Juntendo Medical Journal
Online ISSN : 2188-2134
Print ISSN : 0022-6769
ISSN-L : 0022-6769
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Volume 53, Issue 1
Displaying 1-21 of 21 articles from this issue
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Contents
  • Effect of LCPUFA on Infant Cognitive Development
    YAYOI SATOH
    2007 Volume 53 Issue 1 Pages 2-10
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.2
    JOURNAL FREE ACCESS
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    It is widely known that long-chain polyunsaturated fatty acids (LCPUFA), such as docosahexaenoic acid (DHA) and arachidonic acid (AA), are major components in the brain and retina, I structures, and that nutrition plays an important role in the normal development of the neural system. In particular, n-3 PUFA including DHA has received a great deal of attention, since it was demonstrated that the nutrition is a key factor for the development of neural functions in infants. Several experimentally controlled studies have demonstrated an effect of LCPUFA supplementation during prenatal and postnatal periods on the development of infant cognitive functions. Those studies assessed specific cognitive functions, such as visual attention and problem solving ability, and the results consistently showed a positive effect of LCPUFA intake on infant cognitive functions at an early stage of their development. Having joined an ongoing research project by Dr. Peter Willatts at the University of Dundee, which focuses on the effects of LCPUFA on infant cognitive development, I studied various practical assessment methods for infant cognitive development. This article reviews the effect of LCPUFA on the development of infant neural functions and also introduces some of the most up-to-date tools to assess infant cognitive development.
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  • Molecular biology of podocyte
    KATSUHIKO ASANUMA
    2007 Volume 53 Issue 1 Pages 11-19
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.11
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    Glomerular visceral epithelial cells, also known as podocytes, are highly specialized epithelial cells that cover the outer aspect of the glomerular basement membrane (GBM). Podocytes consist of cell bodies, major processes and foot processes of neighbouring cells, with filtration slits being bridged by the slit membrane between these filtration slits. The function of podocytes is largely based on their specialized cell architecture ; functions include stabilization of glomerular capillaries and participation in the barrier function of glomerular filter. Podocytes therefore form the final barrier to protein loss, which explains why podocyte injury is typically associated with marked proteinuria. Chronic podocyte injury may lead to podocyte detachment from GBM. Podocyte injury is involved in many forms of human and experimental glomerular disease. Based on recent insights into the molecular pathology of podocyte injury, at least four major causes have been identified that lead to the uniform reaction of FP (foot process) effacement and proteinuria (1) interference with the SD (slit diaphragm) complex and its lipid rafts ; (2) direct interference with the actin cytoskeleton; (3) interference with the GBM or with podocyte GBM interaction; and (4) inteference with the negative charge of podocytes. Ongoing studies in many laboratories are investigating the dynamic relationship between SD proteins, the actin cytoskeleton, and the dynamics of FP structure in nephrotic syndrome and focal segmental glomerulosclerosis. Such studies will potentially translate into more refined treatment strategies and the prevention of proteinuria and progressive glomerular disease.
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  • Biology and imaging of vascular inflammation and atherosclerosis.
    MASANORI AIKAWA
    2007 Volume 53 Issue 1 Pages 20-30
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.20
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    Proinflammatory macrophages participate importantly in the pathogenesis of cardiovascular diseases such as atherosclerosis, in- stent stenosis, myocardial infarction, and heart failure. Macrophages adapt to the local microenvironment and acquire various functions associated with physiological and pathological processes. In the context of atherosclerosis, activated macrophages participate critically in every stage of lesion progression, from fatty streak formation to the onset of acute thromobotic complications. Matrix-degrading enzymes and prothrombotic molecules elaborated from activated macrophages may promote plaque disruption and subsequent thrombosis. Clinical studies established that lipid-lowering therapy reduces the onset of acute coronary events. Preclinical evidence has further suggested that lipid lowering attenuates macrophage activity and inflammation. However, these features that are typical of plaques prone to the onset of acute thrombotic events are not often associated with plaque size or angiographical luminal stenoses. Molecular imaging, an emerging technology, can detect specific cell types or visualize biological processes responsible for the pathogenesis of atherothrombosis, unlike conventional anatomical imaging. Therefore, detection of plaque inflammation and macrophages in vivo using molecular imaging may identify subclinical atherosclerotic lesions, predict future risk, and help to establish more personalized therapeutic strategies for the prevention of fatal complications.
