Impact of Resistance Exercise under Hypoxia on Postexercise Hemodynamics in Healthy Young Males.

We investigated the effects of resistance exercise under hypoxia on postexercise hemodynamics in eight healthy young males. The subjects belonged to a track & field club (sprinters, hurdlers, and long jumpers) and engage in regular physical training (1-2 h per day, 3-5 days per week). Each participant performed eight sets of bilateral leg squats with a one-minute interval under normoxia (room air) and hypoxia (13 % FiO2). During a 60-minute recovery, we set normoxic condition either after normoxic or hypoxic exercise. These two experimental protocols (normoxia and hypoxia) were performed in a random order with a one-week washout period. The leg squat exercise consists of 50 % 1-RM (14 repetitions) × 5 sets and 50% 1-RM (repetitions max; 7 repetitions) × 3 sets. The resting period between each set was 1 min, and a total of 91 repetitions were performed. Blood pressure, heart rate (HR), and several biomarkers were measured pre- and postexercise. The mean arterial pressure (MAP) significantly decreased after exercise compared to the pre-exercise values under both conditions (P < 0.05). The MAP at 20 and 30 min of recovery in hypoxia was significantly lower than in normoxia (P < 0.05, respectively). The antidiuretic hormone significantly increased after 60 min of recovery in both conditions; moreover, the values in hypoxia were significantly higher than those in normoxia (P < 0.05). The delta changes in MAP from baseline (pre-exercise) were significantly related to changes in HR from baseline in normoxia (r = 0.560, P < 0.001) but not in hypoxia. These results suggest that the hypoxic condition elicits greater hypotension after resistance exercise in comparison to normoxia. Moreover, the underlying mechanisms for the attenuation of hypotension after resistance exercise may differ between normoxia and hypoxia.

Risk factors of converting to laparotomy in laparoscopic appendectomy for acute appendicitis.

PURPOSE: Laparoscopic appendectomy (LA) for acute appendicitis has several advantages over open appendectomy (OA). In cases of complicated appendicitis, LA is converted to OA at a constant rate, though converting appendectomy (CA) has several disadvantages. We retrospectively determined preoperative risk factors for failure of LA and subsequent conversion to OA. METHODS: Consecutive cases of preoperative computed tomography (CT) and attempted LA were retrieved from our hospital database and grouped by procedure (LA versus CA). Patients with negative appendectomies (n = 28), opened appendectomy (n = 210), delayed interval appendectomy (n = 3), or who were <14 years of age were excluded. RESULTS: Average patient age, preoperative C-reactive protein (CRP) level, and diffuse peritonitis were significantly different between the groups. CT inflammation and occurrence of complicated appendicitis were significantly higher in CA than LA. Conversion to OA was mostly because of dense adhesions, diffuse peritonitis, and difficulties in excision of the appendix due to perforation or severe inflammation from surgical point of view. Postoperative complications were significantly lower in LA than CA, although the rate of intraoperative abscess was not different. CONCLUSION: Most patients with acute appendicitis can be successfully treated with LA. We identified the following significant risk factors of CA: CT inflammation grade 4 or 5; complicated appendicitis; higher preoperative CRP level; and diffuse peritonitis.

[Case of adenocarcinoma in situ accompanied by an intrapulmonary lymph node with a sarcoid-like reaction].

A 65-year-old male underwent a chest CT scan, which revealed an 8 mm nodule on the wall of a bulla in the left lower lobe of the lung, and was thus suspected to be lung cancer. Pulmonary wedge resection of the left lower lobe by means of video-assisted thoracoscopic surgery was thus performed. A specimen of the lung revealed the presence of intrapulmonary lymph node on the wall of a bulla. The histopathological findings of the resected lung specimen showed non-caseating granulomas in the lymph node, and adenocarcinoma in situ. We concluded that the sarcoid-like reaction observed in the intrapulmonary lymph node was therefore related to the adenocarcinoma in situ.

A survey of the effects of sivelestat sodium administration on patients with postoperative respiratory dysfunction.

