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Biomedical subjects

A Ott

Publications and source records attributed to A Ott.

At least 55 records · Page 3Linked to original sources

Acting on actin: the electric motility assay.

We have developed a novel technique which allows one to direct the two dimensional motion of actin filaments on a myosin coated sheet using a weak electric field parallel to the plane of motion. The filament velocity can be increased or decreased, and even reversed, as a function of orientation and strength of the field. PMMA (poly(methylmethacrylate)) gratings, which act as rails for actin, allow one for the first time to explore three quadrants of the force velocity diagram. We discuss effective friction, duty ratio and stall force at different myosin densities. A discontinuity in the velocity force relationship suggests the existence of dynamical phase transition.

Actins↗

Risk factors for respiratory syncytial virus associated apnoea.

UNLABELLED: Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO2, pCO2 and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO2 and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8-6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3-12.9) in children with recurrent episodes of apnoea. CONCLUSIONS: Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea.

Acid-Base Equilibrium↗

Trapping and wiggling: elastohydrodynamics of driven microfilaments.

We present an analysis of the planar motion of single semiflexible filaments subject to viscous drag or point forcing. These are the relevant forces in dynamic experiments designed to measure biopolymer bending moduli. By analogy with the "Stokes problems" in hydrodynamics (motion of a viscous fluid induced by that of a wall bounding the fluid), we consider the motion of a polymer, one end of which is moved in an impulsive or oscillatory way. Analytical solutions for the time-dependent shapes of such moving polymers are obtained within an analysis applicable to small-amplitude deformations. In the case of oscillatory driving, particular attention is paid to a characteristic length determined by the frequency of oscillation, the polymer persistence length, and the viscous drag coefficient. Experiments on actin filaments manipulated with optical traps confirm the scaling law predicted by the analysis and provide a new technique for measuring the elastic bending modulus. Exploiting this model, we also present a reanalysis of several published experiments on microtubules.

Actin Cytoskeleton↗

Primary mucosal melanomas of the nasal cavity and paranasal sinuses. A clinicopathological analysis of 14 cases.

We present 14 patients with primary sinonasal melanomas (SM) identified from 1984-1997 in our archives (11/14 lateral nose, 1/14 nasal septum, 2/14 paranasal sinuses; 8M/6F, mean age 67.7 years, range 39-88 years). Survival was poor (median 9 months) with death related to extensive local disease and/or widespread hematogenous metastases. The following histological subtypes were identified in descending order: amelanotic small blue cell, pleomorphic, epithelioid, spindle cell and myxoid. High mitotic rate and vascular invasion, absence of tumor-infiltrating lymphocytes and regression were features shared by all SM. Negative staining of B- and T-cell markers, LCA, neuroendocrine markers such as NSE, chromogranin and synaptophysin, and CK-negativity excluded olfactory neuroblastoma, small cell undifferentiated carcinoma, and lymphoma. S-100 protein was expressed in all SM, but demonstrated variable staining intensity with areas of complete negativity. HMB45 was strongly and uniformly (>80%) expressed in all undifferentiated small blue cell SM. The pigmented SM were predominantly HMB45-negative. The strong HMB45 staining in amelanotic small blue cell SM is explained by the reaction of HMB45 antibody with an oncofetal antigen found in immature melanosomes. In these poorly differentiated amelanotic malignant melanomas, antibody to HMB45 proved to be a superb diagnostic marker. We therefore strongly advocate the inclusion of HMB45 antibody in the panel of antibodies for initial work-up of undifferentiated mucosal neoplasms, since a negative S-100 stain in small biopsy material may result in incorrect classification of these neoplasms.

Adult↗

Apolipoprotein E epsilon4 and the risk of dementia with stroke. A population-based investigation.

OBJECTIVE: To investigate the association between the apolipoprotein E (APOE) genotypes and dementia in patients with stroke, defined as either vascular dementia (VaD) or Alzheimer disease with cerebrovascular disease (AD with CVD). DESIGN AND SETTING: Population-based, case-control study from Rotterdam, the Netherlands, and New York City. PARTICIPANTS: A total of 187 patients with dementia and stroke were compared with 507 controls similar in age and ethnic group. MAIN OUTCOME MEASURES: The APOE allele frequencies in patients and controls; the odds ratio of dementia with stroke, VaD, and AD with CVD, adjusted for age, sex, residency, and education; and the percent attributable risk related to the APOE epsilon4 allele. RESULTS: Overall, patients with dementia and stroke had a higher APOE epsilon4 allele frequency than controls. Compared with APOE epsilon3 homozygote individuals, APOE epsilon4 homozygotes had a 7-fold increased risk of dementia with stroke (OR=6.9; 95% CI, 1.6-29.4), while APOE epsilon4 heterozygotes had nearly a 2-fold increase in risk (OR=1.8; 95% CI, 1.2-2.7). Risks associated with APOE epsilon4 were elevated regardless of the subtype of dementia with stroke or age or sex. The percent attributable risk related to the APOE epsilon4 allele among demented patients with stroke was 41% overall, 33% among those with VaD, and 44% among those with AD with CVD. CONCLUSION: The APOE epsilon4 allele is a genetic risk factor for dementia with stroke, including VaD and AD with CVD. This may imply shared genetic susceptibility to dementia associated with stroke and AD. Alternatively, the category of patients with dementia and stroke, including VaD as currently defined, may include patients with AD.

