. In this study, the mutagenic activity of triethyllead acetate (Et3PbAc) was determined by measuring the induction of chromosomal aberrations in Chinese hamster ovary cells. The results indicate that Et3PbAc is very cytotoxic and a potent clastogen. In preliminary cytotoxicity studies used to determine appropriate test concentrations for chromosomal aberration analysis, the LC50 of Et3PbAc was approximately 10 microM in the absence of metabolic activation, and 80 microM in the presence of metabolic activation. The maximal response was greater with metabolic activation than without. However, a much higher dose was required to elicit a significant response in the presence of metabolic activation than in its absence.
Animals↗
Bilateral malignant glaucoma.
Two cases of bilateral malignant glaucoma are presented. In one case the condition developed sequentially in the two eyes; pars plana vitrectomy was eventually needed in the operated eye, whereas the condition responded to medical treatment in the fellow eye. In the second case the two eyes were involved simultaneously nearly 1 year after surgery, and the glaucoma responded to medical treatment.
Female↗
Light-sense, flicker and resolution perimetry in glaucoma: a comparative study.
A total of 106 eyes of 106 patients with different types of glaucoma were examined by automated light-sense, flicker and resolution perimetry (Humphrey Field Analyzer, program 30-2; flicker perimeter as described by Lachenmayr [16, 18]; resolution perimeter as devised by Frisén [4, 6, 8-11]). The fields were classified in a masked fashion as being normal or as having purely diffuse loss, purely localized loss or diffuse as well as localized loss. As compared with light-sense perimetry, resolution perimetry had a markedly lower sensitivity in the detection of glaucomatous damage (77%) but a high specificity (93%); the comparison of resolution perimetry with flicker perimetry showed similar results (sensitivity, 75%; specificity, 85%). When flicker perimetry was compared with light-sense perimetry and vice versa, the sensitivity was high (95% and 94%, respectively), but the specificity was low (57% and 62%, respectively). The prevalence of detection of diffuse loss by both light-sense and resolution perimetry was related to visual acuity, whereas flicker perimetry did not show such a relationship.
Adult↗
Adrenergic and adrenolytic effects on intraocular pressure.
We compared the pressure-lowering effects of timolol, pindolol, epinephrine and the mixture of timolol and epinephrine with that of placebo over a 12-h period. All agents reduced the pressure significantly but with varying time courses. The mixture of timolol and epinephrine reduced the pressure significantly more than did timolol or epinephrine alone, especially at 12 h after the last administration of the drops.
Administration, Topical↗
Recommended protocols based on a survey of current practice in genotoxicity testing laboratories, IV. Chromosome aberration and sister-chromatid exchange in Chinese hamster ovary, V79 Chinese hamster lung and human lymphocyte cultures.
A recommended protocol has been developed for chromosomal aberration and sister-chromatid exchange assays in CHO, V79 and human lymphocyte cultures. The protocol was based on the responses to a detailed questionnaire completed by North-American and European governmental, university, and contract laboratories using these tests. This report identifies those modifications to previously described methods that are used on a regular basis and clarifies confusing or inconsistent practices. These protocols can be modified for use in other types of cells.
Animals↗
A comparison of treated and untreated glaucoma suspects.
One hundred forty-three patients with intraocular pressures (IOPs) above 22 mmHg and without visual field defects or any obvious evidence of optic nerve damage were randomly assigned to either a timolol treatment group or no treatment in a 6-year prospective clinical trial. Endpoints were defined as reproducible visual field defects on automatic perimetry, disc hemorrhages, or stereophotographically documented optic nerve head changes. Endpoints developed in 42 patients: 28 visual field defects, 8 changes in disc appearance, and 6 disc hemorrhages. Of the 42 patients, 20 were treated and 22 were not. Survival analysis showed no statistically significant differences in failure time to any endpoints between the two groups. In the untreated group, the time to failure of disc change was related to the mean IOP during the study and also to the changes in the IOP from baseline. A significant correlation was found between initial cup-to-disc ratio and survival time to visual field defects in the untreated group.
Aged↗
The use of visual field indices in detecting changes in the visual field in glaucoma.
