The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 218, Issue 2
June
Displaying 1-10 of 10 articles from this issue
Review
  • Michael Stamatakos, Emmanuel Douzinas, Charikleia Stefanaki, Constanti ...
    2009 Volume 218 Issue 2 Pages 83-92
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Ischemic colitis is the most common type of intestinal ischemia, and it represents the consequences of acute or, more commonly, chronic blockage of blood flow through arteries that supply the large intestine. Ischemic colitis is manifested through a continuum of injury and considered as an illness of the elderly. The incidence of ischemic colitis has been underestimated, because many mild cases may go unreported. Patients experience abdominal pain, usually, localized to the left side of the abdomen, along with tenderness and bloody diarrhea. Severe ischemia may lead to bowel necrosis and perforation, which results in an acute abdomen and shock, frequently, being accompanied by lactic acidosis. Although computed tomography may have indicative findings, colonoscopy is the golden standard of diagnosis. Supportive care with intravenous fluids, optimization of hemodynamic status, avoidance of vasoconstrictive drugs, bowel rest, and empiric antibiotics will produce clinical improvement within 1 to 2 days in most patients. The condition resolves completely with conservative treatment, in most cases, but late diagnosis or severe ischemia can be associated with high rates of complications and death. However, when the interruption to the blood supply is more severe or more prolonged, the affected portion of the large intestine may have to be surgically removed. The present paper aims at bringing ischemic colitis up to date, by reviewing the current medical literature and extracting the contemporary data, about its presentation, diagnosis and treatment, which is of benefit to the readership, who may encounter this potentially fatal entity.
    Download PDF (395K)
Regular Contributions
  • Hiroshi Suzuki, Ken Toba, Kiminori Kato, Takuya Ozawa, Naohisa Tomosug ...
    2009 Volume 218 Issue 2 Pages 93-98
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Hepcidin, a key iron-regulator secreted from the liver, consists of 25 amino acids (hepcidin-25), blocks iron release from macrophages via internalization and degradation of cellular iron exporter ferroportin, and restrains the use of iron in organs. Hepcidin mRNA and protein are also expressed in the human heart. A short form of hepcidin that lacks 5 amino-acid residues in the N-terminus (hepcidin-20) has been found in human serum, although its physiological role is unknown. Here, we successfully measured the serum levels of hepcidin-25 and hepcidin-20 in 12 patients with acute myocardial infarction (AMI) using surface-enhanced laser desorption ionization time of flight mass spectrometry. Among the selected 10 patients, whose blood samples were taken within 4 hours after a heart attack, all the patients showed elevated serum levels of hepcidin-20 [between 31.7 and 285.1 arbitrary unit (AU); normal level < 9.3 AU], while 8 patients showed high levels of hepcidin-25 (9.3-271.4; normal < 25.5 AU). The hepcidin-20 level was decreased to nearly the normal level on day 7 (range of 2.9 to 12.5 AU) in the 12 patients, whereas the hepcidin-25 level remained high on day 7 in 8 patients. Furthermore, the elevated levels of hepcidin-25 and hepcidin-20 were not correlated with the serum levels of markers for inflammation, interleukin-6 and C-reactive protein, in the patients with AMI. In conclusion, the serum hepcidin-20 is transiently elevated in response to acute cardiac ischemia. Measurement of serum hepcidin-20, rather than hepcidin-25, is helpful for diagnosis of acute myocardial infarction.
    Download PDF (345K)
  • Akemi Osaka, Katsunori Yanagihara, Yasuaki Yamada, Hiroo Hasegawa, Nao ...
