Single water solvation dynamics in the 4-aminobenzonitrile-water cluster cation revealed by picosecond time-resolved infrared spectroscopy

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The dynamics of a solvent is important for many chemical and biological processes. Here, the migration dynamics of a single water molecule is triggered by the photoionization of the 4-aminobenzonitrile-water (4ABN-W) cluster and monitored in real time by picosecond time-resolved IR (ps TRIR) spectroscopy. In the neutral cluster, water is hydrogen-bonded to the CN group. When this CN-bound cluster is selectively ionized with an excess energy of 1238 cm(-1), water migrates with a lifetime of tau = 17 ps from the CN to the NH2 group, forming a more stable 4ABN(+)-W(NH) isomer with a yield of unity. By decreasing the ionization excess energy, the yield of the CN -> NH2 reaction is reduced. The relatively slow migration in comparison to the ionization-induced solvent dynamics in the related acetanilide-water cluster cation (tau = 5 ps) is discussed in terms of the internal excess energy after photoionization and the shape of the potential energy surface

てんかんの神経機構における脳内セロトニン系の関与: ネコの海馬キンドリングモデルを用いた実験的研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1104号, 学位授与年月日：平成6年3月25日,学位授与年：199

Pharmacokinetic analysis of in vivo metabolism of amino acid or dipeptide conjugates of salicylic acid in rabbit intestinal microorganisms

We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine, and tyrosine) or SA-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by intestinal microorganisms and, also, by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behavior was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.without figuresグラフな

The role of Kyoto classification in the diagnosis of Helicobacter pylori infection and histologic gastritis among young subjects in Japan

　BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection induces inflammation of the gastric mucosa and leads to erosions, gastro-duodenal mucosa atrophy, and intestinal metaplasia. The Kyoto classification diagnoses H. pylori infection via endoscopic findings. We aimed to clarify the role of the Kyoto classification in diagnosing H. pylori infection and histologic gastritis in young Japanese individuals.　METHODS: From1031 consecutive subjects aged ≤29 years who underwent esophagogastroduodenal endoscopy at our two hospitals from 2010 to 2017, 220 were selected for participation in the present study. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic and histological interpretations were based on the Kyoto classification and updated Sydney System. H. pylori infection was confirmed by histology and Giemsa or Gimenez staining.　RESULTS: Endoscopic findings were normal in 103 cases. Atrophy was found in 56 cases; diffuse redness, in 45 cases; nodularity, in 38 cases; and mucosal swelling, in 34 cases. The infection rate was 30.9% (68/220). In total, 67 subjects with H. pylori -positive endoscopic findings and confirmed as H. pylori -positive had histologic gastritis of the antrum and corpus. In contrast, of 153 subjects with H. pylori -negative endoscopic findings only 1 was subsequently confirmed to be H. pylori positive. Among the 67 subjects with H. pylori -positive endoscopic findings, 23 (34.3%) presented with histological atrophic gastritis of the corpus and 6 (9.0%) with intestinal metaplasia.　CONCLUSIONS: Our findings show that H. pylori infection is strongly associated with endoscopic and histologic gastritis in young subjects and both H. pylori infection and histologic gastritis can be evaluated endoscopically based on the Kyoto classification. Furthermore, prompt H. pylori eradication may prevent gastric cancer development given the high prevalence of atrophic gastritis and intestinal metaplasia in young Japanese individuals

Expression of Intercellular Adhesion Molecule-1 in the Livers of Rats Treated with Diethylnitrosamine

It has been reported that levels of soluble intercellular adhesion molecule-1 (ICAM-1) in the blood are elevated in hepatocellular carcinoma patients. In the present study, serial observations of the localization of ICAM-1 in the liver were made by light and electron microscopy in rats with carcinogen-induced cancer. Male Fisher rats were given diethylnitrosamine (DEN) orally in their drinking water. Rats were sacrificed at 6, 8, 12, or 14 weeks after the start of DEN administration and the liver tissue was collected. ICAM-1 expression in liver was assessed using indirect immunoperoxidase staining with anti-rat ICAM-1 antibody. Although ICAM-1 expression by endothelial cells in livers of DEN-treated rats was lower than in the control group at 8 weeks, it was higher in the membrane and cytoplasm of hepatocytes. The expression of ICAM-1 in mesenchymal cells was decreased, paralleling development of cellular atypia, whereas in hepatocyte membranes and cytoplasm it was increased in these atypia. ICAM-1 was localized to the cytoplasm of cancer cells, but to the membrane of hepatocytes in the treated livers at 14 weeks. Furthermore, the levels of ICAM-1 in mesenchymal cells tended to be lower in the cancerous area than in the atypical hyperplastic nodule, and were reduced as the density of cell atypia increased, in comparison to cells in areas without cancerous nodules. We concluded that ICAM-1 may be influenced the development of cancer induced in the rat liver by a chemical carcinogen

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α₂, integrin α₄, and integrin α₅and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p

Four cases of gastric cancer in patients with autoimmune gastritis

　Here, we report on four cases of gastric cancer in patients with autoimmune gastritis (AIG). AIG is characterized by the corpus-predominant atrophic gastritis with preserved antrum caused by autoimmune mechanisms. Although AIG is a high risk factor for gastric cancer and neuroendocrine tumors (NET), there are few reports describing the characteristics of gastric cancer in patients with AIG. In this case report, all four cases were diagnosed as having AIG by endoscopic findings and the presence of extra-gastric autoimmune diseases before the treatment for gastric cancer