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  • Recent developments in multislice computed tomography in neuroradiology
    ATSUSHI NAKANISHI
    2007 Volume 53 Issue 1 Pages 47-53
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.47
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    The advanced tecnological developments in multislice computed tomography (MSCT) include multidetector-row and submillimeter section. The clinical advantages of MSCT are shorter scanning time, wider scanning area, higher temporal resolution and higher z-axis resolution. MSCT made it possible to obtain isotrophic voxel data, resulting in improved image quality on multiplanar reconstruction (MPR) and 3-dimensional images include CT angiography (CTA).CTA is becoming a diagnostic tool for the evaluation of cerebrovascular disease. Especially, in acute stroke, the combination of CTA and perfusion CT (CTP) are employed to evaluate patients suspected of acute stroke. We discuss the utility of MSCT-in the evaluation of cerebrovascular disease for clinical management and preoperative planning.
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  • Application of multislice computed tomography to diagnostic imaging
    KOREMOCHI TAKATA
    2007 Volume 53 Issue 1 Pages 54-60
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.54
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    Multislice computed tomography (MSCT) has high spatial and temporal resolution, which allows isotropic voxel data collection contributing to the diagnostic image. With these isotropic voxel data sets, we can obtain high resolution 3D images, such as multiplanar reconstructive (MPR) images, maximum intensity projection (MIP) images, volume rendering (VR) images, and virtual endoscopy. It is important to select appropriate and effective imaging method in each setting of vascular, thoracic, and abdominal imaging.
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  • Digital mammography
    AKIHIKO SHIRAISHI
    2007 Volume 53 Issue 1 Pages 61-66
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.61
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    Mammography is the first choice for diagnosis of breast disease, and it has been playing an important role in both screening and diagnostic examination. Recently, digital mammography systems, such as Full Field Digital Mammography (FFDM) and Computed Radiography (CR), have been developed and acquired widely in Japan. In this paper, we discuss the digital mammography system, soft copy reading, a new application (computer-aided detection system) and a new image acquisition system (tomosynthesis).
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  • PET scan as a functional diagnostic tool
    SHINSUKE KYOGOKU, SHOICHI OGAWA, MAKI AMANO
    2007 Volume 53 Issue 1 Pages 67-72
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.67
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    Morphological diagnostic imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI) have undergone rapid development of hardware and imaging technique. However, these imaging modalities have some limitations in determining whether lymph node swelling is malignant or benign. It is difficult for the radiologist and physician to differentiate malignant lesion from benign lesion based solely on lymph node size. Mass media has sensationalized the efficacy of positron emission tomography (PET) scan. PET scans have now become a well-known medical examination among the general public. The ministry of health, labor and welfare approved F-18 fluorodeoxyglucose (FDG) as a commercially available isotope in 2005 and PET centers have rapidly spread in Japan. PET scan is considered a breakthrough in cancer detection, as a functional diagnostic tool. This article discusses simple methods and isotopes for PET scan and the diseases for which FDG-PET scan is covered by the medical insurance system. The preparation and workflow of FDG-PET examination are also discussed. Finally, I describe the usefulness of FDG-PET scan using an illustrative case presentation.
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  • Screening for genes involved in apoptosis of hepatic stellate cells : a role of caspase-7
    YOSHIAKI KAWAKUBO, YOSHIYUKI TAKEI, KOSUKE IZUMI, SHUNHEI YAMASHINA, K ...