    2009 Volume 218 Issue 2 Pages 99-105
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Patients with hematological malignancies frequently suffer from lung diseases as a complication. However, it is difficult to discriminate leukemic invasion into the lung from infectious pulmonary complications. The serum level of Krebs von den Lungen-6 (KL-6), which is a mucin-like glycoprotein, is increased in more than 70% of patients with interstitial pneumonia. Surfactant protein-D (SP-D) is produced mainly in the lung by alveolar type II and bronchiolar epithelial cells and is a useful serum marker for interstitial pneumonia. We therefore measured the levels of KL-6 and SP-D in sera from 128 patients (76 males and 52 females, mean age: 59 years) with hematological malignancies, including adult T-cell leukemia (ATL). Overall, the increase in KL-6 or SP-D, above each cut-off value (500 U/ml for KL-6 and 110 ng/ml for SP-D), was detected in 11 patients (8.6%) or 10 patients (7.8%), respectively. In contrast, among 67 ATL patients, 15 patients had high serum levels of KL-6 and/or SP-D; both were elevated in 2 patients, only KL-6 was elevated in 6 patients and only SP-D was elevated in 7 patients. Thus, serum KL-6 and SP-D appear to be elevated in a mutually exclusive manner in ATL. Indeed, high serum levels of KL-6 were closely related to the stage of ATL, while the serum SP-D was elevated in ATL patients with pulmonary infection. In conclusion, the combined measurement of KL-6 and SP-D in ATL may become a useful means to discriminate leukemic pulmonary lesions from infectious pulmonary complications.
    Download PDF (986K)
  • Keiichi Matsubara, Naoyuki Uchida, Yuko Matsubara, Shinji Hyodo, Masah ...
    2009 Volume 218 Issue 2 Pages 107-113
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    It has been reported that fetal cells migrate into maternal blood and organs. Since these fetal chimeric cells could be involved in maternal allogeneic tolerance to the fetus, the fetal chimeric cells might be implicated in maternal-fetal immunology and development of maternal autoimmune diseases. However, the mechanism and role of fetal microchimerism remains unclear. We aimed to describe the mechanism by which fetal cells become associated with maternal organs during pregnancy, using a mouse fetal microchimerism model. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice, which are useful for tracking the behavior of fetal cells in the maternal body, were mated with transgenic males expressing enhanced green fluorescent protein (GFP), and the presence of GFP-positive cells were examined in peripheral blood and organs of pregnant mothers. By flow cytometry, we showed that 0.95 ± 0.48% of mononuclear cells detected in the maternal peripheral blood were GFP-positive, and thus of fetal origin, during the first gestational week. This value decreased to 0.10 ± 0.13% during the third gestational week (p < 0.05). GFP-positive cells were detected in the extraglomerular mesangial region and among the epithelial cells of the proximal renal tubule of the maternal kidney. These GFP-positive cells also expressed angiotensin II receptor subtype 2 (AT2), which is known to participate in regulating organogenesis and vasoreactivity. Fetal cells expressing AT2 may therefore be involved in the regulation of vascular tone in the maternal kidney. These observations suggest that fetal cells could influence maternal renal function through activation of the AT2 signaling.
    Download PDF (2178K)
  • Hisashi Masugata, Shoichi Senda, Takashi Himoto, Hiroyuki Okuyama, Mic ...
    2009 Volume 218 Issue 2 Pages 115-119
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Cardio-ankle vascular index (CAVI) has been established as a marker of arterial stiffness, which is increased in hypertensive patients. CAVI reflects the stiffness of the aorta, femoral artery, and tibial artery. Sunitinib, multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activities, has been proved effective in patients with gastrointestinal stromal tumors. However, the treatment with sunitinib is often complicated by side effects such as hypertension. We describe an 84-year-old woman with gastrointestinal stromal tumor, who showed changes in arterial stiffness preceding the appearance of hypertension in the early phase after sunitinib initiation. The patient received sunitinib (50 mg given daily) for gastrointestinal stromal tumor. We assessed the influence of sunitinib on arterial stiffness every 7 days by measuring CAVI. The CAVI, which reflects arterial stiffness, was increased from 9.95 at baseline to 11.65 at 7 days after the initiation of sunitinib, whereas the blood pressure remained unchanged (117/72 and 119/76 mmHg). At 14 days after sunitinib initiation, the blood pressure was increased to 159/89 mmHg, indicating the occurrence of hypertension, while the CAVI was 11.90, the similar level detected at 7 days. Subsequently, sunitinib treatment was discontinued, because of the marked decrease in blood platelets. Both blood pressure and CAVI, together with blood platelets, were restored to the baseline values at 12 days after cessation of sunitinib. In conclusion, the increase in the CAVI preceded the appearance of sunitinib-induced hypertension. Arterial stiffness assessed by CAVI may be useful for early detection of sunitinib-induced hypertension.
    Download PDF (1353K)
  • Huazhi Wen, Hong Jiang, Zhibing Lu, Bo He, Xiaorong Hu, Jing Chen, Don ...
