The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 220, Issue 4
April
Displaying 1-10 of 10 articles from this issue
Invited Review for the 90th Anniversary
  • Yukihiro Terada, Gerald Schatten, Hisataka Hasegawa, Nobuo Yaegashi
    2010 Volume 220 Issue 4 Pages 247-258
    Published: 2010
    Released on J-STAGE: April 06, 2010
    JOURNAL FREE ACCESS
    Fertilization is a lengthy process that culminates when the male and female pronuclei fuse in the oocyte cytoplasm. The final stage of fertilization is mediated by the sperm centrosome, which induces microtubule organization into the first mitotic spindle. Despite its critical role, only few functional analyses of the sperm centrosome have been performed until now. Here, we review the recent literature with regard to sperm centrosomal functions during human fertilization, as well as the development of functional assays for the human sperm centrosome. We then address various challenges for fertilization failure resulting from centrosomal dysfunction. Cytological analyses of oocytes that fail to complete fertilization following intracytoplasmic sperm injection (ICSI) have shown that some cases are associated with sperm centrosomal dysfunction. Human sperm can organize a sperm aster even within the oocytes of other mammals. This property has been utilized as a means of assessing the centrosome function. In some patients with teratozoospermia, the sperm does show evidence of impaired centrosomal function. Some clinical and basic challenges for overcoming the fertilization failure caused by sperm centrosomal dysfunction have been reported. The sperm centrosome plays an important role in the phase of the fertilization process after ICSI, i.e. within the oocyte's cytoplasm. The next generation of assisted reproductive technologies (ART) will likely incorporate analyses of sperm centrosomal function as well as techniques designed to counter sperm centrosome dysfunction.
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Review
  • Evridiki Karanikola, Christos Tsigris, Konstantinos Kontzoglou, Nikola ...
    2010 Volume 220 Issue 4 Pages 259-265
    Published: 2010
    Released on J-STAGE: April 08, 2010
    JOURNAL FREE ACCESS
    Laparoscopic adrenalectomy (LA) has become the procedure of choice for the surgical removal of the vast majority of small sized adrenal tumors (≤ 6 cm), because of its significant and multiple advantages: reduced hospital stay and wound morbidity, decreased transfusion requirements, postoperative pain and complications. The role of LA in patients with large adrenal lesions or potential malignancy remains controversial. The aim of this article is to review the current and up-to-date surgical approaches for LA, which include: 1) transabdominal anterior or flank approach and 2) retroperitoneal technique with the patient in either lateral or prone position. Specific advantages and disadvantages are referred to for each of them. The choice of each of these techniques is determined particularly by the preference and the experience of the surgeon, but other objective criteria must be taken into consideration, such as the size of the adrenal and history of previous abdominal surgeries.
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Regular Contributions
  • Mika Umabiki, Kokoro Tsuzaki, Kazuhiko Kotani, Narumi Nagai, Yoshiko S ...
    2010 Volume 220 Issue 4 Pages 267-271
    Published: 2010
    Released on J-STAGE: April 08, 2010
    JOURNAL FREE ACCESS
    Leptin may influence sweet taste sensitivity. However, there are no reports on an association between the sweet taste threshold and serum leptin levels during weight loss in humans. We investigated the changes in the sweet taste threshold and the serum leptin levels during a weight-loss program, in connection with a leptin receptor polymorphism (Lys109Arg) that may be related to insulin and glucose metabolism. The study included 20 obese, but otherwise healthy, females (mean age: 55 ± 7 years, body mass index: 26.1 ± 1.7 kg/m2). Participants completed a 12-week weight-loss program based on energy restriction through diet and exercise, which aimed at achieving their optimal weight. The sweet taste threshold was determined according to the whole-mouth gustatory method. Genetic analyses were performed using the allele-specific DNA assay. Serum leptin levels were decreased from 9.2 ± 4.5 to 7.9 ± 4.9 ng/ml (p = 0.014) after body weight loss. The sweet taste threshold also decreased significantly from 0.59 ± 0.42 to 0.22 ± 0.20% in a solution of sucrose (p = 0.004). In contrast, there were no differences in changes of the threshold between participants with and without the Lys109 allele. A multiple regression analysis revealed that the changes in serum leptin levels were significantly correlated with those in the sweet taste threshold, independent of the initial threshold levels and the Lys109 allele. In conclusion, the serum leptin levels are decreased significantly during a weight-loss program in obese females, which may be associated with the decrease in the sweet taste threshold.