PURPOSE: To clarify the clinical significance of sivelestat sodium (SIV) administration, we surveyed the status of 40 patients treated with SIV for respiratory dysfunction following surgery. METHODS: The subjects were patients who received SIV administration due to systemic inflammatory response syndrome (SIRS) and respiratory dysfunction (PaO(2)/F(I)O(2) ratio ≤300 mmHg) after surgery at the Department of Surgery and Science, Kyushu University, and related facilities between April and December 2008. RESULTS: The most frequent underlying condition was perforation of the digestive tract, followed by cancer of the upper digestive organs. The main causes of SIRS were surgical stress and infection. The mean P/F ratio at the initiation of SIV administration was 185.5 ± 72.0 mmHg. The ratio increased, and the number of SIRS-related factors decreased with time after SIV administration. Sivelestat sodium was administered within 24 h after the onset of respiratory dysfunction in 87.5% of the patients, and the survival rate at 28 days after the initiation of SIV administration was 90.0%. CONCLUSION: Our findings suggest that multidisciplinary postoperative management, including the administration of SIV, during the early phase after the onset of respiratory dysfunction leads to improvements in respiratory function and survival.

Hepatic resection for the treatment of liver metastases in gastric carcinoma: review of the literature.

This article presents a review of the literature on hepatic resection for the treatment of liver metastases in gastric carcinoma, and discusses the indications, mortality rates, prognostic factors and long-term results. Reports on hepatectomy for liver metastases from gastric cancer are rare, the results are disappointing, and further studies are required.

Changes in hepatic parenchymal ultrasound images in tamoxifen medication patients.

We experienced changes in ultrasonographic features of hepatic parenchyma in 156 patients treated with Tamoxifen (TAM) as an adjuvant hormonal therapy for breast cancer. After the treatment with TAM subsequent to the surgery for breast cancer, 36% of patients showed changes in ultrasonographic features of the liver more than Grade 2, despite no obvious hepatic involvement at the start of the medication. Forty-five percent of affected patients showed Grade 2 or 3 changes in hepatic parenchymal images within the first 6 months of TAM medication, while the average interval of change was 11.3 months. Abdominal ultrasound inspection should be undertaken within 6 months of surgery to aid the early detection of liver metastasis and fatty liver changes, which may play an important role in determining postoperative follow-up care for breast cancer patients.

Purification and characterization of a co(II)-sensitive alpha-mannosidase from Ginkgo biloba seeds.

An alpha-mannosidase was purified from developing Ginkgo biloba seeds to apparently homogeneity. The molecular weight of the purified alpha-mannosidase was estimated to be 120 kDa by SDS-PAGE in the presence of 2-mercaptoethanol, and 340 kDa by gel filtration, indicating that Ginkgo alpha-mannosidase may function in oligomeric structures in the plant cell. The N-terminal amino acid sequence of the purified enzyme was Ala-Phe-Met-Lys-Tyr-X-Thr-Thr-Gly-Gly-Pro-Val-Ala-Gly-Lys-Ile-Asn-Val-His-Leu-. The alpha-mannosidase activity for Man(5)GlcNAc(1) was enhanced by the addition of Co(2+), but the addition of Zn(2+), Ca(2+), or EDTA did not show any significant effect. In the presence of cobalt ions, the hydrolysis rate for pyridylaminated Man(6)GlcNAc(1) was significantly faster than that for pyridylaminated Man(6)GlcNAc(2), suggesting the possibility that this enzyme is involved in the degradation of free N-glycans occurring in developing plant cells (Kimura, Y., and Matsuo, S., J. Biochem., 127, 1013-1019 (2000)). To our knowledge, this is the first report showing that plant cells contain an alpha-mannosidase, which is activated by Co(2+) and prefers the oligomannose type free N-glycans bearing only one GlcNAc residue as substrate.

[Effects of nitrendipine on circadian variation of blood pressure in inpatients with renal parenchymal hypertension: assessment by ambulatory blood pressure monitoring].

