The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 227, Issue 1
May
Displaying 1-11 of 11 articles from this issue
Regular Contributions
  • Xiaona Sheng, Takero Nakajima, Lixuan Wang, Xiaowei Zhang, Yuji Kamijo ...
    2012 Volume 227 Issue 1 Pages 1-12
    Published: 2012
    Released on J-STAGE: April 12, 2012
    JOURNAL FREE ACCESS
    Serum sulfatides are the major glycosphingolipids in lipoproteins. Although serum sulfatides are mainly synthesized and secreted by the liver, they are significantly decreased when the kidneys are impaired. Our recent experimental study using a murine protein-overload nephropathy model suggested a hypothetical mechanism whereby serum sulfatides were reduced due to kidney dysfunction. This was the result of decreased hepatic expression of a sulfatide synthetic enzyme, cerebroside sulfotransferase (CST), which is associated with systemic enhancement of oxidative stress. However, there is a possibility that the experimental process, protein-overload itself, directly affected the sulfatide metabolism and oxidative stress in the liver. To determine whether kidney dysfunction actually reduces the hepatic synthesis of sulfatides via oxidative stress, we examined sulfatide levels, the hepatic content of metabolic sulfatide enzymes, and the degree of oxidative stress in protein-overload mice subjected to renoprotective therapy using clofibrate, a representative hypolipidemic medicine. Protein-overload mice exhibited marked kidney injuries, enhancement of hepatic oxidative stress, decreased levels of serum and hepatic sulfatides, and decreased expression of hepatic CST. The clofibrate treatment attenuated kidney damage and hepatic oxidative stress while maintaining serum/hepatic sulfatide levels and hepatic CST content in the mice. Because clofibrate monotherapy without protein-overload treatment only minimally affected these hepatic parameters, the hepatic synthesis of sulfatides appeared to be strongly influenced by kidney dysfunction and subsequent oxidative stress. This study suggests that the crosstalk between kidney dysfunction and hepatic sulfatide metabolism is mediated by oxidative stress. These results should help to understand the phenomenon in patients with end-stage kidney disease.
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  • Akira Ando, Hideaki Suda, Yoshihiro Hagiwara, Yoshito Onoda, Eiichi Ch ...
    2012 Volume 227 Issue 1 Pages 13-22
    Published: 2012
    Released on J-STAGE: April 18, 2012
    JOURNAL FREE ACCESS
    Joint immobilization, which is used in orthopaedic treatments and observed in bedridden people, usually causes restricted joint motion. Decreased joint motion diminishes activities of daily living and increases burden of nursing-care. The purpose of this study was to clarify the reversibility of immobilization-induced capsular changes and restricted joint motion in rat knee joints. The unilateral knee joints of adult male rats were immobilized with an internal fixator for 1, 2, 4, 8, and 16 weeks as a model of immobilization after surgery or disuse of the joint. After the fixation devices were removed, the rats were allowed to move freely for 16 weeks. Sham-operated rats were used as controls. Sagittal sections at medial midcondylar regions were made and assessed with histological, histomorphometric, and immunohistochemical methods. Joint motion was measured using a custom-made device under x-ray control after removal of the periarticular muscles. In the 1/16-week and 2/16-week immobilization-remobilization (Im-Rm) groups, cord-like structures connecting the superior and inferior portions of the posterior capsule (partial adhesion) were observed without restricted joint motion. In the 4/16-, 8/16-, and 16/16-week Im-Rm groups, global adhesion of the posterior capsule and restricted joint motion were observed. The restricted joint motion was not completely restored after incision of the posterior capsule. These data indicate that immobilization alone causes irreversible capsular changes and arthrogenic restricted joint motion. Besides the joint capsule, other arthrogenic factors such as ligaments might influence the restricted joint motion. Prolonged immobilization over 4 weeks should be avoided to prevent irreversible joint contracture.
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  • Yumiko Okubo, Naoko Ishiguro, Taiyo Suganuma, Toshio Nishikawa, Toshio ...
