Induction of in vitro proliferation and maturation of human aneuploid myelogenous leukemic cells.

Human leukemic cells were induced to proliferate and mature to macrophage-like cells in primary cultures supplemented with conditioned medium (CM) from phytohemagglutinin and alloantigen-stimulated normal T lymphocytes. Blast and promyelocyte-enriched preparations, isolated after depletion of adherent phagocytic cells and lymphoid cells from samples of myelogenous leukemia patients, were suspended in liquid cultures with 30% CM. Cell cycle analysis was performed throughout the course of induced cellular maturation. Within 24 h of exposure to CM, cells with macrophage-like morphology were identified among the developing adherent cells. Approximately 15-30% of the cells in culture suspensions also developed macrophage-like morphology and esterase reactivity with alpha-napthyl acetate after incubation for 2 d. The number of these nonproliferating cells increased and became predominant in the later culture period. Flow cytometric measurement of DNA content showed that these mature cells had the same aneuploid stemline as the undifferentiated leukemic cells, indicating that genetically abnormal leukemic cells can be induced to differentiate. Reduction in the total RNA content of the macrophage-like cells was also determined by flow cytometry. Reduction in RNA and development of adherent cells served as early markers of maturation, in addition to the later acquisition of complement receptors and phagocytic capacity. Cell cycle analysis showed that CM stimulated the proliferation of immature cells. This initial proliferation may precede intertwined events of proliferation and concurrent maturation of immature cells. Later in the culture period, cellular proliferation decreased, leading to termination of the cultures.

Investigation of the crystallization process of CSD-ErBCO on IBAD-substrate via DSD approach.

REBa2Cu3O7-δ (REBCO, RE: rare earth, such as Y and Gd) compounds have been extensively studied as a superconducting layer in coated conductors. Although ErBCO potentially has better superconducting properties than YBCO and GdBCO, little research has been made on it, especially in chemical solution deposition (CSD). In this work, ErBCO films were deposited on IBAD (ion-beam-assisted-deposition) substrates by CSD with low-fluorine solutions. The crystallization process was optimized to achieve the highest self-field critical current density (Jc) at 77 K. Commonly, for the investigation of a CSD process involving numerous process factors, one factor is changed keeping the others constant, requiring much time and cost. For more efficient investigation, this study adopted a novel design-of-experiment technique, definitive screening design (DSD), for the first time in CSD process. Two different types of solutions containing Er-propionate or Er-acetate were used to make two types of samples, Er-P and Er-A, respectively. Within the investigated range, we found that crystallization temperature, dew point, and oxygen partial pressure play a key role in Er-P, while the former two factors are significant for Er-A. DSD revealed these significant factors among six process factors with only 14 trials. Moreover, the DSD approach allowed us to create models that predict Jc accurately. These models revealed the optimum conditions giving the highest Jc values of 3.6 MA/cm2 for Er-P and 3.0 MA/cm2 for Er-A. These results indicate that DSD is an attractive approach to optimize CSD process.

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.

Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice.

Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.

Inhibitory effects of interferon-gamma on the T suppressor cell circuit in contact sensitivity.

The effects of a partially purified, splenocyte-derived murine interferon (MuIFN-gamma N) and a recombinant IFN-gamma (MuIFN-gamma R) on the T suppressor pathway and on the T effector cells of delayed type hypersensitivity were investigated in a 2,4-dinitrofluorobenzene contact sensitivity model. Various T cell subpopulations, suppressor T cells of afferent and efferent types, and an auxiliary T suppressor cells as well as a T effector cell of delayed type hypersensitivity were induced and the functions assessed in transfer experiments. Confirming the results of earlier experiments obtained with IFN-alpha, beta, the MuIFN-gamma N preparation and the rec. MuIFN-gamma R: enhanced the decreased response in animals sensitized with an antigen overload to an optimal response; inhibited the afferent-acting T suppressor cell in vivo and in vitro; inhibited the Ts-eff response; blocked the auxiliary T suppressor cell response after intravenous injection to recipients of Ts-eff cells on day 0 and 1; and did not suppress the activity of the T effector cell of delayed type hypersensitivity in vivo and in vitro (the MuIFN-gamma R was not tested). We conclude that IFN-gamma preferentially inhibited the T suppressor cell circuit of contact allergy. These results are similar to our observations on the inhibitory effects of a pure interferon-alpha, beta on the regulatory T suppressor cell circuit in contact allergy. Selective suppression of different T subpopulations by IFN-gamma may be an important regulatory mechanism in delayed type hypersensitivity.

Mood effects of alcohol and expectancies across the menstrual cycle.

To examine menstrual cycle phase variations in alcohol absorption and mood before and after drinking alcohol, 96 volunteers female heavy drinkers, unaware they were in a menstrual cycle study, were randomly assigned to 12 equal-sized groups with controls for the effects of alcohol, expectancy, and menstrual cycle phase. Alcohol subjects received sufficient alcohol to raise their blood alcohol level to .07 mg %. Mood, assessed with the Profile of Mood States, did not differ across menstrual cycle phases at baseline, failing to support the notion of menstrual phase-related moods. The only mood changes were a Beverage by Trials interaction on the Vigor and Confusion scales and a main effect for trials on the Tension-Anxiety and Vigor scales. Peak intoxication level did not differ across phases. The present findings of an absence of menstrual cycle phase-related differences in mood or alcohol absorption support social learning theory and suggest that phasic variations in mood are socially learned. They also suggest the need for systematic study of methodologic factors in this research area.

Evaluation of dietary and environmental risk factors for hyperthyroidism in cats.