OBJECTIVE: To study the effect of once-daily administration of a nitrendipine tablet 10 mg on 24-hour ambulatory blood pressure in inpatients with renal parenchymal hypertension. METHODS: Sixteen patients participated in the present study, and one patient was withdrawn because the baseline office blood pressure was less than 140/90 mmHg. In the baseline period, ambulatory blood pressure was monitored every 30 minutes for 30 hours. After the baseline measurement, nitrendipine 10 mg was orally administered once daily every morning for 7 days. The 30-hour ambulatory blood pressure monitoring was repeated after Day 6. RESULTS: Fifteen patients (aged 64.9 +/- 15.0 years) completed the study protocol. Baseline office blood pressure was 157.9 +/- 17.5/84.7 +/- 12.5 mmHg (mean +/- SD). Nitrendipine 10 mg tablets significantly reduced both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at least for 11 hours after administration compared with those at baseline. The rate of "Decrease" (reduction in blood pressure > or = 20/10 mmHg and/or achieved blood pressure < 140/90 mmHg at trough point) was 60.0% (9/15). Eleven patients were considered as effective cases at peak point (maximal reduction in blood pressure > or = 20/10 mmHg). The rate of "Decrease" in effective cases at peak point was 72.7% (8/11). CONCLUSION: These results suggest that a once-daily administration of nitrendipine 10 mg tablets is effective for the 24-hour control of blood pressure in patients with renal parenchymal hypertension.

Negative and positive effects of an IAP-LTR on nearby Pcdaalpha gene expression in the central nervous system and neuroblastoma cell lines.

Intracisternal A-particles (IAPs) are defective retrovirions encoded by members of a large family of endogenous proviral elements in the murine genome. An intact IAP element was found in the protocadherin alpha (Pcdhalpha) gene cluster of five laboratory mouse strains. However, IAP insertion was not detected in three wild mouse strains we investigated. This IAP insertion caused the disruption of one variable exon of laboratory mouse and down-regulated expression of the Pcdhalpha v8 exon, which is located just downstream of the IAP in the brain following the methylation of 5' regulatory region of Pcdhalpha v8. In contrast, the Pcdhalpha v8 exon was highly expressed in mouse neuroblastoma cell lines. This suggested that the IAP insertion activates the expression of the nearby Pcdhalpha v8 exon in these cell lines. In fact, the Pcdhalpha v8 exon expression was driven by the IAP-long terminal repeat (LTR) following the de-methylation of 5' regulatory region of Pcdhalpha v8. To investigate the promoter activity of the IAP, we constructed an IAP-LTR-ECFP reporter gene and introduced it into neuroblastoma, melanoma, lymphoma, and plasmacytoma cell lines. Interestingly, ECFP-positive cells were observed only in the neuroblastoma cell lines. Moreover, there were no differences in the promoter activities of the IAP-LTR whether it was in the sense or complimentary orientation. Thus, this IAP-LTR has negative and positive regulation on near by gene expression in the brain and neuroblastoma cell lines.

Intron-less processed Pcdhalpha genes in the central nervous system.

The genomic organization of the Pcdhalpha is remarkably similar to those of T-cell receptor and immunoglobulin genes. To elucidate the somatic rearrangements of the genomic DNAs of Pcdhalphas in the central nervous system, we screened a genomic brain library of the C57BL/6 mouse strain. From this screening we isolated an unusual, rearranged genomic Pcdhalpha DNA. This clone contained an intron-less Pcdhalpha v6 gene resembling the cDNA generated from its mRNA, inserted into the 28S rDNA gene locus. The intron-less Pcdhalpha v6 gene possessed a putative promoter region and 10 nucleotide substitutions but no poly(A) signal. Both edges of the integration site had additional 5-bp duplicated sequences. PCRs that were performed using primers for intron-less Pcdhalphas amplified products from genomic DNAs only in the brain; moreover, using the size-fractionated genomic DNA by sucrose density gradient centrifugation, intron-less Pcdhalpha is mainly amplified in the small size fraction of the genomic DNA. Inverted PCR for this small size fraction also amplifies the Pcdhalphas connecting the both ends with repeat sequences. These features suggest the somatic reverse-transcription, circularization, and rare occasion of integration into the genome of Pcdhalpha in the brain.

Solitary splenic metastasis derived from esophageal cancer.

Solitary splenic metastasis from esophageal cancer is so rare that such an occurrence in our Japanese patient should be reported. In a 58-year-old Japanese man we detected a solitary splenic tumor by abdominal computed tomography done 6 months after he had undergone an esophagectomy. Transarterial embolization of the splenic artery was without effect. A splenectomy was then done and histological examination of the resected specimen revealed squamous cell carcinoma derived from the esophageal carcinoma.

Interrelation between expression of matrix metalloproteinase 7 and beta-catenin in esophageal cancer.

