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Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 451 records · Page 25Linked to original sources

Ultrastructure and reproduction behaviour of single CHO-K1 cells exposed to near infrared femtosecond laser pulses.

In the present work, the authors investigated ultrastructural changes as well as the reproduction behaviour of preselected single CHO-K1 cells exposed to 170 femtosecond laser pulses at different power output levels in comparison with cells outside the illumination volume. The ultrashort laser pulses were provided by an 80 MHz Ti:sapphire laser at 780 nm. The cells were scanned ten times with a scan rate of 1/16 s(-1). Single CHO-K1 cells exposed to low mean power of 2 mW revealed no significant changes in ultrastructure after laser exposure. In some cases, changes of mitochondria with slight disordering of cristae were found. Cytoplasm was filled with vesicles that seemed to be released from Golgi stacks. Cells irradiated with higher powers demonstrated more dramatic changes in ultrastructure. A considerable number of swollen mitochondria in conjunction with loss of cristae was observed. The main event of mitochondrial changes was the formation of electron dense bodies in the mitochondrial matrix. In addition, lumen of endoplasmatic reticulum was enlarged. Highest applied mean laser power of 12.5 mW lead to complete destruction of mitochondria and their transformation to electron dense structures containing membrane material. Compared with cell targets irradiated with 2 mW mean power, the release of vesicles from Golgi stacks seemed to be rather moderate. Cells localised outside the laser beam revealed no ultrastructural changes. Low mean laser power at 2 mW was unable to impair the reproduction behaviour of CHO-K1 cells. At higher laser power output levels, CHO-K1 cells started to delay cell division. At 12.5 mW, no cell division occurred. The obtained results may be helpful in recommending parameters for safe femtosecond laser microscopy of living specimens.

Animals↗

The effect of (+/-)-dobutamine on adrenergic nerve endings.

Possible effects of (+/-)-dobutamine on adrenergic nerve endings were determined in experiments with ghosts of bovine chromaffin granules, with rat phaeochromocytoma (PC-12) cells and with the rat vas deferens. Dobutamine inhibited the vesicular uptake of a mixture of 70% adrenaline + 30% 3H-noradrenaline into ghosts, with an IC50 of 1.7 mumol/l. Dobutamine inhibited uptake1 of 3H-noradrenaline in PC-12 cells (with an IC50 of 0.38 mumol/l) without being a substrate. However, dobutamine easily entered PC-12 cells by diffusion. After inhibition of MAO, COMT and vesicular uptake dobutamine (15 and 45 mumol/l) released tritium from rat vasa deferentia preloaded with 3H-noradrenaline. Equi-inhibitory concentrations of dobutamine and desipramine (against uptake1) were equi-releasing. On the other hand, when MAO and vesicular uptake were intact, dobutamine (15 mumol/l) increased the efflux of tritium from preloaded vasa deferentia much more than did an equi-inhibitory concentration of desipramine. Most of the released tritium was then 3H-DOPEG. Dobutamine is a potent inhibitor of uptake1 as well as of vesicular uptake; moreover, it easily diffuses into adrenergic nerve endings. Hence, it blocks the neuronal and the vesicular re-uptake of noradrenaline; consequently, when MAO and vesicular uptake are intact, dobutamine increases the net leakage of noradrenaline from the storage vesicles, thereby leading to an efflux of deaminated metabolites. However, dobutamine is virtually unable to release noradrenaline into the extracellular space.

Adenosine Triphosphate↗

Effect of low-dose acute X-irradiation on the frequencies of chromosomal aberrations in human peripheral lymphocytes in vitro.

In a coordinated research programme sponsored by the International Atomic Energy Agency, the frequencies of chromosomal aberrations induced in peripheral blood lymphocytes (in vitro) by 250 kV X-rays at low doses (0.4, 1, 2, 3, 5, 10 and 30 rad) were determined. Blood from 2 donors was used to conduct one master experiment at these dose levels. The culture time used was 48 h and all samples including the controls were processed according to a standard protocol. The coded slides were scored by investigators from 10 participating laboratories. The main results are the following: (1) the frequencies of all types of chromosome aberrations at 0.4 rad are significantly lower than the control values; (2) there is no increase in the frequencies of dicentrics up to 2 rad and in those of terminal deletions up to 5 rad; (3) the mean frequencies of all aberrations considered together are not significantly different from one another at 1, 2 and 3 rad (P = 0.05); and (4) over the entire dose range the dose-effect relationship is clearly non-linear. A fit of these data to a linear quadratic model (E(D) = c + alpha D + beta D2) showed that the observed total aberration frequencies at doses 1, 2, 3 and 5 rad are below the curve defined by the model. The deviations can be explained by an altered kinetics of aberration production at very low doses probably due to DNA repair mechanisms operating these cells.

