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Biomedical subjects

S E Moss

Publications and source records attributed to S E Moss.

At least 163 records · Page 9Linked to original sources

Neuroretinal rim area in diabetes mellitus.

Neuroretinal rim area (NRA) may indicate the amount of viable optic nerve tissue. Changes in the NRA have been found to occur in people with glaucoma. We sought to determine whether there were effects of retinopathy and intraocular pressure (IOP) on NRA in eyes of people with diabetes. Measurements of optic discs and cups were taken from 35-mm stereoscopic slides taken with a Zeiss fundus camera. The photographs were taken during a population-based study. The difference between disc and cup area was taken to be the NRA. Median photographic NRA from 2085 right eyes was 10.5 mm2. In younger- and older-onset persons, NRA showed a tendency to increase with age and, inconsistently, with the severity of diabetic retinopathy; it decreased with increasing IOP in older-onset persons not taking insulin. The cohort was reevaluated 4 yr later. NRA increased in all groups. Measurements from photographs taken of a nondiabetic comparison group showed no change over the same interval. These data suggest that NRA may be affected by diabetes. This could be due to nerve swelling.

Adolescent↗

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years.

Population-based epidemiologic data on the incidence and progression of diabetic retinopathy are important in medical counseling and rehabilitative services and for developing approaches to preventing diabetic retinopathy. We performed a population-based study in southern Wisconsin of insulin-taking diabetic persons diagnosed before 30 years of age. Of the 271 who had no retinopathy at the first visit, 160 (59%) developed it by the time they were reexamined four years later, and 75 (11%) of the 713 free of proliferative diabetic retinopathy developed it. Overall, worsening of retinopathy occurred in 41% of the population, whereas improvement occurred in only 7%. The incidence of proliferative retinopathy rose with increasing duration until 13 to 14 years of diabetes, thereafter remaining between 14% and 17%. These incidence data underscore the need for careful ophthalmologic follow-up of these people.

Adolescent↗

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more.

The four-year incidence and progression of retinopathy were investigated in a population-based sample of people with diabetes diagnosed at 30 years of age or older. For insulin users, 73 (47%) of the 154 who did not have any retinopathy at the first visit developed it in the four-year interval, and 31 (7%) of the 418 free of proliferative retinopathy developed it. Worsening of retinopathy occurred in a total of 34% (142/418). For nonusers of insulin, corresponding rates were 34% (110/320) for incidence of any retinopathy, 2% (11/486) for developing proliferative retinopathy, and 25% (121/486) for worsening. These population-based data clearly indicate the risk of retinopathy worsening in a short interval (four years) in a large proportion of people with older-onset diabetes, a group previously thought to be relatively protected from retinopathy. Such patients who make up the largest proportion of diabetic patients in the United States need examination when diabetes is first diagnosed and regular follow-up.

Adult↗

The relationship of retinal microaneurysm counts to the 4-year progression of diabetic retinopathy.

The relationship of retinal microaneurysms to the progression of diabetic retinopathy over a 4-year period was examined in a population-based sample of diabetic persons. The number of microaneurysms in color stereoscopic fundus photographs of seven standard fields was counted in the eyes of diabetic persons (n = 236) who had only microaneurysms in photographs at the baseline examination. If only one eye was involved (n = 121), the mean number of microaneurysms was 2.3; with bilateral involvement (n = 115), the mean was 9.3 in the more involved eye. The number of microaneurysms at the baseline examination was positively associated with significant progression of retinopathy. This relationship remained after controlling for the level of glycosylated hemoglobin. These data suggest that the number of microaneurysms at baseline is an important predictor of progression of diabetic retinopathy. Microaneurysm counts may prove to be a useful early end point in clinical trials.

Adult↗

The Wisconsin epidemiological study of diabetic retinopathy: a review.

The WESDR has provided precise estimates of the prevalence, and 4-year incidence and progression of diabetic retinopathy. It has provided evidence of a possible causal relationship between specific risk factors, such as hyperglycemia and the development and progression of retinopathy. Our data support current recommendations for ophthalmologic examinations for people with diabetes. In 1990 we will reexamine the cohort to determine the 10-year incidence and progression of diabetic retinopathy, macular edema, and visual impairment.

Diabetes Mellitus, Type 1↗

The gene coding for the p68 calcium-binding protein is localised to bands q32-q34 of human chromosome 5, and to mouse chromosome 11.

The gene coding for human p68, a membrane-associated calcium-binding protein, has been assigned to chromosome 5, using a cDNA clone to probe genomic DNA from rodent-human somatic cell hybrids by Southern hybridisation. The gene was localised, by in situ hybridisation, to 5q32-34. The murine gene was assigned to chromosome 11, using a murine cDNA clone to probe genomic DNA from rodent-rodent somatic cell hybrids.

