Desmoglein, the target molecule in autoimmunity and infection]

To form the human body and maintain the integrity of its complex tissues, individual cells need to hold tightly to each other. The desmosome is the major type of intercellular adhesive junction, and has desmoglein (Dsg), a cadherin type cell-cell adhesion molecule, as a transmembrane component. Dsg is now known to be targeted in autoimmune diseases, infectious diseases, as well as inherited diseases. Patients with pemphigus, an autoimmune blistering disease of the skin and mucous membrane, have IgG autoantibodies directed against Dsg1 and Dsg3. A subset of patients with pemphigus have Dsg1/Dsg4 crossreacting IgG autoantibodies. Exfoliative toxins produced by Staphylococcal aureus, which causes Staphylococcal Scalded Skin Syndrome (SSSS) and bullous impetigo, specifically digest Dsg1. A subset of patients with SSSS develop a low titer of anti-Dsg1 IgG autoantibodies. A mutation in DSG1 gene causes striate palmoplantar keratoderma and a mutation in DSG4 gene causes inherited hypotrichosis. It is not clear why so many diseases are clustered in desmogleins, but there must be a reason for this. Studies on desmogleins will provide an important framework to understand the mysteries between autoimmunity and infection.     

Functional and immunohistochemical studies of cultured rat microglia

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model.

Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-alpha, and interleukin-beta concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.     

Light exposure required for optimum conversion of light activated resin systems

OBJECTIVE: The aim of this study was to evaluate the relationship between the degree of conversion (DC) of composites and the light intensity using LED-curing units and also to determine the amount of exposure required to achieve optimal curing. METHOD: The light outputs of light-curing units and the depths of cure of composites exposed to these units were determined using the methods outlined in modified ISO standards, ISO/TS10650 and ISO 4049, respectively. The distributions of DC in composites were investigated by IR spectra of microareas obtained at various depths from the irradiated surface of thin specimens cut out from the cured composites. IR spectra were measured using a Fourier transform infrared spectrometer equipped with a microscopic unit. DC was calculated from the changes in the amount of C=C double bonds in the IR spectra. RESULTS: The light intensity at various depths through the cured composite was calculated from the attenuation coefficient of each material, obtained from the linear relationship between the depth of cure and the logarithm of the amount of exposure, which is defined as the product of the irradiance and irradiation time. There was a third or fourth order regression relationship between DC and the logarithm of total light energy at a particular depth. SIGNIFICANCE: The minimum light energy required to produce a saturated DC was about 1000 s mW/cm2.     

Characterization of dehydrochlorinated poly(vinylidene chloride) and the shock-compressed material

Dehydrochlorinated poly(vinylidene chloride) proved to be a conjugated polyene-polyene polymer. Shock compression of the polymer formed a large portion of graphite and trace amounts of diamond and of an unknown carbon. The unknown carbon belongs to the hexagonal crystal system and possesses the cell dimension α₀ = 0.338 nm. A comparison with known carbynes was made in terms of the crystalline parameters.     

An estimation of a model explaining the mechanism causing neurotic disorders using a theory of fuzzy sets

Constructing and estimating a model to explain the mechanism of neurotic disorders is important and significant. The model helps the rearrangement or representation of knowledge obtained from professional physicians. However, it is a very difficult problem, because the objects requiring analysis are mental activities of human beings, and they originally include a comparatively large variance between individuals. The object data were obtained from patients with neurotic disorders who were diagnosed by several doctors for 10 years in a subagricultural areas in Japan. We analyzed the data and calculated the weights attached for personal information depending upon the similarity between the information and the kinds of neurotic disorders using the theory of fuzzy sets. From the results of our analysis, we constructed and estimated a model explaining the mechanism causing neurotic disorders as several linear equations. From data processing points of view, the estimation we attempted is placed in a kind of effective data compression with respect to discrete statistical data.     

Ruptured congenital aneurysm of the sinus of valsalva in the aged

Ruptured aneurysm of the sinus of Valsalva is a rare cardiac lesion. A ruptured aneurysm of the sinus of Valsalva in the right ventricle of a 64-year-old man was successfully repaired. The patient was admitted to the hospital with high fever and chest oppression. Diagnosis was made by two dimensional echocardiography, cardiac catheterization, and cardiac angiography. An aortotomy, main pulmonary arteriotomy, and right ventriculotomy were performed. There was no VSD, and the aneurysm originated from the right coronary sinus, rupturing into the right ventricle inlet portion. The ruptured aneurysm of the sinus of Valsalva was closed with a Dacron patch from inside the aorta. He is doing well after surgery. There was no heart murmur. CTR decreased and pulmonary blood flow fell to a normal value. As far as we know, this patient is the second oldest patient in Japan with surgical repair.