Adult↗

Calculation abilities in dementia of Alzheimer's type and in vascular dementia.

Calculation abilities tested by 12 additive and 12 multiplicative tasks were investigated in 19 patients suffering from vascular dementia and in 23 patients suffering from dementia of Alzheimer's type as well as in 17 age-matched controls. Arithmetic impairment expressed by the number of correct results showed a significant correlation with the degree of dementia, measured by the Mini-Mental State Examination. An error type analysis was performed, but was of no help in the differential diagnosis of dementia. Calculation abilities are similarly impaired in both vascular dementia and dementia of Alzheimer's type.

Journal Article↗

On the relationship between measles virus and Alzheimer neurofibrillary tangles in subacute sclerosing panencephalitis.

We have studied the relationship between measles virus and the accumulation of abnormally phosphorylated tau (PHF-tau) in nine cases of subacute sclerosing panencephalitis (SSPE). By assessing the presence of viral intranuclear inclusions and neurofibrillary tangles (NFT) in each case, we found no correlation between presence and amount of measles virus and the numbers of neurons containing PHF-tau. Immunohistochemical double labeling in a case with long duration of disease and severe histopathologic change revealed no strict colocalization of measles virus antigen and PHF-tau throughout different brain regions. In areas containing both antigens, most neurons carrying measles virus did not have a tangle and vice versa, eventhough some colocalization beyond that expected by chance was observed in specific cortical areas. These results indicate that, although secondary to viral infection, NFT formation in SSPE is not restricted to cells carrying viral antigen. Conversely, measles virus infected cells do not necessarily accumulate PHF-tau. This lack of colocalization at the cellular level, throughout different brain areas and among different cases suggests that the formation of NFT in SSPE is not directly induced by the infectious agent. The formation of NFT in this disease appears to be elicited through a specific type of tissue damage and, thus, to be an epiphenomenon. This pathogenetic detail may be of interest for our understanding of the role of neurofibrillary degeneration in the pathogenesis of other more frequent neurodegenerative diseases with cytoskeletal pathology.

Adolescent↗

Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy at 1.5 tesla.

Myo-inositol (mI) as a precursor in the phosphatidylinositol second messenger system has been reported to be reduced in depression. By means of proton-magnetic resonance spectroscopy (1H-MRS) the mI levels in the frontal brain were investigated in vivo in the present study. Twenty-two patients (mean age: 42.8 +/- 10.7 years) with depressive episodes according to ICD 10 (HAMD score > 17) were compared to 22 healthy subjects (28.0 +/- 5.3 years). Two voxels (30 x 20 x 20 mm3) in the frontal lobes were examined in a Siemens Magnetom SP 4000 at 1.5 T (STEAM sequence: TR = 3500 ms, TE = 55 ms). With the total creatine (Cr) as an internal standard, mI/Cr ratios were calculated to follow the mI levels. In the left frontal lobe, mI/Cr was 0.43 +/- 0.06 in depressive patients and 0.46 +/- 0.07 in healthy subjects; concerning the right frontal lobe, mI/Cr was 0.46 +/- 0.08 and 0.48 +/- 0.06, respectively. There were neither significant differences between the two groups nor between the hemispheres. Since there was a significant positive correlation (R = 0.6) between the age and the mI/Cr in the right frontal lobe of depressed patients, age matched pairs analysis was performed (n = 2 x 10, in each group: nine females, one male, < 40 years). In the right frontal lobe, the patients' mI/Cr of 0.40 +/- 0.05 was now significantly lower than the controls' mI/Cr of 0.45 +/- 0.06. However, most of the patients were on antidepressive medication. Interestingly, it was exactly this group of patients which showed significantly lower mI levels. We regard our investigation as a pilot study which suggests an influence of age and antidepressants on mI levels and should be taken into consideration in further investigations in depressive patients.

Adult↗

Aircraft and road traffic noise and children's cognition and health: a cross-national study.

BACKGROUND: Exposure to environmental stressors can impair children's health and their cognitive development. The effects of air pollution, lead, and chemicals have been studied, but there has been less emphasis on the effects of noise. Our aim, therefore, was to assess the effect of exposure to aircraft and road traffic noise on cognitive performance and health in children. METHODS: We did a cross-national, cross-sectional study in which we assessed 2844 of 3207 children aged 9-10 years who were attending 89 schools of 77 approached in the Netherlands, 27 in Spain, and 30 in the UK located in local authority areas around three major airports. We selected children by extent of exposure to external aircraft and road traffic noise at school as predicted from noise contour maps, modelling, and on-site measurements, and matched schools within countries for socioeconomic status. We measured cognitive and health outcomes with standardised tests and questionnaires administered in the classroom. We also used a questionnaire to obtain information from parents about socioeconomic status, their education, and ethnic origin. FINDINGS: We identified linear exposure-effect associations between exposure to chronic aircraft noise and impairment of reading comprehension (p=0.0097) and recognition memory (p=0.0141), and a non-linear association with annoyance (p<0.0001) maintained after adjustment for mother's education, socioeconomic status, longstanding illness, and extent of classroom insulation against noise. Exposure to road traffic noise was linearly associated with increases in episodic memory (conceptual recall: p=0.0066; information recall: p=0.0489), but also with annoyance (p=0.0047). Neither aircraft noise nor traffic noise affected sustained attention, self-reported health, or overall mental health. INTERPRETATION: Our findings indicate that a chronic environmental stressor-aircraft noise-could impair cognitive development in children, specifically reading comprehension. Schools exposed to high levels of aircraft noise are not healthy educational environments.

