The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 236, Issue 1
May
Displaying 1-10 of 10 articles from this issue
Regular Contribution
  • Yoshihide Kawasaki, Akihiro Ito, Narihiko Kakoi, Shuichi Shimada, Jun ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 1-7
    Published: 2015
    Released on J-STAGE: April 10, 2015
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    About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no significant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the significantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no significant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability.
  • Utako Shimizu, Yuji Mitadera, Hagiko Aoki, Kouhei Akazawa
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 9-19
    Published: 2015
    Released on J-STAGE: April 17, 2015
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    Hemodialysis patients in Japan are aging and thus more patients need support for attending hemodialysis facilities. This study aimed to clarify how dialysis patients utilize the services covered by Japan’s public long-term care insurance (LTCI) system. This cross-sectional study was based on LTCI data of March 31, 2009, the latest available data provided by Niigata City, located on the northwest coast of Honshu. Among 30,349 LTCI users in Niigata City, there were 234 dialysis patients. To clarify the characteristics of the dialysis patients, we compared the utilization of LTCI services between the dialysis patients (234 users) and randomly selected 765 non-dialysis users. We also calculated the annual transportation service costs per patient for dialysis patients who continued home care (home care group) and those who switched to long-term hospital care at LTCI care levels 4 and 5 (hospital admission group). These care levels indicate difficulty in walking or maintaining a sitting posture without assistance. The dialysis group more frequently utilized home care and equipment services, such as renting or purchasing care-support products and support for home equipment repair, and utilized facility services and short-stay services (respite care) less frequently (both p < 0.001). Cost per patient was higher in the home care group than in the hospital admission group, because the transportation services for dialysis patients at care levels 4 and 5 involve higher costs. These findings indicate that LTCI services usable for dialysis patients were limited. Therefore, instead of merely subsidizing transportation expenses, transportation services must be improved.
  • Hongbin Xu, Yonghui Feng, Guang Chen, Xiaotong Zhu, Wei Pang, Yunting ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 21-31
    Published: 2015
    Released on J-STAGE: April 29, 2015
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    L-Arginine (L-Arg), the substrate for nitric oxide (NO) synthase, has been used to treat malaria to reverse endothelial dysfunction in adults. However, the safety and efficacy of L-Arg remains unknown in malaria patients under the age of five, who are at the greatest risk of developing cerebral malaria (CM), a severe malaria complication. Here, we tested effects of L-Arg treatment on the outcomes of CM using a mouse model. Experimental cerebral malaria (ECM) was induced in female C57BL/6 mice infected with Plasmodium berghei ANKA, and L-Arg was administrated either prophylactically or after parasite infection. Surprisingly, both types of L-Arg administration caused a decline in survival time and raised CM clinical scores. L-Arg treatment increased the population of CD4+T-bet+IFN-γ+ Th1 cells and the activated macrophages (F4/80+CD36+) in the spleen. The levels of pro-inflammatory cytokines, IFN-γ and TNF-α, in splenocyte cultures were also increased by L-Arg treatment. The above changes were accompanied with a rise in the number of dendritic cells (DCs) and an increase in their maturation. However, L-Arg did not affect the population of regulatory T cells or the level of IL-10 in the spleen. Taken together, these data suggest that L-Arg may enhance the Th1 immune response, which is essential for a protective response in uncomplicated malaria but could be lethal in CM patients. Therefore, the prophylactic use of L-Arg to treat CM, based on the assumption that restoring the bioavailability of endothelial NO improves the outcome of CM, may need to be reconsidered especially for children.
Case
  • Hiroki Saitoh, Nobuo Koizumi, Junji Seto, Satoshi Ajitsu, Akio Fujii, ...
    Article type: Case
    2015 Volume 236 Issue 1 Pages 33-37
    Published: 2015
    Released on J-STAGE: May 01, 2015
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    Leptospirosis is a zoonotic and disaster-related infectious disease. It is mainly endemic in subtropical or tropical countries and has not been reported since 2009 in the Tohoku region (northern Japan), including the Yamagata and Miyagi Prefectures. However, we experienced four patients with leptospirosis in the Tohoku region from 2012 to 2014; three patients (#1-3) live in the agricultural areas of the Yamagata Prefecture and one patient (#4) was a visitor to the Miyagi Prefecture. Patient 1 (81-year-old female) is a villager, with a rat bite, while Patient 2 (77-year-old male) and Patient 3 (84-year-old female) are farmers and were infected probably during agriculture work. Patient 4 (40-year-old male US citizen) was infected while traveling in Thailand. They had chief complaint of fever, headache, and myalgia and showed manifestations of hyperbilirubinemia (mean, 4.35 mg/dL), thrombocytopenia and acute kidney injury (AKI). All patients were diagnosed by polymerase chain reaction using blood and/or urine samples and a microscopic agglutination test for the anti-Leptospira antibody. All the patients were treated with infused antibiotics, including minocycline. The patients underwent hemodialysis due to severe AKI (mean serum creatinine, 4.44 mg/dL), except for Patient 2 with the normal serum creatinine level (1.12 mg/dL). All the patients recovered and were discharged. The presence of the three patients in the Yamagata Prefecture implies that leptospirosis does re-emerge in the Tohoku region. Therefore, careful survey of the pathogen is necessary for febrile patients with AKI who engage in agriculture or have a recent history of travelling in subtropical or tropical countries.