    2007 Volume 53 Issue 1 Pages 73-81
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.73
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    Objective : Hepatic stellate cells (HSCs) play an important role in liver fibrogenesis. Therefore, induction of apoptosis in activated HSCs should lead to an effective modality to diminish and/or prevent liver fibrosis. Gliotoxin has been shown to induce apoptosis in the activated HSCs, although the molecular mechanisms remain obscure. To explore the molecular mechanisms involved in gliotoxin-induced HSC apoptosis, we used a randomized ribozyme library and screened genes that are associated with gliotoxin-induced HSC apoptosis. Materials & Methods : A stellate cell line was transiently transfected with a randomized ribozyme library. After 48 hours, cells were treated with gliotoxin (1.5μM) for another 24 hours, and then Rz-expressing plasmids from surviving cells were isolated. After the third round of selection with gliotoxin, the ribozymes were isolated and their sequences were determined. The target genes were analyzed on the BLAST database. Results : We identified caspase-7 as one of the participants in gliotoxin-induced apoptosis. A plasmid harboring the identified sequence was transiently transfected into HSC-T6 cells. The transfected cells were resistant to apoptosis due to gliotoxin. Conclusion : It is suggested that caspase-7 is implicated in the mechanism of gliotoxin-induced apoptosis.
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  • Prediction of the effect of alpha-1 blocker on benign prostatic hyperplasia
    KAZUO KOIZUMI
    2007 Volume 53 Issue 1 Pages 82-88
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.82
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    Objective : The effect of alpha-1 blocker on various parameters of benign prostatic hyperplasia were studied. Methods : Studies were carried out on thirty-three patients with BPH. These patients were given alpha-1 blocker at our university hospital for one month each between July 2003 and March 2004. Tamsulosin and Naftopidil were administered to six and twenty-seven patients, respectively. These patients were evaluated by patient age, PSA, International Prostate Symptom score (I-PSS), QOL score, prostate volume (PV), transition zone volume (TZV), TZ index (TZV/PV), h (intravesical prostatic protrusion), H/W (the ratio of the height/width of the maximal horizontal section of prostate on transrectal ultrasound), peak flow rate and residual urine after voiding within a month before medication. After each patient had received one month dose of medication, the effects were evaluated. Results : Compared to other parameters, h, H/W and TZ index were better predictors of the effect of medication with alpha-1 blocker. Logistic analysis demonstrated h, H/W, TZ index strongly correlated with the therapeutic effects. Conclusions : H / W, h, TZ index were useful in predicting the therapeutic efficacy of alpha-1 blocker for benign prostatic hyperplasia.
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  • An Experimental study of double innervation using End-to-Side Neurorrhaphy in Rats
    MASAYUKI ICHIDA, AYATO HAYASHI, YUZO KOMURO, AKIRA YANAI
    2007 Volume 53 Issue 1 Pages 89-96
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.89
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    Introduction : We investigated double innervation, innervation of a single muscle by two different nerves, using an end-to-side neurorrhaphy model. Materials : We used ten male-wistar rats (350-450g). Method : The sciatic nerve was dissected, and transplanted between the left and right median nerve in an end-to-side fashion. Then, the left median nerve was transected proximal to the neurorrhaphy, In group one, the left median nerve was not repaired. In group two, the left median nerve was repaired immediately after transection. After 180 days, we evaluated nerve regeneration based on dry muscle weight, action potential, electromyography, and histology. End-to-side neurorrhaphy (distal end) was also studied morphometrically with Dil and DiA neural tracers. Results : In group two, electromyographic and electrophysiological findings showed the possibility of double innervation. In addition, regenerating axons from both the grafted sciatic and median nerves were observed in the distal left median nerve. Discussion : Our findings suggest double innervation of a single muscle, however, further study of individual muscle fibers is still required.
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  • Expression of Toll-like receptor in tonsils, and therapeutic outcome of tonsillectomy and steroid pulse therapy in patients with IgA nephropathy
    TATSUYA KANO, YUSUKE SUZUKI, HITOSHI SUZUKI, TOSHINAO TSUGE, SATOSHI H ...