Animals↗

The Wisconsin epidemiologic study of diabetic retinopathy. XI. The incidence of macular edema.

As part of a population-based study of diabetes mellitus, the 4-year incidence of macular edema and its relationship to various risk factors was examined in a group of younger onset insulin-taking persons (n = 610) and older onset persons (n = 652). The presence of macular edema at the baseline and follow-up examinations was determined from gradings of stereoscopic fundus photographs. The overall incidence of macular edema in the younger onset group was 8.2% (50/610); in the group of older onset persons using insulin, 8.4% (23/273) and in the group of those not using insulin, 2.9% (11/379). The incidence of macular edema was associated with higher level of glycosylated hemoglobin, longer duration of diabetes, and more severe retinopathy at the baseline examination in both younger and older onset groups. These data provide accurate population-based estimates of incidence of macular edema, and suggest that the level of glycemia is a significant risk factor for the development of macular edema.

Adolescent↗

Are seven standard photographic fields necessary for classification of diabetic retinopathy?

Stereoscopic fundus photography of seven fields has become standard procedure for detecting diabetic retinopathy. However, the question has arisen as to whether adequate detection of retinopathy can be achieved with fewer fields. This question was investigated in a population-based study of 2694 diabetic persons. Retinopathy levels derived from the detailed grading of all seven fields were compared with those derived from combinations of two, three or four fields, the data for these being selected from the grading of the full seven fields. For eight retinopathy levels, the rate of agreement with seven fields ranges from 80% for two fields to 91% for four fields. For four retinopathy levels, agreement increases to 85 to 95%. The rate of agreement also varies with the specific retinopathy level, with level 65 being especially sensitive to the number of fields. The sensitivity of two to four fields compared to seven fields for detecting any retinopathy varies from 87 to 95%. For detecting proliferative retinopathy, sensitivity varies from 74 to 90%, and for Diabetic Retinopathy Study high-risk characteristics, it varies from 81 to 91%. Analysis of two groups of 50 eyes in which the combinations of fields were graded independently shows a small but nonsignificant effect of field overlap. These results indicate that in some situations, fewer fields may be adequate.

Diabetic Retinopathy↗

Is blood pressure a predictor of the incidence or progression of diabetic retinopathy?

The relationship between blood pressure and the 4-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Blood pressure was measured using the Hypertension Detection and Follow-up Program protocol. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of systolic blood pressure, the relative risk for developing any diabetic retinopathy was 1.8 and for diastolic blood pressure it was 1.2; for progression of diabetic retinopathy, it was 1.1 and 1.3 for systolic and diastolic blood pressure, respectively. After controlling for other risk variables, systolic blood pressure remained a significant predictor of the incidence of diabetic retinopathy; diastolic blood pressure was of borderline significance in predicting progression in the younger-onset group. Blood pressure was not related to incidence or progression of retinopathy either in the older-onset group using insulin or the older-onset group not using insulin.

Age Factors↗

Optic disc cupping: prevalence findings from the WESDR.

Increased cupping of the optic disc is considered to be an indication of pressure-related damage of the optic nerve. This paper explores the relationship of intraocular pressure and cupping in persons with diabetes mellitus, a group of people whose optic nerves may be more susceptible to the effects of intraocular pressure. Stereoscopic fundus photographs of the seven standard fields were obtained in all persons participating in the Wisconsin Epidemiologic Study of Diabetic Retinopathy at the time of the initial prevalence survey. Measurements of disc and cup diameters in the vertical and horizontal meridia were made by two trained graders. Cup-to-disc ratios were computed for both diameters of each eye and the mean of the two gradings was used. A history of glaucoma was significantly associated with larger cup-to-disc ratios at the prevalence examination. Cup-to-disc ratios were not larger in those with high IOP, nor in those who had panretinal photocoagulation.

Adult↗

Optic disc cupping: four year follow-up from the WESDR.

Change in optic disc cupping was evaluated in a 4-year follow-up of a well defined cohort of people with diabetes mellitus. Cup-to-disc ratios were computed for both vertical and horizontal diameters of each eye at the baseline and 4-year follow-up examinations. Graders were masked as to the identity of participants and to the dates of the photographs. Increases of at least 0.1 between baseline and follow-up were used as clinically significant change in the ratios. None of the following factors at baseline were consistent predictors of such a change: intraocular pressure, age, duration of diabetes, hypertension or severity of diabetic retinopathy. People who developed proliferative retinopathy by the follow-up examination were not more likely to have such an increase in ratio at the follow-up. We conclude that clinically significant increases in cup-to-disc ratio cannot be consistently predicted in people with diabetes from the risk factors evaluated with the grading system used in this study.

Diabetes Complications↗

Relation of ocular and systemic factors to survival in diabetes.

