Differential oncogenic potential of geographically distinct Helicobacter pylori CagA isoforms in mice

Infection with cagA‐positive Helicobacter pylori is associated with gastric carcinoma. The cagA‐encoded CagA protein is delivered into gastric epithelial cells and, upon tyrosine phosphorylation at the C‐terminal EPIYA segments, binds and deregulates SHP‐2 oncoprotein. On the basis of the differential alignment of the EPIYA segments, CagA can be subdivided into Western CagA, which is produced by H. pylori isolated in Western countries, and East Asian CagA, which is produced by H. pylori circulating in East Asian countries. Western CagA contains EPIYA‐A, EPIYA‐B and variable numbers of EPIYA‐C segments, whereas East Asian CagA contains EPIYA‐A, EPIYA‐B and variable numbers of EPIYA‐D segments. Upon tyrosine phosphorylation, EPIYA‐C and EPIYA‐D, respectively, serve as low‐affinity and high‐affinity SHP‐2‐binding sites. We previously reported that systemic expression of East Asian CagA (CagA‐ABDD) induces gastrointestinal and hematopoietic malignancies in mice. In this study, we generated transgenic mice that systemically express Western CagA (CagA‐ABCCC), the levels of which are comparable to those in mice expressing East Asian CagA. The mice developed gastric epithelial hypertrophy and gastrointestinal tumors and also showed lymphoid abnormality but not myeloid abnormalities such as granulocytosis and myeloid leukemia found in mice carrying East Asian CagA. The incidence of tumors in mice expressing Western CagA was significantly lower than that in mice expressing East Asian CagA. Our results indicate that Western CagA is qualitatively less oncogenic than East Asian CagA. Differential oncogenic potential of geographically distinct CagA isoforms may contribute to the differential prevalence of gastric carcinoma between East Asian countries and Western countries. © 2009 UICC     

Gastric carcinosarcoma presenting as a huge epigastric mass

Gastric carcinosarcoma often presents with an elevated lesion or increased thickness of the stomach wall. Histological diagnosis is achieved using conventional hematoxylin and eosin staining to confirm the coexistence of both epithelial and mesenchymal elements. We report a case of gastric carcinosarcoma presenting as a large mass in the epigastric region. Specimens obtained by endoscopic biopsy and surgical excision showed diffuse proliferation of atypical cells in sheet formation. No mucus production or glandular structures were apparent, but immunoreactivity for both epithelial and mesenchymal markers was noted. These findings led to a definitive diagnosis of gastric carcinosarcoma. Immunohistochemical analysis is useful for the early diagnosis and treatment of gastric carcinosarcoma.     

Structural and functional diversity in the PAR1b/MARK2‐binding region of Helicobacter pylori CagA

Helicobacter pylori (H. pylori) cagA‐positive strains are associated with gastritis, peptic ulcerations, and gastric adenocarcinoma. Upon delivery into gastric epithelial cells, the cagA‐encoded CagA protein specifically binds and aberrantly activates SHP‐2 oncoprotein in a manner that is dependent on CagA tyrosine phosphorylation. CagA‐deregulated SHP‐2 then elicits aberrant Erk activation while causing an elongated cell shape known as the hummingbird phenotype. In polarized epithelial cells, CagA also binds to PAR1b/MARK2 and inhibits the PAR1b kinase activity, thereby disrupting tight junctions and epithelial cell polarity independent of CagA tyrosine phosphorylation. We show here that the CagA‐multimerization (CM) sequence that mediates interaction of CagA with PAR1b is not only essential for the CagA‐triggered junctional defects but also plays an important role in induction of the hummingbird phenotype by potentiating CagA‐SHP‐2 complex formation. We also show that the CM sequence of CagA isolated from East Asian H. pylori (referred to as the E‐CM sequence) binds PAR1b more strongly than that of CagA isolated from Western H. pylori (referred to as the W‐CM sequence). Within Western CagA species, the ability to bind PAR1b is proportional to the number of W‐CM sequences. Furthermore, the level of PAR1b‐binding activity of CagA correlates with the magnitude of junctional defects and the degree of hummingbird phenotype induction. Our findings reveal that structural diversity in the CM sequence is an important determinant for the degree of virulence of CagA, a bacterial oncoprotein that is associated with gastric carcinogenesis. (Cancer Sci 2008; 99: 2004–2011)     

