The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 222, Issue 1
September
Displaying 1-13 of 13 articles from this issue
Review
  • Katsuhiro Toda, Toshihide Harada
    2010 Volume 222 Issue 1 Pages 1-5
    Published: 2010
    Released on J-STAGE: August 25, 2010
    JOURNAL FREE ACCESS
    Parkinson's disease (PD) is characterized by resting tremor, slow and decreased movement (hypokinesia and akinesia), rigidity, postural instability, problems with gait, and coordination. The prevalence of PD is between 0.1% and 0.3% in the general population and between 1% and 2% in persons 65 years of age or older. Patients with PD are more likely to suffer from pain. Indeed, the chief complaint of patients with severe motor disturbance and severe pain is pain rather than motor disturbance. Fibromyalgia (FM) is defined by widespread pain (pain in the left and right sides of the body, pain above the waist, pain below the waist, and axial skeletal pain) for more than 3 months and the presence of at least 11 of the 18 specified tender points. FM and chronic widespread pain (CWP), which is usually an incomplete form of FM, cause pain in the musculoskeletal region, but their etiologies are unknown. Therefore, it is almost impossible to determine whether or not pain in the musculoskeletal region is in the musculoskeletal origin. We suspect that dysfunction or degeneration of the nerves that control pain, mind, and movement in the brain causes FM, depression, and PD, respectively. When pain in PD is discussed, FM and CWP should be considered because their prevalence is high. Patients with PD may be likely to suffer from FM and CWP; however, the prevalence of FM and CWP in patients with PD has not been reported. Here, we discuss the relationship between PD and FM or CWP.
    Download PDF (154K)
Regular Contributions
  • Guang Li, Jianguo Li, Qing Zhou, Xuemin Song, Hui Liang, Lili Huang
    2010 Volume 222 Issue 1 Pages 7-13
    Published: 2010
    Released on J-STAGE: August 25, 2010
    JOURNAL FREE ACCESS
    Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are the most common complications of sepsis, and the mortality of sepsis-induced ALI remains high in critically ill patients. Growth hormone releasing peptide-2 (GHRP-2), a ghrelin agonist, has been shown to exert beneficial effects on various inflammatory diseases. We therefore explored whether GHRP-2 possesses anti-inflammatory properties in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Male Sprague-Dawley rats were intratracheally instilled with LPS (2 mg/kg) to induce ALI. ALI was confirmed with lung tissue injury (histopathological examination), enhanced lung edema (wet-to-dry weight ratio), and neutrophil infiltration (myeloperoxidase activity) at 6 h after LPS exposure. The analyses of bronchoalveolar lavage fluid showed the significant increases in pulmonary permeability (total cells and protein) and the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In contrast, these lung injury indexes were attenuated in rats that received a subcutaneous injection of GHRP-2 (100 μg/kg) 0.5 h prior to LPS administration. To further explore the potential anti-inflammatory mechanism of GHRP-2 in LPS-induced ALI, we assessed of nuclear factor-κB (NF-κB) activity in lung tissues at 6 h after LPS challenge. We thus found that pretreatment with GHRP-2 markedly suppressed the activation of NF-κB in lung tissues. These results indicate that GHRP-2 attenuated LPS-induced ALI. Early protection appears to be mediated partly through the inhibition of NF-κB pathway activation. The present study indicates that GHRP-2 acts as a potential therapeutic reagent for treating ALI.
    Download PDF (633K)
  • Hui Cao, Zhong Xu, Hao Long, Xiao-Qing Li, Shao-Lin Li
    2010 Volume 222 Issue 1 Pages 15-21
    Published: 2010
    Released on J-STAGE: August 27, 2010
    JOURNAL FREE ACCESS
    Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Human colorectal carcinogenesis is a complex, multistep and multigenetic process. Cyclooxygenase-2 (COX2), a key enzyme in arachidonic acid metabolism, is overexpressed in several epithelial malignancies including colorectal cancer. COX2 expression can be induced by pro-inflammatory and mitogenic stimuli. The -765G/C polymorphism of the COX2 gene promoter has been reported to affect CRC susceptibility, but recent studies have demonstrated conflicting results. To shed light on these inconclusive findings, we performed a meta-analysis for assessing the involvement of COX2 -765G/C polymorphisms at the onset of colorectal carcinoma. Literature-based searching was guided to gather data and either fixed-effect or random-effect model was used to pool the odds ratio (OR) according to the test of heterogeneity. The 10 eligible case-control studies included 3,322 colorectal cancer cases and 5,166 controls. Overall, no evidence has indicated that individuals carrying GC+CC genotypes had significantly increased colorectal cancer risk compared with GG genotype [OR = 1.06, 95% confidence interval (95% CI) = 0.94-1.20]. However, stratified analysis with ethnicity indicated that individuals carrying GC+CC genotypes had an increased risk of colorectal cancer (OR = 1.40, 95% CI = 1.11-1.76) among Asian population. In conclusion, although not all bias could be eliminated, the -765C allele of the COX2 gene may be a potential risk factor for colorectal cancer in Asians.