OBJECTIVE: To identify dietary and environmental risk factors for hyperthyroidism in cats. DESIGN: Case-control study. ANIMALS: 100 cats with hyperthyroidism and 163 control cats. PROCEDURE: Medical records were examined, and owners completed a mailed questionnaire. Data collected included information regarding demographic variables, environmental exposures, and diet, including preferred flavors of canned cat food. RESULTS: Case cats were significantly less likely to have been born recently than control cats. Housing; exposure to fertilizers, herbicides, or plant pesticides; regular use of flea products; and presence of a smoker in the home were not significantly associated with an increased risk of disease, but cats that preferred fish or liver and giblets flavors of canned cat food had an increased risk. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that prefer to eat certain flavors of canned cat food may have a significantly increased risk of hyperthyroidism.

Inhibition of the anti-receptor antibody response of contact sensitivity by interferon.

Mice sensitized with optimal doses of 2,4-dinitrofluorobenzene (DNFB) develop maximum delayed hypersensitivity in 4-5 days; the intensity of this reaction declines rapidly 14 days after sensitization. In the serum of mice 14 days after sensitization, an anti-receptor antibody has been described. It has been suggested that this antibody might be responsible for this rapid decline of contact sensitivity. We studied the effect of interferon alpha, beta (IFN alpha, beta) and cyclophosphamide (Cy) in this model. IFN alpha, beta (2 X 10(4) units/ mouse) or Cy (200 mg/kg) injected at Days 0 and 1 during sensitization, or at Day -2 before sensitization, respectively, partially prevented the decline of contact sensitivity as compared to the controls. In the serum of mice treated with IFN or Cy, no anti-receptor antibody could be detected 14 days after sensitization. These results suggest that anti-receptor antibody may be partially responsible for the waning of contact sensitivity. It is further suggested that IFN inhibited the anti-receptor antibody response by preventing the generation of the anti-receptor-antibody-inducing auxiliar T-suppressor cell. It is concluded that IFN alpha, beta enhances the delayed hypersensitivity response in contact allergy by inhibition of the T-suppressor circuit, as previously reported, and by suppression of the anti-receptor antibody response.

The changing role of the hospital chief financial officer.

Things are changing. That statement is obviously true of things political, economic and scientific. Not surprisingly, therefore, the statement applies to the activities, responsibilities, qualifications and, ultimately, status of the hospital chief financial officer (CFO).

Aberration analysis in aerial images formed by lithographic lenses.

A test procedure for the final assembly of lenses that does not need exposed photographic plates is introduced. It is based on the metrological simulation of optical ray tracing. A measuring example illustrates its suitability for ultraviolet optical systems in particular. The measuring apparatus displays the distortion vectors directly in the aerial image, gives a wave-front analysis, and performs an analogous distortion analysis.

[Swimming performance in the aged]. / Schwimmleistungen im Alter.

The deterioration of performance caused by aging was examined in 3,469 swimmers divided into 9 age groups and 4 styles of swimming. Comparisons using cross and longitudinal sections show that older swimmers become progressively slower, and the reduction of speed in all styles of swimming follows a quadratic trend. The losses of efficiency increase with age group, being by far the most in back-stroke and the least in crawl swimming. The combined longitudinal and cross sectional comparisons confirm this result, but not without any exception, for very often no statistically significant differences could be recognized between adjacent age groups. The interindividual comparison shows that it is also possible to maintain or even improve the efficiency over 10 to 12 years, even in the fifth or sixth decade of age, if the intensity and volume of training can be increased. The curve comprising reductions in the later stages of life may additionally be caused by the smaller number of persons per group and the deficient homogeneity within these groups. In addition to this, the tendency towards higher losses in older age groups is not significant, if only the best competitors of each age group are compared.

Inhibition of the T suppressor circuit of delayed-type hypersensitivity by interferon.

The effects of electrophoretically pure murine interferon (Mu-IFN-alpha beta) on the T suppressor pathway and on the T effector cell of delayed hypersensitivity (TDH) were investigated in BALB/c mice, in a 2,4-dinitrofluorobenzene (DNFB) contact-sensitivity model. Various T cell subpopulations, suppressor T cells of the afferent (Ts-aff) and efferent (Ts-eff) types, an auxiliary Ts (Ts-aux), as well as TDH were induced, and their function was assessed in transfer experiments. The results were as follows. At a dose of 5 X 10(3) U, IFN was shown to inhibit the Ts-aff response, when given to the donor animal shortly after induction of the Ts-aff subpopulation or when injected into the recipient 2 hr after spleen cell transfer. Pretreatment in vitro with IFN of the splenic cells to be transferred also abolished the Ts-aff response. Similar amounts of IFN were able to inhibit the generation of Ts-eff in the donor animals, whereas 10-fold-higher amounts were needed in vivo or in vitro to block the functional expression of Ts-eff in the recipient animal. Intravenous injection of IFN into recipients of Ts-eff on day 0 and 1 after sensitization inhibited the expression of the Ts-eff transferred 1 day before ear challenge. This suggests that the Ts-aux response required for the TDH suppression by Ts-eff is blocked by IFN. Secretion of a suppressor factor by Ts in vitro was not blocked by IFN. Treatment of the donor of suppressor factor-secreting Ts with IFN, however, blocked the induction of this Ts. The TDH were not sensitive to IFN even at amounts approximately 100 times higher than those used for the Ts inhibition in vivo as well as in vitro. These results demonstrate that low amounts of IFN may selectively block the suppressor pathway, because induction of these regulatory T cell subsets appears to be particularly sensitive to IFN. The exact mechanism of the IFN-mediated inhibition of Ts is not yet clear. The data suggest an important regulatory function of IFN in delayed-type hypersensitivity (DTH) reactions.