A buried lysine that titrates with a normal pKa: role of conformational flexibility at the protein-water interface as a determinant of pKa values.

Previously we reported that Lys, Asp, and Glu residues at positions 66 and 92 in staphylococcal nuclease (SNase) titrate with pK(a) values shifted by up to 5 pK(a) units in the direction that promotes the neutral state. In contrast, the internal Lys-38 in SNase titrates with a normal pK(a). The crystal structure of the L38K variant shows that the side chain of Lys-38 is buried.

Adalimumab for the treatment of severe psoriasis and psoriatic arthritis.

Background: Psoriasis is a chronic, genetically determined, immunomediated, inflammatory skin disease affecting approximately 2 - 3% of the Caucasian population. Systemic treatment is required in moderate to severe plaque-type psoriasis forms or psoriatic arthritis. However, cumulative organ toxicity, lack of efficacy over time and other underlying diseases may limit long-term use of conventional treatments.

Two HLA-B27 alleles differently associated with spondylarthritis, B*2709 and B*2705, display similar intracellular trafficking and oligomer formation.

Objective: To examine whether and to what extent the intracellular trafficking features of HLA-B*2705, which is associated with the development of spondylarthritis (SpA), differ from those of HLA-B*2709 and HLA-B*0702, which are not associated with SpA.

Methods: HeLa cells were transfected with complementary DNA encoding for HLA-B proteins fused to Renilla luciferase or yellow fluorescent protein. The subcellular distribution of properly folded and unfolded/misfolded HLA-B proteins was examined by flow cytometry and confocal microscopy of cells labeled with ME1 and HC-10 antibodies, respectively.

Adalimumab for severe psoriasis and psoriatic arthritis: an open-label study in 30 patients previously treated with other biologics.

Background: Psoriasis is a chronic, genetically determined, immune-mediated, inflammatory skin disease affecting approximately 2% to 3% of the Caucasian population. Previously reported data demonstrated adalimumab to be an efficacious treatment of psoriatic arthritis and plaque-type psoriasis. Adalimumab is a fully human monoclonal antibody IgG1 against tumor necrosis factor alpha.

Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA-B27.

Objective: To investigate the molecular mechanism responsible for the reduced capacity of dendritic cells (DCs) from HLA-B27-transgenic rats to form conjugates with naive T cells.

Methods: We monitored interactions between DCs derived from HLA-B27-transgenic, HLA-B7-transgenic control, and nontransgenic rats and naive CD4+ T cells. Chemoattraction was studied in Transwell assays, and the formation of an immunologic synapse was examined by videomicroscopy and electron microscopy.

Effects of inhibition of fatty acid amide hydrolase vs. the anandamide membrane transporter on TRPV1-mediated calcium responses in adult DRG neurons; the role of CB receptors.

The aim of the present study was to investigate the relationship between TRPV1 stimulation and endocannabinoid-driven CB(1) receptor-mediated inhibition of activity in adult rat dorsal root ganglion (DRG) neurons, a model of primary afferent nociceptors. Calcium-imaging studies were performed to compare the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 microm) vs. the anandamide (AEA) uptake inhibitor UCM707 (1 microm) on capsaicin (100 nm) and N-arachidonoyl dopamine (NADA; 1 microm)-evoked changes in intracellular calcium [Ca(2+)](i) in DRG neurons.

Glycosylated or non-glycosylated G-CSF differently influence human granulocyte functions through RhoA.

Granulocyte function may be altered after in vivo G-CSF administration and this has been related to both an immaturity of mobilized cells and to a defect in F-actin polymerization. In this paper we show that in resting Filgrastim (non-glycosylated G-CSF)-pulsed cells, F-actin polymerization, membrane-linked RhoA and cell polarization are enhanced compared to those found in resting Lenograstim (glycosylated G-CSF)-cells. The basal hyper-activation of RhoA could be responsible for the morphological and functional modifications of Filgrastim-mobilized cells.

Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathy: a role for scintigraphy with 99mTc-infliximab.

Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid arthritis, ankylosing spondylitis, and Behcet's disease. We used intraarticular infliximab to treat resistant knee monarthritis in a patient with spondylarthropathy. Clinical and laboratory improvement was associated with improvement in scintigraphic findings.

LEGO bricks used as chemotactic chambers: evaluation by a computer-assisted image analysis technique.

One of the main techniques used to explore neutrophil motility, employs micropore filters in chemotactic chambers. Many new models have been proposed, in order to perform multiple microassays in a rapid, inexpensive and reproducible way. In this work, LEGO bricks have been used as chemotactic chambers in the evaluation of neutrophil random motility and chemotaxis and compared with conventional Boyden chambers in a "time-response" experiment.

High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis.