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  • Mustafa Akcakoyun, Selcuk Pala, Ozlem Esen, Goksel Acar, Ramazan Kargi ...
    2010 Volume 220 Issue 4 Pages 273-277
    Published: 2010
    Released on J-STAGE: April 08, 2010
    JOURNAL FREE ACCESS
    The pathogenesis of ascending aortic aneurysm (AAA) involves many factors; elastin degradation could lead to initial dilation, and changes in the collagen structure predispose the aneurysm to rupture. Prolidase is an enzyme that catalyzes the final step of collagen breakdown by liberating free proline for collagen recycling. The enzyme activity may be a step-limiting factor in the regulation of collagen biosynthesis. Consequently, in this study we sought to determine serum prolidase activity in AAAs. Eighty consecutive patients with the diagnosis of hypertension or chest pain, referred for echocardiographic examination in the outpatient cardiology clinic, were included in the study. The subjects were grouped into three categories according to the aortic diameter; control group without aortic dilatation (≤ 3.7 cm, n = 20), medium (3.8-4.3 cm, n = 36), and large (≥ 4.4 cm, n = 24) group. We assessed the association of serum prolidase activity with the presence and severity of AAAs, clinical characteristics and laboratory parameters. Serum prolidase activity was significantly higher in the patients without aortic dilatation (1386.3 ± 320.5 U/L) compared to medium group (1212.0 ± 282.5 U/L) and large group (1072.2 ± 192.3 U/L): control group vs. medium group (P = 0.023) and control group vs. large group (P < 0.001). Ascending aortic diameter was inversely correlated with serum prolidase activity and in multivariate analysis, serum prolidase activity was the only independent predictor of aortic dilatation (β = −0.44, P = 0.006). In conclusion, the presence of AAAs is associated with low serum prolidase activity.
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  • Murat Yuce, Vedat Davutoglu, Burcu Ozbala, Suleyman Ercan, Nese Kizilk ...
    2010 Volume 220 Issue 4 Pages 279-283
    Published: 2010
    Released on J-STAGE: April 08, 2010
    JOURNAL FREE ACCESS
    Reliable non-invasive new indices reflecting severity of rheumatic valve disease would be highly beneficial. Recently, presence of fragmented QRS (fQRS) in ECG was accepted as a marker of myocardial fibrosis. fQRS is defined as the presence of RSR' patterns such as additional R wave (R'), notching in the R wave or the S wave in 2 contiguous leads. Purpose of our study was to establish frequency of fQRS in isolated rheumatic mitral stenosis compared with control group. We studied 193 patients with mitral stenosis and age/gender matched 97 healthy subjects. Patients were categorized according to the New York Heart Association (NYHA) functional class. Severity of mitral stenosis, left ventricular ejection fraction, and pulmonary artery pressure were obtained by means of echocardiography. fQRS was defined on routine 12-lead ECG. fQRS was more frequent in subjects with mitral stenosis than in control group (p < 0.001). fQRS was associated with low ejection fraction, pulmonary hypertension, poor functional NYHA class, increased mean mitral valve gradient and decreased mitral valve area (R = 0.1, p = 0.02; R = 0.1, p = 0.001; R = 0.1, p = 0.01; R = 0.1, p = 0.04; and R = −0.1, p = 0.009, respectively). Mitral valve area was the only independent predictor of fQRS in multiple logistic regression anlysis. In conclusion, fQRS is predictive of severe mitral stenosis, lower ejection fraction, inreased pulmonary artery pressure, and poor functional class. fQRS might be considered as a novel indicator of mitral stenosis severity and associated complications.
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  • Shinya Adachi, Heima Sakaguchi, Takashi Kuwahara, Yasushi Uchida, Tosh ...