    Download PDF (1312K)
  • Hyun-Uk Shin, Chang-Wan Han, Masahiro Kohzuki
    2010 Volume 222 Issue 1 Pages 23-31
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Social mobility is the movement of individuals, families and groups from one social position to another. Researchers indicate that people with psychiatric disabilities tend to come from lower socioeconomic status groups, and that the causal relationship between lower socioeconomic status and mental illness occurs through social mobility process. The purpose of this study was to examine the occupational social mobility process of a sample of self-identified psychiatrically disabled individuals who have been active members of the labor force for most of their adult lives. A total of 200 participants were recruited from the customers of a One-Stop Career Center in Gloucester County, New Jersey. The social mobility pattern of persons with psychiatric disabilities was compared to that of persons without psychiatric disabilities (n = 100 for each group). That is, the social selection and the social causation hypotheses were applied to the social mobility patterns of people with psychiatric disabilities. It was revealed that the social class distribution for fathers of people with psychiatric disabilities was not different from that of people without psychiatric disabilities and also there was no significant social mobility difference between the two groups. These findings do not support the social causation and the social selection hypotheses. Specifically, the findings demonstrate that occupational capabilities and skills of people with psychiatric disabilities have been stabilized and are similar to those of people without psychiatric disabilities. Furthermore, these results may dispute several biases and prejudices with regard to social mobility process of persons with psychiatric disabilities.
    Download PDF (166K)
  • Tadashi Terada
    2010 Volume 222 Issue 1 Pages 33-37
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Cryptococcus neoformans is present in our surroundings, and is particularly common in bird feces, such as pigeon droppings. Autopsy cases of cryptoccocal meningoencephalitis in young individuals are very rare. The aim of this study is to describe the autopsy findings of cryptococcal meningoencephalitis of the brain and spinal cord in a young man who presented no apparent immunosuppression. A 36-year-old Japanese man presented with hemoptysis and admitted to our hospital. Chest X-ray revealed a small cavity in the left lung. He soon developed somnolence, neck stiffness, positive abnormal neurological reactions, and increased muscular tonus. Cryptococcus neoformans was detected in the cerebrospinal fluid. Despite appropriate chemotherapy (amphotericin B), he died 18 days after the admission. Autopsy revealed clouding of the leptomeninges of the brain and spinal cord. The brain (1,830 g, normal 1,300 − 1,500 g) showed marked edema and bilateral tonsillar herniation. The lung revealed a cavity in the left lower lobe. Microscopically, the leptomeninges were diffusely infiltrated with numerous cryptococcus fungi and mononuclear cells. Cryptococcus fungi were also present in the parenchyma of the brain and spinal cord, in which mild gliosis and vascular proliferation were recognized. The lung cavity revealed a presence of Cryptococcus neoformans and gram-positive bacteria with granulomatous tissue reactions. The cryptococcal granulomas were also recognized in the liver and spleen. The cause of death was thought to be tonsillar herniation. The present study indicates that severe cryptococcosis involving leptomeninges and parenchyma of the brain and spinal cord may occur in an otherwise healthy individual.
    Download PDF (1757K)
  • Kanako Sakurai, Hiroshi Fukazawa, Zenei Arihara, Katsumi Yoshida
    2010 Volume 222 Issue 1 Pages 39-44
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.
    Download PDF (483K)
  • Koji Sugioka, Koji Yoshida, Aya Kodama, Hiroshi Mishima, Kosuke Abe, H ...
