The effect of x-irradiation on the functioning of adrenal auto-transplants, as measured by the response to stress

Thesis (Ph.D.)--Boston UniversityMany studies have been made on the response of tissues to radiation. However, in the majority of them, only morphological alterations were investigated. The few which attempted a determination of possible physiological alterations were restricted to the irradiation of a specific area of the body and were complicated by systemic reactions resulting from the inability to confine the radiation to a specific tissue. It has been proposed that following irradiation, the adrenal gland may present alterations of a physiological nature even in the absence of any apparent morphological change. The adrenal gland of the rat, can be completely removed from the body, irradiated in vitro, and implanted into the dorsal musculature, where it will regenerate and regain some degree of functional efficiency. Moreover, the rat can be used conveniently for various tests of adrenocortical function, some of which are quantitative as well as qualitative. A review of the literature of adrenal physiology, adrenal transplantation, stress, and the biological effects of radiation is presented, with particular attention to those factors which might enter into the evaluation of the results of this study. An intensive study of the morphology of transplants, identical to those tested in the present study, was performed simultaneously in this laboratory and the histological and histochemical findings are discussed. Male Wistar rats, weighing about one hundred and twenty grams, were structured in six groups: intact normal, sham operated, immediate transplants (glands removed and implanted without delay), one hour delay transplants (stored in saline solution in vitro before implantation), irradiated transplants (2000 r. in vitro), and adrenalectomized. The animals with one hour delay transplants were the controls for those with irradiated transplants, since the combination of operative and irradiation procedures delayed implantation for one hour. The other groups were studied to establish standards for measuring relative cortical function. Fourteen days following operation all rats, except the adrenalectomized, were stressed by either histamine acid phosphate, histamine c.p., or water intoxication. Adrenalectomized rats were stressed on the tenth day after operation, since few could survive the fourteen day period. The percentage of each group surviving from the second to the fourteenth day of the postoperative period, and the weight gained during this period, was determined for each operative group. The data from the study of postoperative survival were analyzed by establishing the mean of each operative group and testing these for significant difference by means of the Student Fisher t test. The results of the weight gain study were treated similarly. The doses per hundred grams of body weight of histamine c.p. and equivalent histamine as the acid phosphate which were lethal to fifty percent of the animals of each operative type were determined by the method of Litchfield and Wilcoxon. Differences in the LD50 values were tested for statistical significance by their method. Six c.c. of water per hundred grams of body weight were administered by gavage at hourly intervals for four hours and the amount of urine excreted in an eleven hour collection period was expressed as a percentage of the total volume administered. Mean percent excretion was determined for each operative group and the differences were tested statistically by the t test. A ninety-five percent probability level was used throughout. The results of the histamine intoxication stress and the percent survival study showed thnt irradiated transplants are as efficient as their controls. However, the results of the water intoxication stress and the weight gain study reveal that the response of animals with irradiated transplants under these measures is much worse than that of their controls and, in fact, no better than that of adrenalectomized rats. A review of the factors affecting each of these measures is presented in detail, and the apparent dichotomy is explained as follows. Irradiation does not reduce the amount of protection afforded by a transplant against histamine intoxication. In fact all types of transplants provide the same amount of protection, less than that afforded by an intact gland, but of considerable value when the mortality of the adrenalectomized group is considered. This was determined using both histamine c.p. and histamine acid phosphate as stressing agents. The discussion presented leads to the conclusion that while slight differences in functional ability in meeting such an acute stress probably exist between different types of transplants, these differences are merely reflections of the variation in cell depths, and are not detectable in histamine intoxication, or any other stress which necessitates production of additional amounts of hormone for only a relatively short time. A comparison is made between histamine c.p. and histamine acid phosphate. While use of the histamine c.p. is more economical, the greater variability in response obtained with it and it s more lethal nature may render it unsatisfactory for many studies. From the discussion of survival of unstressed animals during the post operative period it may be concluded that only very small amounts of hormone are required for life maintenance. Moreover, it is concluded that irradiation does not alter the nature of the adrenal secretion, since there is no statistical difference between the survival of animals with irradiated transplants and their controls. Evidence is presented that weight gain requires a continuous supply of adequate amounts of cortical hormone. Irradiation of the gland before implantation results in a long lasting depression of mitotic activity, and reduction in the rate of maturation of cells. Fourteen days after operation, the secretory capacity of an irradiated transplant is still less than that of the controls as shown by the smaller cell depth and lower concentrations of ascorbic acid and sudanophilic lipids. The failure of the animals with irradiated transplants to gain as much weight as their controls in the fourteen day postoperative period is believed to result from a delay in reaching levels of secretion commen sura te wi th t ~e demands of the growing organism. This conclusion is supported by the observation that during a thirty day postoperative period, the animals with irradiated transplants begin to approximate the weight gain seen in the control group during a similar period. Water intoxication is shown to be a stress which requires large amounts of cortical hormone for a considerable time. It is therefore not surprising that animals with irradiated transplants, which at fourteen days contain relatively few cells and are just beginning to store reserves of hormone precursors, are apparently little better than adrenale ctomized animals in meeting the severe demands of this stress. The conclusion reached in this study is that the alterations in the function of adrenal transplants which are detectable after x-irradiation with two thousand roentgens are attributable to the reduced rate of regeneration and maturation, and not to any alteration of the nature of the secretion