We present results from 64 glaucoma patients and glaucoma suspects followed up for a median period of 7.4 yr who had a median of seven examinations using Program 31 on the Octopus perimeter. The patients also had manual visual fields recorded on either the Tübinger or Goldmann perimeter during the same period. By examining all manual fields over the follow-up, we classified 37 patients as deteriorating and 27 as nondeteriorating by using predetermined field criteria which we believed to be clinically significant. In a masked fashion, the indices mean defect (MD) and corrected loss variance (CLV), in addition to the three cluster analysis indices SIZ, CLUS, and PCLUS were computed for each patient and regressed on time. When a significant positive index/time slope (P less than 0.05) was defined as indication of deterioration, all indices had remarkably poor sensitivities because their slopes did not reach statistical significance in the great majority of patients. When, regardless of statistical significance, positive slopes were defined as indication of deterioration and negative slopes as nondeterioration, the most sensitive index, PCLUS, still had a sensitivity of less than 65%. The indices were better in detecting the presence or absence of visual field deterioration in fields that were initially normal than in those that were initially abnormal. Since the testing modalities of manual and automated perimetry are different, our study was not designed to compare the sensitivity of one technique over the other. Our study does, however, demonstrate that the indices used currently may not be clinically reliable in the assessment of changes in the visual field.
Analysis of Variance↗
The role of excision repair in the removal of transient benzo[a]pyrene-induced DNA lesions in Chinese hamster ovary cells.
In Chinese hamster ovary (CHO) cells, benzo[a]pyrene induces both persistent and transient lesions that are detected by alkaline sucrose gradient sedimentation analysis (ASG sites). The transient lesions disappear within 15 min while the persistent lesions can be detected for several hours following treatment. Although the persistent ASG sites are believed to be repaired by excision repair, the process responsible for the disappearance of the transient ASG sites is unknown. To determine the contribution of excision repair to the removal of these transient lesions, CHO cells were treated with benzo[a]pyrene (B(a)P) in the presence of the inhibitors of excision repair, araC and novobiocin. The results indicate that: (1) araC inhibits the removal of persistent, but not the transient B(a)P-induced ASG sites; (2) novobiocin, a putative inhibitor of the incision step of DNA excision repair, reduced the number of lesions detected immediately following treatment, indicating that many of these lesions may represent single-strand discontinuities generated during repair; and (3) the lesions detected in the presence of novobiocin disappear rapidly following treatment. Based on these results, we concluded that B(a)P-induced transient ASG sites are repaired by a process other than excision repair.
Animals↗
The inclusion of an assay for inherited congenital malformations in the assessment of mutagenicity.
A number of national guidelines and regulations on the mutagenicity of chemical substances mandate the assessment of inherited genetic effects. While inherited congenital malformations represent a major component of genetically-based adverse human health effects, tests for such effects are not used by regulatory agencies to evaluate inherited genetic effects. This paper is intended to highlight some of the salient characteristics of inherited congenital malformations which promote a rationale for their use in a regulatory context.
Abnormalities, Drug-Induced↗
Biostatistical evidence for two distinct chronic open angle glaucoma populations.
Twenty-six eyes of 26 patients with low-tension glaucoma and 34 eyes of 34 patients with high-tension glaucoma were studied. Fifty-one measurements were available on each patient, including visual field indices, finger blood flow measurements, as well as haematological, coagulation, and biochemical and rheological variables. Multivariate analysis revealed two statistically distinct groups of patients, with low and high tension glaucoma cases equally distributed in both. The smaller group (15 patients) showed a suggestion of vasospastic finger blood flow measurements, and had a high positive correlation between the mean deviation (MD) index of field severity and the highest intraocular pressure (r = 0.715, p = 0.0008). The second, larger group (45 patients) showed disturbed coagulation and biochemical measurements, suggestive of vascular disease, and had no correlation between the MD index and the highest intraocular pressure.
Aged↗
Lens opacity as a predictor of visual field impairment due to cataract.