Regular Contribution
  • Hitoshi Kagaya, Michio Yokoyama, Eiichi Saitoh, Daisuke Kanamori, Chia ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 39-43
    Published: 2015
    Released on J-STAGE: May 02, 2015
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    Swallowing is one of the basic activities in humans. The pharynx functions as an airway and a food channel, and a pharyngeal swallow usually occurs after bolus transport from the oral cavity. However, direct fluid infusion through a catheter into the hypopharynx produces a pharyngeal swallow without the oral stage in experimental situations. The purpose of this study was to examine whether a pharyngeal swallow, which is not accompanied by bolus transport, can occur during normal human feeding. Fifty-three healthy volunteers (25-89 years) were recorded, via videofluoroscopic examination of swallowing, during 3 different swallowing trials: command swallow of 10 ml liquid barium, chew-swallow of corned beef, and chew-swallow of a mixture of corned beef and liquid barium. Subsequently each swallow was classified as being either a consecutive pharyngeal swallow (CPS), following transport, or an isolated pharyngeal swallow (IPS), without immediately prior transport. The location of the bolus at swallow initiation was also noted. Of 307 trials, 681 swallows were identified, which included 43 IPS and 638 CPS. IPS only occurred as the first swallow of a trial, but the frequency of IPS did not differ between 28 younger (< 60 years) and 25 older (≥ 60 years) people. Of the three food types, IPS occurred more frequently with the mixed food than with liquid. These results suggest that IPS may represent an airway protective mechanism. In conclusion, IPS occurs in normal swallowing during a daily eating situation. Swallowing is more complex than a simple reflex.
Invited Review
  • Miki Fujimura, Teiji Tominaga
    Article type: Invited Review
    2015 Volume 236 Issue 1 Pages 45-53
    Published: 2015
    Released on J-STAGE: May 13, 2015
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    Moyamoya disease is a chronic cerebrovascular disease with unknown etiology, which is characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. Moyamoya disease is known to have unique and dynamic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki’s angiographic staging established in 1969. Insufficiency of this ‘IC-EC conversion system’ may result in cerebral ischemia, as well as in intracranial hemorrhage from inadequate collateral vascular network, both of which represent the clinical presentation of moyamoya disease. Therefore, surgical revascularization by extracranial-intracranial bypass is the preferred procedure for moyamoya disease to complement ‘IC-EC conversion’ and thus to avoid cerebral infarction and/or intracranial hemorrhage. Long-term outcome of revascularization surgery for moyamoya disease is favorable, but rapid increase in cerebral blood flow on the affected hemisphere could temporarily cause unfavorable phenomenon such as cerebral hyperperfusion syndrome. We would review the current status of revascularization surgery for moyamoya disease based on its basic pathology, and sought to discuss the significance of measuring cerebral blood flow in the acute stage and intensive perioperative management.
Regular Contribution
  • Satoko Sato, Mika Watanabe, Shinji Taniuchi, Atsuko Kasajima, Koji Mit ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 55-61
    Published: 2015
    Released on J-STAGE: May 14, 2015
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    Prostate needle biopsy plays a pivotal role not only in the diagnosis but also the management of patients with prostate cancer. Prostate cancer is often multifocal and diagnosis of the lesion could therefore be difficult with diagnostic imaging only; thus, multiple core biopsies are taken from several different regions of the prostate. In current practice, 10- or 12-core needle biopsy is considered the clinical standard. Several techniques have been reported to improve the orientation of the specimens, but tissue marking, which could theoretically provide important information on the location of the lesion in the prostate, has been rarely reported. Therefore, in this study, we evaluated the clinical significance of systematic 12-core needle biopsy with tissue marking for preoperative prediction of lesion sites and clinicopathological features of patients. We evaluated 93 patients who underwent 12-core prostate biopsy and subsequent radical prostatectomy. We correlated the biopsy results to the prostate sites in which biopsies were performed and prognostic factors of the patients, especially the degree of extraprostatic extension (EPE) obtained in surgical specimens. Among 253 cancer foci detected in 93 prostatectomy specimens, 168 (66.4%) foci were detected by biopsy. All patients had proven cancer. EPE-positive cancers were associated with a larger number of positive cores, larger tumor length, and higher percentage of cancer tissue in the corresponding cores. Systematic 12-core prostate biopsy with tissue marking is useful for preoperative detection of cancer foci and provides valuable information that enables effective surgical strategies.
  • Shigeru Ehara, Kei Takahashi, Jun Nishida, Masataka Uetani, Kenjirou O ...