Matrix metalloproteinase 7 (MMP-7) may play a key role in the progression of various human malignant tumors. Nuclear beta-catenin enhances the activating expression of MMP-7 genes by binding with the T-cell factor/lymphoid enhancer factor family of transcription factors. We immunohistochemically examined the expression of MMP-7 and beta-catenin to better understand the significance of these factors in the progression of esophageal squamous cell carcinoma. The entire coding region of beta-catenin exon 3 was also analyzed by direct sequencing in all cases. We found that MMP-7 was expressed in 7 (20.6%) of 34 esophageal squamous cell carcinomas. There was a significant relationship between MMP-7 expression and tumor invasion into adjacent structures (P < 0.05). Aberrant nuclear expression of beta-catenin was found in 12 of 34 (35.3%) esophageal cancers and correlated with MMP-7 expression, the statistical difference being (P < 0.05). None of the 34 esophageal cancers examined carried mutations in beta-catenin exon 3. MMP-7 expression correlates with penetrating tumor progression in esophageal cancer. Nuclear translocation of beta-catenin, without mutations in beta-catenin exon 3, is associated with MMP-7 expression.

p53 protein accumulation in multiple oesophageal squamous cell carcinoma: relationship to risk factors.

To clarify mechanisms involved in the carcinogenesis of multiple oesophageal squamous cell carcinoma, the expression of p53 protein in 46 lesions surgically excised from 13 Japanese patients was investigated immunohistochemically and the relation of p53 protein accumulation to the patient's history of alcohol consumption and cigarette smoking was analyzed. p53 protein accumulation was observed in 13 main lesions, that is in 6 (85.7%) of 7 subjects with a history of heavy drinking and smoking, but only in 1 (16.7%) of 6 with no such history (Fisher's exact test, p = 0.025). As regards the 46 lesions, p53 protein accumulation was evident in 22 (88.0%) of 25 lesions of the high-risk patients, but in 7 (33.3%) of 21 lesions of the other subjects (Fisher's exact test, p < 0.001). p53 protein accumulation was similarly recognized in all oesophageal lesions in 5 of 7 high-risk patients. Thus, use of both alcohol and cigarettes is clearly associated with a high frequency of p53 protein accumulation in multiple oesophageal squamous cell carcinoma present at the same time. These findings are considered to support the concept of field carcinogenesis of the oesophagus.

The relation of alcohol consumption and cigarette smoking to the multiple occurrence of esophageal dysplasia and squamous cell carcinoma.

BACKGROUND: The unique pathologic features of esophageal tumors in patients with esophageal cancer includes the presence of multiple occurrence within the esophagus. The aim of this study is to clarify the molecular mechanism of carcinogenesis of multiple esophageal squamous cell carcinomas in the Japanese. METHODS: We studied the relationship between the incidence of patients with multiple carcinomas and the coexistence of dysplasia lesions with p53 protein accumulation, alcohol consumption, and cigarette smoking. Among 76 cancer lesions and 60 cases of dysplasia, p53 accumulation was studied by means of immunohistochemical analysis. RESULTS: The incidence of patients with multiple carcinomas in the high-risk group was 33%, and the incidence of patients with a coexistence of dysplasia in the high-risk group was 67%. The incidence of patients with multiple carcinomas or the coexistence of dysplasia in the high-risk group was much higher than that of the middle-risk and low-risk groups (P <.0001 and P =.04, respectively). The average number of abnormal epitheliums, such as cancer and dysplasia, in the high-risk group was 3.2 +/- 2.1. The average number of abnormal epitheliums was much higher than that of the other groups (P =.02). For carcinoma lesions, the incidence of lesions with a positive p53 protein accumulation in the high-risk group was 91%. Regarding dysplasia lesions, the incidence of lesions with a positive p53 protein accumulation in the high-risk group was 80%. The incidence of both cancer and dysplasia lesions with a positive p53 protein accumulation in the high-risk group was higher than that of the other groups. CONCLUSIONS: The pattern of p53 accumulation in dysplasia in the high-risk group was closely similar to that in cancer of the high-risk group. These findings support the concept of field carcinogenesis of the esophagus.

Biologic and clinical significance of squamous epithelial dysplasia of the esophagus.