Cultivation and preparation of <Emphasis Type="Italic">Lithospermum</Emphasis> roots quantification of total pigment in slender lateral roots

Development of a new preparation method of Lithospermi Radix enabled almost all the slender lateral roots (diameter smaller than 2 mm) to be preserved. The weight ratio of slender lateral roots was about 5.5% in the whole root. The amount of acetylshikonin in the slender lateral roots was two-fold greater than in its tap and thick lateral roots (diameter larger than 2 mm). The acid-insoluble ash content in slender lateral roots was 1.16%.     

In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans

AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans. METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined. RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability. When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001). The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction. CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.     

Key factors influencing bowel function after ileal W-pouch anal anastomosis: A spectral analysis of W-pouch motor activity

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure–volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = −0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch. Received: May 6, 1999 / Accepted: May 30, 2000     

Thoracic Esophagectomy Combined with Pylorus-Preserving Pancreatoduodenectomy in a One-Stage Procedure: Report of a Case

(Received for publication on Oct. 12, 1998; accepted on July 13, 1999)     

Off-pump coronary artery bypass grafting: comparison between standard CABG and off-pump CABG

We have performed 321 cases of coronary artery bypass grafting (CABG), between October 15 1995 and November 20 2000. We have evaluated the operative results of 142 cases (44.2%) of conventional CABG and 179 cases (55.8%) of off-pump CABG performed during this period. The average numbers of bypassed grafts was 3.53 for conventional CABG, and 1.62 for off-pump CABG. The total number of 369 grafts were anastomosed to 501 coronary arteries for conventional CABG, and 283 grafts were anastomosed to 290 coronary arteries for off-pump CABG. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using RITA, LITA, GEA and RA. Three site of stenosis in 18 LITAs and 2 in 16 RITAs were recognized in off-pump CABG without the use of stabilizers. One site of stenosis in 130 LITAs and 3 string signs in 44 GEA were recognized in off-pump CABG with the use of stabilizers. Postoperative angiography in 52 off-pump CABG cases at one year later showed no new lesion. CONCLUSION: The use of stabilizers and LIMA suture enables adaptation of the MIDCAB procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.     

The influence of thermal history on water associated with polyelectrolytes and cellulose

The formation of freezing water as a function of temperature and time has been studied in polyelectrolytes and in cellulose. In such systems, a portion of the sorbed water is not crystallizable under normal conditions. However, it was observed that in rapidly cooled systems the ratio between freezing and non-freezing water is variable and depends on the annealing temperature. The difference between the saturated concentration of freezable water and the concentration of freezing water which is formed immediately after the rise of the sample's temperature is dependent on the materials geometry. It is assumed that the rise of the annealing temperature above room temperature increases the amount of mobile water which can crystallize. By comparing the measured concentration of freezing water with desorption analysis, the average distance of transportation of mobile water for sodium carboxymethylcellulose was calculated as 8–10 μm.     

Successful treatment of gallbladder carcinoma producing alpha-fetoprotein with segmental adenomyomatosis

The successful treatment of hepatoid adenocarcinoma of the gallbladder with elevated serum alpha-fetoprotein (1243 ng/ml) and segmental adenomyomatosis in a 58-year-old woman is described. The woman had alpha-fetoprotein (AFP)-producing carcinoma of the gallbladder with regional lymph node metastasis and was treated by extended radical resection and postoperative adjuvant chemotherapy. She is alive, showing normal serum AFP concentration and no recurrence, 57 months after surgery. The tumor cells were stained immunohistochemically for AFP by the peroxidase anti-peroxidase method. Serum AFP reactivity to concanavalin A and lentil lectin was similar to the pattern shown in hepatocellular carcinoma. Only a few cases of AFP-producing gallbladder carcinoma have been reported and there have been no reports of long-term survivors. The combination of aggressive radical resection and chemotherapy seems to have been effective for achieving long-term survival without liver metastasis.