Aged↗

Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study.

BACKGROUND: Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimer's disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. METHODS: We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's disease, and 1698 individuals who were not demented. Indicators of atherosclerosis included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography, and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis) to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms were assessed in 246 patients and in 928 controls. FINDINGS: All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8) and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimer's disease in those with severe atherosclerosis compared with those without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001). INTERPRETATION: These findings suggest that dementia and its two major subtypes Alzheimer's disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.

Aged↗

Dietary fat intake and the risk of incident dementia in the Rotterdam Study.

A high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease. Cardiovascular disease has been associated with dementia. We investigated the association between fat intake and incident dementia among participants, age 55 years or older, from the population-based prospective Rotterdam Study. Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food-frequency questionnaire. At baseline and after an average of 2.1 years of follow-up, we screened for dementia with a three-step protocol that included a clinical examination. The risk of dementia at follow-up (RR [95% CI]) was assessed with logistic regression. After adjustment for age, sex, education, and energy intake, high intakes of the following nutrients were associated with an increased risk of dementia: total fat (RR = 2.4 [1.1-5.2]), saturated fat (RR = 1.9 [0.9-4.0]), and cholesterol (RR = 1.7 [0.9-3.2]). Dementia with a vascular component was most strongly related to total fat and saturated fat. Fish consumption, an important source of n-3 polyunsaturated fatty acids, was inversely related to incident dementia (RR = 0.4 [0.2-0.91), and in particular to Alzheimer's disease (RR = 0.3 [0.1-0.9]). This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia, whereas fish consumption may decrease this risk.

Aged↗

Epidemiological features of sudden infant death after a German intervention campaign in 1992.

UNLABELLED: After national intervention campaigns, considerable declines in incidence for both sudden infant death (SID) and prone position have been observed worldwide. In the following investigation. German data on postinterventional risk factor patterns are presented for the first time. We analysed data from a 2-year population-based case-control study on SID carried out in two German districts between 1993 and 1994. We confirmed Complete covering of the baby (OR = 44.9, 95%-CI 95, 291), prone sleeping position (OR = 11.7; 5.3, 26.2), heavy maternal smoking during pregnancy (OR = 8.5; 3.2, 33.2 for > ten cigarettes per day), nonbreastfeeding (OR = 7.7; 2.7, 22.3) and missing maternal professional training (OR = 7.6; 3.6, 16.2) as risk factors for cot death. After adjustment for other major risk factors in a logistic regression model, sleeping on cushions lost statistical significance, whereas all other major risk factors remained relevant. CONCLUSIONS: Despite intervention campaigns, complete covering of the baby, prone position and heavy maternal smoking are still major risk factors for cot death. Except for sleeping on cushions, all major epidemiological risk factors for cot death act independently. Despite encouraging success in the reduction of risk factors for cot death, there is still substantial need for future endeavours towards a further reduction of modifiable risk factors for SID.

Bedding and Linens↗

Local variability in respiratory syncytial virus disease severity.

Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children's Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children's Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.

Age Distribution↗

Atrial fibrillation and dementia in a population-based study. The Rotterdam Study.

BACKGROUND AND PURPOSE: Atrial fibrillation is a frequent disorder in the elderly and a known risk factor for cerebrovascular stroke. We investigated the association of atrial fibrillation with dementia and cognitive impairment in a large cross-sectional, population-based study in the elderly. METHODS: Of the 6584 participants in the Rotterdam Study aged 55 to 106 years, detailed information on dementia status and ECG abnormalities was available. Dementia was diagnosed in three phases. First, participants were screened. Screen-positive subjects were tested further. Those with possible dementia underwent an extensive diagnostic workup. Dementia and dementia subtypes were diagnosed according to prevailing criteria. Cognitive impairment was defined as a Mini-Mental State Examination test score of < 26 points for a nondemented subject. RESULTS: Atrial fibrillation was diagnosed in 195, dementia in 276, and cognitive impairment in 635 subjects. We found significant positive associations of atrial fibrillation with both dementia and impaired cognitive function (age- and sex-adjusted odds ratios, 2.3 [95% confidence interval, 1.4 to 3.7] and 1.7 [95% confidence interval, 1.2 to 2.5]), respectively). The strongest association was found not for vascular dementia but rather for Alzheimer's disease with cerebrovascular disease. The associations were stronger in women, and the relation with dementia was more pronounced in the relatively younger elderly. A history of stroke in subjects with atrial fibrillation could not account for these associations. CONCLUSIONS: Dementia and subtypes Alzheimer's disease and vascular dementia may be related to atrial fibrillation even if no clinical stokes have occurred.

