Differential activation of mouse hepatitis virus-specific CD4+ cytotoxic T cells is defined by peptide length.

In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4+ cytotoxic T lymphocyte (CTL) clones HS1 and B6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4+ clones respond to the promiscuous peptide fragment S-329-343 of the glycoprotein S of MHV-A59. The results indicate that the core peptides of both clones overlap but are not identical. The core region of the HS1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises the amino acid residues S-334-342. The peptide fragment S-329-343 activates all T-cell effector functions, including proliferation, cytokine secretion and cytolysis. However, in the present study we show that T-cell activation is not an all-or-none phenomenon, in which T-cell stimulation leads to activation of all T-cell effector functions. It appears that changes in the length of a peptide ligand can differentially activate the cytolytic machinery from proliferation and cytokine secretion. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytokine profile of polarized T-helper type-1 (Th1) clones into a Th2-type pattern.     

A microiontophoretic study of the action of kainic acid and putative neurotransmitters in the rat mesencephalic trigeminal nucleus

The ‘excitotoxic’ hypothesis proposes that neurotoxic amino acids exert their effect through neuronal excitation (Olney, Ho &;Rhee, 1971).Colonnier, Steriade &;Landry (1979) have found that trigeminal mesencephalic neurons in the cat are resistant to the neurotoxic effect of kainic acid. In the present study it was found that the same neurons in the rat also resist the cytotoxic action of this amino acid. In addition, kainic acid, applied iontophoretically onto these neurons failed to alter their firing frequency. The resistance of these neurons to both neurotoxic and excitatory actions of kainic acid is consistent with the ‘excitotoxic’ hypothesis.Other putative neurotransmitters were applied by microiontophoresis on these neurons and none were found to alter their rate of discharge. Procaine however applied with relatively low ejecting currents consistently reduced their firing rates. The failure of the putative neurotransmitters tested to influence the rate of discharge of the trigeminal mesencephalic neurons suggests that the chemical synapses present on these neurons in the rat (Hinrichsen &;Larramendi, 1970) utilize another neurotransmitter from those tested. Alternatively the synapses might have a role other than the direct regulation of the firing frequency of these primary afferent neurons.     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.     

Risk factors for antibiotic-resistant Escherichia coli isolated from hospitalized patients with urinary tract infections: a prospective study

From November 1998 to February 1999 we prospectively evaluated the prevalence of resistance to penicillins, cephalosporins, carbapenem, quinolones, aminoglycosides, and trimethoprim-sulfamethoxazole (SXT) in 320 Escherichia coli isolates isolated from hospitalized patients with acute urinary tract infections (UTIs). We also studied for these strains risk factors for resistance to amoxicillin-clavulanic acid (AMC), fluoroquinolones (FQs), and SXT. Resistance rates were consistent with those from major recent studies reported in the literature. Multivariate analyses selected the following factors as being significantly associated with E. coli resistance: (i) for resistance to AMC, prior (1 year) UTI (odds ratio [OR] = 2.71, P = 0.006), prior (1 year) urinary catheter (OR = 2.98, P = 0.0025), and prior (6 months) antibiotic exposure (OR = 2.68, P = 0.005); (ii) for resistance to FQs male sex (OR = 3.87, P = 0.03), with a trend toward significance for age >65 years (OR = 7.67, P = 0.06) and prior (1 year) UTI (OR = 2.98, P = 0.07); and (iii) for resistance to SXT, male sex (OR = 1.91, P = 0.046), hospitalization in an intermediate-term-care unit (OR = 2.18, P = 0.008), and prior (1 year) UTI (OR = 2.03, P = 0.03). Ours results suggest that prior UTI is a common risk factor for resistance to the different antibiotics tested. Although few studies on risk factors for E. coli resistance to antibiotics have been published, careful interpretation of their findings, taking into consideration the population, infection site, and period studied, should contribute to the formulation of a better strategy that can be used to overcome antibiotic resistance.     

Detection of human immunodeficiency virus type 1 (HIV-1) in heel prick blood on filter paper from children born to HIV-1-seropositive mothers.

The human immunodeficiency virus type 1 (HIV-1) DNA PCR results of 94 dried blood spot (DBS) samples on filter paper and corresponding venous blood in EDTA obtained from infants born to HIV-1-seropositive mothers were compared. In addition, the results of HIV-1 DNA PCR on DBS and the HIV-1 RNA PCR from plasma of 70 paired samples were compared. A 100% specificity and a 95% sensitivity for HIV-1 DNA PCR on DBS compared with results for venous blood were observed for the 94 paired samples. The results of the DBS HIV-1 DNA PCR and HIV-1 RNA PCR of 70 corresponding plasma samples correlated perfectly (100%). The DBS HIV-1 DNA PCR method proved reliable for HIV-1 detection.     

