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Accurate single-pair Förster resonant energy transfer through combination of pulsed interleaved excitation, time correlated single-photon counting, and fluorescence correlation spectroscopy.

Quantitative distance measurements are difficult to obtain in spite of the strong distance dependency of the energy transfer efficiency. One problem for the interpretation of the Forster resonant energy transfer (FRET) efficiency is the so-called zero-efficiency peak caused by FRET pairs with missing or nonfluorescent acceptors. Other problems occurring are direct excitation of the acceptor, spectral crosstalk, and the determination of the quantum efficiency of the dyes as well as the detector sensitivity. Our approach to overcome these limitations is based on the pulsed-interleaved excitation (PIE) of both the acceptor and the donor molecule. PIE is used to excite the acceptor dye independently of the FRET process and to prove its existence via fluorescence. This technique enables us to differentiate a FRET molecule, even with a very low FRET efficiency, from a molecule with an absent or non-fluorescent acceptor. Crosstalk, direct acceptor excitation, and molecular brightness of acceptor and donor molecules are determined by analyzing the data with fluorescence correlation spectroscopy (FCS). FRET efficiencies of the same data set are also determined by analyzing the lifetimes of the donor fluorophores. The advantages of the PIE-FRET approach are demonstrated on a polyproline assay labeled with Alexa-555 and Alexa-647 as donor and acceptor, respectively.

Algorithms↗

Clinical correlates of postmortem brain changes in schizophrenia: decreased brain weight and length correlate with indices of early impairment.

From a postmortem study of the brains of 56 patients with schizophrenia and 56 controls, 38 cases whose clinical state had been objectively documented in life were examined to determine whether relations existed between features of the illness and postmortem findings. Decreased brain weight was significantly related (p < 0.05) to poor premorbid global function and to poor academic record, and decreased brain length was related to poorer premorbid global function (p < 0.05) and more severe negative symptoms. These relations are consistent with the view that morphological changes in the brain occur early in the course of the disease--that is, they are in some sense "developmental." An excess of "focal damage" in the patient group relative to controls was unrelated to the presence of morphological change or to features of illness, but was more common in female schizophrenic patients and was also correlated with evidence of cerebrovascular disease. This may possibly be due to a discrepancy between the groups in mode and cause of death.

Brain↗

Biopsychobehavioral correlates of insomnia, V: Clinical characteristics and behavioral correlates.

The authors compared two large samples of insomniac patients with a group of control subjects. Sleep difficulty usually began before the age of 40 and generally persisted for many years (average duration, 14 years). Several characteristic behaviors were correlated with the symptom of insomnia. During the day and at bedtime, patients reported difficulty relaxing and frequently described themselves as tense, anxious, overly preoccupied, worried, and depressed. Reports of poor mental and physical health were far more prevalent in the insomniac patients than in control subjects. These results indicate that psychiatric factors need to be a primary focus in the multidimensional treatment of chronic insomnia.

Adult↗

Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep.

Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta-sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature.

Adrenocorticotropic Hormone↗

Positive correlation between 'the arterial oxygen extraction tension' and mixed venous pO2 but lack of correlation between 'the oxygen compensation factor' and cardiac output in 38 patients.

pH and blood gases were measured in simultaneous samples of arterial blood from the radial artery and mixed venous blood from the pulmonary artery using an ABL300 and OSM3 (Radiometer A/S, Denmark). Cardiac output was measured by thermodilution. The patients were suffering from chronic obstructive pulmonary disease or adult respiratory distress syndrome. The data indicate that patients respond to a decreased arterial oxygen availability by allowing the mixed venous pO2 to fall rather than by increasing the cardiac output to maintain a normal mixed venous pO2. In other words, the arterial oxygen extraction tension and the oxygen compensation factor were both highly correlated to the mixed venous pO2 but unrelated to the cardiac index. For this reason the arterial oxygen extraction tension appears to be a more relevant parameter of the overall arterial oxygen availability than the oxygen compensation factor. Comparison of the arterial and mixed venous data confirms the accuracy of the Oxygen Status Algorithm for calculating the various oxygen parameters, including the p50, the estimated 2,3-diphosphoglycerate concentration, and the estimated physiological shunt, on the basis of a single arterial blood sample.