Aircraft↗

A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous phenytoin (Dilantin) in hospital emergency departments.

The cost of emergency department services has become a major concern for patients, providers, and payers. Solid economic information is needed to provide a rationale for the selection of therapeutic options and the provision of care that is both clinically and financially prudent. To assess the full cost of care for patients with seizures who are treated in an acute care setting, a modified activity-based cost-accounting model was developed. The model was populated with data from a double-masked, parallel-group, single-dose, multicenter clinical trial designed to investigate the safety and tolerability of phenytoin (Dilantin) and fosphenytoin (Cerebyx) given intravenously in equivalent loading doses according to established recommendations. A total of 52 patients were enrolled in the trial; 13 were given phenytoin and 39 were given fosphenytoin. Salaries and benefits of emergency medical services personnel, drug acquisition costs, and direct and indirect overhead expenditures common to a large hospital emergency department comprised the total costs to treat enrolled patients and manage adverse events. The average cost to treat patients with fosphenytoin was lower than the cost to treat similar patients with phenytoin based on the frequency of adverse events associated with each comparator and the resources (human and material) consumed in the management of those events.

Adult↗

Estimation of long-term average exposure to outdoor air pollution for a cohort study on mortality.

Recent prospective cohort studies have suggested that long-term exposure to low levels of particulate matter (PM) air pollution is associated with increased mortality due to, especially, cardio-pulmonary disease. Exposure to ambient air pollution was estimated mostly as city average concentrations, assuming homogenous exposure within the city. We used an ongoing cohort study - The Netherlands Cohort Study (NLCS) on diet and cancer - to investigate the relationship between traffic-related air pollution and mortality. The baseline data collection took place in 1986. A study was conducted to develop methods for exposure assessment and evaluate the contrast in exposure to air pollution within the cohort. Assessment of long-term exposure to two traffic-related air pollutants, Black Smoke (BS) and Nitrogen Dioxide (NO(2)), consisted of separate estimation of regional background, urban background, and local traffic contributions at the home address. Interpolation of concentration data from a routine monitoring network was used to estimate the regional background concentration. A regression model relating degree of urbanization to air pollution was used to allow for differences between different towns/neighborhoods of cities. Distance to major roads was calculated to characterize local traffic contributions, using a Geographic Information System (GIS). Interpolation resulted in reasonably precise regional background estimation when distant sites were not used and distance squared was used as the weight. Cross-validation showed that prediction errors were about 15% of the range in regional background concentration. Urban and local scales contributed significantly to the contrast within the cohort. Prediction errors for estimating the urban background were about 25% of the range in background concentrations. When the developed model was applied to the study cohort, there was substantial contrast in estimated exposure to BS and NO(2). About 90% of the study population lived 10 years or more at its 1986 home address - supporting the use of the estimated concentration at the 1986 address as a relevant exposure variable.

Aged↗

The effect of salicylate infusion on the alveolar epithelial membrane in the isolated perfused lung.

We observed two patients with aspirin (ASA) ingestion (blood levels of 87 and 56.5 mg/100 ml) who presented with noncardiogenic pulmonary edema (adult respiratory distress syndrome. To determine if ASA had a direct effect on the alveolar epithelial membrane, we established an in vitro isolated lung model and perfused it with platelet free plasma. T1/2 (in minutes), the time for 50% equilibration between the plasma and the saline filled lung, was determined before and after 500 mg salicylate infusion for various molecular weight dextrans. T1/2 decreased significantly (p less than 0.05) as follows: 3000 MW dextran, 2273 +/- 932 to 961 +/- 375; 40,000 MW dextran, 4059 +/- 1550 to 733 +/- 275; 70,000 MW dextran, 11,730 +/- 2750 to 7700 +/- 2230. Histamine levels in plasma and lung liquid did not change significantly with ASA infusion. We conclude that ASA directly increases alveolar epithelial permeability to dextrans less than 70,000 MW.

Aged↗