Any-order propagation of the nonlinear Schroedinger equation

We derive an exact propagation scheme for nonlinear Schroedinger equations. This scheme is entirely analogous to the propagation of linear Schroedinger equations. We accomplish this by defining a special operator whose algebraic properties ensure the correct propagation. As applications, we provide a simple proof of a recent conjecture regarding higher-order integrators for the Gross-Pitaevskii equation, extend it to multi-component equations, and to a new class of integrators.Comment: 10 pages, no figures, submitted to Phys. Rev.

Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model

Staphylococcus aureus is an important human pathogen that is also able to kill the model nematode Caenorhabditis elegans. We constructed a 2,950-member Tn917 transposon insertion library in S. aureus strain NCTC 8325. Twenty-one of these insertions exhibited attenuated C. elegans killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different S. aureus strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in nagD exhibited attenuated virulence. Interestingly, Tn917 was shown to have a very strong bias for insertions near the terminus of DNA replication

Management of a capital stock by Strotz's naive planner

http://dx.doi.org/10.1016/j.jedc.2007.09.01

A Randomized Controlled Trial of a Mindfulness-Based Weight Loss Intervention on Cardiovascular Reactivity to Social-Evaluative Threat Among Adults with Obesity.

Objective:Mindfulness-based interventions have been found to reduce psychological and physiological stress reactivity. In obesity, however, stress reactivity is complex, with studies showing both exaggerated and blunted physiological responses to stressors. A nuanced view of stress reactivity is the "challenge and threat" framework, which defines adaptive and maladaptive patterns of psychophysiological stress reactivity. We hypothesized that mindfulness training would facilitate increased challenge-related appraisals, emotions, and cardiovascular reactivity, including sympathetic nervous system activation paired with increased cardiac output (CO) and reduced total peripheral resistance (TPR) compared to a control group, which would exhibit an increased threat pattern of psychophysiological reactivity to repeated stressors.Methods:Adults (N=194) with obesity were randomized to a 5.5-month mindfulness-based weight loss intervention or an active control condition with identical diet-exercise guidelines. Participants were assessed at baseline and 4.5 months later using the Trier Social Stress Task. Electrocardiogram, impedance cardiography, and blood pressure were acquired at rest and during the speech and verbal arithmetic tasks to assess pre-ejection period (PEP), CO, and TPR reactivity.Results:Mindfulness participants showed significantly greater maintenance of challenge-related emotions and cardiovascular reactivity patterns (higher CO and lower TPR) from pre to post-intervention compared to control participants, but groups did not differ in PEP. Findings were independent of changes in body mass index.Conclusions:Mindfulness training may increase the ability to maintain a positive outlook and mount adaptive cardiovascular responses to repeated stressors among persons with obesity though findings need to be replicated in other populations and using other forms of mindfulness interventions

long term treatment outcome in ipex syndrome patients an international multicenter retrospective study

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The Brown Dwarf Kinematics Project (BDKP) I. Proper Motions and Tangential Velocities for a Large Sample of Late-type M, L and T Dwarfs

We report proper motion measurements for 427 late-type M, L and T dwarfs, 332 of which have been measured for the first time. Combining these new proper motions with previously published measurements yields a sample of 841 M7-T8 dwarfs. We combined parallax measurements or calculated spectrophotometric distances and computed tangential velocities for the entire sample. We find that kinematics for the full and volume-limited 20 pc samples are consistent with those expected for the Galactic thin disk, with no significant differences between late-type M, L, and T dwarfs. Applying an age-velocity relation we conclude that the average kinematic age of the 20 pc sample of ultracool dwarfs is older than recent kinematic estimates and more consistent with age results calculated with population synthesis models. There is a statistically distinct population of high tangential velocity sources whose kinematics suggest an even older population of ultracool dwarfs belonging to either the Galactic thick disk or halo. We isolate subsets of the entire sample, including low surface-gravity dwarfs, unusually blue L dwarfs, and photometric outliers in J-Ks color and investigate their kinematics. We find that the spectroscopically distinct class of unusually blue L dwarfs has kinematics clearly consistent with old age, implying that high surface-gravity and/or low metallicity may be relevant to their spectral properties. The low surface-gravity dwarfs are kinematically younger than the overall population, and the kinematics of the red and blue ultracool dwarfs suggest ages that are younger and older than the full sample, respectively. We also present a reduced proper motion diagram at 2MASS Ks for the entire population and find that a limit of H_Ks > 18 excludes M dwarfs from the L and T dwarf population regardless of near-infrared color.Comment: Accepted for publication in the Astronomical Journal, 21 pages text, 12 tables, 12 figure

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management