The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 223, Issue 2
February
Displaying 1-11 of 11 articles from this issue
Review
  • Kosaku Nitta, Tetsuya Ogawa
    2011 Volume 223 Issue 2 Pages 79-84
    Published: 2011
    Released on J-STAGE: January 19, 2011
    JOURNAL FREE ACCESS
    Vascular calcification is very common in end-stage renal disease, especially in hemodialysis patients. Vascular calcification is associated with poor prognosis in hemodialysis patients. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification. In addition to traditional risk factors including hypertension and dyslipidemia, hemodialysis patients possess a number of non-traditional cardiovascular risk factors, which may be associated with the pathogenesis of vascular calcification, such as duration of dialysis and imbalance of mineral metabolism. The severity of vascular calcification can be assessed with computed tomography (CT), but a simple technique is required as a routine practice. In an attempt to evaluate the extent of vascular calcification, we have proposed a simple non-invasive technique for estimating aortic arch calcification (AoAC) in hemodialysis patients. The present review summarizes the following aspects: (i) a method of estimating AoAC and the correlation between AoAC score estimated by chest X-ray and AoAC volume evaluated by multi-detector CT as a gold standard, (ii) relation of the presence of AoAC to the prevalence of cardiovascular diseases, and (iii) Kaplan-Meier analysis in terms of cardiovascular mortality in patients with AoAC compared to those without AoAC. We suggest that screening patients undergoing dialysis for the presence of AoAC is a cost-effective, efficient way to identify those patients at the highest risk of cardiovascular events and will allow for the treatment strategies to prevent vascular calcification.
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Regular Contributions
  • Hisashi Masugata, Shoichi Senda, Michio Inukai, Koji Murao, Naohisa Ho ...
    2011 Volume 223 Issue 2 Pages 85-90
    Published: 2011
    Released on J-STAGE: January 20, 2011
    JOURNAL FREE ACCESS
    Hypertension and osteoporosis are two common diseases in the elderly population. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. Reduced bone mineral density is associated with increased arterial stiffness in chronic dialysis patients and healthy postmenopausal women. However, relationships between bone mineral density and arterial stiffness in hypertensive patients have not been fully assessed. We examined the relationships between bone mineral density and both arterial stiffness and nutritional status in 52 hypertensive patients (27 male and 25 female subjects; mean age 71 ± 8 years) who had been treated with antihypertensive drugs for at least one year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device, and the stiffness index was determined as a parameter of the bone mineral density. We measured the cardio-ankle vascular index (CAVI) to assess arterial stiffness and used the serum albumin to assess nutritional status. Increased arterial stiffness as assessed with CAVI is associated with reduced bone mineral density (r = −0.289, p = 0.038). However, the correlation between CAVI and bone mineral density is not as strong as the correlation between serum albumin and bone mineral density (r = 0.501, p < 0.001). In conclusion, nutritional status is an important indicator of bone mineral density in hypertensive patients. Moreover, increased arterial stiffness is associated with reduced bone mineral density in hypertensive patients. Therefore, hypertensive patients with increased arterial stiffness may have a high risk of bone fracture due to osteoporosis.
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  • Takanobu Kojimahara, Kenji Nakahara, Tadahiro Shoji, Toru Sugiyama, Ta ...
    2011 Volume 223 Issue 2 Pages 91-96
    Published: 2011
    Released on J-STAGE: January 20, 2011
    JOURNAL FREE ACCESS
    Pseudomyxoma peritonei (PMP) is a rare condition of mucinous ascites associated mainly with mucinous tumors of appendix or ovary. PMP often recurs after treatment and may eventually cause death by abdominal visceral dysfunction via compression with mucinous ascites. Although radical peritonectomy and hyperthermic intra-peritoneal chemotherapy are becoming popular globally, the optimal treatment of PMP has not been established in Japan. We conducted a retrospective multicenter study to clarify the optimal treatment and the prognostic factors of PMP. A total of 23 patients with PMP were analyzed in the Tohoku Gynecologic Cancer Unit (TGCU). Clinical and follow-up data were retrieved and a central pathology review was performed. The median follow-up period was 46 months. Eleven patients underwent complete resection. There were 7 deaths out of 13 recurrences/progressions in this period. All the recurrence/progression was confined to the abdomen. Unexpectedly, neither radical peritonectomy nor hyperthermic intra-peritoneal chemotherapy had been performed, indicating that both radical peritonectomy and hyperthermic intra-peritoneal chemotherapy are not yet popular in Japan. The medians of overall survival and disease-free period were 166 months and 30 months, respectively. Univariate and multivariate analyses revealed that the only prognostic factor was macroscopic residual tumor (P = 0.022). Although chemotherapy was not a prognostic factor (P = 0.16), those who received intra-peritoneal chemotherapy tended to have a better prognosis than those who received systemic or no chemotherapy (P = 0.064). In conclusion, the macroscopic residual tumor is an important prognostic factor in Japanese patients with PMP.
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  • Jun Chen, Mieko Sadakata, Mayumi Ishida, Naoto Sekizuka, Mitsuko Sayam ...