    2007 Volume 53 Issue 1 Pages 97-105
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.97
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    Objetive : IgA nephropathy (IgAN) patients show macroscopic hematuria and/or proteinuria after upper respiratory tract infections such as tonsillitis. Toll-like receptors (TLR) are key molecules that trigger innate immune responses and thus contributed to host defenses against infections by production of inflammatory mediators from immune-competent cells including macrophages or dendritic cells (DC). In the present study, we investigated TLR expression in tonsils from subjects with IgAN and determined the cell types expressing TLR. Correlations between the magnitude of TLR expression and therapeutic outcome were also examined. Materials : Sixteen patients who were considered to have a poor or relatively poor prognosis based on the prognostic criteria for IgAN in Japan and treated by tonsillectomy were examined in this study. Methods : Clinical data were collected before tonsillectomy or each course of steroid pulse therapy. Real-time PCR for TLR and cytokines (IFN-alpha/gamma) was performed using mRNA isolated from tonsils. Immunohistochemical analysis of tonsils was performed to identify localization of TLR expression and cell types. Results : Levels of mRNA expression of TLR2 and TLR4 in the tonsils did not differ among the patients, although markedly higher expression of TLR9 was observed in three patients. These three patients also showed markedly higher expression of IFN-α and-γ with a significant correlation among them. We defined these three patients as the high TLR9 group and the remaining patients as the low TLR9 group. Immunohistochemical analysis confirmed markedly higher TLR9 expression in the tonsils of the high TLR9 group. TLR9 expression was mainly localized in BDCA-2 and CD123 positive plasmacytoid dendritic cells (pDC). There were higher numbers of pDC in tonsils of the High TLR9 group than in those of the low TLR9 group. However, there was no significant difference in the serum level of IFN-α and-γ between the two groups. Seven patients (High ; N=3, Low ; N=4) completed the steroid pulse therapy protocol. The high TLR9 group showed a significant improvement in proteinuria (P < 0.05) and hematuria (P< 0.01) just after therapy. Moreover, the serum IgA level and IgA/C3 ratio were also significantly decreased in the high TLR9 group (serum IgA : P<0.05, IgA/C3 ratio : P< 0.01). Conclusion : It is suggested that tonsillectomy with steroid pulse therapy may provide rapid and good therapeutic outcomes in IgAN patients who show high TLR9 expression in tonsillar pDC. These findings indicated that TLR9 activation in the mucosa may be involved in the pathogenesis of IgAN.
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  • RhoA kinase inhibitor, fasudil, protects against crescentic glomerulonephritis via podocyte protection.
    TERUO HIDAKA, YUSUKE SUZUKI, MICHIFUMI YAMASHITA, YUICHI TANAKA, SATOS ...
    2007 Volume 53 Issue 1 Pages 106-112
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.106
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    Objective : The Rho family of small GTPases is involved in cell cytoskeletal rearrangement. RhoA has an important role in the podocyte structure, especially in stress fiber formation. RhoA is activated by several G protein-coupled receptors, including angiotensin II type 1 receptor (AT1R). Therefore, the roles of RhoA have been discussed in angiotensin II (Ang II) -induced signaling pathways. In addition, several reports indicated that the local renin-angiotensin system (RAS) is involved in podocyte injury that would induce glomerular crescentic formation. We have previously demonstrated that crescentic glomerular injury in Fc receptor (FcR)-deficient mice [γ (-/-)] with an anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was markedly suppressed by AT1R antagonist. Indeed, anti-GBM GN was completely attenuated in bone marrow chimeras between γ (-/-) and AT1R (-/-) mice. Accordingly, we hypothesized that the RhoA kinase inhibitor, fasudil, may attenuate AT1R- dependent crescentic glomerulonephritis. Materials and Methods : We induced anti-GBM GN in γ (-/-) mice with or without fasudil (10mg/ kg i.p.) and analyzed the disease course. In addition, we stimulated cultured podocytes by Ang II with or without fasudil pretreatment. Then we analyzed the mRNA expression of nephrin. Results : Fasudil markedly attenuated proteinuria (p<0.01) and hematuria (p<0.01) with prevention of sclerotic change (p<0.01) and crescentic formation (p<0.01). Moreover, WT-1 and nephrin expressions in podocytes were conserved only in the fasudil treatment group. An in vitro study with cultured podocytes further confirmed that fasudil preserves nephrin expression under Ang II stimulation. Conclusion : Our present findings demonstrated that fasudil prevents AT1R-dependent crescentic formation in and-GBM GN via podocyte protection.
