Intraepithelial lymphocytes in colon have similar properties to intraepithelial lymphocytes in small intestine and hepatic intermediate TCR cells

Recently, properties of intraepithelial lymphocytes (IEL) in the colon (C-IEL) have been analyzed in comparison with those of IEL in the small intestine (SI-IEL). We compared the properties of C-IEL with those of SI-IEL and hepatic intermediate TCR cells, two other types of extrathymic T cells. C-IEL and intermediate TCR cells contain many NK1⁺T cells, although SI-IEL contain few. V and V usage of C-IEL was the same as that of SI-IEL, and that of intermediate TCR cells was different. C-IEL responded to Con A while SI-IEL did not. As to adhesion molecules, C-IEL include both extrathymic and thymus-originated type T cells. With age, TCR-⁺CD4⁺CD8⁺ cells do not increase among C-IEL but do increase among SI-IEL. IL-2R⁺ or CD4^–CD8^– C-IEL increase as observed in the liver. These results indicate that these organ-specific T cells have different roles at their respective sites and that they may be of different lineages.     

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.     

Induction of granulocyte colony-stimulating factor by globular adiponectin via the MEK-ERK pathway

Adiponectin, an adipocyte-derived cytokine, affects a number of physiological processes, including immune function and inflammation. We investigated whether globular adiponectin (gAd) affects the expression of inflammation-related genes in murine macrophages (RAW264 cells). DNA microarray analysis indicated that granulocyte colony-stimulating factor (G-CSF) showed the largest increase in expression in gAd-stimulated RAW264 cells. The gAd-induced secretion of G-CSF increased in a time- and dose-dependent manner. U0126 (MEK1/2 inhibitor) and PD98059 (MEK1 inhibitor) reduced the gAd-induced G-CSF mRNA expression and G-CSF protein production. gAd induced the phosphorylation of MEK1/2 and ERK1/2 in RAW264 cells. In addition, the gAd-induced phosphorylation of MEK1/2 and ERK1/2 was dramatically reduced by PD98059 and U0126, respectively. Collectively, these results suggest that MEK1/2-ERK1/2 signaling is involved in the adiponectin-induced secretion of G-CSF.     

Electrocardiographic characteristics of the variants of idiopathic left ventricular outflow tract ventricular tachyarrhythmias

Background: Despite similar QRS morphology, idiopathic repetitive monomorphic ventricular tachyarrhythmias (VTs) of left ventricular outflow tract (LVOT) are known to have the variants of different adjacent origins, including the aorto-mitral continuity (AMC), anterior site around the mitral annulus (MA), aortic sinus cusps (ASC), and epicardium. However, the electrocardiographic characteristics of those variants previously have not been evaluated fully.
Methods and Results: Based on the mapping site and successful ablation in 45 consecutive patients with LVOT-VTs, we classified them into VTs of AMC (n = 3), MA (n = 8), ASC (n = 32), and epicardial (n = 2) origins. In all patients, we performed activation mapping and an electrocardiographic analysis. All AMC-VTs patients had monophasic R waves in almost all the precordial leads, while those with anterior MA-VTs had an Rs pattern in some precordial leads except for lead V6, and those with ASC-VTs had a variable transitional zone in leads V1–4. There was no S wave in lead V6 in any group except for one patient with anterior MA-VTs. The intrinsicoid deflection time in the AMC-VTs patients and anterior MA-VTs patients was significantly greater than in those with ASC-VTs (P < 0.05). There was no significant difference in the R-wave amplitude in the inferior leads among the groups. Successful radiofrequency catheter ablation (RFCA) was achieved in all patients except for in those with epicardial origin VT.
Conclusions: Despite many morphological similarities, the LVOT-VTs originating from the AMC, anterior MA and ASC could be identified by our proposed electrocardiographic characteristics in order to safely perform RFCA.     

Long-term follow-up of transvenous defibrillation leads: high incidence of fracture in coaxial polyurethane lead.

BACKGROUND: As a result of longer follow-up after implantation of cardioverter defibrillators (ICD), fatigue of the leads has become a concern. The aim of this study was to determine the incidence and clinical presentation of ICD lead failures. METHODS AND RESULTS: The study population consisted of 241 patients with 249 ICD leads who underwent implantation of an ICD with a transvenous lead system. After device implantation, the patients were routinely followed up every 4 months. Five lead failures (2.0%) occurred as an oversensing of artifact during the follow-up period (2.6+/-2.1 years); 4 of those 5 patients received inappropriate shocks and 1 case of lead failure was identified in a patient with frequent episodes of non-sustained ventricular fibrillation. In particular, the right ventricular polyurethane transvenous lead in the Medtronic model 6936 failed in 4 (13%) of 31 cases. Percutaneous lead extraction was not available in all cases, so an additional ICD lead was inserted through the same site of the subclavian vein. CONCLUSIONS: Lead failures may occur 5 years after ICD implantation and polyurethane leads have an especially high incidence of failure. However, there were no follow-up parameters observed that predicted lead failures.     

Modeling on social spread from immunity

We are now planning to make a transmission model of infectious diseases in the scale of a city. People live in the city contacting other persons with daily life. The model regards a contact as a source of infection. A person will be simulated as a simple system of differential equations. As a candidate of differential equations, we are now investigating Marchuk's simple model. We adopt Marchuk's simple model because it has formation time, i.e., latent time. As Dr. Takeuchi showed, latent time is very important. There remain problems of choosing parameters for special diseases. We are now planning to use Marquardt method to minimize residuals form clinical data to estimate parameters. As for contacts, there are many approaches. The approach of the MIDAS project is very intensive. Our approach is simple. There are about 30,000 Japanese every 15 minutes daily life data, sleeping, eating, work, study, house keeping, etc. Our approach is to make virtual families, husband, wife, children in a city and assign actions from the every 15 minutes data statistically and estimate their contacts in the companies or schools, etc.     

A case of limited Wegener granulomatosis with hypereosinophilia]

A 51-year-old female was admitted to Nagano Matsushiro General Hospital because of fever, cough and dyspnea on exertion. Her laboratory data revealed leukocytosis with hypereosinophilia, a high erythrocyte sedimentation rate and c-reactive protein. Chest radiography revealed an infiltration shadow with a cavity in the right upper lobe. A lung abscess was diagnosed and antibiotics were administered. Laboratory results showed improvement, but chest radiography continued to show cavities. She was admitted to our hospital because of fever, left pleural effusion and progression of cavities on chest radiographs. She showed no abnormalities of the upper airway or kidney, and was negative for c-antineutrophil cytoplasmic antibody (c-ANCA). Because a positive c-ANCA was seen on day 8 of hospitalization, L-type limited Wegener granulomatosis (WG) was diagnosed according to Gross et al. Prednisolone (PSL) was administered, which improved the anemia, eosinophilia and the cavities. On day 7 of PSL administration, of the left pneumothorax occurred as a complication caused by perforation of the left chest cavity, but her clinical course was good after a cavernectomy was performed. Some studies have reported that limited WG shows a negative c-ANCA, and that antibiotic therapy improves inflammation. The L-type of limited WG revealed a low-grade positive ratio and titer of c-ANCA. Moreover, L-type limited WG responds well to therapy. We therefore selected PSL administration only against L-type limited WG. We have reported L-type limited WG with eosinophilia and the negative effects of c-ANCA at an early clinical stage.     

Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease

Background & Aims: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). Methods: The contents of IL-15, tumor necrosis factor α, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [³H]thymidine incorporation into DNA. Results: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor α activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. Conclusions: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells.GASTROENTEROLOGY 1998;114:1237-1243