Juntendo Medical Journal
Online ISSN : 2188-2134
Print ISSN : 0022-6769
ISSN-L : 0022-6769
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Volume 51, Issue 1
Displaying 1-16 of 16 articles from this issue
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Contents
  • Role of renin angiotensin system in pathogenesis of glomerulonephritis
    YUSUKE SUZUKI
    2005 Volume 51 Issue 1 Pages 2-10
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.2
    JOURNAL FREE ACCESS
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    Recent findings from large clinical trials and experimental studies have emphasized the importance of inhibiting the renin angiotensin system (RAS) in a wide variety of diseases. They have demonstrated that the benefits of RAS blockade may be due to inhibition of the pressor and non-pressor actions of RAS. In addition, since RAS effects may be partly dependent on the compartment in which Ang II, its major effector peptide, is generated, the importance of local RAS in the pathogenesis of many diseases including glomerulonephritis (GN) is discussed. Special attention has been paid to Ang II-induced TGF-β expression and Ang II-dependent mechanism for proteinuria in the progression of GN. This aspect affords an additional therapeutic rationale to the RAS blockade in progressive GN independently of the etiology. However, increasing evidence indicates that RAS may participate, not only in the progression, but also in the induction of several diseases through Ang II-related leukocyte extravasation. These findings lead to the notion that RAS may influence the prognosis of GN in association with immune system activation. However, the implication of Ang II in antigen-specific T cell recruitment into the glomeruli has not yet been demonstrated. We recently found that the susceptibility of antigen-specific T cell-mediated GN is regulated by immune complex-induced RAS activation and subsequent Th1-specific chemokine regulation. Our data suggest that in some settings glomerular RAS activation may be partly involved in immunological processes and contribute to the pathogenesis of GN. Thus, this line of research could indicate new directions concerning RAS blockade in GN.
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  • Immunological abnormalities in hematological diseases
    MICHIAKI KOIKE
    2005 Volume 51 Issue 1 Pages 11-17
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.11
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    In some myelodysplastic syndromes (MDS), immune mechanisms may contribute to the impaired blood cell production. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in peripheral blood mononuclear cells (PBMC) cultured for 3 days were measured by ELISA. The average levels of those cytokines were higher in aplastic anemia (AA) or in refractory anemia (RA). TNF-α, a potent inhibitor of hematopoiesis, has been hypothesized to mediate the suppressive effects in MDS : TNF-α correlated with marrow apotosis and cytopenia. The anti-TNF-α agent, Remivid, has shown marked efficacy in MDS patients. Loss of a whole chromosome 7 (-7), or the long arm of chromosome 7 del (7q) occurs frequently in MDS or acute myeloid leukemia (AML). This findings suggest the presence of a putative tumor suppressor gene not currently recognized. Vitamin D3 inhibits clonal growth of myeloid leukemia, another cancer, and this finding needs further study in animals before clinical trials can be considered. We found that the ratio of CD4+ to CD8+ T cells (CD4/CD8 ratio) was decreased in patients with multiple myeloma (MM). The serum level of interleukin-16 (IL-16) was significantly higher in stage III patients, which is produced by activated CD8+ T cells and can induce CD4C+ T cell activation. Taken together, anti-cytokine therapies and anti-proliferative therapies appear more important.
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  • Pathogenesis of and therapy for Parkinson's disease
    HIDEKI MOCHIZUKI
    2005 Volume 51 Issue 1 Pages 18-24
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.18
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    Dopaminergic neuron loss in the substantia nigra (SN) is the central pathogenic event in the brains of patients with Parkinson's disease (PD), although the mechanism (s) of cell loss is not fully understood. Because many factors have been implicated in the pathogenesis of PD, such as aging, inflammation, chemicals and genetic factors, the pathogenetic mechanisms are presumably heterogeneous. Abnormal protein accumulation including a -synuclein plays important roles in many types of PD as shown by the studies of familiar PD. As a new therapeutic strategy for PD, gene therapy and regenerative medicine have emerged aiming at neuroprotection of nigral neurons. Autosomal-recessive juvenile Parkinsonism (ARJP) is caused by mutations in the PARK2 gene coding for parkin and constitutes the most common familial form of PD. The majority of ARJP-associated parkin mutations are thought to be loss of function-mutations. Therefore, gene therapy using parkin may be crucial in the treatment of ARJP.