    2012 Volume 227 Issue 1 Pages 23-29
    Published: 2012
    Released on J-STAGE: April 19, 2012
    JOURNAL FREE ACCESS
    Acquiring clinical reasoning skills in lectures may be difficult, but it can be learnt through problem-solving in the context of clinical practice. Problem finding and solving are skills required for clinical reasoning; however, students who underwent problem-based learning (PBL) still have difficulty in acquiring clinical reasoning skills. We hypothesized that team-based learning (TBL), a learning strategy that provides the opportunity to solve problems by repeatedly taking tests, can enhance the clinical reasoning ability in medical students with PBL experiences during the pre-clinical years. TBL courses were designed for 4th year students in a 6-year program in 2008, 2009, and 2010. TBL individual scores, consisting of a combination of individual and group tests, were compared with scores of several examinations including computer-based testing (CBT), an original examination assessing clinical reasoning ability (problem-solving ability test; P-SAT), term examinations, and Objective Structured Clinical Examination (OSCE). CBT, OSCE and P-SAT scores were compared with those of students who learned clinical reasoning only through PBL tutorials in 2005, 2006, and 2007 (non-TBL students). Individual TBL scores of students did not correlate with scores of any other examination. Assessments on clinical reasoning ability, such as CBT, OSCE, and P-SAT scores, were significantly higher in TBL students compared with non-TBL students. Students found TBL to be effective, particularly in areas of problem solving by both individuals and teams, and feedback from specialists. In conclusion, TBL for clinical reasoning is useful in improving clinical reasoning ability in students with PBL experiences with limited clinical exposure.
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  • Minami Yamada-Fujiwara, Koichi Miyamura, Tohru Fujiwara, Yasuo Tohmiya ...
    2012 Volume 227 Issue 1 Pages 31-37
    Published: 2012
    Released on J-STAGE: April 25, 2012
    JOURNAL FREE ACCESS
    Severe diarrhea is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Acute graft-versus-host disease (GVHD) has been one of the major causes of diarrhea after HSCT, which is triggered by donor-derived cytotoxic T-lymphocytes. On the other hand, intestinal thrombotic microangiopathy (TMA) sometimes coexists with acute GVHD, and intensified immunosuppression to treat acute GVHD could exacerbate intestinal TMA, presumably through the vascular endothelial cell damage. The differential diagnosis between intestinal TMA and acute GVHD of the gut has mainly relied on the pathological findings, as clinical diagnosis of intestinal TMA has not been established. Therefore, we aimed to assess the feasibility of our clinical diagnosis for the patients with diarrhea after HSCT. We made tentative clinical criteria for intestinal TMA and acute GVHD of the gut, based on the clinical manifestations, laboratory data and colonoscopic findings, and started treatment before pathological diagnosis were made. Subsequently, a pathologist retrospectively assessed the accuracy of clinical diagnosis in a blind manner. In this study, we enrolled 19 patients complicating watery diarrhea after HSCT, and diagnosed as having acute GVHD (n = 10), intestinal TMA (n = 3), or both (n = 6) according to our criteria. We demonstrated that our clinical diagnosis for intestinal TMA and acute GVHD of the gut was overall correct, in terms of the response to the therapy and the pathological diagnosis. The present study may provide a clue on making clinical diagnosis of patients with watery diarrhea after HSCT, which enables us to start a prompt therapy.
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  • Takahiro Ito, Hiroki Tanabe, Tokiyoshi Ayabe, Chisato Ishikawa, Yuhei ...
    2012 Volume 227 Issue 1 Pages 39-48
    Published: 2012
    Released on J-STAGE: April 25, 2012
    JOURNAL FREE ACCESS
    Paneth cells in the small intestine are able to sense luminal bacteria and secrete granules that contain antibacterial peptides. Human defensin (HD)-5 and -6 are antimicrobial peptides found in human Paneth cell granules, and are major bactericidal components. We investigated whether any constituents in the Paneth cell secretions showed chemotactic activity or stimulated cytokine secretion from intestinal epithelial cells, and assessed to what extent HD-5 and -6 were responsible for these activities. The secretions from human Paneth cells and recombinant HD-5 and -6 were evaluated to elucidate their effects on the chemotaxis of dendritic cells (DCs) in a migration assay. The Paneth cell secretions were chemotactic for immature DCs at concentrations ranging from 10 to 1,000 μg/ml. HD-6 was active at 100 ng/ml, but HD-5 was not. Next, the stimulation of cytokine production by the T84 intestinal cell line was assessed using ELISA and/or an antibody array. The secretions more strongly stimulated interleukin (IL)-8 production than did the defensin peptides, and induced production of various cytokines by the antibody array. The secretions were also analyzed by high performance liquid chromatography (HPLC) and mass spectrometry (MS) in order to determine the components. A large number of molecules was found in the secretions, and HD-5 was identified as an immature propeptide. In conclusion, some constituents other than defensin in human Paneth cell secretions activated the migration of DCs and induced the production of inflammatory cytokines. Therefore, Paneth cells may play a role in the innate immunity associated with adaptive immune responses.
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  • Kenichi Watanabe, Masanori Amano, Ayako Nakanome, Daisuke Saito, Sho H ...