Age Factors↗

Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation.

Many essential phenomena in biology involve changes in cell shape. Cell deformation occurs in response to physical forces either coming from the external environment or intracellularly generated. In most tests of cell rheology, an external constraint is usually superimposed on an already mechanically active cell, thus the measurements may reflect both active motion and passive viscoelastic deformation. To show that active and passive processes could be distinguished on a time scale basis, we designed a novel piezo-controlled micromanipulation system to impose dynamic mechanical deformations on individual cells. Chick fibroblasts were seized between two glass microplates; one of the plates, more flexible, served as a sensor of the applied force. Controlled amounts of unidirectional compression and traction in the range of 10(-8)-10(-7) N were applied, using either step functions or sinusoidal signals at chosen frequencies. These tests allowed identification of three time scale dependent regimes. (1) A dominant elastic response, characterized by a linear stress-strain relationship, was especially apparent at short times (seconds); (2) A viscous behavior, characterized by force relaxation and irreversible cell deformation, was noticeable at intermediate times (minutes). Data from traction and oscillatory excitation tests were well fitted by a three-element Kelvin viscoelastic model, allowing the calculation of two elastic moduli in the range of 600-1,000 N/m2 and an apparent viscosity of about 10(4) Pa.s. (3) A contractile regime, in which actin-dependent traction forces were developed in response to uniaxial load was apparent at longer times (several tens of minutes). These forces were in the order of 4 x 10(-8) N above viscous relaxation. Thus we could distinguish, on a time scale basis, the specific contributions of passive viscoelasticity and active traction, and evaluate their mechanical characteristics within one experiment on a single cell.

Animals↗

Insulin and cognitive function in an elderly population. The Rotterdam Study.

OBJECTIVE: To examine the association between insulin and cognitive function in the population-based Rotterdam Study. RESEARCH DESIGN AND METHODS: Serum insulin was measured 2 h after an oral glucose load, while global cognitive function was assessed by the Mini Mental State Examination in 5,510 subjects, aged 55 years and over. RESULTS: An increase in postload insulin only in women was associated with a decrease in cognitive function (age-adjusted regression coefficient -0.10 per 50 mU/l insulin; 95% CI -0.16 to -0.04). The association between insulin resistance, assessed by the ratio of postload insulin over glucose, and cognitive function was not statistically significant. Further adjustment for the individual risk factors of serum glucose, BMI, HDL, systolic blood pressure, smoking, or use of estrogen did not change the results. The association was present in women with and without cardiovascular disease and present after excluding subjects with diabetes. Women with dementia, the extreme of cognitive dysfunction, had increased age-adjusted insulin levels (76.3 +/- 4.9 vs. 66.8 +/- 1.0 mU/l [means +/- SE], P = 0.06). CONCLUSIONS: The results of this study suggest that increased serum insulin may be associated with decreased cognitive function and dementia in women. These findings are more compatible with a direct effect of insulin on the brain than with an effect through an increase in cardiovascular risk factors.

Aged↗

Critical centrifugal forces induce adhesion rupture or structural reorganization in cultured cells.

Cultured epithelial cells were exposed to accelerations ranging from 9,000 to 70,000g for time periods of 5, 15, or 60 min, by centrifugation in a direction tangential to their plastic substrate. Three regimes describe the cellular response: (1) Cell morphology and density remain unaltered at forces below a threshold of about 10(-7) N; (2) Between this critical force and a second threshold of about 1.5 10(-7)N, the number of adherent cells decreases exponentially with time and acceleration, with no alteration of cell morphology. This behavior can be modeled by a constant probability of detaching and by an exponential distribution of cell-to-substrate adhesive forces; (3) Past the second threshold, cells that are still adherent exhibit elongated morphologies, the degree of elongation increasing linearly with the force. The fact that cells lose their vinculin-rich focal contacts past the first threshold and that cells cultured on gelatin-coated plastic show an increased resistance to detachment suggests a rupture of cell-to-substrate adhesions upon centrifugation. Immunofluorescent labeling of cells for actin and tubulin shows a reorganization of the cytoskeleton upon centrifugation, and treatment of cells with the drugs cytochalasin D and nocodazole demonstrates that cytoskeletal elements are actively involved in the structural deformation of cells past the second acceleration threshold, microtubules and microfilaments paying antagonistic roles.