Theory of mind and motion perception in schizophrenia

This study investigated the relationship between theory of mind (ToM) deficits and visual perception in patients with schizophrenia (N=52; 17 remitted and unmedicated) compared with healthy controls (N=30). ToM was assessed with the Eyes Test, which asked participants to choose which of 4 words best described the mental state of a person whose eyes were depicted in a photograph. Visual perception was evaluated with form and motion coherence threshold measurements. Results revealed that patients with schizophrenia (both remitted and nonremitted) showed deficits on the Eyes Test and the motion coherence task. ToM dysfunctions were associated with higher motion coherence thresholds and more severe negative symptoms. This suggests that ToM deficits are related to motion perception dysfunctions, which indicates a possible role of motion-sensitive areas in the pathophysiology of schizophrenia.     

Histological and ultrastructural appearance of the hydroxyapatite-bone interface

This article describes the histological and ultrastructural appearance of the interface created in the implantation bed, between bone tissue and implants made of dense sintered hydroxyapatite (HA). Biopsies from dog subjects included: a) loaded permucosal dental implants for tooth substitution, b) subperiosteally placed implants for alveolar bone correction, c) endosseously placed dental root implants to retain ridge form following extraction. The light and electron microscopical results show extensive bone apposition on the osseous sides of the implant surfaces. There is an intimate, direct bone contact without any visible interruption. The bone is of normal lamellar type and continuously connected with the trabecular bone. Bone has grown into the finest surface irregularities of the implant. Collagen fibers of the calcified bone matrix are observed within a distance less than 500 A from the implant surface. The thin (20-100 A) electron dense layer at the bone-implant interface resembled the lamina limitans of organic bone matrix, also seen at the inner walls of the osteocytes lacunes. Deposition of bone gives rise to a biologically stable bone-implant interface, without disturbance of the physiological bone turnover. This is seen as very favorable for desired long term fixation of implant to bone.     

Borrelia burgdorferi sensu lato infection in larval Ixodes ricinus (Acari: Ixodidae) feeding on blackbirds in northwestern Italy

Birds belonging to 59 species (n = 1,206) were live captured in Piemonte, northwestern Italy, in 2001. Ixodes ricinus (L.) larvae were collected from 59 birds belonging to nine species, and nymphs were recovered on 79 birds belonging to 10 species. Eurasian blackbirds, Turdus merula L., had significantly higher levels of infestation by ticks than other passerine species. Larval I. ricinus of blackbirds peaked in summer, when prevalence was 39% (95% confidence interval 24.2-55.5) and mean number of ticks per host was 3.3 (1.6-7.2), whereas nymphs peaked in spring, when prevalence was 72.2% (54.8-85.8) and mean number of ticks per host was 6.9 (4.4-10.7). Immature I. ricinus were coincidentally aggregated on blackbirds, with 15 blackbirds feeding 67.4% of nymphs and 40.3% of larvae, and coinfestation by both stages was relatively high in summer: Kappa = 0.64 (0.40-0.88). Borrelia burgdorferi sensu lato was identified by polymerase chain reaction (PCR) in 58.3% (35.9-78.5) of larvae with engorgement ratio > or = 3 that were collected from blackbirds. Larvae that were collected from other passerine species gave negative PCR results. Sixteen of 21 PCR-positive samples belonged to B. garinii (76.2%), and five (23.8%) were Borrelia valaisiana. Results of this study suggest that blackbirds play an important role as hosts for immature I. ricinus and as reservoir of Borrelia garinii in northwestern Italy.     

Allergy to cooked white potatoes in infants and young children: A cause of severe,chronic allergic disease

BACKGROUND: Cases of allergy to cooked potato in children have been reported, some with immediate and others with late reactions. The clinical effects of chronic allergic reactions to potato and the effectiveness of diet on such reactions have not been described previously. OBJECTIVE: We sought to evaluate the importance of cooked potato as an allergenic food in individual cases of atopy in children. METHODS: Eight atopic children were selected on the basis of suspicion of allergy to cooked potatoes: all had potato-specific IgE, 2 of 8 had experienced immediate allergic reactions, and 6 of 8 had eczema that improved with a potato-elimination diet (decrease in severity scoring of atopic dermatis [SCORAD] index of >50%). The patients were evaluated by using skin prick tests with homemade cooked and noncooked potato extracts and with a commercial extract and by using IgE immunoblots from SDS-PAGE patterns of potato extract. Seven patients were challenged with cooked potato. The control group consisted of 9 age-matched atopic children, 8 of them with eczema. RESULTS: The mean SCORAD index decreased from 43.3 before to 11.5 after elimination of potato from the diet. Potato CAP values ranged from 3.71 to greater than 100 kUa/L. Potato challenge results were positive in 7 of 7 patients. Skin prick test responses were positive for cooked potato extracts in 7 of 7 patients, for noncooked extracts in 7 of 7 patients, and for the commercial extract in 8 of 8 patients compared with in 0 of 9, 1 of 9, and 1 of 9 subjects in the control group, respectively. During immunoblotting, 8 of 8 patient sera recognized one or more protein bands compared with 0 of 9 control subject sera. CONCLUSION: Allergy to cooked potatoes is a cause of severe allergic disease, with immediate reactions and eczema in some atopic infants and young children.