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  • Th2 cytokine induces aberrant O-glycosylation in the hinge region of IgA1 via downregulation of core1β1, 3-galactosyltransferase and its molecular chaperone Cosmc
    KOSHI YAMADA, NORIYOSHI KOBAYASHI, TOMOMI IKEDA, YUSUKE SUZUKI, TOSHIN ...
    2007 Volume 53 Issue 1 Pages 113-120
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.113
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    Objective : IgA1 molecules display abnormal O-glycosylation of the hinge region in patients with IgA nephropathy (IgAN). Several studies have proposed that increased production of Th2 cytokines and functional abnormality of the enzyme (core1 β1, 3-galactosyltransferase : C1 β 3Gal-T) responsible for O-glycosylation of IgA1 might be the mechanism involved in the altered glycosylation of IgA1. However, these mechanisms have not yet been clearly elucidated. To assess the effect of T cell cytokines on IgA1 glycosylation, we analyzed the mRNA expression of both C1 β3 Gal-T and its molecular chaperone Cosmc, and glycosylation of IgA1 secreted from the human B cell line with stimuli of these cytokines. Materials & Methods : The human B lymphoma cell line, DAKIKI, which shows surface expression of IgA1, was cultured with recombinant human IFN-γ, IL-4 and IL-5 for 5 days to analyze cell proliferation, and the production and glycosylation of IgA1. The production and glycosylation of IgA1 were determined by sandwich ELISA and enzyme-linked lectin binding assay, respectively.Real-time PCR was performed to measure the mRNA expression of C1 β 3 Gal-T and Cosmc in cells with IFN-γ and IL-4 stimuli after 12 and 48 hours. Results : IL-4 or IL-5 stimulation induced significantly greater cell proliferation than IFN-γ stimulus or control. IgA1 concentration in supernatant from IL-4-stimulated cells was significantly higher than those in supernatant from cells stimulated by other cytokinesand control cells. IL-4 stimulation significantly decreased the mRNA expression of both C1 β 3Gal-T and Cosmc, and altered the terminal glycosylation of secreted IgA1. Conclusion : It appears that Th2 cytokines induced B cell proliferation and IL- 4 may affect mRNA expression of both C1 β 3Gal-T and Cosmc, and subsequently altered the glycosylation of IgA1.
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  • Analysis of IgAl-binding protein using liquid chromatography electron spray ionization mass spectrometry (LC-ESI MS) in patients with IgA nephropathy (IgAN)
    KEIKO SAKAMOTO, YUSUKE SUZUKI, YUICHI TANAKA, REIKO MINEKI, TSUTOMU FU ...
