A link between hyperthyroidism and pulmonary hypertension has been reported, but the underlying mechanisms of these two conditions have not been clearly identified. The aim of this study was to determine the clinical correlates of pulmonary hypertension in patients with Graves’ disease. Among 50 consecutive patients with Graves’ disease referred for echocardiography, 18 patients (36 %) had pulmonary hypertension measured by continuous-wave Doppler echocardiography (pulmonary artery systolic pressure >35 mmHg). The patients with pulmonary hypertension had significantly higher pulmonary vascular resistance (PVR), cardiac output and thyroid-stimulating hormone receptor antibody (TRAb) compared to those without (p < 0.001, p = 0.028 and p < 0.001, respectively). Pulmonary artery systolic pressure had a good correlation with TRAb (r = 0.74, p < 0.001), but was not related to free T4 (r = 0.12, p = 0.419) and free T3 (r = 0.22, p = 0.126). To determine the important variables present in patients with Graves’ disease that may be related to pulmonary artery systolic pressure, 4 variables (PVR, cardiac output, TRAb and free T3) were used in the multivariate analysis. In addition to PVR (standard regression coefficient = 0.831, p < 0.001) and cardiac output (standard regression coefficient = 0.592, p < 0.001), TRAb (standard regression coefficient = 0.178, p < 0.001) emerged as a significant variable related to pulmonary artery systolic pressure. Thus, in addition to the effect of thyroid hormone on the cardiovascular system, autoimmune-mediated pulmonary vascular remodeling may play a role in Graves’ disease-linked elevated pulmonary artery systolic pressure.

No abstract

Helicobacter pylori (H. pylori), a gram-negative spiral bacterium, colonizes the human stomach and establishes a persistent infection associated with gastrointestinal inflammatory diseases including peptic gastric ulcer, duodenal ulcer, gastric cancer (31) and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (2). The diversity or adaptive mutation in H. pylori genes like babA (1) generally alters the biological aspect of the microbe to response to individual conditions and eventually establishes a persistent infection in the human stomach. We previously reported that cdrA, a unique gene of H. pylori, has a repressive function on cell division. A wild-type strain HPK5 formed multinuclear filamentous cells in the early stationary phase and adopted coccoid forms in the stationary phase when grown in a high-salt level medium. On the other hand, a cdrA-disrupted mutant HPKT510 did not show such an abnormality and remained as short rods under the same conditions (30). By microarray analysis, the cdrA gene was found to be lost in 3 out of 4 colonies recovered

In IL-5 transgenic mice (C3H/HeN-TgN(IL-5)-Imeg), in which 50% of peripheral blood leukocytes are eosinophils, the development of infection by Leishmania amazonensis was clearly suppressed. To determine mechanistically how this protozoan parasite is killed, we performed in vitro killing experiments. Either IL-4 or IFN-gamma effectively stimulated eosinophils to kill Leishmania amazonensis promastigotes, and most of the killing was inhibited by catalase but not by the NO inhibitor L-N5-(1-iminoethyl)-ornithine, suggesting that hydrogen peroxide is responsible for the killing of L. amazonensis by eosinophils. There was no significant degranulation of eosinophils in the culture, because eosinophil peroxidase was not detected in culture supernatants when L. amazonensis promastigotes were killed by activated eosinophils. Such resistance was also observed in BALB/c mice, which are highly susceptible to L. amazonensis. Expression plasmids for IL-4, IL-5, and IFN-gamma were transferred into muscle by electroporation in vivo starting 1 week before infection. Expression plasmid for IL-5 was most effective in slowing the development of infection among three expression plasmids. Expression plasmid for IL-4 was slightly effective and that for IFN-gamma had no effect on the progress of disease. These results suggest that IL-5 gene transfer into muscle by electroporation is useful as a supplementary protection method against L. amazonensis infection.

No abstract

Background/Aim: Among various kidney disease models, there are few rat glomerulonephritis (GN) models that develop in a short time, and with mainly glomerular lesions. Hypoxia-inducible factor (HIF)-1α is a transcriptional factor that induces genes supporting cell survival, but the involvement of HIF-1α in attenuating the progression of GN remains to be elucidated. We developed a new model of rat GN by coadministration of angiotensin II (AII) with Habu snake venom (HV) and investigated whether HIF-1α is involved in renal protection. Methods: Male Wistar rats were unilaterally nephrectomized on day 1, and divided into 4 groups on day 0; N group (no treatment), HV group, A group (AII), and H+A group (HV and AII). To preinduce HIF-1α, cobalt chloride (CoCl₂) was injected twice before injections of HV and AII in 11 rats. Results: GN was detected only in the H+A group; observed first on day 2 and aggravated thereafter. HIF-1α was expressed in the glomeruli and renal tubules in the A and H+A groups. In the H+A group, GN was remarkably reduced by CoCl₂ pretreatment (44.9 to 12.2%, p < 0.01). Conclusion: Both HV and AII were critical for the development of GN, and HIF-1α remarkably attenuated the progression of GN.

Infection with H. pylori possessing the cagA gene is associated with the development of severe gastric damage such as gastric atrophy, leading to gastric cancer, and probably influences the differences in GCI between Costa Rican regions.

We investigated the correlation between the SOD activity of Helicobacter pylori (H. pylori) and gastroduodenal diseases and the characteristics of strains exposed to oxidative stress. Two sequenced strains, 26695 and J99, and clinical isolates from 156 Japanese patients with gastroduodenal diseases such as gastric cancer (n = 59) and non-cancer (n = 97) were used. SOD activities of all 158 isolates were measured and were divided into three groups: high-SOD activity (>0.22, n = 2), moderate-SOD activity (0.15 0.22, n = 16) and low-SOD activity (<0.15, n = 140). Expressions of H. pylori Fe-SOD were examined by western blotting with anti-H. pylori Fe-SOD antibody prepared inhouse, and the profiles of Fe-SOD activity were investigated by zymogram with activity staining in native-PAGE. The characteristics of strains from high-SOD and low-SOD groups were examined under oxidative stress by paraquat. The average of H. pylori SOD activity was significantly higher in the cancer group than in the non-cancer group (P < 0.05). However, irrespective of SOD activity level, the amount of Fe-SOD expressed was variable among individual strains. Zymogram revealed a single band in moderate-SOD and low-SOD strains, but multiple bands in high-SOD strains were observed. These bands were confirmed as H. pylori Fe-SOD. Under oxidative stress with paraquat, low-SOD strains were drastically eliminated without inducible SOD activity; however, high-SOD strains were still viable with increased SOD activity. This study is the first to exhibit the characteristics of high-SOD activity strains representing multiple bands in zymograms and the correlation between H. pylori SOD activity and gastric cancer. Key words