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S E Moss

Publications and source records attributed to S E Moss.

At least 19 recordsLinked to original sources

Membrane segregation and downregulation of raft markers during sarcolemmal differentiation in skeletal muscle cells.

Muscle contraction implies flexibility in combination with force resistance and requires a high degree of sarcolemmal organization. Smooth muscle cells differentiate largely from mesenchymal precursor cells and gradually assume a highly periodic sarcolemmal organization. Skeletal muscle undergoes an even more striking differentiation programme, leading to cell fusion and alignment into myofibrils. The lipid bilayer of each cell type is further segregated into raft and non-raft microdomains of distinct lipid composition. Considering the extent of developmental rearrangement in skeletal muscle, we investigated sarcolemmal microdomain organization in skeletal and smooth muscle cells. The rafts in both muscle types are characterized by marker proteins belonging to the annexin family which localize to the inner membrane leaflet, as well as glycosyl-phosphatidyl-inositol (GPI)-anchored enzymes attached to the outer leaflet. We demonstrate that the profound structural rearrangements that occur during skeletal muscle maturation coincide with a striking decrease in membrane lipid segregation, downregulation of annexins 2 and 6, and a significant decrease in raft-associated 5'-nucleotidase activity. The relative paucity of lipid rafts in mature skeletal in contrast to smooth muscle suggests that the organization of sarcolemmal microdomains contributes to the muscle-specific differences in stimulatory responses and contractile properties.

Annexins↗

Annexin 2 has an essential role in actin-based macropinocytic rocketing.

Annexin 2 is a Ca(2+) binding protein that binds to and aggregates secretory vesicles at physiological Ca(2+) levels [1] and that also associates Ca(2+) independently with early endosomes [2, 3]. These properties suggest roles in both exocytosis and endocytosis, but little is known of the dynamics of Annexin 2 distribution in live cells during these processes. We have used evanescent field microscopy to image Annexin 2-GFP in live, secreting rat basophilic leukemia cells and in cells performing pinocytosis. Although we found no evidence of Annexin 2 involvement in exocytosis, we observed an enrichment of Annexin 2-GFP in actin tails propeling macropinosomes. The association of Annexin 2-GFP with rocketing macropinosomes was specific because Annexin 2-GFP was absent from the actin tails of rocketing Listeria. This finding suggests that the association of Annexin 2 with macropinocytic rockets requires native pinosomal membrane. Annexin 2 is necessary for the formation of macropinocytic rockets since overexpression of a dominant-negative Annexin 2 construct abolished the formation of these structures. The same construct did not prevent the movement of Listeria in infected cells. These results show that recruitment of Annexin 2 to nascent macropinosome membranes 16656is an essential prerequisite for actin polymerization-dependent vesicle locomotion.

Actins↗

How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy.

OBJECTIVE: To determine whether a 1-step or more or 2-step or more progression on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale over a 4-year period is meaningful in predicting the subsequent incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) over the following 6 years. DESIGN: Population-based study of diabetic persons with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in southern Wisconsin. There were 1025 persons with diabetes who had fundus photographs at baseline and at 4- and 10-year follow-up examinations. MAIN OUTCOME MEASURES: Incidence of PDR or CSME between the 4- and 10-year follow-up examinations as determined by masked grading of color stereoscopic fundus photographs of 7 standard fields. RESULTS: In a univariate analysis, those with 1 or more steps of progression (n = 551) over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with no progression (n = 474) (26% vs 4%) (relative risk, 5.85; 95% confidence interval, 4.05-8.47). Similarly, those with 2 or more (n = 364) (33%) or 3 or more (n = 231) (41%) steps of progression over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with lesser progression (n = 661 [7%] and n = 794 [9%], respectively) (relative risk, 5.10; 95% confidence interval, 3.83-6.80; and relative risk, 4.61; 95% confidence interval, 3.57-5.99, respectively). Similar associations were apparent at every level of retinopathy, duration of diabetes, and glycosylated hemoglobin, and by type of diabetes at baseline. There were also associations between retinopathy progression and incidence of CSME. CONCLUSIONS: It seems that 1 or more or 2 or more steps of progression of retinopathy over a 4-year period strongly predict the development of PDR over the next 6 years. Therefore, using these end points of progression would result in the need for fewer subjects or shorter follow-up in some clinical trials.