    2010 Volume 220 Issue 4 Pages 285-290
    Published: 2010
    Released on J-STAGE: April 09, 2010
    JOURNAL FREE ACCESS
    Kawasaki disease is an acute vasculitis syndrome of unknown etiology that mainly affects small and medium-size arteries, particularly the coronary artery. Coronary artery lesions may develop into aneurismal formation and thrombotic occlusion, and progress to ischemic heart disease. The aim of the present study was to investigate the effect of steroid pulse therapy following intravenous immune globulin (IVIG) treatment on the regression rate of aneurysms in Kawasaki disease. Among 93 sequential patients referred to us, because of coronary artery lesions in the acute phase, we found 23 aneurysms in 12 patients during the period from January 1997 to January 2008. We divided them into two groups: a non-steroid group, 7 patients (13 aneurysms) treated with single or multiple IVIG but no steroid pulse therapy; and a steroid group, 5 patients (10 aneurysms) treated with multiple IVIG followed by steroid pulse therapy. We compared the regression rate of the aneurysms between the two groups, retrospectively. The regression rates of the aneurysms in the steroid group were significantly higher than those in the non-steroid group when we analyzed 1) all aneurysms (p = 0.007), 2) giant aneurysms (aneurismal diameter was 4 or more × normal, or > 8 mm) (p = 0.018), and 3) aneurysms in IVIG-resistant patients who were resistant to initial IVIG therapy (p = 0.035). All aneurysms, including the giant aneurysms in the steroid group, regressed, and the regression rate of the aneurysms in the non-steroid group was about 46%(6/13). Steroid pulse therapy may be beneficial for IVIG-resistant patients. Our data suggest that steroid pulse therapy may lead to regression of aneurysms.
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  • Weixin Lu, Bo Feng
    2010 Volume 220 Issue 4 Pages 291-297
    Published: 2010
    Released on J-STAGE: April 09, 2010
    JOURNAL FREE ACCESS
    The receptor for advanced glycation end products (RAGE) is a multi-ligand member of the immunoglobulin superfamily and may be involved in the development of diabetic vascular complications. The -374T/A polymorphism in the RAGE gene promoter has been suggested to affect gene transcription. However, the studies on the association between the -374T/A polymorphism and vascular complications in type 2 diabetes mellitus (T2DM) have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all eligible studies concerning this polymorphism was conducted. The PubMed and EMBASE databases were searched for relevant articles up to January 2010. Data on genotypes, allele frequencies and number of cases and controls were extracted. A pooled estimate of the genetic association, the heterogeneity between studies, the sensitivity for HWE (exclusion of studies not in Hardy-Weinberg equilibrium), and the publication bias were investigated. Nine articles with 3,799 cases and 4,899 controls were enrolled in the meta-analysis. The main analysis indicated significant heterogeneity and no association for the allele contrast [random effects odds ratio (RE OR) = 0.92 (0.83∼1.02)]. However, sensitivity analysis for HWE diminished the heterogeneity and showed a marginal association [fixed effects OR = 0.92 (0.86∼0.99)]. The comparison of AA genotype with TA+TT genotypes revealed significant results overall [RE OR = 0.70 (0.57∼0.86)]. Subgroup analyses in Caucasians and macrovascualr disease also produced significant association. In conclusion, the -374A allele of the RAGE gene might be a protective factor for vascular complications in T2DM, especially in Caucasians and macrovascular disease.
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  • Dalia Akramiene, Ceslava Aleksandraviciene, Grazina Grazeliene, Rimant ...
    2010 Volume 220 Issue 4 Pages 299-306
    Published: 2010
    Released on J-STAGE: April 09, 2010
    JOURNAL FREE ACCESS
    Photodynamic therapy (PDT) combines a drug or photosensitizer with a specific type of light to kill cancer cells. The cellular damage induced by PDT leads to activation of the DNA damage repair, which is an important factor for modulating tumor sensitivity to this treatment. β-Glucans are natural polysaccharides that bind complement receptor 3 on the effector cells, thereby activating them to kill tumor cells during PDT. The hypothesis of the present study was that adjuvant therapy with β-glucans would increase the efficacy of PDT. C57BL/6 female mice were subcutaneously implanted with Lewis lung carcinoma cells. Ten days after implantation, the mice were administered intravenously sodium porfimer (10 mg/kg) 24 h prior to laser irradiation, with or without oral administration of β-glucan (400 μg/d/mouse, 5 days) from either barley, baker's yeast, or marine brown algae that contains the storage glucan, laminarin. Tumor volume and necrotic area in excised tumors were measured. The expression of proliferating cell nuclear antigen (PCNA) was determined as an indicator of the activity of the DNA damage repair system. PDT in combination with each β-glucan significantly reduced tumor growth (P < 0.05, n = 10) and expression of PCNA (P < 0.001, n = 9), and increased necrosis in tumor tissues (P < 0.001, n = 9). Furthermore, each structurally different <β-glucan exerted similar potentiating effects on PDT. The present findings show that β-glucans enhance the tumor response to PDT, resulting in pronounced necrosis of PDT-treated tumors and suppression of the DNA damage repair system.
