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.     

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.     

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.     

Development of a novel microperfusion chamber for determination of cell membrane transport properties

A novel microperfusion chamber was developed to measure kinetic cell volume changes under various extracellular conditions and to quantitatively determine cell membrane transport properties. This device eliminates modeling ambiguities and limitations inherent in the use of the microdiffusion chamber and the micropipette perfusion technique, both of which have been previously validated and are closely related optical technologies using light microscopy and image analysis. The resultant simplicity should prove to be especially valuable for study of the coupled transport of water and permeating solutes through cell membranes. Using the microperfusion chamber, water and dimethylsulfoxide (DMSO) permeability coefficients of mouse oocytes as well as the water permeability coefficient of golden hamster pancreatic islet cells were determined. In these experiments, the individual cells were held in the chamber and perfused at 22 degrees C with hyperosmotic media, with or without DMSO (1.5 M). The cell volume change was videotaped and quantified by image analysis. Based on the experimental data and irreversible thermodynamics theory for the coupled mass transfer across the cell membrane, the water permeability coefficient of the oocytes was determined to be 0.47 micron. min-1. atm-1 in the absence of DMSO and 0.65 microns. min-1. atm-1 in the presence of DMSO. The DMSO permeability coefficient of the oocyte membrane and associated membrane reflection coefficient to DMSO were determined to be 0.23 and 0.85 micron/s, respectively. These values are consistent with those determined using the micropipette perfusion and microdiffusion chamber techniques. The water permeability coefficient of the golden hamster pancreatic islet cells was determined to be 0.27 microns. min-1. atm-1, which agrees well with a value previously determined using an electronic sizing (Coulter counter) technique. The use of the microperfusion chamber has the following major advantages: 1) This method allows the extracellular condition(s) to be readily changed by perfusing a single cell or group of cells with a prepared medium (cells can be reperfused with a different medium to study the response of the same cell to different osmotic conditions). 2) The short mixing time of cells and perfusion medium allows for accurate control of the extracellular osmolality and ensures accuracy of the corresponding mathematical formulation (modeling). 3) This technique has wide applicability in studying the cell osmotic response and in determining cell membrane transport properties.     

Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy

Brain areas damaged by stroke and seizures express high levels of the 72-kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin-induced seizures.     

Alteration of signal-transducing molecules in tumor-infiltrating lymphocytes and peripheral blood T lymphocytes from human colorectal carcinoma patients

An analytical method for the rapid isolation and recovery of the homologous series of 2-aminoethanols, a class of organic compounds of importance to wood preservative treatment, is successfully developed. The method is applied to an aqueous solution of copper amine (copper[II] hydroxide complexed monoethanolamine) and to copper-amine-treated sawdust. The method incorporates a gas chromatograph-ion-trap mass spectrometer. A discussion of the secondary equilibrium effects involved when ionizable analytes are extracted from an aqueous phase with respect to organic bases is presented. Using 2-propanol as the extractant coupled to a salt-saturated aqueous phase results in recoveries of 63% for 2-aminoethanol, 51% for N,N-dimethyl-2-aminoethanol, and 56% for N-methyl-2-aminoethanol for a single liquid-liquid extraction. The choice of 2,2,2-trifluoroethanol as an internal standard is found to be quite suitable. A comparison of the precision and accuracy for an external versus an internal mode of instrument calibration demonstrates that the internal standard mode is preferable for this manual injection.     

Control of expression, glycosylation, and secretion of HIV-1 gp120 by homologous and heterologous signal sequences

The HIV-1 gp120 signal sequence of 30 amino acids is longer than most glycoprotein signal sequences and contains an average of 5 positively charged amino acids. The HIV-1 gp120 gene with its natural signal sequence expressed in any prokaryotic or eukaryotic expression systems showed extremely low levels of synthesis and secretion. However, deletion of the HIV-1 gp120 signal sequence results in production of large quantities of a nonglycosylated form of gp120 in Spodoptera frugiperda cells. Substitution of the gp120 natural signal sequences with the signal sequences from honeybee mellitin or murine interleukin 3 promotes a high level of expression of a glycosylated form of gp120 and efficient secretion. These heterologous signal sequences contain one (mellitin) or no (IL-3) positively charged amino acids and led us to investigate the role of the positively charged amino acids in the signal sequence of HIV-1 gp120. Four charge-altered forms of the gp120 signal sequence of HIV-1 were constructed by site-directed mutagenesis in which the positively charged amino acids were sequentially substituted with neutral amino acids. The results of these experiments showed that the expression and secretion of gp120 was progressively increased by eliminating the positively charged amino acids in a stepwise fashion. However, the substitution of all positively charged amino acids resulted in the accumulation of nonglycosylated gp120 within the cells with decreased amounts of the glycosylated form of gp120. These results demonstrate that the positively charged amino acids in the signal sequence of HIV-1 gp120 are key factors in determining its poor expression and secretion. Analyses of intracellular transport and folding of gp120 further indicate that the presence of a highly charged, uncleaved signal sequence is an important factor limiting transport of gp120 from the rough ER to the Golgi apparatus.