Immunologic basis of chronic allergic diseases: clinical messages from the laboratory bench

During the past decade there have been significant advances in our understanding of the mechanisms underlying allergic responses. Immediate hypersensitivity reactions are mediated primarily by mast cells in an IgE-dependent manner. After the local release of various mediators, proinflammatory cytokines, and chemokines, there is a cell-mediated response that is dominated by eosinophils and T lymphocytes. The majority of T cells in early allergic reactions are memory T cells secreting helper type 2 (TH2)-like cytokines, i.e. IL-4, IL-5, and IL-13, but not interferon-gamma. These cytokines regulate IgE synthesis and promote eosinophil differentiation and cell survival, thus contributing to allergic inflammatory responses. Failure to control immune activation early in the course of allergic inflammation may blunt the response to glucocorticoid therapy and contribute to long-term morbidity of disease. The identification of key cells and cytokines involved in the initiation and maintenance of allergic inflammation is likely to become an important therapeutic target in the future management of this important group of diseases.     

Differential stimulation of interleukin-12 (IL-12) and IL-10 by live and killed Helicobacter pylori in vitro and association of IL-12 production with gamma interferon-producing T cells in the human gastric mucosa

The objective of these experiments was to examine the ability of Helicobacter pylori to stimulate interleukin-10 (IL-10) or IL-12 and select for either Th1 or Th2 cells. Gastric biopsy specimens were collected from patients who were categorized with respect to the presence of H. pylori and gastric disease as well as their age, gender, medications, and other factors. As Th1 and Th2 cells are selected by IL-12 and IL-10, respectively, biopsy specimens were screened for mRNA and protein for these cytokines. Although mRNA for IL-12 and IL-10 was detected in biopsy specimens obtained from both infected and uninfected patients, IL-12 protein predominated. Levels of IL-10 and IL-12 in gastric tissue did not change in response to infection. Moreover, gamma interferon (IFN-gamma)-producing T cells were found in both the infected and the uninfected gastric mucosa. Stimulation of peripheral blood leukocytes from either infected or uninfected donors with various concentrations of live or killed H. pylori induced immunoreactive IL-12 and IL-10. After stimulation with live H. pylori, IL-12 levels increased more than 30-fold, whereas IL-10 levels increased only 2- to 5-fold, compared to cells stimulated with medium alone. Interestingly, killed H. pylori induced significantly more IL-10 (P < 0.05) than live H. pylori, while recombinant urease only induced IL-10. These results demonstrate that live H. pylori selectively stimulates the induction of IL-12 and Th1 cells that produce IFN-gamma, whereas preparations used in oral vaccines induce more IL-10 and may favor Th2 cell responses.     

Differences between responses of naive and activated T cells to anergy induction

OBJECTIVES: To assess the safety and efficacy of the Alexandrite laser for intracorporeal lithotripsy of renal and ureteral stones in conjunction with ureterorenoscopy or percutaneous nephrostolithotomy. METHODS: We retrospectively analyzed the records of 137 patients with 169 calculi in 143 renoureteral units who were treated with the Alexandrite laser via a retrograde (91.5%) or antegrade (8.5%) endoscopic approach. RESULTS: Adequate intraoperative fragmentation of the stone was observed in 88.8% of the cases. No intraoperative complications were attributable to the laser. At a mean follow-up of 34 days, the overall stone-free rate was 74.4%. The stone-free rate for ureteral stones (n = 115) was 80%, whereas the stone-free rate for renal stones (n = 22) was only 44%. In the best subgroup of ureteral stones (10 mm or less in the distal ureter), the stone-free rate was 97.4%. CONCLUSIONS: The Alexandrite laser is a safe modality for intracorporeal lithotripsy and is highly effective for ureteral stones less than 10 mm in size.     