2,3-Diphosphoglycerate↗

[Correlation of maternal androgens in early and late pregnancy. A correlation with fetal size and sex].

In the course of prospective investigations blood was withdrawn for steroid analysis in 50 gravidae between 12th and 16th and between 26th and 30th week of gestation. The levels of androstenedione, testosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone and sex hormone binding globuline were determined by radioimmuno-assay evaluating a possible correlation between the androgen values and growth retardation or the sex of the fetus. Neither during the early nor during the late period of pregnancy significant differences concerning the androgen levels could be detected among both sexes. Worth mentioning is the significant decrease of the DHEA-S levels during the late period of gestation, which occurred in both groups, whereas the androstenedione, testosterone and especially the 17-OH-P levels showed a significant increase. The SHBG values almost did not change at all.

17-alpha-Hydroxyprogesterone↗

Accordion BIRD-HMBC experiments: improved one-bond correlation suppression in accordion heteronuclear multiple-bond correlation-type experiments.

Modifications of the BIRD-HMBC experiment, in which the accordion principle and a constant time period have been introduced, are presented. With the simple accordion BIRD-HMBC, the use of a BIRD(r, X) element in the middle of the variable long-range couplings evolution period efficiently eliminates unwanted (1)J(CH) signals and samples a broad range of long-range heteronuclear couplings. While the accordion BIRD-HMBC experiment shows reduced F(1) modulation, superior suppression of unwanted (1)J(CH) signals and sensitivity comparable to the ACCORD-HMBC, the addition of another constant time period suppresses F(1) modulation due to (1)H-(1)H coupling, while preserving the excellent suppression of unwanted (1)J(CH) signals. The constant-time (CT) accordion BIRD-HMBC experiment combines sensitivity similar to the CIGAR-HMBC and superior suppression of unwanted (1)J(CH) signals. Results of identically optimized ACCORD-HMBC, accordion BIRD-HMBC, CT accordion BIRD-HMBC and CIGAR-HMBC experiments performed on a sample of strychnine are compared and discussed.

Journal Article↗

Leisure-time physical exercise: prevalence, attitudinal correlates, and behavioral correlates among young Europeans from 21 countries.

BACKGROUND: Increasing leisure time physical exercise is a major target of public health programs throughout the developed world, but few international comparisons of exercise habits among people from diverse cultures have been published. The objectives of this study were to assess the prevalence of exercise among young adults from 21 European countries, to analyze associations with health beliefs and risk awareness, and to investigate relationships among exercise, other health-related behaviors, and emotional well-being. METHODS: The European Health and Behaviour Survey, a questionnaire survey of 7,302 male and 9,181 female university students ages 18-30 years from 21 countries, was analyzed. RESULTS: Age-adjusted prevalence of physical exercise in the past 2 weeks averaged 73.2% among men and 68.3% among women, but varied markedly from more than 80% to less than 60% across country samples. Beliefs in the health benefits of exercise were consistently associated with physical exercise, as was desire to lose weight. Awareness of the influence of exercise on heart disease averaged 52% among men and 54% among women, but was not strongly associated with engagement in exercise. Associations among exercise, lack of smoking, and sleep time were observed, but results for alcohol consumption were inconsistent. Social support and depression were independently associated with physical exercise. CONCLUSIONS: Physical exercise levels are highly variable across samples of relatively privileged young Europeans from different countries. Associations with other health behaviors and with emotional well-being suggest that regular physical exercise is consistent with a healthy lifestyle. Links with health beliefs are consistent despite sociocultural differences, but deficient knowledge of the health consequences of a sedentary lifestyle remains a cause for concern.

Adolescent↗

Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines: correlation to etoposide and vincristine sensitivity and inverse correlation to carmustine sensitivity.