The relationship of survival to systemic and ocular factors in diabetic persons was studied using data collected as part of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Six years after the baseline examination, 9.5% of 996 insulin-taking people who were younger than age 30 years when their diabetes was diagnosed (younger onset) had died. Of 1370 people whose diabetes was diagnosed after age 30 years (older onset), 35.3% had died. After adjusting for age and sex, longer duration of diabetes, presence of proteinuria, a history of cardiovascular disease, higher blood pressure, diuretic use, a history of smoking, poorer visual acuity, and more severe retinopathy were significantly associated with decreased survival in both groups. Glaucoma was associated with decreased survival in the younger onset group and cataract in the older onset group. These findings suggest that some ocular complications are important risk indicators for death. Their presence in diabetic patients suggests the need for frequent examinations to detect systemic complications and to intervene to minimize their effect.

Adult↗

Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy.

The relationship between hyperglycemia, measured by glycosylated hemoglobin at the initial examination, and the four-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Younger- (n = 891) and older-onset (n = 987) persons participating in baseline and follow-up examinations were included. Glycosylated hemoglobin was measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. In the younger-onset group, comparing the highest with the lowest quartile of glycosylated hemoglobin, the relative risk for developing any diabetic retinopathy was 1.9; for proliferative retinopathy, 21.8; and for progression, 4.0. Among older-onset persons taking insulin, the corresponding relative risks were 1.9, 4.0, and 2.1. Among older-onset persons not taking insulin, relative risks were 4.0 for any retinopathy and 6.2 for progression. A positive relationship between incidence and progression of retinopathy and glycosylated hemoglobin remained after controlling for duration of diabetes, age, sex, and baseline retinopathy. These data suggest a strong and consistent relationship between hyperglycemia and incidence and progression of retinopathy.

Adult↗

Molecular cloning of murine p68, a Ca2+-binding protein of the lipocortin family.

A plasmid cDNA library prepared from a T-lymphocyte clone of murine strain B10.A origin was screened by cross-species DNA hybridisation using a partial human p68 cDNA clone, identified as containing coding sequences for previously determined amino-acid sequences. The longest p68 cDNA insert from this library and a full-length cDNA insert from a second similar library were fully sequenced. A comparison of the derived amino-acid sequence with that of human p68 revealed extensive homology (95% overall). Homology at the nucleotide level was 89% in the open reading frame and 85% and 50% in the 5' (33 nucleotides) and 3' (347 nucleotides) non-coding regions respectively. Eight segments of internal homology were observed, each containing a highly conserved consensus region of 17 amino acids correlating with that described for several membrane associated calcium-binding proteins [Geisow, M. J., Fritsche, U., Hexham, J. M. & Johnson, T. (1986) Nature (Lond.) 320, 636-638]. These results provide further evidence that p68 is a member of the same gene family as p32,p36 and lipocortin I and demonstrate an unusually high level of inter-species sequence conservation of p68 between mouse and human.

Amino Acid Sequence↗

Primary structure of the human, membrane-associated Ca2+-binding protein p68 a novel member of a protein family.

cDNA clones encoding human 'p68', a membrane-associated Ca2+-binding protein, were isolated from a lambda gt11 expression library of the human T-leukaemia cell line J6, by using a rabbit antiserum against denatured purified lymphocyte p68, and from a liver cDNA library by using 32P-labelled p68 cDNA fragments. The amino acid sequence of p68, deduced from the sequences of overlapping cDNA clones, is described. The results show that p68 is closely related to a family of proteins which includes intracellular substrates of the EGF receptor and pp60src tyrosine kinases. The p68 amino acid sequence is internally repetitive, being constructed from eight repeats of varying lengths, each of which contains a highly conserved sequence. Multiple copies of the latter sequence are also present in the related proteins p36, lipocortin I and protein II. We discuss how the common structural features of these proteins may reflect common functions and, furthermore, how the eight repeat structure of p68 may have evolved. The sequences of independent cDNAs suggest that alternatively-spliced mRNAs could encode different p68 protein species. This suggestion is consistent with the observation that purified p68 migrates as a closely-spaced doublet when analysed by SDS-PAGE.

Amino Acid Sequence↗

The nature of lysosomal enzyme glycosylation in ALL: relevance to abnormal beta-hexosaminidase expression.

The glycosylation of beta-hexosaminidase was investigated in the transformed cell-line, CCRF/CEM, derived from a human acute lymphoblastic leukaemia, and comparisons were made with enzyme from normal human skin fibroblasts. A series of studies including neuraminidase sensitivity, lectin chromatography, Biogel P4 chromatography of [3H]-mannose-labelled glycopeptides and endoglycosidase susceptibility, provided clear evidence that in CCRF/CEM cells, beta-hexosaminidase was abnormally glycosylated. The results indicate that leukemia-associated changes in beta-hexosaminidase expression are probably due to increased sialylation of highly-branched complex oligosaccharides.

Acetylglucosaminidase↗