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  • Recent advances in Otorhinolaryngology, Head and Neck Oncology
    KATSUHISA IKEDA
    2005 Volume 51 Issue 1 Pages 25-33
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.25
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    This study reviews recent advances and topics in the fields of otology, rhinology, pharyngolaryngology, and head and neck surgery in the Department of Otorhinolaryngology, Juntendo University School of Medicine. In otology, several animal model of genetic deafness have been developed and studied in order to promote further advances in clinical therapy. A new implantable hearing aid generated by magnetic power has been developed for clinical trial. This device would provide presbyacusis with a better amplification of hearing. Clinical works in the field of rhinology focus on surgical therapy for allergic rhinitis and chronic rhinosinusitis. Surgical modalities of allergic rhinitis include argon plasma ablation in the inferior turbinate and resection of the posterior nasal nerve. Minimally invasive surgery used using an endonasal endoscopic approach is being applied to treatment of chronic rhinosinusitis. In the field of pharyngolaryngology, patients with obstructive sleep apnea and snoring have been investigated by overnight sleep studies and a variety of medical managements and surgical procedures including nasal continuous positive pressure and laser-assisted uvulopalatoplasty have been applied with short-term stay. Head and neck carcinoma has been treated with multidisciplinary modalities of chemoradiation and surgery accompanied by plastic reconstruction to preserve quality of life.
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  • Advances of High-Precision Radiation Therapy
    YUTAKA HIROKAWA
    2005 Volume 51 Issue 1 Pages 34-44
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.34
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    Recently, the ability to accurately deliver highly conformation dose distributions to amorphously shaped target volumes has rapidly advanced. However, setup accuracy and internal motion limit our ability to reduce margins. Even in the presence of significant interfractional organ motion, the image-guided technique that involves daily imaging of a target in the treatment room can minimize the effect of these movements. Prostate cancer shows one of the most rapidly increasing cancer incidence. Localized prostate cancer can be effectively treated by high-precision radiation therapy including three-dimensional conformational therapy, intensity-modulated radiation therapy, particle radiotherapy, and brachytherapy. In this article, advances in high-precision radiotherapy for prostate cancer will be presented with some discussion.
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  • In commemoration of the 200th aniversary of the birth of Taizen Sato -Cancer philosophy-
    OKIO HINO
    2005 Volume 51 Issue 1 Pages 45-49
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.45
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    Environment and heredity both contribute to the origin of human cancer.Carcinogenesis can be compared to an opened Japanese fan, because initiated cells growing in several directions will develop into tumors having many gene abnormalities, and this is suggested by the edge of the fan. To search for such genetic alterations, we identified genes that were expressed more abundantly in tumors than in the normal tissue. I will discuss cancer prevention and the delay of carcinogenesis.
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  • Susceptibility gene for type 2 diabetes and related phenotypes in a KK/Ta mouse model
    KENJI SHIINA, YASUHIKO TOMINO
    2005 Volume 51 Issue 1 Pages 50-56
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.50
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    Objective : The KK/Ta strain serves as a suitable polygenic mouse model for type 2 diabetes associated with fasting hyperglycemia, glucose intolerance, hyperinsulinemia, mild obesity and dyslipidemia. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In the present study, to identify susceptibility genes for type 2 diabetes and related disorders, GeneChip Expression Analysis was employed to survey gene expression profiles in the liver of KK/Ta and BALB/c mice. Materials and Methods : Livers from KK/Ta and BALB /c mice at 20 weeks of age were disected. Total RNA was extracted and labeled for hybridizing to the Affymetrix Murine Genome U74Av2 array. Genes that were differentially expressed between KK/Ta and BALB / c mice were confirmed by RT-PCR analysis and direct sequencing was performed. The relationship between polymorphisms and various phenotypes in 208 KK/Ta × (BALB / c × KK/ Ta) F1 backcross mice was analyzed. Results : M-cadherin showed increased expression in the liver of KK/Ta mice by GeneChip analysis. M-cadherin mRNA levels were increased in the liver and muscle of KK/Ta mice by RT-PCR analysis and sequence analysis demonstrated three missense mutations. Statistical analysis of the relationship between polymorphisms and phenotypes in backcross mice demonstrated that M-cadherin exhibits linkage to levels of triglyceride and insulin in sera, glucose tolerance and body weight. Conclusions : Although it has been postulated that M-cadherin may be important for the regulation of morphogenesis of skeletal muscle cells, these results suggest that M - cadherin may influence hypertriglyceridemia, glucose intolerance, hyperinsulinemia and obesity, a constellation of symptoms called Metabolic syndrome in KK/Ta mice.