Adult↗

The NEI-VFQ-25 in people with long-term type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVES: To examine the association of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) overall and specific scale scores with visual acuity, diabetic retinopathy, and other characteristics, in a cohort of persons with type 1 diabetes. DESIGN: Population-based cohort study. SETTING: An 11-county area in southern Wisconsin. PARTICIPANTS: Six hundred two persons with diabetes whose conditions were diagnosed when they were younger than 30 years and who were currently taking insulin participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. MAIN OUTCOME MEASURES: An interview that consisted of the 25-item NEI-VFQ was completed. Visual acuity was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol and the presence and severity of retinopathy and macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the ETDRS retinopathy severity scheme. RESULTS: Univariate analyses revealed that the total NEI-VFQ-25 score was lower in persons who were older, had a longer duration of diabetes, higher glycosylated hemoglobin, were in renal failure, had a history of cardiovascular disease, hypertension, or amputation of a lower limb, had poorer visual acuity, more severe diabetic retinopathy, macular edema, glaucoma, cataract, abnormalities in tactile sensation or temperature sensitivity, smoked more total pack-years, led a more sedentary lifestyle, and had poor peak expiratory flow. In multivariate analyses, while controlling for the physical and mental component scores from the Medical Outcomes Survey 36-Item Short-Form Health Survey as measures of comorbidity, lower total NEI-VFQ-25 scores were independently associated with poorer visual acuity, more severe retinopathy, older age, history of loss of tactile sensation, and more total pack-years of cigarettes smoked. CONCLUSIONS: In this cross-sectional study, the 25-item NEI-VFQ seems to be strongly associated with vision, independent of severity of retinopathy and other complications associated with type 1 diabetes. It may be a useful measure of health-related quality of life as it relates to vision in epidemiological studies and clinical trials in persons with diabetes.

Adolescent↗

The relation of socioeconomic factors to the incidence of early age-related maculopathy: the Beaver Dam eye study.

PURPOSE: To investigate the relationship between socioeconomic factors and the 5-year incidence of age-related maculopathy. METHODS: The Beaver Dam Eye Study, a population-based cohort study, examined 3681 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, at baseline and 5 years later. Standardized protocols for physical examination, including administration of a questionnaire that included questions regarding income, education level, and status and type of employment, and fundus photography to determine age-related maculopathy, were performed. RESULTS: While controlling for age and sex, less education, and being in a service-related occupation compared with a white collar professional occupation, was associated (P <.05) with the incidence of early age-related maculopathy. CONCLUSION: These data show an association of education and occupation but not income with the incidence of early age-related maculopathy that appears independent of smoking or vitamin supplement use status.

Adult↗

Asteroid hyalosis in a population: the Beaver Dam eye study.

