Expression of GPIV and Naka antigen on monocytes in Naka-negative subjects whose platelets lack GPIV

Summary. The platelet antigen Nak^a was once considered to be a platelet-specific alloantigen and is carried on platelet membrane glycoprotein (GP) IV. Recent studies suggest that Nak^a-negative subjects lack platelet GPIV. GPIV is an important adhesive receptor and expressed on the surface of monocytes as well as of platelets. In the present study, flow cytometry was used to detect GPIV and Nak^a antigen on the surface of monocytes. Nak^a antigen was expressed on monocytes as well as on platelets in Nak^a-positive subjects ( n = 6) (P-GPIV-positive subjects). To our surprise, monocytes of Nak^a-negative subjects ( n = 7) (P-GPIV-negative subjects) having no anti-Nak^a antibody in their serum expressed GPIV and Nak^a antigen to almost the same degree as did the monocytes of P-GPIV-positive subjects. Competitive experiments using OKM5 (a monoclonal antibody against GPIV) and anti-Nak^a antibody showed that the epitope of anti-Nak^a antibody on monocytes was very close to that of OKM5. In two P-GPIV-negative subjects having anti-Nak^a antibody in their serum, GPIV and Nak^a antigen were not expressed on the surface of either monocytes or platelets. These results indicate that the GPIV molecules and Nak^a antigen are expressed on the surface of monocytes in the majority of P-GPIV-negative subjects, but that in a very few P-GPIV-negative subjects neither GPIV nor Nak^a antigen is expressed on the surface of their monocytes. We hypothesize that P-GPIV-negative subjects who carry neither GPIV nor Nak^a antigen on their monocytes produce anti-Nak^a antibody as a result of transfusion or pregnancy.     

Synchronous triple primary cancers of the pharynx and esophagus

A 72-year-old male with nausea and heartburn was found to have early pharyngeal squamous cell carcinoma, superficial and advanced esophageal squamous cell carcinoma and early esophageal adenocarcinoma by esophagogastroduodenoscopy. Computerized tomography demonstrated left cardiac lymph node swellings. We prioritized the treatment for esophageal squamous cell carcinoma, as this was the most advanced cancer among the triple primaries. The patient underwent neoadjuvant chemotherapy for esophageal squamous cell carcinoma followed by esophagectomy. Four months after esophagectomy, endoscopic submucosal dissection for pharyngeal squamous cell carcinoma was performed. This is a first report of pharyngeal squamous cell carcinoma, esophageal squamous cell carcinoma and esophageal adenocarcinoma occurring as triple primary cancers in a single patient. Smoking-induced tumor formation through DNA methylation is a common risk factor for patients with triple primary malignancies, being an example of epigenetic field cancerization induced by exposure to carcinogenic factors.     

Antidiabetogenic MHC class II promotes the differentiation of MHC-promiscuous autoreactive T cells into FOXP3+ regulatory T cells

Polymorphisms in MHC class II molecules, in particular around β-chain position-57 (β57), afford susceptibility/resistance to multiple autoimmune diseases, including type 1 diabetes, through obscure mechanisms. Here, we show that the antidiabetogenic MHC class II molecule I-A^b affords diabetes resistance by promoting the differentiation of MHC-promiscuous autoreactive CD4⁺ T cells into disease-suppressing natural regulatory T cells, in a β56–67-regulated manner. We compared the tolerogenic and antidiabetogenic properties of CD11c promoter-driven transgenes encoding I-A^b or a form of I-A^b carrying residues 56–67 of I-Aβ^g7 (I-A^b-g7) in wild-type nonobese diabetic (NOD) mice, as well as NOD mice coexpressing a diabetogenic and I-A^g7–restricted, but MHC-promiscuous T-cell receptor (4.1). Both I-A transgenes protected NOD and 4.1-NOD mice from diabetes. However, whereas I-A^b induced 4.1-CD4⁺ thymocyte deletion and 4.1-CD4⁺Foxp3⁺ regulatory T-cell development, I-A^b-g7 promoted 4.1-CD4⁺Foxp3⁺ Treg development without inducing clonal deletion. Furthermore, non–T-cell receptor transgenic NOD.CD11cP-I-A^b and NOD.CD11cP-IA^b-g7 mice both exported regulatory T cells with superior antidiabetogenic properties than wild-type NOD mice. We propose that I-A^b, and possibly other protective MHC class II molecules, afford disease resistance by engaging a naturally occurring constellation of MHC-promiscuous autoreactive T-cell clonotypes, promoting their deviation into autoregulatory T cells.     