The effect of leukotriene D4 on the patency of nasal passage in the guinea pig

BACKGROUND: Demodex folliculorum has been reported in rosacea in a number of clinical studies. As the Demodex mite is also present in many healthy individuals, it has been suggested that the mite may have a pathogenic role only when it is present in high densities. Moreover, some authors have proposed that a mite density above 5/cm2 may be a criterion for the diagnosis of inflammatory rosacea. In this study, the possible role of D. folliculorum and the importance of mite density in rosacea were investigated using a skin surface biopsy technique. METHODS: Thirty-eight patients with rosacea and 38 age-and-sex-matched healthy subjects entered the study. With the skin surface biopsy technique, we obtained samples from three facial sites. We then determined the mite positivities, the mean mite counts in both study groups, the mean mite densities at each facial site and in the rosacea subgroups, and the mite densities above 5/cm2. RESULTS: The mean mite count in the rosacea group (6,684) was significantly higher than that in controls (2,868; p < 0.05). The cheek was the most frequently and heavily infested facial region. Ten rosacea patients and five normal subjects had mite densities over 5/cm2; the difference was not statistically significant (p > 0.05). CONCLUSIONS: Rosacea is a disease of multifactorial origin, and individual properties may modify the severity of the inflammatory response to Demodex. We suggest that a certain mite density is not an appropriate criterion in the diagnosis of the disease; nevertheless, large numbers of D. folliculorum may have an important role in the pathogenesis of rosacea, together with other triggering factors.     

Influence of an applied magnetic field on shielding current paths in a high TC superconductor

The influence of an applied magnetic field on shielding current paths in a bulk high T_c superconductor was investigated. This issue is very important for the quantitative analysis of levitation force, since the distortion and localization of the current paths have been found to be a major source of discrepancy between computed and experimental results. Furthermore, it has been speculated that the current paths vary, depending on the applied magnetic field. The magnetic field due to superconducting currents was measured by a Hall sensor when a permanent magnet was positioned at different gaps from a superconductor. The current paths were then reconstructed from the measured field data by an inverse analysis. A genetic algorithm, which is a robust probabilistic optimizing method, was used for the inverse analysis. It was found that the current paths merged into larger loops as the permanent magnet was retreating from the superconductor. It implies that a stronger applied magnetic field locally degrades the current density (J_c) and the shielding current paths are localized by these low-J_c areas which act as insulating boundaries.     

Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice

Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.     

An analysis of the scalar Helmholtz equation using the integralequation method

The scalar Helmholtz equations are investigated by using the integral equation method (IEM). In the IEM analysis, the fundamental solution of the Laplace equation is used as a weighting function. Two IEM formulations are obtained: one is a standard formulation and the other is obtained from an elimination of the unknown boundary value. The accuracy and computational time of the IEM are compared with those of the finite element method in two dimensional scalar Helmholtz problems. The analysis of a resonant cavity is reduced to a simple eigenvalue problem. Resonant frequencies of the IEM agree well with those of the finite difference method. Usefulness of the IEM is confirmed through the analyses of the scalar Helmholtz equations     

Immediate ipsilateral fibular transfer in a large tibial defect using a ring fixator. A case report

A 57-year-old man with monoclonal gamma-globulinemia was admitted because of edema and proteinuria. A renal biopsy specimen showed lobular glomerulonephritis associated with deposition of material that was positive for IgG, C3, C1q, fibrin, kappa light chain, and lambda light chain but was not stained by Congo red. Glomeruli showed massive electron-dense deposits with two kinds of unusual, highly organized crystalline structures in the mesangial matrix and peripheral capillary loops. Clinically, the patient had nephrotic syndrome, microscopic hematuria, and hypertension. No Bence-Jones protein or cryoglobulin was found in the urine or serum. Immunoelectrophoresis of blood and urine revealed increased IgG-lambda paraprotein, but no free light chains were found. This case was not associated with amyloidosis, systemic lupus erythematosus, light chain deposition disease, cryoglobulinemia, or multiple myeloma. Immunotactoid glomerulopathy was diagnosed. Treatment with oral prednisone was effective for the management of nephrotic syndrome and renal dysfunction. Glomerular deposition of two kinds of microtubular structure in immunotactoid glomerulopathy has rarely been reported.     

First-pass versus second-pass parsing processes in a Wernicke's and a Broca's aphasic: electrophysiological evidence for a double dissociation

The present paper is a first attempt to integrate the classical brain lesion behavioral impairment approach of functional neuroanatomy and the electrophysiological brain mapping approach in the domain of syntactic processing. In a group of normal age-matched controls we identified three electrophysiological components previously observed in correlation with language comprehension processes: an early left anterior negativity normally seen in correlation with syntactic first-pass parsing processes (ELAN), a centroparietal negativity seen in correlation with processes of lexical-semantic integration (N400), and a late centroparietal positivity observed in correlation with secondary syntactic processes of reanalysis and repair (P600). The early left anterior negativity was absent in a patient with an extended lesion in the anterior part of the left hemisphere sparing the temporal lobe, although the late centroparietal positivity and the centroparietal N400 were present. In a patient with a left temporal-parietal lesion the early left anterior negativity was found to be present, whereas the N400 component was absent. These findings suggest that first-pass parsing and secondary processes are subserved by distinct brain systems.