PURPOSE: To estimate the prevalence of asteroid hyalosis and to examine correlates of asteroid hyalosis in a population-based cohort. METHODS: The population of Beaver Dam, Wisconsin, that was 43 to 86 years of age was examined from 1988 to 1990 (n = 4926). The population is predominantly white (99.4%) northern European. Asteroid hyalosis was determined from stereoscopic fundus photographs of three standard fields. RESULTS: Fundus photographs were gradable in 4747 subjects. Asteroid hyalosis was present in 1.2% (95% confidence interval, 0.9,1.5%). In subjects in which it was present, asteroid hyalosis was bilateral in 9%. Prevalence increased significantly (P <.001) with age from 0.2% in subjects 43 to 54 years to 2.9% in subjects 75 to 86 years. After adjusting for age, men were more likely (1.8%) to have asteroid hyalosis than women (0.8%). After adjusting for age and sex, asteroid hyalosis was significantly more likely to be found in subjects with greater body mass (P =.02) and higher alcohol consumption (P =.03). There were nonsignificant trends with systolic blood pressure (P =.07), serum cholesterol (P =.09), and serum albumin (P =.09). It was not significantly associated (P >.05) with diastolic blood pressure, hypertension, diabetes, cardiovascular disease history, high-density-lipoprotein cholesterol, serum calcium, cigarette smoking, physical activity, intraocular pressure, or refractive error. These relationships were confirmed in a multivariable logistic model. CONCLUSIONS: The current study documents the infrequency of asteroid hyalosis in the population as graded from three photographic fields of the fundus. It does not support previous observations of an association of asteroid hyalosis with diabetes or refractive error. The relevance of the new associations reported (body mass, alcohol) remains to be determined.

Adult↗

Is the pulse rate useful in assessing risk of diabetic retinopathy and macular oedema? The Wisconsin Epidemiological Study of Diabetic Retinopathy.

AIM: To describe the relation between pulse rate and incident diabetic retinopathy. METHODS: Population based cohort study of people with diabetes. Resting pulse rate was measured in 30 second intervals. Diabetic retinopathy was evaluated from masked gradings of fundus photographs. RESULTS: People with higher pulse rates were more likely to have 4 year progression of retinopathy, progression to proliferative retinopathy, and incident macular oedema than those with lower pulse rates. However, these associations were attenuated after controlling for blood pressure, glycosylated haemoglobin, and other risk factors. CONCLUSION: Pulse rate may be a clinical indicator of overall risk of diabetic retinopathy, but is not independently associated with the condition.

Adult↗

Peak expiratory flow rate: relationship to risk variables and mortality: the Wisconsin Epidemiologic Study of diabetic retinopathy.

OBJECTIVE: To examine correlates of peak expiratory flow rate in people with type 1 diabetes and to evaluate the relationship of peak expiratory flow rate to mortality. RESEARCH DESIGN AND METHODS: A cohort study that was originally designed to determine the prevalence, incidence, and severity of diabetic retinopathy also provided the opportunity to measure peak expiratory flow rate. This was first measured at a 10-year follow-up and was evaluated in regard to risk factors for microvascular complications of diabetes. Mortality during 6 years of follow-up after the measurement was also ascertained. RESULTS: In multivariable analysis, peak expiratory flow rate was associated with sex, age, height, BMI, history of cardiovascular disease, pulse rate, duration of diabetes, glycosylated hemoglobin, and end-stage renal disease. Peak expiratory flow rate was significantly associated with survival in categorical analyses. Even after considering age, sex, renal disease, history of cardiovascular disease, respiratory symptoms, duration of diabetes, cigarette smoking, and hypertension, peak expiratory flow rate was still significantly related to survival (hazard ratio 0.61 [95% CI 0.46-0.82]). CONCLUSIONS: These data indicate that peak expiratory flow rate is associated with risk factors for other complications of diabetes. In addition, peak expiratory flow rate is a significant predictor of survival over even a relatively short period of time (6 years) in patients with younger-onset diabetes.

Adolescent↗

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

BACKGROUND: Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. OBJECTIVE: To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. METHODS: We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. RESULTS: Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). CONCLUSIONS: Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.

Aged↗

Prevalence of and risk factors for dry eye syndrome.

