T cells discriminate between differentially phosphorylated forms of alphaB-crystallin, a major central nervous system myelin antigen

Factors such as developmental stage or physiological and infectious stress may change patterns of post-translational protein modification. In order to determine whether such regulated types of modification may influence T cell responsiveness to self proteins we examined the T cell response of SJL (H-2s) mice to alphaB-crystallin, a small heat shock protein that can exist in differentially phosphorylated forms. Epitope mapping revealed the presence of two T cell epitopes that are presented by I-As. One major epitope including residues 41-56 contains an amino acid residue (Ser45) that can be phosphorylated as the result of aging or stress. Accordingly, T cells from SJL mice discriminate between preparations of alphaB-crystallin that differ in their extent of phosphorylation at the level of whole protein as well as at the level of determinant-specific responses. Phosphorylation at Ser45 does not prevent binding of the peptide 41-56 to I-As and computer-assisted modelling of the peptide-MHC complex suggests that the phosphate group of the bound peptide extends outwards from the peptide-binding cleft and may thus be available for direct contact with TCR. Together, our data provide evidence that stress-inducible phosphorylation of alphaB- crystallin creates neo-determinants for T cells and, therefore, may contribute to the breakdown of peripheral tolerance to this self protein.      

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.     

Imaging Human Cerebral Pain Modulation by Dose-dependent Opioid Analgesia: A Positron Emission Tomography Activation Study Using Remifentanil

Background: Previous imaging studies have demonstrated a number of cortical and subcortical brain structures to be activated during noxious stimulation and infusion of narcotic analgesics. This study used 15O-water and positron emission tomography to investigate dose-dependent effects of the short-acting [mu]-selective opioid agonist remifentanil on regional cerebral blood flow during experimentally induced painful heat stimulation in healthy male volunteers.

Methods: Positron emission tomography measurements were performed with injection of 7 mCi 15O-water during nonpainful heat and painful heat stimulation of the volar forearm. Three experimental conditions were used during both sensory stimuli: saline, 0.05 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil, and 0.15 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil. Cardiovascular and respiratory parameters were monitored noninvasively. Across the three conditions, dose-dependent effects of remifentanil on regional cerebral blood flow were analyzed on a pixel-wise basis using a statistical parametric mapping approach.

Results: During saline infusion, regional cerebral blood flow increased in response to noxious thermal stimulation in a number of brain regions as previously reported. There was a reduction in pain-related activations with increasing doses of remifentanil in the thalamus, insula, and anterior and posterior cingulate cortex. Increasing activation occurred in the cingulofrontal cortex (including the perigenual anterior cingulate cortex) and the periaqueductal gray.     

Tissue segmentation-assisted analysis of fMRI for human motor response: an approach combining artificial neural network and fuzzy C means

The authors have developed an automated algorithm for segmentation of magnetic resonance images (MRI) of the human brain. They investigated the quantitative analysis of tissue-specific human motor response through an approach combining gradient echo functional MRI and automated segmentation analysis. Fifteen healthy volunteers, placed in a 1.5 T clinical MR imager, performed a self-paced finger opposition throughout the activation periods. T1-weighted images (WI), T2WI, and proton density WI were acquired for segmentation analysis. Single-slice axial T2* fast low-angle shot (FLASH) images were obtained during the functional study. Pixelwise cross-correlation analysis was performed to obtain an activation map. A cascaded algorithm, combining Kohonen feature maps and fuzzy C means, was applied for segmentation. After processing, masks for gray matter, white matter, small vessels, and large vessels were generated. Tissue-specific analysis showed a signal change rate of 4.53% in gray matter, 2.98% in white matter, 5.79% in small vessels, and 7.24% in large vessels. Different temporal patterns as well as different levels of activation were identified in the functional response from various types of tissue. High correlation exists between cortical gray matter and subcortical white matter (r = 0.957), while the vessel behaves somewhat different temporally. The cortical gray matter fits best to the assumed input function (r = 0.957) followed by subcortical white matter (r = 0.829) and vessels (r = 0.726). The automated algorithm of tissue-specific analysis thus can assist functional MRI studies with different modalities of response in different brain regions.     

Use of povidone–iodine during the first trimester of pregnancy: a correct practice?

Povidone–iodine (PVP-I) has been widely used as an antiseptic agent during invasive procedures for prenatal diagnosis. Women have been reported of thyroid dysfunction after simple exposure to PVP-I. We studied the effect on thyroid function and urinary iodine excretion after a single topical application of PVP-I in 31 women who had a miscarriage during the first trimester of pregnancy. PVP-I is absorbed through the skin and the vaginal mucosa, resulting in a sudden increase in the urinary excretion of iodine and a short-term variation in concentrations of thyroid hormones in maternal serum. This metabolic effect could have consequences for the embryo and the fetus during crucial stages of development.     

Evidence for non-selective colour channel involvement in diabetic eyes especially after laser treatment

Purpose : We consider the hypothesis that proliferative diabetes produces selective loss of colour channels. We also consider the possibility that laser treatment for this condition does not affect macula function. Methods : We tested for the possibility of a selective colour channel involvement in 35 eyes of 33 cases of proliferative diabetes by considering the outcomes of saturation and hue testing before and after pan-retinal photocoagulation (PRP). Saturation testing was achieved with the Sahlgren Saturation Test (SST) and hue testing was via the Farnsworth-Munsell 100 (FM100) hue test. Our results were compared to a recent model¹ that was developed to predict the saturation processing of diseased eyes. Results : All diabetic eyes with normal hue (FM100) scores passed the saturation test (SST). Most pre-treatment eyes (29 of 35 or 83 per cent) failed the FM100 hue test but only 16 of 35 (46 per cent) failed the saturation test. Following laser treatment, 97 per cent of eyes were abnormal on the FM100 hue test but only seven per cent failed the saturation test.