    2010 Volume 222 Issue 1 Pages 45-50
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Corneal wound healing is a complex process involving the integrated actions of various growth factors, cytokines and extracellular matrix produced by corneal cells and inflammatory cells. Connective tissue growth factor (CTGF) has been linked to wound healing, and fibronectin (FN) is a major component of the extracellular matrix. However, the functions of CTGF and FN in corneal epithelial cells are not well understood. We therefore investigated the coordinated function of CTGF and FN in the attachment and migration of corneal epithelial cells. Treatment of human corneal epithelial cells (HCECs) with transforming growth factor (TGF) β1 up-regulated the expression of CTGF, but did not noticeably affect FN expression, as judged by immunoblot analysis of cell lysates. In contrast, the amount of FN accumulated in the cultured media was increased in a time-dependent manner, but CTGF was undetectable in the cultured media. The expression level of FN was decreased by the knockdown of CTGF expression with a specific short hairpin RNA, indicating that CTGF acts as an upstream mediator of FN expression. CTGF augmented the FN-mediated increase in the attachment of HCEC by about twofold, although CTGF alone did not influence the attachment. Moreover, the migration assay with rabbit corneal blocks revealed that CTGF (390 nM) alone or in combination of FN (10 μg/mL) promoted corneal epithelial migration; the mean migration distances of control, CTGF, and CTGF + FN were 272, 325, and 626, μm, respectively. In conclusion, CTGF cooperates with FN in enhancing the attachment and migration of corneal epithelial cells.
    Download PDF (357K)
  • Yosuke Togashi, Young Hak Kim, Ryo Miyahara, Kaoru Irisa, Yuichi Sakam ...
    2010 Volume 222 Issue 1 Pages 51-53
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Fibrosing mediastinitis (FM) is a rare benign disorder that is characterized by excessive fibrotic reactions in the mediastinum. FM is associated with various diseases, including Histoplasma capsulatum infection and IgG4-related disease, and may compromise the airways, great vessels, and other mediastinal structures. Chylothorax is not a common manifestation of FM, and there is no standard treatment for FM or chylothorax. Recently, however, somatostatin and octreotide, a somatostatin analogue, were successfully used for the treatment of chylothorax due to various causes, and they are considered as putative therapeutic interventions for chylothorax. Here, we present a 28-year-old Japanese man with chylothorax due to idiopathic FM, who was successfully treated with octreotide. The patient visited our hospital because of dyspnea on exertion. On admission, chest computed tomography revealed pericardial effusion, bilateral pleural effusion, and a mass in the mediastinum. The right pleural effusion appeared chylous, with the triglyceride level of 253 mg/dl. The biopsy specimen from the mediastinal mass showed collagenous fibers and fibroblasts with moderate infiltration of lymphocytes. Neither fungi nor bacteria were cultured from the biopsy specimen. Steroid therapy was not effective. The patient was then treated with subcutaneous octreotide (100 μg three times daily). Five days after starting the treatment, the drained pleural fluid was decreased to ∼150 ml/day from ∼1,000 ml/day. The mediastinal mass decreased in size 2 weeks after the initiation of octreotide treatment. After discharge, the patient has received octreotide treatment for 6 months without serious adverse events. We suggest octreotide as a treatment option for FM.
    Download PDF (378K)
  • Kenji Tsuiji, Takashi Takeda, Bin Li, Akiko Kondo, Mamoru Ito, Nobuo Y ...
    2010 Volume 222 Issue 1 Pages 55-61
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Uterine leiomyomas are the most common gynecological benign tumor and greatly affect reproductive health and wellbeing, but the pathophysiology and epidemiology of uterine leiomyoma are poorly understood. One of the major reasons for the slow progress in leiomyoma research is the lack of a good in vivo model system. We therefore aimed to develop a novel model by transplanting human uterine leiomyoma xenografts in an immunodeficient mouse strain (NOD/SCID/γc-null: NOG). Human uterine leiomyoma tissues were cut into small pieces and inserted subcutaneously into the right and left flanks of NOG mice. Estrogen supplementation was needed to maintain the features of uterine leiomyoma in xenografted tissues. After 4 weeks or 8 weeks of transplantation, xenografted tissues were harvested and analyzed regarding tissue morphology, collagen content, and proliferation and apoptosis of uterine leiomyoma smooth muscle cells. The xenografts that were harvested after 4 weeks and 8 weeks retained the histological architecture of original uterine leiomyoma tissue both in cellular and collagen components. The expression profiles of key markers of uterine leiomyoma were also maintained, including estrogen receptor, progesterone receptor, and α-smooth muscle actin, as judged by immunohistochemical staining. The proportion of proliferating cells was significantly increased (1.5-fold) in the xenografts after 8 weeks of transplantation, whereas that of the apoptotic cells remained unchanged. Importantly, the reproducible results were obtained with the tumor tissues derived from six patients. The present in vivo model may provide a useful tool for development of novel therapeutic strategies for uterine leiomyoma.