    2012 Volume 227 Issue 1 Pages 49-52
    Published: 2012
    Released on J-STAGE: April 27, 2012
    JOURNAL FREE ACCESS
    Fish bones are one of the most frequently observed ingested foreign bodies in the pharynx-esophagus. Fish bones have a tendency to stick and penetrate the mucosa, which can occasionally lead to severe or lethal complications. The extraluminal migration of fish bones in the upper digestive tract is a rare event, and it is even more unlikely that the foreign body will remain in the neck for a prolonged period. We report the unique case of a 69-year-old woman who remained asymptomatic, while a fish bone was lodged in her neck for 9 months. Finally, after her anterior neck had become swollen, she underwent neck exploration, which revealed that the fish bone was embedded in the scar tissue running from within the thyroid gland to outside of the thyroid. Treatment proceeded without complications, and the foreign body was removed successfully. The length of the fish bone was 34 mm. Intraoperative ultrasonography was able to identify the fish bone in situ using real-time imaging; therefore, we recommend this technique for locating migrated foreign bodies in the neck.
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  • Takenori Ogawa, Takahiro Suzuki, Maya Sakamoto, Mika Watanabe, Yutaka ...
    2012 Volume 227 Issue 1 Pages 53-57
    Published: 2012
    Released on J-STAGE: April 28, 2012
    JOURNAL FREE ACCESS
    Warthin tumor (WT) is a benign tumor of the salivary gland primarily affecting middle-aged men. WT is almost exclusively located in the parotid gland and tend to grow slowly without symptoms. Although fine needle aspiration cytology (FNAC) often correctly diagnoses these tumors, they are occasionally misdiagnosed as malignant. Our study sought to distinguish between WT and non-WT using dynamic MRI. In dynamic MRI, a series of images are taken over time measuring the intensity of gadolinium uptake by the parotid. We examined two patients for this study. The first was a 53-year old male, heavy smoker, experiencing manic-depressive episodes. He received a brain MRI at which time his parotid tumor was discovered. Parotid FNAC indicated a squamous cell carcinoma. The second patient was a 76-year old male, moderate smoker and drinker, who had been complaining about swelling in the neck. FNAC of the parotid indicated acinic cell carcinoma and gadolinium-enhanced MRI suggested the tumor was malignant. Prior to surgically extracting of these masses, we performed dynamic MRI on each patient. Both tumors exhibited a pattern consisting of rapid enhancement and rapid attenuation, the pattern of which is characteristic of WT. The surgical specimens confirmed that both were WTs without malignant transformation. Our findings indicate that dynamic MRI is a useful tool for preoperative diagnosis of WT, where other examinations indicate malignancy. Early and correct diagnosis of WT can minimize the use of invasive procedures, and eliminate the stress placed on the patient from a diagnosis of cancer.
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  • Rei Enatsu, Minoru Asahi, Masato Matsumoto, Osamu Hirai
    2012 Volume 227 Issue 1 Pages 59-61
    Published: 2012
    Released on J-STAGE: April 28, 2012
    JOURNAL FREE ACCESS
    Pituitary apoplexy is defined as a sudden loss of blood supply to the pituitary gland, leading to tissue necrosis and hemorrhage. Its clinical symptoms are characterized by sudden onset of headache, nausea, vomiting, ophthalmic symptoms and hormonal dysfunction. A 65-year-old woman presented with left-sided ptosis and blurred vision. These ophthalmic symptoms gradually worsened for one month without headache, visual acuity and field deficit. Neuro-ophthalmic examination revealed left oculomotor nerve palsy. Magnetic resonance imaging (MRI) revealed a round mass lesion in the left cavernous sinus, which was initially suspected as thrombosed cerebral aneurysm or hemorrhagic Rathke's cleft cyst. The mass lesion was finally diagnosed as pituitary apoplexy. The patient underwent trans-sphenoidal surgery and oculomotor nerve palsy improved after the surgery. Early diagnosis and treatment including surgical decompression are crucially important in patients with oculomotor nerve palsy in pituitary apoplexy, but the symptoms of pituitary apoplexy may slowly progress. It should be noted that pituitary apoplexy could be misdiagnosed as cerebral aneurysm or Rathke's cleft cyst.
