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Biomedical subjects

S E Moss

Publications and source records attributed to S E Moss.

At least 91 records · Page 5Linked to original sources

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVI. The relationship of C-peptide to the incidence and progression of diabetic retinopathy.

The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy.

Adult↗

Ten-year incidence of gross proteinuria in people with diabetes.

There are few population-based epidemiological data describing the long-term incidence of gross proteinuria in people with diabetes. We performed a population-based study in southern Wisconsin of individuals with diabetes diagnosed at either < 30 years of age and taking insulin (younger-onset, n = 666) or > or = 30 years of age either taking (older-onset taking insulin, n = 376) or not taking insulin (older-onset not taking insulin, n = 418). The presence of gross proteinuria (> or = 0.3 g/l) was determined by means of a reagent strip. The incidence of proteinuria in the 10-year interval was 28% in the younger-onset group, it was 40% in the older-onset group taking insulin, and it was 33% in the older-onset group not taking insulin. After we controlled for other risk factors, the 10-year incidence of proteinuria was significantly related to higher glycosylated hemoglobin level and diastolic blood pressure at baseline and to an increase in glycosylated hemoglobin level and an increase in diastolic blood pressure from baseline to the 4-year follow-up in the younger-onset group and to higher glycosylated hemoglobin level, higher systolic blood pressure, and higher total pack-years of cigarettes smoked at baseline and an increase in systolic blood pressure from baseline to the 4-year follow-up in the older-onset groups. These data suggest that modification of three factors--hyperglycemia, high blood pressure, and smoking--may lead to a reduction in the long-term incidence of proteinuria.

Adult↗

Digoxin does not accelerate progression of diabetic retinopathy.

OBJECTIVE: To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy. RESEARCH DESIGN AND METHODS: We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant. RESULTS: After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin. CONCLUSIONS: These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Adult↗

Older-onset diabetes and lens opacities. The Beaver Dam Eye Study.

PURPOSE: To determine the prevalence of lens opacities in older-onset diabetic persons. METHODS: A study of age-related eye disease in a population (n = 4926) of adults in Beaver Dam, Wisconsin. Study participants were examined and interviewed according to protocol. Photographs were taken of the lenses of both eyes of all study participants. Photographs were graded in a standard fashion. Diabetes was defined by history, doctors' records and serum glucose criteria. RESULTS: Persons who were diabetic were significantly more likely to have cortical lens opacities (age-adjusted odds ratio 1.72, 95% CI 1.29-2.30 for right eyes) and were more likely to have previously undergone cataract surgery (age-adjusted odds ratio 2.01, 95% CI 1.43-2.82 for either eye) than people without diabetes. Longer duration of diabetes significantly increased the odds of having cortical opacity. CONCLUSION: Older-onset diabetes is associated with increased frequency of a specific age-related lens change, cortical opacity. It is also associated with increased frequency of cataract surgery.

Adult↗

The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity.

PURPOSE: To investigate the relationship of age-related maculopathy, cataract, and glaucoma to visual acuity in the population-based Beaver Dam Eye Study. METHODS: A cross-sectional, population-based study was performed in people 43 through 86 years of age residing in Beaver Dam, Wisconsin, who were identified between 1987 and 1988 and examined (n = 4926) between 1988 and 1990. Of those who participated, 99.4% were white. Visual acuity was measured (n = 4886) using a modification of the Early Treatment Diabetic Retinopathy Study protocol. Stereoscopic color fundus photographs and slit lamp and retroillumination photographs of the lens were graded in a masked fashion using standardized protocols to determine the presence of age-related maculopathy and central cataract. RESULTS: Fifty-seven percent of those who were legally blind had late age-related maculopathy in both eyes. The frequency of visual acuity of 20/200 or worse was not significantly different in eyes with exudative macular degeneration (48%) than in eyes with pure geographic atrophy (42%). While controlling for other factors (age, central cataract, and glaucoma) in participants with both gradable age-related maculopathy and visual acuity measurable in at least one eye (n = 4716), investigators found that each of the early age-related maculopathy lesions was associated with a decrease in visual acuity of approximately two letters or fewer when compared to eyes without these lesions. Late age-related maculopathy was associated with a decrease of approximately seven lines of letters read correctly. CONCLUSION: These data demonstrate that exudative macular degeneration and pure geographic atrophy are the most important causes of legal blindness in this population and that early age-related maculopathy, central cataract, and glaucoma had a small effect on visual acuity.