    2007 Volume 53 Issue 1 Pages 121-130
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.121
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    Objective : Although the major pathogenic abnormalities of IgAN are considered present in the systemic immune system rather than the kidneys, the pathogenesis of this disease remains unclear. Abnormalities of IgA including under-glycosylation and polymeric IgA immune complex (IC) formation have been discussed in relation to pathogenesis. Since upper respiratory tract infection exarcerbates IgAN and tonsillectomy has therapeutic effects on this disease, previous studies have examined the involvement of antigens in this disease. However, obvious antigens that form IgAIC have not been identified. In this study, we analyzed IgA binding protein (BP) in serum from IgAN patients using LC-ESI TOF MS to determine whether exogeneous antigens are involved in IgAIC formation. Materials : Six patients with IgAN (n=1 good prognosis, n=1 relatively good prognosis, n=3 relatively poor prognossis, n=1 poor prognosis), five patients (n=4 relatively poor prognosis, n=1 poor progonosis) who had undergone tonsillectomy and 3 courses of steroid pulse therapy and eight healthy volunteers were examined in this study. Methods : Serum 400 μ1 was added to jacalin, and IgA1/lgA1-BP was eluted using O.8M galactose. The eluted protein was fractionated on a Superdex 200 10/300GL column. When 1.5μg of protein from each fraction was electrophresed on acrylamide gel, 30 to 40 bands confirmed by silver staining of each sample were analyzed by LC-ESI MS. Moreover, changes in IgA1-BP due to the therapy were also analyzed. Jacalin-binding protein, which was obtained from 25 μ1 of serum, was subjected to Western blotting to quantitatively evaluate the identified protein. The protocol for steroid therapy was as follows; intravenous pulse administration of methylprednisolone of 0.5g/dayX 3 days every two months and oral administration of prednisolone at 0.5 mg/kg every other day after each pulse therapy. Results : The eluted protein showed 4 peak fractions (170kDa, 340kDa, 680kDa, and higher than 680kDa). In each fraction of IgA1/IgA1-BP, MS identified apolipoprotein, immunoglobulin (Ig) heavy chain (α, μ, γ) and light chain, Ig J chain, fibronectin, C1INH, C4bp and α 1MG. C4bp was frequently observed in the patient group (patients; 3/6, volunteers; 1/5). This system failed to determine any obvious exogeneous antigen in the IgA1-BP. Interestingly, tonsillectomy with steroid pulse therapy increased concentrations of the 170 and higher than 680kDa peaks and decreased that of the 340kDa peak. After this therapy, IgA1-binding IgG decreased in the 340kDa and 680kDa fractions, while IgA1-binding C4bp decreased in the 680kDa and higher fractions. Conclusions : Although we could not confirm exogeneous antigen in IgA1-BP, the present findings suggested that IgG and C4bp might be involved in the formation of pathological IgAIC.
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  • Do Japanese diagnostic criteria for metabolic syndrome (MS) reflect the severity on coronary arteriography?
    ATSUMARO SUSO
    2007 Volume 53 Issue 1 Pages 131-137
    Published: March 31, 2007
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.53.131
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    Objective : To compare the Japanese diagnosis criteria for metabolic syndrome (MS) with the Gensini score of coronary arteries. Patients : The study group comprised 379 patients who underwent coronary arteriography in Juntendo Hospital between December 2005 and June 2006. Methods : The patients were classified into two groups designated MS and non-MS based on the Japanese diagnostic criteria for MS and the AHA diagnostic criteria for MS. Then the Gensini Score of coronary arteries was compared between the two groups. We also compared the number of diagnosis items for MS with the extent and severity of coronary arteries. Measurement and Results : The percentages of patients diagnosed as having MS by Japanese diagnosis criteria and by AHA diagnosis criteria were 35.4% and 39.8%, respectively. The Gensini Score in the MS group diagnosed by Japanese criteria was 37.1 which was significantly higher than that in the non-MS group, 27.8 (P=0.0027). In addition, the Gensini Score of the MS group diagnosed by AHA criteria was 36.3 which was significantly larger than that of the nonMS group, 25.4 (P=0.003). The mean values of the Gensini Score in relation to the number of diagnostic items, 0, 1, 2, 3, 4, and 5 by Japanese diagnostic criteria were 12.7, 21.6, 31.4, 36.0, 39.9 and 42.0, respectively. The mean value of the Gensini score strongly correlated with the amount number of diagnostic items (P=0.0004). Conclusions : The Japanese diagnostic criteria for MS correlated well with the Gensini Score and reflect the severity of findings on coronary arteriography.
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