    Download PDF (1695K)
  • Jun Zhao, Huaqin Sun, Wenqian Deng, Dan Li, Yanyan Liu, Yilu Lu, Yunqi ...
    2010 Volume 222 Issue 1 Pages 63-68
    Published: 2010
    Released on J-STAGE: August 28, 2010
    JOURNAL FREE ACCESS
    Piwi (P-element-induced wimpy testis) proteins have been shown to play important roles in maintenance of germ line stem cells, germ cell proliferation and differentiation, and control of Piwi-interacting RNAs (PiRNAs). PiRNAs comprise a broad class of small noncoding RNAs that function as an endogenous defense system against transposable elements. Fibroblast growth factor (Fgf) signals, mediated partly by no tail gene (ntl), are responsible for patterning embryo and mesoderm formation. To understand the function of Piwi proteins, we used zebrafish as a model system. In zebrafish, piwi-like 2 gene (piwil2) is also required for germ cell differentiation and meiosis. Here we report that piwil2 knockdown is able to inhibit the expression of fibroblast growth factor 8a (fgf8a). In contrast, injection with piwil2 mRNA enhances fgf8a expression. Knockdown of piwil2 reduces the inductive effect of fgf8a on dorsalized phenotype, in which embryos extend to an oval shape at the end of epiboly stage. Coinjection with fgf8a and piwil2 mRNAs led to more seriously dorsalized phenotype than coinjection with fgf8a mRNA and piwil2-cMO. In addition, knockdown of piwil2 inhibits the inductive effect of fgf8a on ntl, whereas overexpression of piwil2 enhances the inductive effect of fgf8a on ntl. We also demonstrate that piwil2 positively regulates ntl expression at bud stage, while piwil2 negatively regulates ntl expression at 24 hours post-fertilization. Thus, the functional consequences of piwil2 expression vary during early development of zebrafish embryo. Taken together, we suggest that zebrafish piwil2 is a mediator of Fgf signals in gastrula period.
    Download PDF (1192K)
  • Hiroo Matsuse, Takeshi Nago, Yoshio Takano, Naoto Shiba
    2010 Volume 222 Issue 1 Pages 69-75
    Published: 2010
    Released on J-STAGE: September 01, 2010
    JOURNAL FREE ACCESS
    Resistance exercise is a physiological stimulus for acute increases in growth hormone (GH) secretion, and it also causes lactate accumulation and stimulates norepinephrine (NE) secretion as a sympathetic nervous response. The hybrid exercise method (HYB) is a novel resistance exercise method that combines a voluntary concentric muscle contraction and an electrically stimulated eccentric muscle contraction. This study was designed to compare the hormonal responses of HYB with typical weight training (WT), as regards GH, lactate, and NE. Twenty-four healthy male subjects (20-27 years) were divided into the HYB group and the WT group. All the subjects performed bilateral leg exercises with 10 sets of 10 reciprocal 2-second (45°/sec) knee flexion-and-extension contractions, and with 1-min interset rest intervals. Plasma concentrations of GH, lactate, and NE were determined before exercise and immediately after exercise (0 min) as well as at 15, 30, 60, and 120 min. The plasma concentrations of GH and lactate were significantly increased immediately after HYB or WT (P < 0.05). Moreover, the degree of the increases of GH and lactate after HYB was significantly higher than that after WT (P < 0.05). The plasma concentration of NE was significantly increased after HYB or WT (P < 0.01), but no significant difference was observed between the two groups. These results indicate that HYB is more efficient in stimulating acute increases in plasma GH and lactate without enhancing sympathetic nerve stimulation, compared to WT. Therefore, HYB may be an effective countermeasure to muscle disuse associated with bed rest or spaceflight.