Adult↗

Identification and partial sequence analysis of novel annexins in Lytechinus pictus oocytes.

The annexins are a major class of calcium-binding proteins with unknown functions. In an attempt to define novel model systems in which to study members of the annexin family, we have investigated the expression of annexins in eggs from the sea urchin Lytechinus pictus. Western blot analysis of L. pictus eggs using antisera raised against human annexins I, V and VI revealed the presence of immunoreactive proteins of approximately 34 kDa, 35 kDa and 68 kDa respectively. The sea urchin annexins behaved similarly to their mammalian counterparts, both during purification and in their ability to bind calcium-dependently to anionic phospholipids. Of the three sea urchin annexins, the 34 kDa form was most abundant, yielding sufficient quantities for peptide microsequencing. The amino acid sequences derived in this way showed the L. pictus annexin to be closely related both to mammalian annexin I and to annexins IX, X and XII from Drosophila and Hydra. However, N-terminal sequence from the L. pictus annexin showed it to be a novel member of the annexin super-gene family. The results are interesting in view of the complex evolution of the annexin gene family, and also point to the potential usefulness of echinoderm eggs as a model system in which to study annexin function.

Amino Acid Sequence↗

The association of glycemia and cause-specific mortality in a diabetic population.

BACKGROUND: The purpose of this study was to investigate the association of glycemia with cause-specific mortality in a diabetic population. METHODS: The study was a cohort design based in a primary care setting. Participants were all younger-onset diabetic persons (conditions diagnosed when they were younger than 30 years old and taking insulin, N = 1210) and a random sample of older-onset diabetic persons (conditions diagnosed when they were 30 years or older, N = 1780). Glycosylated hemoglobin levels were obtained at baseline examinations in 1980 to 1982 in which 996 younger-onset and 1370 older-onset persons participated. Median follow-up was 10 years in younger-onset and 8.3 years in older-onset persons; four younger-onset and two older-onset persons were unavailable for follow-up. The main outcome measure was cause-specific mortality as determined from death certificates. RESULTS: In the younger-onset group after controlling for other risk factors in proportional hazards models and considering underlying cause of death, glycosylated hemoglobin was significantly associated with mortality from diabetes (hazard ratio [HR] for a 1% change in glycosylated hemoglobin, 1.25; 95% confidence interval [CI], 1.13 to 1.38) and ischemic heart disease (HR, 1.18; 95% CI, 1.00 to 1.40). In the older-onset group, glycosylated hemoglobin was significantly associated with mortality from diabetes (HR, 1.32; 95% CI, 1.21 to 1.43), ischemic heart disease (HR, 1.10; 95% CI, 1.04 to 1.17), and stroke (HR, 1.17; 95% CI, 1.05 to 1.30), but not cancer (HR, 0.99; 95% CI, 0.88 to 1.10). Results for any mention of specific causes of death were similar. CONCLUSION: These results suggest possible benefit to the control of glycemia with respect to death due to vascular disease and diabetes.

Adolescent↗

Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy.