Impact of coronary artery remodeling on misinterpretation of angiographic disease eccentricity: evidence from intravascular ultrasound

This study was designed to examine the impact of coronary artery remodeling, enlargement or shrinkage, on the angiographic disease eccentricity. A total of 82 coronary sites from 73 patients with significant stenosis (>50%) were prospectively analyzed by both quantitative coronary angiography and intravascular ultrasound. By quantitative coronary angiography, the maximal and minimal distances from the center of the stenosis to the outline of the vessel wall were measured, and the eccentricity index was calculated by the formula {(maximal-minimal)/maximal}. By intravascular ultrasound, the maximal and minimal distances from the center of the lumen to the leading edge of the second echogenic zone were measured, and the eccentricity index was calculated by the same formula. For identifying the vessel remodeling, the total vessel area that was determined by tracing the leading edge of the second echogenic zone was measured at the stenotic sites and the adjacent proximal and distal segments. By quantitative coronary angiography, the maximal and minimal distances were 1.76 ± 0.6 and 0.97 ± 0.3 mm, respectively, yielding an eccentricity index of 0.42 ± 0,2. The maximal and minimal distances by intravascular ultrasound were 2.77 ± 0.6 mm and 1.46 ± 0.4 mm, respectively, yielding an eccentricity index of 0.45 ± 0.2 (NS). Although the average eccentricity index was not different between the two methods, there was substantially no correlation between the eccentricity index determined by the two methods (r = 0.38, Y = 0.43x + 0.22). However, this correlation was significantly improved (r = 0.55, Y = 0.73x + 0.12, P < 0.001) when 44 stenotic segments with remodeling were excluded for comparison. These results indicate that coronary artery remodeling could be a major contributing factor to angiographic misinterpretation of disease eccentricity. We suggest that intravascular ultrasound is a powerful method that can accurately determine diseases eccentricity as well as disease severity.     

Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats

Aims. To study the effects of physiological concentrations of rat proinsulin C peptide I and II, respectively, on whole body glucose utilization in streptozotocin diabetic and healthy rats. Methods. A sequential insulin clamp procedure was used (insulin infusion rates 3.0 and 30.0 mU · kg^–1· min^–1) in awake animals. C-peptide infusion rates were 0.05 and 0.5 nmol · kg^–1· min^–1. Blood glucose was clamped at 7.7 ± 0.3 mmol/l in the diabetic rats and at 3.9 ± 0.1 mmol/l in the healthy rats. Results. In diabetic rats infused at lower rates of C peptide and insulin, glucose utilization increased by 79–90 % (p < 0.001) compared with diabetic animals infused with saline and insulin. Increasing the rate of C-peptide infusion tenfold did not elicit a statistically significant further increase in glucose utilization. C peptide I and II exerted similar effects. The metabolic clearance rate for glucose in the diabetic animals infused with C peptide was not different from that of the healthy rats. During high-dose insulin infusion (30.0 mU · kg^–1· min^–1) glucose utilization increased considerably and no statistically significant C-peptide effects were observed. About 85 % of the increase in glucose utilization induced by C peptide could be blocked by treatment with N-monomethyl-l-arginine. Conclusions/interpretation. Physiological concentrations of homologous C peptide stimulate whole body glucose utilization in diabetic but not in healthy rats. C peptide I and II elicit similar effects. The influence of C peptide on glucose utilization may be mediated by nitric oxide. [Diabetologia (1999) 42: 958–964] Received: 8 January 1999 and in final revised form: 20 April 1999     

The vast majority of gastric T cells are polarized to produce T helper 1 type cytokines upon antigenic stimulation despite the absence of Helicobacter pylori infection