OBJECTIVE: To examine risk factors for the prevalence of dry eye syndrome in a population-based cohort. METHODS: The prevalence of dry eye was determined by history at the second examination (1993-1995) of the Beaver Dam Eye Study cohort (N = 3722). RESULTS: The cohort was aged 48 to 91 years (mean +/- SD, 65 +/- 10 years) and 43% male. The overall prevalence of dry eye was 14.4%. Prevalence varied from 8.4% in subjects younger than 60 years to 19. 0% in those older than 80 years (P<.001 for test of trend). Age-adjusted prevalence in men was 11.4% compared with 16.7% in women (P<.001). After controlling for age and sex, the following factors were independently and significantly associated with dry eye in a logistic model: history of arthritis (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.56-2.33), smoking status (past, OR, 1.22; 95% CI, 0.97-1.52; current, OR, 1.82; 95% CI, 1.36-2.46), caffeine use (OR, 0.75; 95% CI, 0.61-0.91), history of thyroid disease (OR, 1.41; 95% CI, 1.09-1.84), history of gout (OR, 1.42; 95% CI, 1.02-1.96), total to high-density lipoprotein cholesterol ratio (OR, for 1 unit, 0.93; 95% CI, 0.88-0.99), diabetes (OR, 1.38; 95% CI, 1.03-1.86), and multivitamin use (past, OR, 1.35; 95% CI, 1. 01-1.81; current, OR, 1.41; 95% CI, 1.09-1.82). Nonsignificant variables included body mass; blood pressure; white blood cell count; hematocrit; history of osteoporosis, stroke, or cardiovascular disease; history of allergies; use of antihistamines, parasympathetics, antidepressants, diuretics, antiemetics, or other drying drugs; alcohol consumption; time spent outdoors; maculopathy; central cataract; and lens surgery. CONCLUSION: The results suggest several factors, such as smoking, caffeine use, and multivitamin use, could be studied for preventive or therapeutic efficacy. Arch Ophthalmol. 2000;118:1264-1268

Adult↗

Arcus senilis and mortality in a population with diabetes.

PURPOSE: To estimate the prevalence of arcus senilis and its association with mortality in a diabetic population. METHODS: A cohort of persons with younger (n = 996) and older onset (n = 1,370) diabetes was examined. Mortality information was obtained from death certificates. RESULTS: Prevalence of arcus senilis increased with age and was higher in men than in women. In the younger onset group, it was also associated with a history of cardiovascular disease. As a risk factor for mortality after controlling for age and sex, arcus senilis was not associated with death from all causes, ischemic heart disease, or stroke. CONCLUSION: Arcus senilis provides no more information about mortality risk than age of the person.

Adult↗

Lens thickness and five-year cumulative incidence of cataracts: The Beaver Dam Eye Study.

PURPOSE: To evaluate whether lens thickness is related to incidence of cataracts. METHODS: Lens thickness was measured from slit-lamp photographs of the lens at the time of the prevalence evaluation in the Beaver Dam Eye Study. Incident cataract was determined by grading standard slit-lamp and retroillumination photographs of the lens at the baseline and five-year follow-up examinations. Medical history was obtained and blood pressures, height and weight were measured according to protocol. RESULTS: Lens thickness was positively associated with incident nuclear cataract and inversely associated with incident cortical cataract after accounting for age, sex, diabetes status, hypertension, heavy drinking and cigarette smoking. CONCLUSIONS: Lens thickness is related to incidence of cataracts. Mechanisms to explain these relationships require further laboratory and epidemiologic investigation.

Adult↗

Calcium signaling and annexins.

The annexins, are a family of calcium ion (Ca2+)-binding proteins whose physiological functions are poorly understood. Although many diverse functions have been proposed for these proteins, such as in vesicle trafficking, this review focuses on their proposed roles as Ca2+ or other ion channels, or as intracellular ion channel regulators. Such ideas are founded mainly on in vitro and structural analyses, but there is increasing evidence that at least some members of this protein family may indeed play a part in intracellular Ca2+ signaling by acting both as atypical ion channels and as modulators of ion channel activity. This review first introduces the annexin family, then discusses intracellular localization, developmental regulation, and modes of membrane association of annexins, which suggest roles in Ca2+ homeostasis. Finally, it examines the structural and electrophysiological data that argue for key roles for annexins in the control of ion fluxes.

Animals↗

Exposure to diagnostic x-rays and incident age-related eye disease.