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 63-69
    Published: 2015
    Released on J-STAGE: May 15, 2015
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    Adult T-cell leukemia-lymphoma (ATLL) is caused by human T-cell lymphotrophic virus I (HTLV-I) infection. Among ATLL cases, 70% of patients present with leukemia and the remaining patients present with lymphoma. Hand osteolysis in the patients with ATLL is considered as paraneoplastic syndrome and caused by parathyroid hormone-related peptide (PTHrP) released from tumor cells. Radiographic features are similar to hyperparathyroidism, but the distribution of osteolysis in hands appears to be slightly different with the authors’ experiences. The objective of this study was to identify radiographic characteristics of hand osteolysis associated with ATLL. We included six ATLL patients (5 men and 1 woman; age range, 45-71 years). All the patients presented with acute leukemia, and three were associated with hypercalcemia and pain in various locations including hands. Patterns of osteolysis on hand radiographs were evaluated and recorded independently by three musculoskeletal radiologists. We analyzed the distribution of the bone resorption in the ray distribution of the hand, finger predilection, and the difference between the ulnar and radial sides. The bone resorption was characterized by frequent involvement of the distal and proximal phalanges, predilection of ring fingers and prominent involvement on the ulnar side, compared with frequent involvement of proximal and middle phalanges, index and middle fingers, and on the radial side in the bone resorption of typical hyperparathyroidism. Such distribution may be a characteristic feature of hand osteolysis in patients with ATLL. The present findings are helpful for physicians to differentiate PTHrP-mediated osteolysis in ATLL from parathyroid hormone-mediated hyperparathyroidism.
  • Ning Jiang, Shuangjian Zhang, Jing Zhu, Jing Shang, Xiangdong Gao
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 71-79
    Published: 2015
    Released on J-STAGE: May 16, 2015
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    Diabetes mellitus is a serious chronic metabolic disorder. To develop novel anti-diabetic drugs from nature sources has always been the focus of research. Red deer (Cervus elaphu Linnaeus) antler is one of the most famous Chinese traditional medicines. We found that the peptides of 5-10 kDa from red deer antlers (PRDA) promoted the growth of cultured rat islet cells. The purpose of this study was to investigate the anti-diabetic actions of PRDA in vivo and purify a pure active peptide. We therefore investigated the hypoglycemic, hypolipidemic and antioxidant effects of PRDA in streptozotocin-induced diabetic mice and isolated a pure anti-diabetic peptide. PRDA, given intraperitoneally (75, 150, or 300 μg/kg), significantly decreased the blood glucose levels, significantly increased the insulin concentrations, and remarkably improved the lipid metabolism in the diabetic mice. PRDA significantly increased the superoxide dismutase activity, catalase activity and the total antioxidant capacity in the serum and liver, and simultaneously decreased the malondialdehyde levels. The activities of hexokinase and pyruvate kinase, two important enzymes involved in glucose utilization, were also significantly increased in the liver of the PRDA-treated diabetic mice. Moreover, a novel anti-diabetic peptide isolated from PRDA significantly promoted the viability of cultured rat insulinoma cells. The molecular mass of the purified peptide was 7064.8 Da under mass spectrometry, and its N-terminal amino acid sequence was identified as LSPFTTKTYFPHFDLSHGSA. Thus, PRDA may be useful in managing the hyperglycemia, hyperlipidemia, and oxidative stress in diabetes, and the anti-diabetic peptide is a promising drug for the treatment of diabetes.
  • Young-Shin Lee, Sea-Hyun Bae, Sung-Hee Lee, Kyung-Yoon Kim
    Article type: Regular Contribution
    2015 Volume 236 Issue 1 Pages 81-88
    Published: 2015
    Released on J-STAGE: May 16, 2015
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    Owing to the reduced capacity for information processing following a stroke, patients commonly present with difficulties in performing activities of daily living that combine two or more tasks. To address this problem, in the present study, we investigated the effects of neurofeedback training on the abilities of stroke patients to perform dual motor tasks. We randomly assigned 20 patients who had sustained a stroke within the preceding 6 months to either a pseudo-neurofeedback (n = 10) or neurofeedback (n = 10) group. Both groups participated in a general exercise intervention for 8 weeks, three times a week for 30 min per session, under the same conditions. An electrode was secured to the scalp over the region of the central lobe (Cz), in compliance with the International 10-20 System. The electrode was inactive for the pseudo-training group. Participants in the neurofeedback training group received the 30-min neurofeedback training per session for reinforcing the sensorimotor rhythm. Electroencephalographic activity of the two groups was compared. In addition, selected parameters of gait (velocity, cadence [step/min], stance phase [%], and foot pressure) were analyzed using a 10-m walk test, attention-demanding task, walk task and quantified by the SmartStep system. The neurofeedback group showed significantly improved the regulation of the sensorimotor rhythm (p < 0.001) and ability to execute dual tasks (p < 0.01). Significant improvements on selected gait parameters (velocity and cadence; p < 0.05) were also observed. We thus propose that the neurofeedback training is effective to improve the dual-task performance in stroke patients.
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