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  • Somatosensory evoked potentials in striatonigral degeneration and olivopontocerebellar atrophy
    A comparative study with Parkinson's disease.
    WENGANG WU, AKITO HAYASHI, HIDETO MIWA, YOSHIKUNI MIZUNO
    2005 Volume 51 Issue 1 Pages 57-66
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.57
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    Objective : We studied the usefulness of clinical neurophysiological findings, especially, somatosensory evoked potentials (SEP) for differential diagnosis of multiple system atrophy (MSA) including striatonigral degeneration (SND) and olivopontocerebellar atrophy (OPCA) with Parkinson's disease (PD) as well as the clinical aspects and neuroimagings. Patients : Fifty-four patients diagnosed as having SND (14 cases), OPCA (9 cases), PD (18 cases) were studied along with disease contols (13 cases). Methods : We compared the clinical features, brain MRI findings and SEPs obtained by median nerve stimulation among 4 groups ; SND, OPCA, PD and disease controls. Results : We could not find any significant differences in age at disease onset among SND, OPCA and PD patients. The degree of disease progression in SND and OPCA was faster than that in PD. Myoclonus was recognized much more frequently in SND (36%) compared with OPCA (22%) and PD (6%). In clinical neurophysiological study, the mean of the amplitudes of N 20-P25 in SND was significantly larger than that in OPCA, while the amplitudes in SND tended tobe slightly larger than those in PD. The mean of the amplitudes of P25-N33 in SND was significantly larger than that in PD. Furthermore, the mean of both N20-P25 and P25-N33 in SND was significantly larger than those in OPCA and PD. In patients with SND with myoclonus, we found premovement cortical spike in three of the four patients examined. Conclusion : From comparative studies of clinical, brain MRI and clinical neurophysiological findings, we found that myoclonus in SND was significantly more frequent than that in PD, and that the amplitudes of cortical parts of SEP (N20-P25 or P25-N 33) in SND were larger than those in OPCA or PD. From the results of C reflex and jerk-locked back averaging triggered with myoclonus, the myoclonus recognized in SND was considered cortical reflex myoclonus. From these findings, SEP study would be useful method for differential diagnosis of SND from PD or OPCA.
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  • Relationship between altered dephosphorylation status of gap junctional protein and cardiac function during hypoxia-reperfusion in rat heart
    SATOSHI MATSUSHITA, HIDETAKE KURIHARA, MAKINO WATANABE, TAKAO OKADA, T ...
    2005 Volume 51 Issue 1 Pages 67-74
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.67
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    Objective : Gap junctions assembled by connexins mediate cell-cell communication by electrical and chemical coupling. Alterations in electrical uncoupling of the myocardium induce arrhythmogenesis in acute and chronic ischemic heart disease. Recently it has been shown that alterations in the phosphorylation status of the connexins result in a functional alteration of cell-cell communication through the gap junctions. Therefore, we focused on the association between alterations in phosphorylation status of connexin43 (Cx43) and cardiac function using an ex vivo perfusion system of rat heart. Animals : We used adult male Wistar rats weighing 280-320g. All the procedures performed on laboratory animals were approved by the institutional animal care and committee (IACUC) of Juntendo University School of Medicine and all the animal experiments were carried out in compliance with the guidelines for animal experimentation of Juntendo University School of Medicine. Methods : Hearts excised from the rats were transferred to a Langendorff apparatus and perfused via an aortic cannula. After stabilization, the hearts were perfused with hypoxic solution for 0 to 40 min, then reoxygenated for 30 min. During perfusion, we recorded the heart rate, developing pressure of left ventricular and end diastolic pressure. In addition, GOT in the coronary effluent collected at a regular interval was measured. The left ventricle was immediately prepared for immunocytochemistry and immunoblot analysis at the end of the perfusion period. Results : We used three kinds of antibodies (ab) against Cx43 for examining the distribution of Cx43. In control rat heart, all Cx43s were phosphorylated and located at the intercalated disc. There were no signals indicating dephosphorylated Cx43 in the entire section. When the isolated rat hearts were subjected to hypoxia, dephosphorylated Cx43 appeared. The signal for dephosphorylated Cx43 was detected over the entire plasma membranes of myocardial cells. The area of cardiomyocytes that were stained with anti-dephosphorylated Cx43ab increased as the hypoxic perfusion time increased. Immunoblot data also demonstrated that hypoxia induced a time-dependent increase in the amount of dephosphorylated Cx43. We also found that the increase in the area positivefore dephosphorylated Cx43 correlated with the decrease in cardiac function. Conclusions : These data indicate that dephosphorylation and redistribution of Cx43 is an early sign of cardiac injury after hypoxia. The detection of dephosphorylated Cx43 may be useful for examining ischemic heart disease.
