IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in patients with immunoglobulin G4-related disease.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a new disease entity characterized by high serum IgG4 concentrations, infiltration of IgG4-positive plasmacytes, and fibrosis of various organs. Several groups have reported that IgG4-RD is a unique inflammatory disorder characterized by an immune reaction predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile, recent studies have demonstrated that interleukin (IL) 18 has a potential to trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18 expression in submandibular glands of patients with IgG4-RD (20 cases) and controls (19 cases) by immunohistochemical analysis and quantitative real-time reverse-transcription polymerase chain reaction. We found that IL-18 was highly expressed in submandibular glands of patients with IgG4-RD than in controls with both protein (P < .05, χ(2) test) and messenger RNA levels (P < .05, Mann-Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual immunofluorescence staining, a few numbers of cells were double positive for IL-13 and interferon γ at the inflammatory infiltrates of submandibular glands of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2 cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of IgG4-RD.

Evaluation of the olfactory nerve transport function by SPECT-MRI fusion image with nasal thallium-201 administration.

PURPOSE: The aim of this study was to visualize the human olfactory transport pathway to the brain by performing imaging after nasal thallium-201 ((201)Tl) administration. PROCEDURES: Healthy volunteers were enrolled in this study after giving informed consent (five males, 35-51 years old). The subjects were nasally administered (201)TlCl into either the olfactory cleft. Twenty-four hours later, uptake of (201)Tl was detected by a single photon emission computed tomography (SPECT)/X-ray computed tomography hybrid system. For each subject, an MRI image was obtained and merged with the SPECT image. RESULTS: The peak of the (201)Tl uptake entered into the olfactory bulb in the anterior skull base through the cribriform lamina 24 h after nasal administration of (201)Tl. No participant had olfactory disturbance after treatment. CONCLUSIONS: Nasal (201)Tl administration was safely used to assess the direct pathway to the brain via the nose in healthy volunteers with normal olfactory threshold.

Olfactory epithelial transplantation: possible mechanism for restoration of smell.

PURPOSE OF REVIEW: To discuss the unique properties of the olfactory epithelium and the potential use of olfactory epithelial grafts to restore olfactory function. RECENT FINDINGS: Sensory neurons in the olfactory epithelium undergo continuous regeneration, grow new axons, and reestablish connections with the olfactory bulb throughout life. When transplanted into different regions of the brain, olfactory epithelial graft cells retain their morphological and regenerative properties. Olfactory cells within the grafts grow axons that enter into the surrounding brain tissue. Recent studies have shown that the olfactory epithelium can be grafted directly to the olfactory bulb. SUMMARY: The olfactory epithelium has a remarkable capacity to continuously generate new sensory neurons and survives grafting into different regions of the brain. A review of the literature and the future use of olfactory grafts as a potential method to restore olfactory function is discussed.

Grafting the olfactory epithelium to the olfactory bulb.

BACKGROUND: Impaired olfactory function leads to a decrease in the quality of life for many patients. Surgical treatment options are limited, especially for those suffering from hyposmia or anosmia after posttraumatic injury to the olfactory nerves. Stem cells located in the olfactory epithelium (OE) have the capacity to grow new neurons, making the OE an ideal candidate for restorative tissue grafting. This study was performed to determine if strips of OE survive transplantation directly to the olfactory bulb (OB). METHODS: Transgenic mice, expressing a green fluorescent protein (GFP), were used to obtain the donor graft tissue. Strips of OE from GFP donor mice were transplanted directly to sites in the OB and cerebral cortex (CC; control sites) of wild-type mice. Graft survival rates at 30 days were determined for transplant sites in the OB and CC. RESULTS: Strips of OE from transgenic mice survived transplantation to the OB and continued to express the GFP marker protein. The 30-day survival rate in the OB (83%, 5 of 6 grafts) was the same as in the CC (10 of 12 grafts). The morphology of the graft revealed characteristics found in normal OE. CONCLUSION: We showed that strips of OE can be successfully grafted to both the OB and CC. Grafts of the OE, if strategically positioned on the ventral surface of the bulb and given access to the nasal cavity, could provide the basis for new surgical treatments to restore olfactory function.

Regulation of Src homology 2-containing protein tyrosine phosphatase by advanced glycation end products: the role on atherosclerosis in diabetes.

Advanced glycation end products (AGEs), among the most important causes of atherosclerosis in diabetes mellitus, stimulate the proliferation of smooth muscle cells (SMCs). Smooth muscle cells are central in the formation of atherosclerotic lesions, where they show both increased migration and accelerated proliferation. In investigating how AGEs stimulate SMC proliferation, we focused on protein tyrosine phosphatase, especially Src homology 2-containing protein tyrosine phosphatase (SHP2), which is considered important in regulating cell proliferation. Advanced glycation end products increased activity of SHP2 in the membrane fraction of rat aortic SMCs compared with control bovine serum albumin (P < .05). Upon characterizing the genomic and promoter structure of SHP2, we detected nuclear factor-kappaB (NF-kappaB) binding sites in the promoter area. Advanced glycation end product stimulation increased luciferase activity in cells transfected with SHP2 promoter region including NF-kappaB binding sites (P < .05) and increased SHP2 expression (P < .05). These data indicate that AGE stimulation appears to activate NF-kappaB. Activated NF-kappaB binds to sites on the SHP2 promoter, resulting in increased SHP2 expression, SHP2 activity, and, ultimately, SMC proliferation. It suggests that AGE stimulation induces SMC proliferation via SHP2, underscoring the importance of control of AGE for suppressing macroangiopathy in diabetes mellitus.

Lipopolysaccharide-induced apoptosis of olfactory receptor neurons in rats.

CONCLUSION: Daily intranasal perfusion of lipopolysaccharide (LPS) for 14 days in rats induced apoptosis of olfactory receptor neurons (ORNs) over >3 but <7 days. OBJECTIVES: Smoking is one of the factors causing olfactory dysfunction. LPS is a major glycolipid component of the gram-negative bacterial cell wall and an active component of cigarette smoke. We studied whether LPS is one of the causes of tobacco-induced olfactory dysfunction by examining apoptosis in the olfactory epithelium after local exposure to LPS. MATERIALS AND METHODS: Rats received intranasal instillation of LPS or saline. Histochemical changes in the olfactory epithelium were examined using antibodies against single-stranded DNA, Bcl-2, Bax, and Caspase-3. We used different concentrations of LPS to examine the dose dependency and observed changes in the olfactory epithelium for a week after exposure cessation to see the duration of the effect of smoking. RESULTS: We found that numbers of cells positive for ssDNA, Bcl-2, Bax, and Caspase-3 were increased on the exposed side. The number of ssDNA-positive cells reached a maximum on the first day and decreased to normal levels on the seventh day after cessation of exposure.