Breast↗

Influence of adhesion and cytoskeletal integrity on fibroblast traction.

Cellular contractility plays an important role in cell morphogenesis and tissue pattern formation. In this context, we examined how the expression of cell traction depends on cell-to-substrate contacts and cytoskeletal organization. Qualitative observation of chick fibroblasts cultured on an elastic film of polydimethylsiloxane indicated a strong spatial relationship between wrinkle pattern and distribution of actin stress fibers and focal contacts. In order to further characterize cell contractility, the projected area of Triton-permeabilized fibroblasts upon ATP-induced retraction was measured in various conditions of substrate adhesivity, cytoskeletal perturbation, and temperature. In all conditions, the relationship between degree of cell retraction and ATP concentration was well described by the laws of enzyme kinetics. Culturing cells on a gelatin-coated substrate, decreasing the temperature, using phosphate ribonucleotides other than ATP, and treating cells with cytochalasin D all diminished the rate of cell retraction, indicating that fibroblast traction is generated by a temperature- and ATP-dependent actin/myosin stress fiber sliding mechanism, transmitted to the substrate through focal adhesions. Treatment of cells with either nocodazole or taxol did not affect retraction of permeabilized fibroblasts upon stimulation with ATP, suggesting that microtubules do not directly resist cell traction. Treatment of cells with vanadate increased cell retraction, suggesting that intermediate filaments help transmit tension.

Adenosine Triphosphate↗

Association of diabetes mellitus and dementia: the Rotterdam Study.

Dementia and non-insulin-dependent diabetes mellitus (NIDDM) are highly prevalent disorders in the elderly. Diabetes has repeatedly been reported to affect cognition, but its relation with dementia is uncertain. We therefore studied the association between diabetes and dementia in the Rotterdam Study, a large population-based study in the elderly. Of 6330 participants, aged 55 to 99 years old, complete information on diabetes and presence of dementia was available. Diabetes was diagnosed as use of anti-diabetes medication or random or post-load serum glucose over 11 mmol/1. Dementia was diagnosed through a stepped approach, including a sensitive screening of all participants and a comprehensive diagnostic work-up. Diabetes was present in 724 (11.4%) subjects. Of the 265 dementia patients 59 (22.3%) had diabetes. Multiple logistic regression analyses, adjusting for age and sex differences, revealed a positive association between diabetes and dementia (odds ratio: 1.3, 95% confidence interval 1.0-1.9). In particular, strong associations were found between dementia and diabetes treated with insulin (odds ratio: 3.2, 95% confidence interval: 1.4-7.5) The relation was strongest with vascular dementia but was also observed with Alzheimer's disease. These associations were independent of educational attainment, smoking, body mass index, atherosclerosis, blood pressure and antihypertensive drug treatment, and could not be explained by clinical cerebra infarctions. The results suggest that NIDDM is associated with dementia. Alzheimer's disease may be more frequent in elderly diabetic patients treated with insulin.

Age Factors↗

Dementia-free life expectancy (DemFLE) in The Netherlands.

To gain an insight into the burden of dementia in an aging society, life expectancy with dementia and its counterpart dementia-free life expectancy (DemFLE) in The Netherlands are presented. Sullivan's method was used to calculate DemFLE. For elderly living either independently or in homes for the elderly prevalence figures on dementia were obtained from the Rotterdam Elderly Study (RES; n = 7528); for elderly in nursing homes the SIG Nursing home Information System was used. Conforming to other authors only the prevalence data on moderate and severe dementia as diagnosed with DSM-III-R criteria are used. The prevalence of mild dementia was not taken into account. At 65 years DemFLE for men is 14.0 years, that is 96.4% of the total life expectancy (14.5 years at this age). At age 90, DemFLE for men is 2.5 years, equal to 77.5% of the total life expectancy (3.3 years). For women DemFLE at age 65 is 17.7 years, that is 93.2% of their life expectancy (19.0 years), and at the age of 90, DemFLE for women is 2.8 years, equal to 74.7% of their remaining life expectancy (3.8 years). The absolute number of years with dementia remains relatively constant with increasing age. About 20-25% of these years with dementia are spent in nursing homes, the other 75-80% living independently. At each age compared with men women have both a higher DemFLE and a higher expectancy of years with dementia. The percentage of life expectancy without dementia however, is always lower for women, because of their higher total life expectancy. This indicates that the burden of dementia in absolute and relative terms is higher for women. Most years with dementia are spent at home, indicating that the burden of dementia rests mainly on the shoulders of informal caregivers.

Aged↗