OBJECTIVE: The purpose of this study was to evaluate whether a self-reported history of computed tomography or other x-rays of the head were associated with the incidence of age-related cataracts and maculopathy five years later. METHOD: A 5-year longitudinal follow-up of the Beaver Dam Eye Study cohort (n=3,684, 43-86 years at baseline). RESULTS: There was no evidence of a relationship between the x-ray exposures and the incidence of nuclear or cortical cataracts, or early maculopathy. There was a significant relationship to the incidence of posterior subcapsular cataract after adjusting for age only. CONCLUSIONS: Adult patients in whom medical conditions warrant diagnostic x-rays of the head appear to be at little or no increased risk of age-related cataract or maculopathy. However, research efforts with more precise measures of x-ray exposure, longer follow-up, and further attempts to define uncontrolled confounders are warranted.

Adult↗

The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study.

PURPOSE: To describe the prevalence and the 5-year incidence of retinal central and branch vein occlusion and associated risk factors. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population-based study in which retinal vein occlusions were detected at baseline (1988-1990) and at a 5-year follow-up examination (1993-1995) by grading of 30 degrees color fundus photographs. RESULTS: The prevalence and 5-year incidence of retinal branch vein occlusion were each 0.6%. The prevalence of retinal central vein occlusion was 0.1%, and the 5-year incidence was 0.2%. While adjusting for age, the prevalence of branch vein occlusion was associated with hypertension (odds ratio [OR] 5.42, 95% confidence interval [CI] 2.18, 13.47), diabetes mellitus (OR 2.43, 95% CI 1.04, 5.70), pulse pressure (OR 1.24 for 10 mm Hg, 95% CI 1.03, 1.48), ocular perfusion pressure (OR 2.09 for 10 mm Hg, 95% CI 1.45, 3.01), arteriovenous nicking (OR 16.75, 95% CI 7.33, 38.24), and focal arteriolar narrowing (OR 22.86, 95% CI 8.43, 62.03). The age-adjusted incidence of retinal branch vein occlusion was associated with current smoking (OR 4.43 95%, CI 1.53, 12.84) compared with nonsmokers and to focal arteriolar narrowing (OR 5.24, 95% CI 1.97, 13.94) at baseline. While controlling for age, the incidence of branch vein occlusion was not associated with serum lipid levels, body mass index, white blood cell count, alcohol consumption, aspirin use, glaucoma, intraocular pressure, or ocular hypertension. CONCLUSIONS: Retinal vein occlusion is infrequent in the population. These data suggest a strong association between retinal branch vein occlusion and retinal arteriolar changes. Data from larger populations are needed to further assess associations between risk factors and the incidence of retinal vein occlusions.

Adult↗

Annexin 5 mediates a peroxide-induced Ca(2+) influx in B cells.

Annexin 5 is a Ca(2+)-binding protein, the function of which is poorly understood. Structural and electrophysiological studies have shown that annexin 5 can mediate Ca(2+) fluxes across phospholipid membranes in vitro [1]. There is, however, no direct evidence for the existence of annexin 5 Ca(2+) channels in living cells. Here, we show that annexin 5 inserts into phospholipid vesicle membranes at neutral pH in the presence of peroxide. We then used targeted gene disruption to explore the role of annexin 5 in peroxide-induced Ca(2+) signaling in DT40 pre-B cells. DT40 clones lacking annexin 5 exhibited normal Ca(2+) responses to both thapsigargin and B-cell receptor stimulation, but lacked the sustained phase of the response to peroxide. This late phase was due to Ca(2+) influx from the extracellular space, demonstrating that annexin 5 mediates a peroxide-induced Ca(2+) influx. Thus, peroxide induces annexin 5 membrane insertion in vitro, and peroxide-induced Ca(2+) entry in vivo in DT40 cells requires annexin 5. Our results are consistent with a role for annexin 5 either as a Ca(2+) channel, or as a signaling intermediate in the peroxide-induced Ca(2+)-influx pathway.

Animals↗