Growth factor receptor-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. We describe a pathway that involves AKT/PI3K to mediate chemoresistance in gastric cancer patients. Primary gastric carcinoma tissues and corresponding normal mucosa were obtained from 76 gastric cancer patients who underwent surgery in the Department of Surgery II in Kyushu University Hospital from the years 1996-2000. AKT activation was investigated by immunostaining with a phosphorylation-specific antibody, and LOH (loss of heterozygosity) of PTEN was studied in the same samples. AKT was phosphorylated in 22 cases (28.9%) of gastric cancer cases. AKT and phosphorylated AKT were not correlated with any clinicopathological factor. We found that the gastric cancer patients who had higher AKT phosphorylation (activated AKT) seemed to have LOH of PTEN (p 5 0.0008). When the chemotherapeutic sensibilities of these patients were studied in an MTT assay, it was found that the activated AKT was associated with increased resistance to multiple chemotherapeutic agents (5-fluorouracil, adriamycin, mitomycin C and cis-platinum). The results of our study indicate that AKT activation and LOH of PTEN plays an important role in conferring a broad-spectrum chemoresistance in gastric cancer patients. It also indicates that AKT may therefore be a novel molecular target for therapies or chemosensitivity tests that improve the outcomes of gastric cancer patients. ' 2005 Wiley-Liss, Inc.

Background The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. Patients and methods We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria.Results Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3-and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3-and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapsefree survival. Conclusions To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Bryophytes form the major seedbed for coniferous trees in the subalpine forests of central Japan. Field experiments were conducted on the floor of a closed stand dominated by Tsuga on Mt Fuji to examine the seedling survival of Abies veitchii and Tsuga diversifolia in seven substrate types in relation to the morphological characteristics of the seeds and seedlings. Neither Abies nor Tsuga seedlings could survive on dwarf-bamboo litter beyond 2 years after the seed rain. Abies seedlings survived not only in all types of bryophyte communities but also in larch litter. In contrast, the survival of Tsuga seedlings was restricted to communities of smaller-statured bryophytes found on logs. The seeds and 1st year seedlings of A.veitchii were larger than those of T. diversifolia. Abies seedlings produced hypocotyls taller than any bryophyte community and radicles which were long enough to penetrate into the moist humus layer, whereas Tsuga seedling radicles presumably penetrate into humus only in bryophyte communities forming a thin mat on logs. The effect of bryophytes on survival of tree seedlings therefore depends on the relationships between the morphology of seeds and seedlings and the structure of bryophyte communities.

These catecholaminergic changes may be caused by chronic hypoxia or ischemia, and also may underlie alterations in respiratory and cardiovascular control in sleep.

Subalpine forest succession was studied on Mt. Fuji, Japan, where various types of forests in different successional phases occur owing to volcanic action. Ninety stands were subjected to ordination using an index (S/) defined by the relative basal area and the life span of component woody species, and the cover of canopy layer of the sample stands. Two different sequences of sample stands were found. One was from deciduous scrubs, through Larix kaempferi forests and Abies forests, to Tsuga diversifolia forests, and the other from Abies-Tsuga thickets to Abies forests. Through analyses of the forest structure and composition, soil survey and identification of fallen logs, the former sequence was recognized as the primary sere and the latter as a regeneration sere following gap formation. During forest succession, basal area reached a maximum in the seral phase with a multi-layered structure. The Tsuga forests, whose understory is restricted to a moss layer, were regarded as the climax. The death or fall of Tsuga stems resulted in gaps, which were subsequently occupied by Abies-Tsuga thickets. The second Abies forests were distinguished from the ones in the primary sere by the occurrence of Drvopteris and Cacalia and the lack of Rhododendron in the understorey. Both Abies forest types included Tsuga saplings. Thus, a cyclic relation is supposed between Abies and Tsuga.

Key wordsErythromycin (EM) was administered to five extremely low birthweight infants (ELBWI) with delayed enteral feeding to evaluate the clinical effect on severely impaired gastrointestinal motility. Five patients studied responded well to EM administration without any adverse effects during the course. Four patients were given 15-30 mg/kg per day EM intravenously as a loading and thereafter 3-5 mg/kg per day as a maintenance dose. One patient responded well without loading. The infants could be fed enterally 4,5,6, 4 and 2 days after the initiation of EM administration, respectively. Erythromycin administration is a safe and useful way to facilitate gastrointestinal motility in ELBWI who require prolonged ventilator

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Background. According to the Consensus 2010 of the International Liaison Committee on Resuscitation (ILCOR), children with moderate to severe hypoxic-ischemic encephalopathy (HIE) should receive brain hypothermic therapy (BHT) after successful resuscitation. Elevated high mobility group box 1 (HMGB1) in the blood at the early stage of brain ischemia-reperfusion injury has been suggested to be involved in the release of various inflammatory cytokines. Methods. In total, 21 neonates plasma HMGB1 concentration was measured. These neonates included 8 with HIE in whom BHT was indicated, 5 controls diagnosed as having HIE but who were not suitable candidates for BHT, and 8 normal controls. Results. The umbilical artery HMGB1 (UA-HMGB1) level before undergoing BHT significantly exceeded reference values. The UA-HMGB1 level in the BHT (−) group did not differ significantly from reference values, but was significantly increased 24 hours after birth. Repeated measure ANOVA showed a significant difference in time course changes between the BHT (+) and BHT (−) groups (P = 0.0002). Conclusions. This study demonstrated hypothermic therapy to significantly decrease HMGB1. Furthermore, HMGB1 is a useful index of the inhibition of early stage inflammation.