Squamous epithelial dysplasia is frequently encountered in the cancerous esophagus. However, its biological and clinical significance have not yet been fully elucidated. Investigations in squamous cell dysplasia of the esophagus have been performed to date in our department. We consider dysplasia to be the earliest malignancy of the esophagus based on such biologic features as the histopathologic findings, the proliferative activity, and the altered expression of cancer-associated genes. It is essential to detect and treat these early lesions endoscopically. Hopefully the findings of further studies of dysplasia can help to elucidate the mechanism of carcinogenesis in esophageal squamous cell carcinoma.

Surgical and oncological advances in the treatment of esophageal cancer.

BACKGROUND: Chemoradiotherapy (CR) and hyperthermochemoradiotherapy (HCR) have been performed on numerous patients with esophageal cancer. These neoadjuvant therapies for esophageal cancer are done widely. The purpose of this study is to demonstrate the recent advances in surgical and oncological treatment. METHODS: From 1967 to 2000, 847 patients who underwent an esophagectomy were classified into 4 groups according to the date of operation. Group 1 consisted of 110 patients who underwent an esophagectomy in the first 10-year period (1967-1976), group 2 consisted of 194 patients who had operations from 1977 to 1986, group 3 comprised 400 patients who had operations from 1987 to 1996, and group 4 comprised 143 patients who had operations from 1997 to 2000. From 1967 to 2000, 322 patients with neoadjuvant therapy and esophagectomy were classified into 6 groups according to the kinds of anticancer drugs that were administered. Group A received regimen A, using BLM (5 mg iv) 6 times as the chemotherapeutic drug in the early period (1965-1990); group B received regimen B, using cis-diaminedichloroplatinum (CDDP) (40 mg/m2) 3 times as the chemotherapeutic drug in the second period (1990-1997); and group C received regimen C, using CDDP (40 mg/m2) and 5FU (250 mg/m2) daily in the most recent period (1997-2000). The HCR group was also divided into the following 3 groups: Group D, who received regimen A and hyperthermia 6 times in the early period; group E, who received regimen B and hyperthermia 6 times in the next period; and group F, who received regimen C and hyperthermia 6 times in the most recent period. The local response and the long-term results were investigated. RESULTS: A complete removal of the primary tumor was achieved in 29%, 39%, 62%, and 68% of the patients in groups 1, 2, 3, and 4, respectively. The 30-day operative mortality rates were 11%, 4%, 1%, and 0% in groups 1, 2, 3, and 4, respectively. The 5-year survival rates for all patients in groups 1, 2, and 3 were 16.7%, 19.2%, and 44.4%, respectively. The cases in which CR or HCR was evaluated to be effective numbered 44 (48.4%) in group A, 22 (73.3%) in group B, 8 (66.7%) in group C, 79 (63.7%) in group D, 36 (73.5%) in group E, and 12 (75.0%) in group F. Our clinical results thus showed CDDP to have a greater effect than BLM, while HCR was shown to have a greater effect than CR. CONCLUSIONS: Preoperative therapy, especially using CDDP and hyperthermia, has improved thanks to recent advances in the treatment of esophageal cancer.

Estimation of angiogenesis with anti-CD105 immunostaining in the process of colorectal cancer development.

BACKGROUND: The expression of panendothelial markers (eg, CD34, CD31, and factor VIII) is not always observed in angiogenic vessels, and such markers are not useful for measuring angiogenesis. In contrast, CD105 is preferentially expressed in angiogenic vessels and thus may be valuable for measuring angiogenesis. We hypothesized that microvessel quantification by means of CD105 might be useful for measuring angiogenesis in the colorectal adenoma-carcinoma sequence. METHODS: We immunohistochemically investigated 54 cases of colorectal adenomas and 20 cases of carcinomas using monoclonal antibodies CD34 and CD105, and microvessel density (MVD) was counted at x200 magnification. RESULTS: Microvessels positive for CD34 were distributed almost uniformly in adenomas. In contrast, microvessels positive for CD105 were preferentially observed in the surface area of adenomas. In carcinomas, CD34 stained only a proportion of blood vessels that were positive for CD105. No significant difference of MVD for CD34 was observed in the colorectal adenoma-carcinoma sequence. In contrast, an increment of MVD for CD105 from low-grade to high-grade dysplasia (P <.0001) and that from high-grade dysplasia to carcinomas (P <.05) was statistically significant. CONCLUSIONS: Assessing neovascularization with CD105 in the process of colorectal cancer development may thus be a valuable marker for predicting the risk of colorectal cancer development.