    2009 Volume 218 Issue 2 Pages 121-127
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Connexin 43 (Cx43) is the most prominent connexin in the mammalian ventricular myocardium and forms gap junctions that are essential for normal conduction of action potential. Carvedilol, a nonselective β-blocker, is widely used to prevent ventricular arrhythmias after myocardial infarction (MI). Here, we examined the effect of carvedilol on the expression of Cx43 protein and ventricular fibrillation threshold (VFT) using a rat MI model. VFT is defined as the lowest voltage, at which ventricular fibrillation is induced by electrical stimulation. Adult male Wister rats were divided into sham-operated group (n = 20) and MI groups treated with intragastric administration of saline (control, n = 30) or carvedilol (2.5 mg/kg, n = 30) twice a day for 7 days immediately after ligation of the left coronary artery. Compared with sham group (100%), total Cx43 protein and phosphorylated Cx43 protein were decreased in the MI rats to 60 ± 21% and 52 ± 19% (both P < 0.05), respectively. Treatment with carvedilol prevented the MI-induced decrease in total and phosphorylated Cx43 levels (91 ± 17% and 80 ± 20%, both P < 0.05), respectively, which were similar to the levels of sham animals. Moreover, the MI rats exhibited a marked decrease in VFT compared with the sham group (7.2 ± 1.30 vs. 13.0 ± 2.12 V, P < 0.05), but the decrease was abolished by carvedilol (11.0 ± 2.65 V). In conclusion, carvedilol might prevent the ischemia-induced ventricular arrhythmias by restoring Cx43 protein and VFT to the basal levels.
    Download PDF (1019K)
  • Hanbyoul Cho, Beom Jin Lim, Eun Suk Kang, Joong Sub Choi, Jae-Hoon Kim
    2009 Volume 218 Issue 2 Pages 129-139
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Ovarian cancer is a leading cause of death among gynecological malignancies. Established cancer cell lines are useful tools for clinical and basic researches. We have therefore established a new human ovarian cancer cell line, YDOV-151, derived from the mucinous cystadenocarcinoma and characterized it by the microarray analyses. A mucinous origin of the YDOV-151 was evident from light microscopy, and its epithelial-like character was confirmed with electron microscopy. No pathogenic mutations were found in the BRCA1 and BRCA2 genes. The subcutaneous transplantation of YDOV-151 cells into nude mice successfully induced the tumor mass after 3 weeks. cDNA microarray analysis revealed 1,926 genes (> 2-fold differences, P < 0.05) that distinguished the YDOV-151 from human ovarian surface epithelial (HOSE) cells. To identify candidate biomarkers, we selected five genes (SFN, RGC32, CDCA7, LAMP3, and SLCO4A1), each of which was up-regulated (> 7-fold) in YDOV-151 and had an available antibody assay for further validation. In SYBR Green real-time PCR, the relative expression levels of RGC32 (651-fold), LAMP3 (1,930-fold), and SLCO4A1 (20,598-fold) were significantly higher in YDOV-151 than in HOSEs (P < 0.001). RGC32 may be involved in cell cycle regulation, LAMP3 may promote metastasis, and SLCO4A1 is a member of anion-transporting polypeptides. The newly established ovarian cancer cell line, YDOV-151, would be a useful model for elucidating the biology and the pathogenesis of mucinous cystadenocarcinoma. In addition, the identification and validation of up-regulated genes may provide a genetic approach for identifying biomarkers in ovarian cancer.
    Download PDF (4168K)
  • Askin Hekimoglu, Zehra Kurcer, Faruk Aral, Füsun Baba, Engin Sahn ...
