Bullous pemphigoid in association with cutaneous lesions specific to a myelodysplastic syndrome

Specific cutaneous lesions are a rare occurrence in myelodysplastic syndromes (MDS). The concurrent association of blistering skin lesions similar to those in bullous pemphigoid (BP), even though a rare event, suggests that BP may be a paraneoplastic syndrome. We report an 86-year-old man who had a refractory anaemia with excess bone marrow blasts in transformation, who developed a generalized pruritic blistering eruption. Immunohistopathological tests showed subepidermal blisters with linear deposits of IgG and C3 along the basement membrane zone of the epidermis surrounding a tumoral dermal infiltrate of CD13+ and CD15+ cells. Immunoblotting studies using epidermal extracts revealed circulating IgG antibodies against three protein bands: a 210–215 kDa band. a 180kDa band which co-migrated with the BP 180 antigen, and a 190kDa band. The tumour infiltrate may have revealed antigenic determinants which led to the onset of BP. The concept of paraneoplastic pemphigoid remains to be either confirmed or invalidated by further epidemiological studies.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.     

Detection of neutral protease (Periocheck) and BANA hydrolase (Perioscan) compared with traditional clinical methods of diagnosis and monitoring of chronic inflammatory periodontal disease

Abstract Perioscan requires a plaque sample to detect the presence of enzymes capable of degrading N-benzoyl-DL-arginine-2-naphthylamide (BANA) from relatively few anaerobic periodontal pathogens. Periocheck assays the presence of neutral proteases in crevicular fluid. The aim of this study was to compare these test kits with traditional clinical methods of detecting periodontal disease and to monitor the ability of the kits to reflect the response to initial therapy. 19 patients with moderately severe chronic periodontitis were seen before and after a course of oral hygiene and root instrumentation consisting of 4 appointments. Clinical measurements and test assays were collected at 5 diseased sites and 2 healthy sites in each subject. Complete data from 125 sites were available for statistical analysis. At baseline Periocheck had a sensitivity of 88% and a specificity of 61% whereas Perioscan had a sensitivity of 99% and a specificity of 55%, when related to the clinical diagnosis. A composite clinical assessment, based on improvement or deterioration of one whole unit change of the subjective clinical indices and 2mm changes or greater in probing depth or probing attachment level, revealed 75 sites which improved following treatment, whereas 45 sites did not change and 5 sites deteriorated. The probability that the tests agreed with the clinical outcome after treatment, was calculated as 50.4% for Periocheck and 52% for Perioscan. The diagnostic kits did not reliably reflect the clinical assessment of periodontal disease in the cross sectional study, or the outcome following treatment.     

Figure-Ground Segregation at Contours: a Neural Mechanism in the Visual Cortex of the Alert Monkey

An important task of vision is the segregation of figure and ground in situations of spatial occlusion. Psychophysical evidence suggests that the depth order at contours is defined early in visual processing. We have analysed this process in the visual cortex of the alert monkey. The animals were trained on a visual fixation task which reinforced foveal viewing. During periods of active visual fixation, we recorded the responses of single neurons in striate and prestriate cortex (areas V1, V2, and V3/V3A). The stimuli mimicked situations of spatial occlusion, usually a uniform light (or dark) rectangle overlaying a grating texture of opposite contrast. The direction of figure and ground at the borders of these rectangles was defined by the direction of the terminating grating lines (occlusion cues). Neuronal responses were analysed with respect to figure-ground direction and contrast polarity at such contours. Striate neurons often failed to respond to such stimuli, or were selective for contrast polarity; others were non-selective. Some neurons preferred a certain combination of figure-ground direction and contrast polarity. These neurons were rare both in striate and prestriate cortex. The majority of neurons signalled figure-ground direction independent of contrast polarity. These neurons were only found in prestriate cortex. We explain these responses in terms of a model which also explains neuronal signals of illusory contours. These results suggest that occlusion cues are used at an early level of processing to segregate figure and ground at contours.     

Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.     

Technetium-99m labelled liposomes to image experimental arthritis

OBJECTIVES—Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with ^99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > ^99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>^99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that ^99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.

     

The human major histocompatibility complex class Ib molecule HLA-E binds signal sequence-derived peptides with primary anchor residues at positions 2 and 9

Human histocompatibility leukocyte antigen E (HLA-E) and mouse major histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same substitutions at two normally conserved positions 143 and 147, which are likely to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide derived from the leader sequence of H-2 D and H-2 L molecules. We developed a peptide binding assay in vitro to compare the binding specificity of HLA-E with the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal sequence-derived peptides from human MHC class I molecules. Using alanine and glycine substitutions, we could define primary anchor residues at positions 2 and 9 and secondary anchor residues at position 7 and possibly 3.     

MRI in hemiballismus due to subthalamic nucleus hemorrhage: An unusual complication of liver transplantation

A 60-year-old man developed hemiballismus due to an intracranial hemorrhage involving the subthalamic nucleus 8 weeks after orthotopic liver transplantation. The hemorrhage was thought to be due to alterations in cerebral blood flow following a period of hypotensive shock due to sepsis, in the presence of anticoagulant therapy and thrombocytopenia. This represents a rare neurologic complication of liver transplantation.