Infection-immunity liaison: Pathogen-driven autoimmune-mimicry (PDAIM)

Autoimmunity causes pathological conditions resulting in autoimmune diseases (ADs). Although autoimmunity is a mystery, immunological dogma suggests that autoreactive cell reactivation (ACR) breaks self-tolerance and induces autoimmunity. Thus, ACR is a royal pathway for ADs. Cumulative evidence implicates environmental factors as secondary triggers of ADs in the genetically susceptible hosts. Infection is the most likely trigger. Although several mechanisms have been proposed to explain how infectious agents trigger ADs, ACR is assumed to be an essential pathway.     

Pulmonary fibrosis in a carpenter with long-lasting exposure to fiberglass

A 56-year-old male carpenter had a history of glass fiber inhalation for 41 years without any protective device. His chest radiograph showed small nodular opacities in lower lung fields and multiple cystic lesions and low attenuation areas in upper lung fields. Light and polarizing microscopic examinations of his transbronchial lung biopsy specimen revealed mild interstitial fibrosis and mononuclear cell infiltration in alveolar walls without birefringent substances. However, widespread depositions of small glass fibers (< 2.5 μm in length and 0.3 μm in diameter) were detected by analytical electron microscopy, which suggested their possible contribution to the development of his pulmonary fibrosis. © 1996 Wiley-Liss, Inc.     

Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects

Background

Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects.

Methods

Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning.

Results

Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference.

Conclusions

The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.     

Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43

It has recently been discovered that G protein-coupled receptors (GPCR) 41 and 43 are characterized by having the short chain fatty acids acetate and propionate as their ligands. The objective of this study was to investigate the involvement of GPCR41, GPCR43, and their ligands in the process of adipogenesis. We measured the levels of GPCR41 and GPCR43 mRNA in both adipose and other tissues of the mouse. GRP43 mRNA expression was higher in four types of adipose tissue than in other tissues, whereas GPCR41 mRNA was not detected in any adipose tissues. A high level of GPCR43 expression was found in isolated adipocytes, but expression level was very low in stromal-vascular cells. Expression of GPCR43 was up-regulated in adipose tissues of mice fed a high-fat diet compared with those fed a normal-fat diet. GPCR43 mRNA could not be detected in confluent and undifferentiated 3T3-L1 adipocytes; however, the levels rose with time after the initiation of differentiation. GPCR41 expression was not detected in confluent and differentiated adipocytes. Acetate and propionate treatments increased lipids present as multiple droplets in 3T3-L1 adipocytes. Propionate significantly elevated the level of GPCR43 expression during adipose differentiation, with up-regulation of PPAR-gamma2. Small interfering RNA mediated a reduction of GPCR43 mRNA in 3T3-L1 cells and blocked the process of adipocyte differentiation. In addition, both acetate and propionate inhibited isoproterenol-induced lipolysis in a dose-dependent manner. We conclude that acetate and propionate short chain fatty acids may have important physiological roles in adipogenesis through GPCR43, but not through GPCR41.     

Covalent immobilization of chitosan derivatives onto polymeric film surfaces with the use of a photosensitive hetero-bifunctional crosslinking reagent

Partially N-acetylated chitosan was covalently immobilized onto polymeric film surfaces using the photosensitive hetero-bifunctional crosslinking reagent, methyl 4-azidobenzoimidate, which was previously attached to the chitosan by the reaction between an imidoester group of the reagent and a free amino group of the chitosan. The grafting was accomplished by irradiating with ultraviolet light the modified chitosan being coated on the film surfaces to photolyse arylazide groups, thus crosslinking the chitosan and the underlying substrate polymer together. For ultraviolet absorption and infrared spectroscopy, the irradiation time of 3 min was found to be sufficient for the photolysis of the azide group. The thickness of the immobilized chitosan layer was estimated to be of the order of 30–150 nm using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). The chitosan molecules immobilized on the surfaces could be chemically modified by several reagents and also treated with a heparin solution to form a polyelectrolyte complex on the surface. The ionically bound heparin was partially released into a phosphate buffer solution.     

Histamine synthesis is required for granule maturation in murine mast cells

Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc^?/? mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc^?/? peritoneal mast cells. Impaired granule maturation was also found in Hdc^?/? BM‐derived cultured mast cells when they were cocultured with fibroblasts in the presence of c‐kit ligand. Exogenous application of histamine and several H₄ receptor agonists restored the granule maturation of Hdc^?/? cultured mast cells. However, the maturation of granules was largely normal in Hrh4^?/? peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter‐2, did not affect granule maturation. In vivo experiments with mast cell deficient Kit^W/Kit^W‐v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator.     

A case of graft replacement of the ascending aorta to the aortic arch and the partial descending aorta in a single stage for thrombosed aortic dissection (debakey type II + IIIB)

We report here a case of graft replacement of the ascending aorta to the aortic arch and the middle portion of the descending aorta in a single stage for thrombosed aortic dissection. The patient was a 53-year-old male who was transfered to our hospital with a diagnosis of thrombosed aortic dissection. Conservative therapy was continued but three weeks after the onset, chest enhanced CT scan and digital subtraction angiography revealed an opacified false lumen in the ascending aorta and a ulcer like projection in the middle portion of the descending aorta. He was therefore diagnosed as having redissection in DeBakey type II + IIIb thrombosed aortic dissec- tion. Graft replacement of the ascending aorta, the aortic arch, and a part of the descending aorta was performed in a single stage via median stenotomy with the aid of extracorporeal circulation and selective cerebral perfusion. Postoperative digital subtraction angiography showd satisfac- tory reconstruction of the thoracic aorta. The patient is still leading a normal life two years after the operation.     

Difference of osteopontin gene regulation between bone and kidney

 Osteopontin is a sialoprotein that is expressed in various cells. It plays a variety of important roles in cell adhesion, migration, signaling, calcification, and immunity. Its diverse functions indicate that the regulation of osteopontin may also vary extensively among tissues. Although osteopontin promoter has been studied in vitro, in vivo analyses may be more appropriate for elucidating osteopontin's functions. In an attempt to investigate osteopontin gene expression, we generated transgenic mice in which the bacterial β-galactosidase reporter gene was conjugated downstream of osteopontin promoter. The osteopontin promoter was a mouse −910 bp upstream fragment, which we had previously found functional in 3T3 cells. Among 34 transgenic founders, 13 mice were transgenic, as determined with the polymerase chain reaction. Osteopontin and β-galactosidase signals were evaluated with in situ hybridization. Among the 13 transgenic mice, 3 were β-galactosidase-positive. In these transgenic mice, osteopontin signals were observed in bones and kidneys, whereas β-galactosidase message was detected only in bones. This suggests that the −910 bp osteopontin promoter is active in bones but not in kidneys. These data imply that the promoter region required for osteopontin expression in kidneys may differ from that in bones. Received: March 22, 2002 / Accepted: December 5, 2002 RID="*" ID="*" Offprint requests to: T. Sakuma Acknowledgments. We greatly appreciate the excellent histotechnological assistance of Mr. Kenji Morihana. This work was supported in part by a grant from The Ministry of Education, Science, and Culture, Japan (no. 12470056).