p53 Overexpression and K-ras Codon 12 Mutations in Submucosal Invasive Colorectal Cancer.

We examined histological findings, p53 overexpression and K-ras codon 12 mutations and the histology of submucosal invasive (sm) colorectal cancers. Sixty specimens of sporadic sm cancer were obtained by surgical resection or endoscopic polypectomy. p53 expression was examined by im-munohistochemical staining using the streptavidin-biotin method. K-ras codon 12 mutations were detected by polymerase chain reaction (PCR) and dot blot hybridization. These tumors were classified as horizontal or nonhorizontal growth sm cancers. Fifteen of 60 (25%) superficial type horizontal growth cancers gave rise to sm cancers. There was no significant difference in size between horizontal and nonhorizontal growth sm cancers. There was no significant difference in the frequency of p53 expression between horizontal [8/15 (53.3%)] and nonhorizontal [22/45 (48.9%)] growth sm cancers. The frequency of K-ras codon 12 point mutations was significantly lower in horizontal growth [0/15 (0%)] sm cancers as compared to nonhorizontal growth [22/45 (48.9%)] sm cancers. We conclude that the development of superficial type horizontal growth cancers may involve a distinct genetic pathway.

High prevalence of gastroesophageal reflux disease with minimal mucosal change in asthmatic patients.

It is known that the prevalence of gastroesophageal reflux disease (GERD) in asthmatic patients is high. Although an endoscopic diagnosis of GERD based on the established Los Angeles (LA) classification requires the detection of erosive mucosal breaks, there are patients with GERD who have prominent erythema of the esophageal membrane without erosive mucosal breaks. Non-erosive mucosal change denotes the minimal change of the discoloring type of reflux esophagitis. This study was undertaken to determine the prevalence of GERD in asthmatic patients using the LA classification with the inclusion of minimal change, compared to the prevalence determined using the established LA classification without minimal change. The presence of GERD in asthmatic patients (n = 78), non-asthmatic disease control patients (n = 56), and healthy subjects (n = 150) was evaluated by endoscopic examination. The frequency of GERD in asthmatic patients based on the LA classification with minimal change was higher (54/78, 69.2%) than in asthmatic patients based on the LA classification without minimal change (37/78, 47.4%) (p < 0.05). The prevalence of GERD in asthmatic patients (69.2%) was higher than that in disease control patients (17/56, 30.4%) and healthy subjects (27/150, 18.0%) based on the LA classification with minimum change. These data indicate that asthmatic patients have a high frequency of GERD. In addition, without the inclusion of minimum change to the diagnosis of GERD, the prevalence of GERD appears to be underestimated in asthmatic patients. Therefore, physicians should carefully observe asthmatic patients with minimal change on endoscopy.

A proton pump inhibitor, lansoprazole, ameliorates asthma symptoms in asthmatic patients with gastroesophageal reflux disease.

Aspiration of acid to the airway causes airway inflammation, and acid stress to the airway caused by gastroesophageal reflux disease (GERD) has been known as a potential mechanism of deteriorated asthma symptoms. However, the efficacy of the acid suppressive drugs, H(2)-receptor blockers (H(2) blocker) and proton pump inhibitors, on asthma symptoms and pulmonary functions remains controversial. We therefore designed the randomized prospective study to determine the efficacy of an H(2) blocker (roxatidine, 150 mg/day) and a proton pump inhibitor (lansoprazole, 30 mg/day) on asthma symptoms of 30 asthmatic patients with GERD. These patients were divided in the two groups (15 patients for each group) and treated with either roxatidine or lansoprazole. The diagnosis of GERD was established by the method of Los Angeles classification including mucosal minimum change of Grade M and questionnaire for the diagnosis of reflux disease (QUEST) score. The efficacy of acid suppressive drugs was evaluated by peak expiratory flow (PEF), asthma control questionnaire (ACQ) that evaluates the improvement of asthma symptoms, and forced expiratory volume in 1 second (FEV(1.0)). Lansoprazole, but not roxatidine, significantly improved PEF and ACQ scores (p < 0.05) with the improved QUEST scores. However, these acid suppressive drugs did not change the pulmonary function of FEV(1.0) in asthmatic patients. In conclusion, treatment with a proton pump inhibitor, lansoprazole, appears to be useful in improvement of asthma symptoms in asthmatic patients with GERD.

Facile intramolecular cyclization in oxidative coupling of acetylenes linked to 1,3-positions of benzene: strained [12]metacyclophanedienetetrayne system.

Oxidative coupling of ethynylpropellane linked to 1,3,5-position of a benzene core 3b did not give the cage dimer 2 but the dimer 4 having a strained [12]metacyclophanedienetetrayne system. The spectral and structural features of the novel ring system were revealed for the simple dibenzo derivative 6, which was also prepared efficiently by the intramolecular cyclization of the open-chain precursor.

Generation and characterization of highly strained dibenzotetrakisdehydro[12]annulene.

We report here the generation of tetrakisdehydro[12]annulene possessing a highly deformed triyne component from the [4.3.2]propellatriene-annelated precursor by its photolysis extruding indan and the characterization of the highly reactive annulene by chemical and spectroscopic methods. In addition to the chemical evidence for the formation of the title compound in solution such as interception as a Diels-Alder adduct, we succeeded in its characterization by UV-vis and FTIR spectra in an argon matrix at 20 K. The experimental IR spectrum agreed well with the theoretical one calculated by the DFT method.