Immunotolerant indoleamine-2,3-dioxygenase is increased in condyloma acuminata.

BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored. RESULTS: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV- site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation. CONCLUSIONS: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.

RU486 (mifepristone) ameliorates cognitive dysfunction and reverses the down-regulation of astrocytic N-myc downstream-regulated gene 2 in streptozotocin-induced type-1 diabetic rats.

Diabetic cognitive dysfunction (DCD), usually accompanied with chronically elevated glucocorticoids and hippocampal astrocytic alterations, is one of the most serious complications in patients with type-1 diabetes. However, the role for chronically elevated glucocorticoids and hippocampal astrocytic activations in DCD remains to be elucidated, and it is not clear whether astrocytic N-myc downstream-regulated gene 2 (NDRG2, involved in cell differentiation and development) participated in DCD. In the present study, three months after streptozotocin (STZ)-induced type-1 diabetes onset, rats showed cognitive impairments in Morris water maze test as well as elevated corticosterone level. Diabetic rats also presented down-regulation of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and NDRG2 in hippocampus revealed by immunohistochemistry staining, real-time PCR and Western blot. Moreover, the diabetic cognitive impairments were ameliorated by 9-day glucocorticoids receptor (GR) blockade with RU486, and the down-regulation of hippocampal NDRG2 and GFAP in diabetic animals was also attenuated by 9-day GR blockade. These results suggest that glucocorticoids-GR system is crucial for DCD, and that astrocytic reactivity and NDRG2 are involved in these processes. Thus, inhibiting GR activation in the hippocampus may be a novel therapeutic strategy for treating DCD.

Estimation of attenuation maps from scatter and photopeak window single photon-emission computed tomographic images of technetium 99m-labeled sestamibi.

BACKGROUND: In single photon-emission computed tomographic imaging of the chest, nonuniform attenuation correction requires use of a patient-specific attenuation map. The aim of this study was to determine whether an estimate of the regions of the lungs and nonpulmonary tissues of the chest could be obtained by segmenting the photopeak and Compton scatter window images in a phantom and in patients to estimate patient-specific attenuation maps. METHODS AND RESULTS: The photopeak and scatter window slices from 16 consecutive 99mTc-labeled sestamibi perfusion studies were segmented interactively. In these studies, visually reasonable regions could be obtained by estimating a "cold" lung region from scatter window data with additional anatomic information of the myocardium region, the backbone and sternum locations, the liver, and the rib cage from the photopeak window data. In an anthropomorphic torso phantom study and a patient study, comparison was made between the attenuation maps based on segmentation of the emission images and transmission imaging with a slant-hole collimator. It was determined that good agreement in the estimation of the body regions can be achieved with segmentation of the emission images in both the phantom and patient data. Attenuation correction using the maximum-likelihood expectation maximization method was performed on the phantom and the patient data. In both studies, attenuation correction with the segmented attenuation map improved uniformity of the inferior wall region in comparison with the other walls. CONCLUSIONS: The estimation of patient-specific attenuation maps by segmenting the scatter and photopeak window slices of 99mTc-labeled sestamibi studies may be a way of reducing the loss of specificity due to attenuation artifacts. The potential limitations on the accuracy of correction inherent in the method due to the estimation of the regions and assignment of the attenuation coefficients need to be determined further, and the method needs to be further automated before it can be considered for routine clinical use.

Influence of OSEM, elliptical orbits and background activity on SPECT 3D resolution recovery.

In maximum-likelihood expectation-maximization (MLEM) reconstruction of SPECT images, if both attenuation correction (AC) and detector response correction (DRC) are included, the reconstruction can be too time consuming to be clinically useful. With use of the ordered-subset expectation-maximization (OSEM) reconstruction, it has been reported that the reconstruction time can be substantially reduced. We investigated the reconstruction of point sources in a non-uniform attenuation medium in terms of the normalized FWHM of these sources. We compared MLEM versus OSEM reconstructions; circular versus elliptical orbits; and the presence versus the absence of background activity in the object. We found: (i) that OSEM does speed up the reconstruction by a factor of 10 over MLEM; (ii) that the resolution recovery does not depend on the type of orbit if both AC and DRC are included in the reconstruction; however, when there is background activity, a significant number of iterations are required to alleviate the effect of orbit; (iii) that background activity significantly slows down the resolution recovery of the point sources; and (iv) that if reconstruction only includes AC, and not DRC, changing orbit can change isotropy of recovered resolution, whereas introducing background activity may degrade the recovered resolution and also changes the isotropy.

A Kalman filtering approach to stochastic global and region-of-interest tomography.

We define two forms of stochastic tomography. In global tomography, the goal is to reconstruct an object from noisy observations of all of its projections. In region-of-interest (ROI) tomography, the goal is to reconstruct a small portion of an object (an ROI) from noisy observations of its projections densely sampled in and near the ROI and sparsely sampled away from the ROI. We solve both problems by expanding the object and its projections in a circular harmonic (Fourier) series in the angular variable so that the Radon transform becomes Abel transforms of integer orders applied to the harmonics. The algorithm has three major components. First, we fit state-space models to each order of Abel transform and thus represent the Radon transform operation as a parallel bank of systems, each of which computes the appropriate Abel transform of a circular harmonic. A variable transformation here allows either the global or ROI problem to be solved. Second, the object harmonics are modeled as a Brownian branch. This is a two-point boundary value system, which is Markovianized into a form suitable for the Kalman filter. Finally, a parallel bank of Kalman smoothing filters independently estimates each circular harmonic from the noisy projection data. Numerical examples illustrate the proposed procedure.

In vitro responses of rainbow trout (Oncorhynchus mykiss) somatotrophs to carp growth hormone-releasing factor (GRF) and somatostatin.

To study the hypothalamic control of growth hormone (GH) release in lower vertebrates, we employed an in vitro technique using a monolayer cell culture system of rainbow trout pituitary glands. Two newly purified carp brain growth hormone-releasing factors, carp GRF(1-45) and carp GRF(1-29), and synthetic somatostatin-14 (SST-14) were applied to the cultured pituitary cells. The results indicate that: (1) The carp GRFs had a dose-related potency in stimulating growth hormone release. The dose of half maximum effect (ED50) for carp GRF(1-45) was 0.107 nM, and an equal potency for carp GRF(1-29) was 0.388 nM. (2) SST-14 inhibited GH release having a dose-dependent potency with an ED50 of 0.186 nM. (3) Osmotic pressure did not influence SST-14 inhibited GH secretion but did affect spontaneous GH release. (4) The response of cultured cells was not affected by length of incubation period with SST-14 or carp GRF but was affected by cell density.