BACKGROUND: The object was to examine the relationship of hyperglycemia, as measured by glycosylated hemoglobin level, to the incidence and progression of diabetic retinopathy over a 10-year period. METHODS: Patients who were younger (n = 682) and older (n = 834) than 30 years at onset of diabetes participated in baseline (1980-1982) and follow-up (1984-1986 and 1990-1992) examinations of a population-based cohort study. Glycosylated hemoglobin levels were measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. RESULTS: Persons with glycosylated hemoglobin levels in the highest quartile at baseline were more likely to have progression of retinopathy than persons with levels in the lowest quartile (younger-onset group: relative risk [RR], 2.9; 95% confidence interval [CI], 2.3 to 3.5; older-onset group taking insulin: RR, 2.1; 95% CI, 1.6 to 2.8; and older-onset group not taking insulin: RR, 4.3; 95% CI, 3.0 to 6.2) and were more likely to develop proliferative diabetic retinopathy (younger-onset group: RR, 7.1; 95% CI, 4.6 to 11.1; older-onset group taking insulin: RR, 3.1; 95% CI, 1.5 to 6.1; and older-onset group not taking insulin: RR, 13.8; 95% CI, 4.8 to 39.5). These relations were significant (P < .005) in all groups examined, even after controlling for other risk variables. CONCLUSIONS: These data are compatible with the hypothesis that long-term control of hyperglycemia, as measured by glycosylated hemoglobin levels, is a significant risk factor for the long-term progression of diabetic retinopathy and that lower levels of glycosylated hemoglobin, even later in the course of diabetes, may modify the risk imposed by higher levels earlier in the course of disease in people with both younger- and older-onset diabetes.

Adult↗

Expression of annexin VI in A431 carcinoma cells suppresses proliferation: a possible role for annexin VI in cell growth regulation.

Human A431 cells exhibit many characteristics typical of transformed cells, such as lack of contact inhibition and reduced growth factor requirement. We have used these cells as a model for the study of annexin VI function, since they do not normally express this protein. In this study we isolated two stably transfected clones, both of which were found to express annexin VI at physiological levels, and examined various growth parameters associated with the transformed phenotype. In low serum, normal A431 cells had doubling times similar to those observed in high serum. However, although the annexin VI transfectants grew only slightly more slowly than controls in high serum, their doubling time was significantly increased in low serum. Moreover, in low serum the annexin VI transfectants stopped proliferating after reaching confluence, indicating contact inhibition. Fluorescence activated cell sorting analysis revealed that the annexin VI+ cells were growth arrested in the G1 phase of the cell cycle when cultured in low serum, whereas annexin VI- clones exhibited the same proportion of mitotic cells in both low and high serum. Thus, expression of annexin VI in a heterologous cell line has a moderating influence on cell proliferation suggesting a possible role for annexin VI in cell growth regulation.

Annexin A6↗

Molecular cloning of a novel N-terminal variant of annexin II from rat basophilic leukaemia cells.

Rat annexin II cDNA clones were isolated from a rat basophilic leukaemia cell plasmid library by cross-species hybridization with a mouse probe, and fully sequenced using the dideoxy-chain-termination method. Alignment of the derived amino-acid sequence with those of other mammalian annexin II species revealed a high level of conservation, characteristic of the annexin family of proteins. One of the cDNAs isolated contained an additional six nucleotides close to the N-terminus, lying in-frame and at a point corresponding to an intron/exon boundary in the human annexin II gene. As the two rat cDNAs were identical apart from the six nucleotide insert, it is likely that these represent alternatively spliced transcripts of a single gene, rather than the products of two separate genes. The six nucleotides encode serine-glutamine and therefore introduce an additional potential phosphorylation site into a region already containing one tyrosine and two serine phosphorylation sites. The discovery of this novel annexin II variant may have important implications both for p11 binding and for regulation of annexin II function by phosphorylation.

Amino Acid Sequence↗

Structure of the human annexin VI gene.

We report the structure of the human annexin VI gene and compare the intron-exon organization with the known structures of the human annexin I and II genes. The gene is approximately 60 kbp long and contains 26 exons. Consistent with the published annexin VI cDNA sequence, the genomic sequence at the 3' end does not contain a canonical polyadenylation signal. The genomic sequence upstream of the transcription start site contains TATAA and CAAT motifs. The spatial organization of the exons does not reveal any obvious similarities between the two halves of the annexin VI gene. Comparison of the intron-exon boundary positions of the annexin VI gene with those of annexins I and II reveals that within the repeated domains the break points are perfectly conserved except for exon 8, which is one codon smaller in annexin II. The corresponding point in the second half of annexin VI is represented by two exons, exons 20 and 21. The latter exon is alternatively spliced, giving rise to two annexin VI isoforms that differ with respect to a 6-amino acid insertion at the start of repeat 7.