Helicobacter pylori infection is associated with chronic infiltration by various cell types, including T cells, whose cytokine production may regulate the inflammatory reaction as well as local immune response to the bacterium. We prospectively analyzed the constituents of the cellular infiltrates and the cytokines produced by T cells in antral biopsies obtained from 73 subjects with and without H. pylori infection, before and after eradication therapy, and compared them with a histological grade of gastritis. We found that T cells predominated in cell number, followed by granulocytes/monocytes and plasma cells in both H. pylori-infected and H. pylori-uninfected subjects. Despite the absence of H. pylori infection, more than 70% of gastric CD4-positive T cells obtained from uninfected tissue produced interferon-γ (IFN-γ) in the cytosol. Upon receptor cross-linking of a CD3 and a CD28 molecule, T cells in both infected and uninfected tissue continuously secreted a far greater amount of IFN-γ than those in peripheral blood mononuclear cell controls for a period of cell culture, whereas the increase in interleukin-4 (IL-4) was very small, and no increase in IL-2 secretion was seen. In H. pylori-infected patients, IFN-γ secretion was correlated with the grade of mononuclear cell infiltration and decreased to an uninfected control level after eradication therapy. We did not see the effect of eradication on IL-4 secretion. Anti-H. pylori antibody of the IgG2 subclass was remarkably increased in H. pylori-infected subjects. These results together suggest that gastric T cells are already differentiated to produce a large amount of IFN-γ by a mechanism unrelated to H. pylori infection. H. pylori infection appeared to activate T cells to secrete even more IFN-γ, which may contribute to maintaining a perpetual inflammation in H. pylori-infected stomach. Received: January 15, 1999 / Accepted: May 28, 1999     

Transcatheter arterial embolization for impending rupture of an isolated internal iliac artery aneurysm complicated with disseminated intravascular coagulation

A 90-year-old male, with impending rupture of an isolated internal iliac artery aneurysm (IIAA) complicated with disseminated intravascular coagulation (DIC) was successfully treated with transcatheter arterial embolization (TAE). After TAE, enlargement of the aneurysm was arrested and coagulation-fibrinolytic abnormalities induced by DIC improved without severe complications. Although IIAA is relatively rare, the post-operative mortality of patients with ruptures is reportedly high. We assessed the usefulness of this procedure for impending rupture of IIAA, especially for patients in high risk groups.     

Antibiotics resistance rate of Helicobacter pylori in Bhutan

AIM:To survey the antibiotic resistance pattern of Helicobacter pylori(H.pylori)strains isolated from Bhutanese population.METHODS:We isolated 111 H.pylori strains from the gastric mucosa of H.pylori-infected patients in Bhutan in 2010.The Epsilometer test was used to determine the minimum inhibitory concentrations(MICs)of amoxicillin(AMX),clarithromycin(CLR),metronidazole(MNZ),levofloxacin(LVX),ciprofloxacin(CIP),and tetracycline(TET).RESULTS:Nineteen of the isolated H.pylori strains were susceptible to all antibiotics tested.The isolated strains showed the highest rate of antibiotic resistance to MNZ(92/111,82.9%).Among the 92 MNZresistant strains,74 strains(80.4%)showed high-level resistance(MIC≥256 g/mL).Three strains were resistance to LVX(2.7%).These strains were also resistance to CIP.None of the strains showed resistance to CLR,AMX and TET.CONCLUSION:CLR-based triple therapy is a more effective treatment approach over MNZ-based triple therapy for H.pylori infection in Bhutan.     

Clinical significance of fat infiltration in the moderator band and right ventricular myocardium in multislice CT,and its association with abnormal conduction seen in electrocardiogram

Purpose

We evaluated the clinical significance of fat infiltration in the moderator-band (MB) of the right ventricle (RV) and in the RV myocardium (RVM) and its association with conduction abnormalities in the electrocardiogram.

Materials and methods

132 subjects (58 male; age 59 ± 27 years) with no findings of organic-disease (all right and left side hearts were normal) undergoing electrocardiogram-gated non-contrast multislice-CT (Light-Speed-Ultra-16) were retrospectively analyzed for the presence of fat infiltrating the MB or RVM.

Results

MB fat infiltration was detected in 42 subjects, but these individuals showed no significant differences in the incidence of right bundle branch-block, mean QRS-width or standard-deviation of the QRS-axis, which would have suggested the presence of hemi left bundle branch-block. Only age (64.3 vs 57.9 years, p = 0.025) was significantly different in subjects with MB fat infiltration. But logistic regression showed none of the factor associated with increased presence of MB fat infiltration. RVM fat infiltration was detected in 35 subjects, again with no significant differences in the incidence of right bundle branch-block, QRS width or standard-deviation of the QRS axis. Only age (65.9 vs 57.8 years, p = 0.001) and gender (71% vs 51% female, p = 0.033) were significantly different in subjects with RVM fat infiltration. Logistic regression showed age (Odd-ratio = 1.05 and 95% CI = 1.01–1.08 p = 0.008) and female sex (Odd-ratio = 2.44 and 95% CI = 1.03–5.88; p = 0.043) were associated with increased RV fat infiltration.

Conclusions

MB or RVM fat infiltration seen on CT may not indicate organized abnormal myocardial conduction, but RVM fat infiltration may indicate only degeneration due to aging, especially in females.