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  • Hiroko Fujii, Takashi Muto, Yasuo Haruyama, Makiko Nakade, Emiko Kobay ...
    2010 Volume 220 Issue 4 Pages 307-318
    Published: 2010
    Released on J-STAGE: April 09, 2010
    JOURNAL FREE ACCESS
    Lifestyle modification is the cornerstone of preventive management for people with cardiovascular disease risks, such as obesity, hypertension, dyslipidemia and diabetes. This study investigated the effect of a 27-month community-based lifestyle intervention on the reduction of cardiovascular disease risks in middle-aged Japanese. Of 549 participants with cardiovascular disease risk factors of overweight, hypertension, dyslipidemia or diabetes enrolled in this non-randomized controlled study, 397 participants aged 39-71 years old completed all 3 serial surveys at baseline, 15 months and 27 months. For the intervention group (39 males and 174 females), 31 specific interventions including individual counselling and group sessions were conducted. The control group (64 males and 120 females) only received 7 newsletters providing health information and results of health checkups. Multiple logistic regression analysis adjusted for sex, each baseline risk category and age category showed that the proportion of those who were overweight or showed dyslipidemia risk were significantly lower in the intervention group only at 27 months [Odds ratio (OR): 0.43 (95% CI 0.20-0.94), OR: 0.43 (95% CI 0.21-0.87), respectively] and the proportion of those showing diabetes risk was significantly lower in the intervention group at both 15 months [OR: 0.42 (95% CI 0.18-0.97)] and 27 months [OR: 0.56 (95% CI 0.32-0.99)]. In conclusion, the 27-month community-based lifestyle modification of cardiovascular disease risks shows significant reductions in risks of diabetes, overweight and dyslipidemia in middle-aged Japanese.
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  • Eiko Honda, Koji Yoshida, Hiroshi Munakata
    2010 Volume 220 Issue 4 Pages 319-327
    Published: 2010
    Released on J-STAGE: April 09, 2010
    JOURNAL FREE ACCESS
    Myofibroblasts are defined as fibroblasts that express certain features of smooth muscle differentiation. Activation of myofibroblasts plays a central role in fibrosis. Transforming growth factor-β (TGF-β) is a potent activator of myofibroblasts; namely, TGF-β causes changes in myofibroblast phenotypes including morphological alterations and the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblasts. Because it has been well known that humoral factors, especially, TGF-β, and extracellular matrix components cause myofibroblast activation, we examined the expression of integrin and related proteins during activation of MRC-5 human myofibroblasts with TGF-β. Western blot analysis revealed that TGF-β treatment for 3 days increased the expression of α-SMA, which was also immunocytochemically observed as actin stress fibers. In the early phase of TGF-β treatment, fibronectin expression was greatly increased, followed by the increased expression of integrin αv and α11 and integrin β1 and β3. Co-immunoprecipitation assays revealed that the integrin αv subunit was co-precipitated with integrin β1 and β3, and that integrin β1 was co-precipitated with α11, αv, α2, and α5. The expression of focal adhesion kinase and integrin-linked kinase proteins was also upregulated by treatment with TGF-β. In addition, the expression of type I collagen mRNA was increased by TGF-β, but not type III collagen mRNA, as judged by real-time PCR analysis. These results suggest the possibility that TGF-β induces fibronectin expression in MRC-5 cells, which subsequently induces the expression of integrin receptors, αvβ3, αvβ1, and α11β1. This report also shows that expression of integrin α11 is upregulated during the TGF-β−mediated activation of myofibroblasts.
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