Alternative Splicing↗

Z-DNA-forming sequences at a putative duplication site in the human annexin VI-encoding gene.

We report here the presence of five stretches of alternating purine/pyrimidine (APP) intronic sequence close to the 5' end of the first exon in the C-terminal half of the human annexin VI-encoding gene (ANX VI). ANX VI, which comprises eight conserved repeats, is considered to have arisen by duplication of a hypothetical four repeat Anx; the location of the duplication would be predicted to occur within the intron where the APP sequences have been identified. The APP sequences have, by computer prediction, been identified as having significant potential to form Z-DNA. We discuss the significance of these potential Z-DNA-forming sequences being located in a region predicted to be the site of duplication which gave rise to the human ANX VI gene.

Animals↗

Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population.

OBJECTIVE: To investigate the relationship of various retinal lesions to systemic hypertension in the population-based Beaver Dam Eye Study. DESIGN: In this cross-sectional population-based study, blood pressure was measured using standardized protocols. Using standardized protocols, stereoscopic color fundus photographs were graded in a masked fashion to determine the presence of retinopathy (defined as retinal microaneurysms only, blot hemorrhages only, hemorrhages and/or microaneurysms, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, venous beading, and retinal new vessels), retinal arteriolar narrowing, and arteriovenous nicking. PARTICIPANTS: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. People with diabetes or retinal vascular occlusions were excluded. RESULTS: Retinopathy was present in 336 subjects (7.8%), arteriolar narrowing in 582 subjects (13.5%), and arteriovenous nicking in 95 subjects (2.2%) in the nondiabetic population. Hypertension was associated with increased frequency of retinopathy, arteriolar narrowing, and arteriovenous nicking. After adjusting for age, hypertension was associated with the presence of retinopathy (in men: relative risk [RR], 1.47; 95% confidence interval [CI], 1.10 to 1.96; in women: RR, 1.69; 95% CI, 1.26 to 2.27), arteriolar narrowing (in men: RR, 1.34; 95% CI, 1.03 to 1.74; in women: RR, 1.37; 95% CI, 1.14 to 1.64), and arteriovenous nicking (in men: RR, 1.87; 95% CI, 0.99 to 3.54; in women: RR, 1.65; 95% CI, 1.00 to 2.73). Retinopathy, arteriolar narrowing, and arteriovenous nicking were more frequent in those subjects whose blood pressure was elevated despite use of antihypertensive medications compared with those subjects whose blood pressure was controlled with antihypertensive medications or those who were normotensive. CONCLUSIONS: These data suggest that retinopathy and retinal arteriolar narrowing are common in people with hypertension. Further longitudinal study is necessary to evaluate the public health significance of these retinal lesions regarding possibly increased risk of renal and cardiovascular disease.

Adult↗

Is age-related maculopathy associated with cataracts?

OBJECTIVE: To evaluate the relationship between three types of cataract or cataract surgery and age-related maculopathy. DESIGN: Population-based prevalence study. PARTICIPANTS: A total of 4926 people participating in The Beaver Dam Eye Study from 1988 through 1990. MAIN OUTCOME MEASURES: Grading of photographs for nuclear sclerosis, cortical cataract, and posterior subcapsular cataract and signs of age-related maculopathy was performed using standardized protocols. RESULTS: After adjusting for other risk factors, nuclear sclerosis was associated with increased odds of early age-related maculopathy (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.28 to 3.01) but not of late age-related maculopathy (OR, 1.38; 95% CI, 0.52 to 3.63). Neither cortical nor posterior subcapsular cataracts were related to age-related maculopathy. There were increased odds of early age-related maculopathy in eyes that had undergone cataract surgery. CONCLUSION: These data suggest a possible commonly shared pathogenesis between nuclear sclerotic cataract and age-related maculopathy.

Adult↗

The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy.