    2009 Volume 218 Issue 2 Pages 141-147
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Testicular torsion is a common syndrome that could lead to infertility. We investigated the therapeutic effects of lycopene, an antioxidant caretenoid, on testicular ischemia/reperfusion (IR) injury that resembles testicular torsion. Male Wistar albino rats were divided into three groups: sham (n = 6), IR (n = 18), and ischemia/reperfusion with lycopene (IRL, n = 18). Left testicular artery and vein was occluded for 1 h, followed by reperfusion of 3 h, 24 h or 30 days in IR and IRL animals. Either corn oil (vehicle) or lycopene (4 mg/kg) was administrated once daily by gavage to IR or IRL animals, respectively, 5 min after ischemia. Sham-operated animals were treated with vehicle by gavage 5 min after the operation. IR decreased sperm motility and concentration in both ipsilateral and contralateral testes and increased abnormal sperm rate in ipsilateral testis after 30 days of reperfusion. Treatment with lycopene increased the motility in bilateral testes and decreased the rate of abnormal sperm in ipsilateral testis to the sham level, but did not increase sperm concentration in bilateral testes. IR increased the activities of catalase and glutathione peroxidase and the level of reduced glutathione by 24 h of reperfusion, but malondialdehyde remained unchanged. Lycopene treatment restored the enzyme activities but not the reduced glutathione level. Lycopene treatment also ameliorated the IR-induced tissue damage in bilateral testes. In conclusion, the therapeutic antioxidant effect of lycopene on germ cells could serve as a promising intervention to oxidative stress-associated infertility problems, such as testicular torsion.
    Download PDF (681K)
  • Hiroko Fujii, Tsuyako Noda, Toshimi Sairenchi, Takashi Muto
    2009 Volume 218 Issue 2 Pages 149-154
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    The increasing proportion of underweight young women may lead to an increase in those with low bone mass. The present study investigated whether bone mass level is associated with lifestyle factors among young Japanese women. A total of 103 Japanese female college students aged 20-21 majoring in food science participated in this cross-sectional study. We measured bone area ratio at the os calcis using quantitative ultrasound (QUS) and assessed lifestyle factors including diet and physical activity using a self-reported questionnaire. Bone area ratio was defined as a proportion of bone substance in a cross section of os trabeculare. Ninety-one subjects who completed the questionnaire were categorized into two groups according to the average bone area ratio of the 103 subjects (30.9%), calculated based on the screening method for osteoporosis prevention: 69 subjects with normal bone mass (bone area ratio: 36.2 ± 3.8%) and 22 subjects with low bone mass (bone area ratio: 28.1 ± 1.6%). In normal group, 12 subjects (17.4%) had a dietary habit of not daily intake of green and yellow vegetables, such as carrot and spinach, while this occurred in 10 subjects (45.5%) in low group (P = 0.007). Adjusted logistic regression analyses showed that the subjects without daily intake of green and yellow vegetables had almost 5-fold risk of low bone mass, compared to the subjects having daily intake of the vegetables [Odds ratio: 4.96 (95%CI 1.36-18.18)]. In conclusion, daily intake of green and yellow vegetables is effective for maintaining bone mass in young women.
    Download PDF (340K)
  • Wei-Dong Jia, Ge-Liang Xu, Wei Wang, Zhi-Hua Wang, Jian-Sheng Li, Jin- ...
    2009 Volume 218 Issue 2 Pages 155-160
    Published: 2009
    Released on J-STAGE: May 29, 2009
    JOURNAL FREE ACCESS
    Occurrence of second primary tumors and metastasis remains the major obstacles to prolonged survival of patients with primary hepatocellular carcinoma (HCC). A somatostatin analogue, octreotide, has been previously reported to inhibit the growth of human HCC xenografts in nude mice through its anti-angiogenic activity. It is therefore important to investigate whether octreotide could prevent second primary hepatomas or distant metastasis following resection of primary HCC. In this study, nude mice, bearing the human HCC xenografts with highly metastatic potential (LCI-D20) in the left liver lobe, underwent tumor resection, and received intraperitoneal administration of octreotide or saline as a control for 35 consecutive days. Compared with the control group, octreotide at the doses of 100 and 200 μg/kg/day significantly inhibited the growth (P < 0.001 and P < 0.001, respectively) and incidence of second primary tumors (P = 0.016 and P = 0.001, respectively), decreased lung metastasis (P < 0.001 and P < 0.001, respectively), and prolonged the life span (P = 0.029 and P = 0.006, respectively). Moreover, intratumoral angiogenesis quantified by microvessel density as well as serum and tissue vascular endothelial growth factor (VEGF) levels were considerably decreased in octreotide-treated animals compared to the control animals. These findings suggest that octreotide may prevent the occurrence of second primary hepatomas and lung metastasis after resection of primary HCC, which may be partially attributed to down-regulation of VEGF and subsequent reduction in tumor angiogenesis. Octreotide administration may be useful as an adjuvant therapy to improve survival of patients with HCC.
    Download PDF (806K)
feedback
Top