The aim of our investigations is to evaluate whether the sensitivity patterns of small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new drugs and in selecting drugs for the optimization of combination therapy. In our attempts to obtain a panel of cell lines demonstrating differential patterns in sensitivity, we have developed three SCLC lines exhibiting different types of multidrug resistance (MDR). In the present investigations we compared the sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in response to six different types of drugs: doxorubicin, cytarabine, carmustine, cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the range of variation in sensitivity to all drugs was within a factor of 10. Cell lines showing low sensitivity to doxorubicin also exhibited low sensitivity to etoposide and vincristine, and vice versa. In contrast, the pattern of sensitivity to carmustine was almost the opposite of that to doxorubicin. A tendency to an inverse relationship between doxorubicin and carmustine sensitivity was also observed when doxorubicin sensitivity was reduced in near stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D-glucose. In agreement with the pattern observed for the wild-type lines, all of the MDR sublines demonstrated collateral sensitivity to carmustine. As to cytarabine, the wild-type lines expressed a sensitivity pattern similar to that shown in response to doxorubicin. Interestingly, the opposite pattern was found in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The combination of alkylating agents and "MDR" drugs are of proven clinical benefit in the treatment of solid tumors, as is the combination of anthracycline and cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin, vincristine) thus resemble the clinical experience with these drugs, and we conclude that the use of a clonogenic assay on the described panel of SCLC cell lines can give valuable information for the selection of agents for combination therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Patterns and correlates of psychiatric hospitalization in a nationwide sample. II. Correlates of length of hospitalization and length of stay out of hospital.

A nationwide random sample of psychiatric patients (n = 832) admitted for hospitalization in Israel in 1980 was followed up until the end of 1984. A multivariate analysis was performed, where the dependent variables were: the cumulative length of all hospitalizations, the mean duration of hospitalization and the mean length of stay out of hospital. The independent variables were: age, sex, marital status, ethnic origin, diagnosis, and various indices of previous hospitalizations. For patients whose hospitalization in 1980 (index hospitalization) was the first in their life, older age and male gender predicted a low probability of readmission, and the diagnosis of schizophrenia a long cumulative stay. For patients whose index hospitalization was not the first in their life, the main variables predictive of long cumulative stay were: old age, being single, long duration and high frequency of previous hospitalizations. Patients tended to maintain the same relative length of inpatient stay and the same frequency of readmission from the beginning of their hospitalization history.

Adolescent↗

Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal squamous cell carcinomas.

Using oesophageal squamous cell carcinoma samples of both intramucosal and advanced types, proliferative activity (Ki-67 labelling index), p53 protein accumulation and apoptosis (in situ DNA nick end labelling) were assessed, and the relation of these values to progression or differentiation grade of tumours was analysed. In terms of proliferative activity and the proportion of positive cases with p53 accumulation, a statistically significant difference was demonstrated between intraepithelial carcinomas and intramucosal carcinomas with stromal invasion (17.2% vs 31.7% for the Ki-67 labelling index, and 23.5% vs 67.4% for the proportion of positive cases of p53 accumulation). Values for the latter were almost comparable to those of advanced carcinomas. Immunohistologically, Ki-67 positive, proliferating cells were distributed preferentially in the peripheral fronts of invading nests. Apoptotic cells were observed in the inner areas of the invading nests of the intramucosal carcinomas with stromal invasion and in more advanced lesions, but were rarely observed in the normal epithelium or intraepithelial carcinomas. Apoptotic cells were seen mainly around areas of keratinization, and the apoptotic cell index was higher in well and moderately differentiated types of advanced carcinomas than in the poorly differentiated type (2.59% vs 1.09%). An increase in proliferative activity and an accumulation of p53 protein are associated with the onset of early carcinomatous invasion, while apoptosis is closely linked with the differentiation grade of carcinoma cells.

Antibodies, Monoclonal↗

Speed of color naming and degree of familial sinistrality: correlation in girls, no correlation in boys.

Twenty-nine male and 35 female right-handed children, aged 5 to 7, were assessed for the effect of familial sinistrality on a rapid color-naming task. Controlling for age and family size, a significant effect for degree of familial sinistrality was found in the girls but not in the boys. Among the girls, those with two or more left-handed or ambidextral relatives were the fastest on the color-naming task, those with no such relatives were the slowest, and those with only one left-handed or ambidextral relative scored between the other two groups in color-naming speed. It is suggested that a gene associated with left-handedness, when present in a right-hander, interacts with sex to produce the superior color-naming performance that we observed in girls but not in boys.

Age Factors↗