High-dose intravenous immunoglobulin has been proposed as an alternative treatment for several immuno-mediated inflammatory skin diseases, usually at a dosage of 1 - 2 g/kg. We describe the treatment of 10 patients affected by toxic epidermal necrolysis using 400 mg/kg per day on 5 consecutive days--a schedule that is lower than previously reported schedules. According to the SCORTEN, the earlier predicted mortality rate was 35%.

Type I lamellar ichthyosis improved by tazarotene 0.1% gel.

The efficacy of tazarotene 0.1% gel in a 30-year-old woman with type I lamellar ichthyosis is reported. The drug was applied to 15% of the total body surface area as follows: once daily for 2 weeks, three times a week for further 2 weeks, followed by a once weekly maintenance application.

Diagnosis of pigmented skin lesions by dermoscopy: web-based training improves diagnostic performance of non-experts.

Background: Dermoscopy has been shown to enhance the diagnosis of melanoma. However, use of dermoscopy requires training and expertise to be effective.

Objectives: To determine whether an Internet-based course is a suitable tool in teaching dermoscopy, and to evaluate the diagnostic value of pattern analysis and diagnostic algorithms in colleagues not yet familiar with this technique.

A Study on Vascular Retinal Alterations in Patients with Coronary Artery Disease.

The paper describes the study carried out on a sample of 27 coronary artery disease patients, aiming to determine a correlation between coronary artery disease and anomalies in the retinal circulation. Patients underwent selective coronary arteriography and fundus fluorescein angiography that allowed us to investigate the dye dynamics and to detect abnormalities of time evolution, vessel walls, and flux. During the fluorescein angiography we measured time events as the choroidal flush (ta) the start of the laminar phase (tb), and the end of the laminar phase (tc) and we took pictures that were digitally processed in order to compute the ROI1/ROI2 value, assumed as a numerical index of ischemia of the optic disc.

An image processing procedure for the assessment of normality curves of motility of human granulocytes in micropore filters.

With the conventional methods used in current practice, the results of human granulocyte motility assays are expressed by a numerical value that defines the leading front of cells into micropore filters. The authors have developed a fast procedure which allows the complete curve of polymorphonuclear leukocyte (PMN) migration to be obtained, from the initial plane of a filter to the maximum propagation depth. In this way, more information is given than that expressed by a single parameter.

Gallium-67 scintigraphy in an AIDS patients presenting tuberculous pericarditis.

The case of a 31-year-old HIV-positive male drug addict, with a history of recurrent intermittent fever is presented. Chest x-ray showed right ilar-node enlargement and moderate venous congestion. A 67Ga-citrate scan of the chest was highly suggestive of Mycobacterial infection.

A computer-assisted method for the study of the trabecular bone of the distal radius on conventional radiographs.

The procedure described is based on the acquisition and processing of x-rays of the distal radius obtained under standard conditions. An x-ray was obtained of the forearm together with an aluminum step wedge to automatically normalize the photometric values of the bone with respect to the photometric values of the reference aluminum wedge. Densitometric values for thickness (T) and a coarseness parameter (C) that depends on the trabecular bone pattern are measured on interactively selected rows and regions of interest (ROIs) of the digital image.

An image processing workstation for automatic evaluation of human granulocyte motility.

Polymorphonuclear (PMN) motility is currently determined by a method using chemotactic chambers with micropore filters. PMN locomotive capacity is measured by evaluating the maximum distance travelled by the cells, or by counting the number of cells which have moved through the filter. Although in recent years some attempts to improve the analysis of chemotaxis data by computer-assisted systems have been made no technique has been shown capable of both measurement and correlation of these parameters in real time.

Decrease of diffusion of glycosylated albumin in retinal microcirculation by peptide fraction from bovine factor VIII.

The diffusion of the glycosylated albumin in the retinal vascular system has been studied in male New Zealand rabbits, using fluorangiographic techniques. A first group of animals was treated for 15 days with the peptide fraction from bovine Factor VIII (Vueffe); a second group, used as control group, was treated with physiological solution. At the end of treatment, glycosylated albumin was made fluorescent and then injected into the marginal vein of the rabbit.

Chromogenic ionophore-based methods for spectrophotometric assay of sodium and potassium in serum and plasma.

We report spectrophotometric methods for quantifying sodium and potassium in serum and plasma without sample pretreatment or solvent-extraction steps. The methods are based on novel chromogenic ionophores characterized by molecular structures highly preorganized for binding, which result in exceptionally high sensitivity and selectivity (negligible responses to sodium at 80 to 200 mmol/L in the potassium assay and to potassium at 0 to 10 mmol/L in the sodium assay). The within-run imprecisions are comparable with those for ion-selective electrodes (for K, 1.