OBJECTIVE: To examine the 10-year incidence and progression of diabetic retinopathy. DESIGN: Population-based incidence study. PARTICIPANTS: Seven hundred sixty-five insulin-taking diabetic persons diagnosed before age 30 years, 251 insulin-taking diabetic persons diagnosed at age 30 years or older, and 282 non-insulin-taking diabetic persons diagnosed at age 30 years or older who participated in baseline, 4-year, and 10-year follow-up examinations. MAIN OUTCOME MEASURES: The 10-year incidence of any retinopathy, progression of retinopathy, and progression to proliferative retinopathy were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study severity scheme. RESULTS: The 10-year incidence of retinopathy (89%, 79%, and 67%), progression of retinopathy (76%, 69%, and 53%), and progression to proliferative retinopathy (30%, 24%, and 10%) were highest in the group diagnosed before age 30 years, intermediate in the insulin-taking group diagnosed at age 30 years or older, and lowest in the non-insulin-taking group, respectively. Increased risk of proliferative retinopathy was associated with more severe retinopathy at baseline. CONCLUSIONS: These data suggest relatively high 10-year rates of incidence and progression of retinopathy, and despite changes in the treatment of diabetes, there has been little change in the incidence and progression of diabetic retinopathy during the 10-year study period.

Adolescent↗

Structural evolution of the annexin supergene family.

The annexin family of calcium-binding proteins is comprised of at least ten mammalian genes, with additional representatives in lower eukaryotes. Recent structural analyses of several annexin genes have provided insights into the relationship between exon organization and functional domains. We discuss the implications of these findings and speculate on the evolutionary origins of the annexin supergene family.

Amino Acid Sequence↗

The relation of socioeconomic factors to age-related cataract, maculopathy, and impaired vision. The Beaver Dam Eye Study.

PURPOSE: To investigate the relations between socioeconomic factors and the prevalence of age-related cataract, maculopathy, and visual impairment. METHODS: A population-based sample of 4926 people 43 to 86 years of age was examined from 1988 to 1990. Education, income, employment status, marital status, nuclear sclerosis, cortical, and posterior subcapsular cataract, age-related maculopathy, and impaired vision were all ascertained using standard protocols. RESULTS: While controlling for age, sex, diabetes status, multivitamin use, alcohol consumption, and cigarette smoking, less education was significantly associated with nuclear and cortical cataract, and lower income was significantly associated with cortical and posterior subcapsular cataract and impaired vision. There was a "U-shaped" relation between income and cataract surgery. Neither income nor education was related to age-related maculopathy. There was no relation of marital status to cataract status or age-related maculopathy. CONCLUSION: These data suggest that education and income are associated with cataract, cataract surgery, and impaired vision. These relations were not explained by other risk factors measured in the study.

Adult↗

The association of alcohol consumption with the incidence and progression of diabetic retinopathy.

PURPOSE: To investigate the association of alcohol consumption with the incidence and progression of diabetic retinopathy. METHODS: The population consisted of a cohort of adult younger-onset (diagnosis received before 30 years of age and taking insulin, n = 439) and older-onset (diagnosis received after 30 years of age, n = 478) persons with diabetes examined from 1984 to 1986 and again from 1990 to 1992. The outcomes were incidence of retinopathy, progression, and progression to proliferative retinopathy. Retinopathy was determined by grading of stereoscopic color fundus photographs. Alcohol consumption was determined by questionnaire and summarized as average or recent consumption. The proportion of heavier drinkers was small, 6% of younger-onset and 4% of older-onset persons. RESULTS: In the younger-onset group, progression of retinopathy occurred in 62%, 51%, 61%, and 71% of nondrinkers, light, moderate, and heavier drinkers, respectively, based on average intake (P = 0.28). Based on recent intake, 55%, 46%, 63%, and 69% of nondrinkers, light, moderate, and heavier drinkers, respectively, progressed (P = 0.10). A similar trend is seen for incidence of retinopathy, but the sample sizes are small. No association is seen with progression to proliferative diabetic retinopathy. After controlling for age, sex, and glycemia in a logistic regression model, alcohol intake is not associated with progression of retinopathy. In the older-onset group, alcohol intake is not related to the incidence or progression of retinopathy. CONCLUSION: Alcohol consumption in moderation (< or = 1 oz/day) does not appear to affect the occurrence of diabetic retinopathy.

Adult↗