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  • Relationship between Fc gamma receptorIII polymorphism and disease severity in patients with IgA Nephropathy
    YUICHI TANAKA, YUSUKE SUZUKI, TOSHINAO TSUGE, SATOSHI HORIKOSHI, YASUH ...
    2005 Volume 51 Issue 1 Pages 75-82
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.75
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    Objective : Fc ϒ receptors (Fc ϒ Rs) may play an important role in positive or negative regulation of immune-cell responses and immune-complex (IC) clearance. Mesangial IgG deposition and circulating IgG / IgA- IC in sera are observed in patients with IgA nephropathy (IgA- N). Therefore, the pathological roles of IgG-IC in IgA-N have been discussed. However, several studies have identified Fc ϒ R polymorphisms (Fc ϒ RIIIa and Fc ϒ RIIIb) that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the present study was to clarify whether Fc ϒ R polymorphisms influence susceptibility to IgA- N, clinical features or severity in patients with IgA-N. Materials and Methods : Japanese patients with IgA-N (n =124) and healthy controls (n =100) were genotyped for Fc ϒ R polymorphisms (Fc ϒ RIIla-176F or V and Fc ϒ RIIIb NA1 or NA2). The genotyping of these polymorphisms was performed using allele-specific PCR methods. Associations among Fc ϒ R polymorphisms and susceptibility, levels of serum IgG, intensity of glomerular mesangial IgG deposition and pathological severity were analysed. Results : These two Fc ϒ R polymorphisms did not show any significant differences in genotype or allele frequencies between IgA- N patients and healthy controls. None of the Fc ϒ R poly morphisms had any apparent influence on age of onset, serum levels of IgG or mesangial IgG deposition in patients with IgA-N. However, Fc ϒ RIIIa-176V homozygous carriers (V/ V) showed more severe injury than Fc ϒ RIIIa-176F carriers (F / F or F /V) (P< 0.04). Conclusion : The present study showed that polymorphisms of Fc ϒ RIIIa influence the severity of IgA-N in Japanese patients but not the incidence, suggesting that IgG-IC may play important roles in the progression and prognosis of this disease via Fc ϒ Rs.
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  • Association of Obesity with Reflux Esophagitis
    KOH MORICHIKA, TAKAYUKI HASHIMOTO, MASAKO KUSANO, SEIYA HOSODA, TAKAO ...
    2005 Volume 51 Issue 1 Pages 83-89
    Published: March 31, 2005
    Released on J-STAGE: November 12, 2014
    DOIhttps://doi.org/10.14789/pjmj.51.83
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    Objective : Reflux esophagitis (RE) is often seen in obese patients on endoscopy. This study investigated the prevalence of RE caused by obesity. Participants : A total of 794 subjects was investigated, consisting of 246 women and 548 men. Methods : Body mass index (BMI) was modified by the criterion of Japan Society for the Study of Obesity (JASSO), and RE on endoscopy was evaluated by the Los Angeles Classification. Results : The prevalence ratio of RE (women : men) was 1.5 : 2.2 at 25?BMI < 27.5, and 2.0 : 2.7 at 27.5?BMI in adults, and 1.9 : 2.4 at BMI < 20, 0.9 : 1.8 at 20?BMI < 22.5, 2.2 : 1.9 at 22.5?BMI<25, 2.5 : 2.6 at 25?BMI<27.5 and 2.8 : 3.1 at 27.5?BMI in the elderly compared with 20?BMI < 25 in adults. Conclusions : There was a higher frequency of RE in more obese subjects and also in the elderly. RE should be kept in mind for improvement of life style including antireflux measures to manage these factors.
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