The contribution of cataract to the decrease of visual field in patients with glaucoma is difficult to ascertain. To attempt to quantitate the change in visual field due to cataract, we examined 27 eyes of 26 patients before and after cataract extraction. The examination consisted of measurement of best refraction with visual acuity, visual field testing with the pupil dilated, measurement of lens opacity, determination of the intraocular pressure, and evaluation of the character of the cataract before surgery and of the posterior capsule after surgery. The results reaffirmed the detrimental effect that cataract may have on the visual field but also showed that the heterogeneity of cataracts limits the usefulness of the lens opacity meter in quantitating the extent of visual field loss due to cataract.
Adult↗
A new glaucoma filter implant.
A new glaucoma filtration procedure was performed in nine rabbits in a preliminary trial. A silastic tube with an internal diameter of 0.35 mm was passed across the anterior chamber through two limbal openings, and the free ends were buried postequatorially in sub-Tenon's space. At a later date, using an Nd:YAG laser in the thermal mode, holes 0.05 to 0.30 mm in diameter were burned in the tube in the anterior chamber. This procedure significantly lowered intraocular pressure in four rabbits on two successive tries; however, a third treatment given in two cases did not further decrease the pressure.
Animals↗
Visual field damage in normal-tension and high-tension glaucoma.
We studied the ocular characteristics of 40 pairs of normal-tension and high-tension glaucoma patients who matched closely for the extent of field damage, pupil size, and visual acuity. To determine if there were differences in visual field damage between patients with normal-tension and high-tension glaucoma, we studied characteristics of the areas of the patients' visual fields that were undisturbed. We computed the number of normal locations, the number of clustered normal locations, and the size of the largest cluster of normal locations. The results showed that for an equivalent extent of damage, the individuals in the normal-tension group had greater areas with normal sensitivity, hence more localized damage. A comparison of the patient data to control data showed that paired differences were larger when the normal-tension member of a pair had a larger value in any of the parameters. The results support the hypothesis that glaucoma patients with lower intraocular pressures have more localized damage and those with higher intraocular pressures have more diffuse damage.
Female↗
The time-course of intraocular pressure in timolol-treated and untreated glaucoma suspects.
We studied the behavior of intraocular pressure in glaucoma suspects randomly selected to receive either topical timolol or no treatment over the course of a long-term prospective follow-up study. All patients who after six years of follow-up showed no localized field defects or disk changes, or whose pressures were not dangerously increased (24 treated and 22 untreated patients), were included in the present study. Overall, the two groups showed an increase in pressure followed by a gentle leveling off and a decrease toward the end of the follow-up period. The pressure-time curves of the two groups were parallel and vertically separated by 4.94 mm Hg. When pressure-time relationships were determined in individual patients, the categorical group differences were not statistically significant. Our results suggest that most glaucoma suspects did not exhibit a random time-course of intraocular pressure and that the effect of treatment was simply to lower the pressure-time curve of the treated group by a fixed level throughout the six-year follow-up period.
Drug Evaluation↗
Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma.
Fifty-nine low-tension glaucoma patients were reviewed with respect to asymmetry of intraocular pressure (IOP) and visual field defects. In the presence of unequal IOP the visual field damage is almost always greater on the side with higher mean IOP. However, only 13 of 47 patients with asymmetric visual field defects had a mean IOP difference between the two eyes of greater than or equal to 1 mmHg. Although in the case of IOP asymmetry visual field damage is greater in the eye with higher mean IOP, other factors must also play an important role in the development of visual field defects in low-tension glaucoma.
Glaucoma↗
A comparative evaluation of three methods of analyzing optic disc topography.
Topographical evaluations of the optic discs of 17 eyes obtained using a clinical planimeter, the Rodenstock video-ophthalmograph, and the IS 2000 image analyzer were compared. The parameters studied were vertical and horizontal cup-to-disc ratios, cup volumes, rim areas, disc areas, and rim area-to-disc area ratios. There was good correlation between the measurements obtained by the three methods (correlation coefficients ranged from 0.46 to 0.88). For various parameters, the correlations between clinical planimetry and image analysis were higher than either those between image analysis and video-ophthalmography, or those between clinical planimetry and video-ophthalmography. The mean horizontal cup-to-disc ratios and rim areas as measured by clinical planimetry were significantly higher than those measured by image analysis. Image analysis measured significantly higher disc area and rim areas and lower cup volumes than video-ophthalmography.
Aged↗