    Download PDF (620K)
  • Hisashi Masugata, Shoichi Senda, Hiroaki Dobashi, Takashi Himoto, Koji ...
    2010 Volume 222 Issue 1 Pages 77-81
    Published: 2010
    Released on J-STAGE: September 01, 2010
    JOURNAL FREE ACCESS
    Aortitis syndrome is a chronic vasculitis that leads to arterial wall thickening and stiffening in large elastic arteries. However, there are no established markers for assessing arterial stiffening in aortitis syndrome. The cardio-ankle vascular index (CAVI) has recently been utilized to assess arterial stiffening that is associated with atherosclerosis-related diseases. We hypothesized that CAVI can be applicable for assessing alterations in arterial stiffness during immunosuppressive therapy for aortitis syndrome. A 69-year-old woman with a 2-month history of recurrent fever, fatigue, and malaise, showed intense 18F-fluorodeoxyglucose (18F-FDG) uptake in the thoracic aorta and common carotid arteries in 18F-FDG-positron emission tomography. These clinical and imaging findings resulted in the diagnosis of aortitis syndrome. The patient also showed the elevated CAVIs on both sides (right, 10.3; left, 10.4) (normal value for her age, 9.1 ± 0.8), indicating the arterial stiffness due to aortitis syndrome. The patient was treated for 34 weeks with immunosuppressive therapy, which included oral prednisolone and methotrexate. C-reactive protein (from 4.24 to 0.49 mg/dL) and immunoglobulin G (from 2,627 to 1,524 mg/dL) were decreased by 7 weeks after initiation of the treatment. The decrease in these inflammatory parameters suggests the effectiveness of the immunosuppressive therapy. In addition, after the 34-week treatment, the CAVIs on both sides (right, 9.3; left, 9.2) were within the normal range. These data indicate that the immunosuppressive therapy ameliorates the degree of arterial stiffness. In conclusion, CAVI may be a promising marker for evaluating the effectiveness of immunosuppressive therapy in patients with aortitis syndrome.
    Download PDF (369K)
  • Youtao Zhang, Yiming Zhao, Shiqi Lu, Mingqing Zhu, Yang He, Changgeng ...
    2010 Volume 222 Issue 1 Pages 83-88
    Published: 2010
    Released on J-STAGE: September 01, 2010
    JOURNAL FREE ACCESS
    Platelet membrane glycoproteins (GPs) are critical for normal platelet adhesion, activation and aggregation. To define the abnormalities in surface GP expression on circulating platelets and provide a better biomarker of bleeding and thrombotic disorders, we have developed a accurate, time-saving and high-throughput biotin-avidin enzyme-linked immunosorbent assay (BA-ELISA) with the monoclonal antibodies (mAbs), 7E3 against the complex of GPIIb and GPIIIa (GPIIb/IIIa), SZ-51 against P-selectin, and SZ-2 against GPIb, respectively. The levels of P-selectin and GPIIb/IIIa were measured in patients with acute myocardial infarction (AMI), intracerebral hemorrhage (ICH), or diabetes mellitus (DM)) and healthy subjects. Inhibition of GP expression was evaluated with SZ-21, an inhibitory mAb against GPIIIa and aspirin, respectively. The sensitivity of BA-ELISA is high enough to detect platelet count as low as 3.13 × 109/L in platelet-rich plasma (PRP). Both the inter-assay and intra-assay coefficient variation are less than 10%. Adenosine diphosphate (ADP)-induced or non-ADP-induced expression of P-selectin and GPIIb/IIIa was significantly higher in AMI, ICH or DM than that in controls (P < 0.01 for each). Either SZ-21 or aspirin can inhibit the ADP-induced expression of P-selectin and GPIIb/IIIa. Importantly, a high correlation was detected between BA-ELISA and flow cytometry methods. These observations indicate that BA-ELISA is a sensitive and high-throughput assay for evaluating platelet GP expression. The newly developed BA-ELISA can be popularized in community hospitals, because it does not require sophisticated equipments and reagents. This method is suitable for screening inhibitors of platelet activation and has a potential in use for diagnostic purposes.
    Download PDF (140K)
feedback
Top