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  • Rei Enatsu, Minoru Asahi, Masato Matsumoto, Osamu Hirai
    2012 Volume 227 Issue 1 Pages 63-67
    Published: 2012
    Released on J-STAGE: May 03, 2012
    JOURNAL FREE ACCESS
    Spontaneous intracerebral hemorrhage represents 20 to 30% of all stroke patients in Japan. However, the treatment strategy of intracerebral hematoma remains controversial. Stereotactic hematoma evacuation is minimally invasive surgery and is beneficial for clot removal with limited tissue damage. The purpose of this study was to investigate the factors affecting motor recovery after stereotactic hematoma evacuation. This retrospective analysis included 30 patients with spontaneous thalamic or putaminal hemorrhage who underwent stereotactic hematoma evacuation. We compared age, presurgical muscle strength, hematoma volume and removal rate between the patients who showed improvement of motor function (improved group) and the patients associated with no motor improvement (unchanged group). Twenty-one patients were classified into the improved group and nine patients into the unchanged group. Statistical analysis revealed that age in the improved group was significantly younger than in the unchanged group (p < 0.01), whereas there was no significant difference in presurgical muscle strength, hematoma volume and removal rate between the two groups. The present results revealed that stereotactic hematoma evacuation is attributable to the improvement of motor function, especially in the younger population, indicating the importance of cortical reorganization during post-surgical rehabilitation. In addition, this procedure could provide functional improvement in severely disabled patients. Proper patient selection to receive this therapy would be beneficial for further advances of this technique. The present result might be useful in elucidating the mechanism of motor recovery and proper patient selection for this technique.
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  • Nao Uchida, Osamu Sakamoto, Masahiro Irie, Daiki Abukawa, Junji Takeya ...
    2012 Volume 227 Issue 1 Pages 69-72
    Published: 2012
    Released on J-STAGE: May 12, 2012
    JOURNAL FREE ACCESS
    Intestinal lactase is required for the hydrolysis of lactose that is the most essential carbohydrate in milk and the primary diet source of newborn. Congenital lactase deficiency [CLD (MIM 223000)] is a severe gastrointestinal disorder and is characterized by watery diarrhea due to an extremely low or the lack of lactase activity in the intestinal wall from birth. CLD is a rare disease and occurs more frequently in Finland. Recent studies have shown that mutations in the coding region of the lactase (LCT) gene underlie CLD in patients from Finland and other European countries. Here, we report two novel mutations in the LCT gene in a Japanese female infant with clinical features consistent with those of CLD. She suffered from severe watery diarrhea from the age of 2 days on breast milk/lactose containing cow's milk formula. With the lactose-free hydrolyzed cow's milk formula, diarrhea was stopped, and she has now developed well on a lactose-free diet. She shows a lactose-intolerance pattern on the lactose challenge test. Sequence analysis revealed the two mutations in her LCT gene: c.4419C>G (p.Y1473X) in exon 10 transmitted from her mother and c.5387delA (p.D1796fs) in exon 16 transmitted from her father. Both mutations cause premature truncation of lactase polypeptide and are supposed to be responsible for CLD. To our knowledge, this is the first report on mutations in the LCT gene in Japan. We suggest that an increased awareness is required regarding CLD.
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  • Chin-Tsung Ting, Ran-Chou Chen, Chien-Cheng Chen, Mao-Ho Liu, Dachen C ...
    2012 Volume 227 Issue 1 Pages 73-81
    Published: 2012
    Released on J-STAGE: May 16, 2012
    JOURNAL FREE ACCESS
    Diabetes is a known risk factor for developing hepatocellular carcinoma (HCC). Reported rates of diabetes are higher in chronic hepatitis, cirrhosis and HCC patients. However, its effects on postoperative recurrence and survival with HCC are controversial. This study offers a retrospective analysis of the impacts of diabetes on postoperative recurrence and survival in patients with cirrhosis and HCC. A total of 389 cirrhotic patients who underwent curative resection for primary HCC at our institution between January 2000 and December 2008 were enrolled. Of them, 272 (70%) patients were classified into a non-diabetes group and 117 (30%) patients into the diabetes group. The diabetes group was divided into an oral hypoglycemic agent (OHA) control group (n = 100) and an insulin control group (n = 17). The result indicates that the diabetes group had a higher postoperative recurrence rate and poorer long-term survival rate (p = 0.001 vs. 0.01). There was no significant difference in recurrence-free survival rate between the OHA control group and the insulin control group (p = 0.17). The insulin control group had a poorer long-term surgical outcome than the OHA control group (p = 0.035). In conclusion, our results suggest that diabetes is an independent risk factor for postoperative recurrence and surgical survival of cirrhotic HCC patients. Cirrhotic HCC patients with diabetes who received hepatic resection should be closely followed-up for postoperative recurrence and long-term outcome. Moreover, an effective peri-operative sugar control planning in HCC patients with diabetes should be established.
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