    2011 Volume 223 Issue 2 Pages 97-102
    Published: 2011
    Released on J-STAGE: January 20, 2011
    JOURNAL FREE ACCESS
    Neonatal jaundice is a common physiological problem affecting over half of all full term and most preterm infants. Thus, newborn infants must be monitored for signs of hyperbilirubinemia to prevent acute bilirubin encephalopathy or kernicterus. Evidence exists supporting the benefits of baby massage as a form of mild hand to skin contact, to increase neonatal physical and mental development. In the present study, the effects of gentle baby massage on neonatal jaundice in full term newborn infants were evaluated by a controlled clinical trial. The inclusion criteria of newborn neonates were as follows: (1) gestational age of 37 ~ 41 weeks, (2) birth weight of 2,800 ~ 3,600 g, (3) Apgar score at birth of 8 ~ 10, and (4) being a healthy neonate without neonatal asphyxia and hemolytic condition. Breastfed newborns without phototherapy were included: 20 in the massage group and 22 in the control group. We found the mean stool frequency of the massaged infants on day 1 and day 2 (4.6 and 4.3) was significantly higher than that of the control group (3.3 and 2.6) (p < 0.05). The transcutaneous bilirubin levels on the second to fifth day and serum total bilirubin levels on fourth day were significantly decreased in the massage group, compared to the control group. In conclusion, baby massage at an early stage after birth could reduce neonatal bilirubin levels. We suggest baby massage is beneficial for ameliorating neonatal jaundice.
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  • Chie Takeda, Masako Notoya, Nobuyuki Sunahara, Katsumi Inoue
    2011 Volume 223 Issue 2 Pages 103-112
    Published: 2011
    Released on J-STAGE: January 22, 2011
    JOURNAL FREE ACCESS
    Recent advances in medical care have facilitated the survival of patients with stroke or traffic-related injuries. However, such patients may suffer from higher brain dysfunction; i.e., an impaired ability to plan and perform behaviors based on prior knowledge. The Trail Making Test (TMT) is a cognitive task that is used to evaluate higher brain dysfunction caused by frontal lobe injury. TMT consists of two tasks; TMT-A involves connecting consecutive numbers, and TMT-B involves connecting numbers and letters alternately. In this study, using near-infrared spectroscopy (NIRS) and the achievement value (TMT score), we investigated the effects of three factors on TMT performance: knowledge of the TMT, the order of TMT-A and TMT-B performance, and gender. The subjects were 48 healthy adults, consisting of college graduates and undergraduates (age: 22.8 ± 2.5 years, education: 16.0 ± 1.2 years, 24 males and 24 females). We measured the changes in oxygenated hemoglobin (oxy-Hb) levels using NIRS, showing that the increase in oxy-Hb was higher in subjects who had no knowledge of the TMT than those who had prior knowledge. In both TMT-A and TMT-B, the subjects who performed their first task displayed higher oxy-Hb levels. Moreover, the oxy-Hb level in males was higher than that in females. In contrast, only the order of TMT performance showed noticeable effect on the TMT score. In the present study, using NIRS we have shown that either knowledge of the TMT, the order of the TMT, or gender affects TMT performance, providing invaluable information for interpreting TMT results.
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  • Wakako Jo, Machiko Endo, Katura Ishizu, Akie Nakamura, Toshihiro Tajim ...
    2011 Volume 223 Issue 2 Pages 113-118
    Published: 2011
    Released on J-STAGE: January 21, 2011
    JOURNAL FREE ACCESS
    Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous type of diabetes mellitus, characterized by early onset (often before 25 years of age) and absence of pancreatic autoimmunity markers. Paired-homeodomain transcription factor 4 (PAX4) functions as a transcriptional repressor and is involved in the differentiation of insulin-secreting β-cells. Here we identified a novel PAX4 mutation in a Japanese patient with MODY. A 15-year-old, non-obese boy was admitted to our hospital because of polyuria and polydipsia. Laboratory evaluation showed an elevated fasting glucose level; however, islet cell antibodies and glutamic acid decarboxylase antibodies were not detected in the patient's serum. The proband's father had been diagnosed as having type 2 diabetes at age of 30 years. We therefore analyzed several candidate genes of MODY, and identified a novel mutation of a 39-base heterozygous deletion in exon 3 (c.374-412 del39) of PAX4 in the proband and his father. This mutation may cause exon 3 skipping that results in a frameshift, thereby producing a premature stop codon in exon 5. As this mutant PAX4 lacks a part of the homeodomain that is critical for binding to the target gene, this mutant was thought to lose the transcriptional repressor function. As expected, luciferase-reporter assays revealed that the mutant PAX4 could not repress the activities of insulin and glucagon gene promoters, unlike the wild-type PAX4 that repressed the promoter activities. The present study demonstrates that a novel mutation of PAX4 is likely to be associated with diabetes in this Japanese family.
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  • Hiroshi Ishii, Satoshi Otani, Atsuko Iwata, Hiroaki Oka, Kosaku Komiya ...
    2011 Volume 223 Issue 2 Pages 119-123
    Published: 2011
    Released on J-STAGE: February 02, 2011
    JOURNAL FREE ACCESS
    The diagnosis of sarcoidosis, a multisystem granulomatous disease of unknown etiology, is established when clinicoradiological findings are supported by histological evidence of non-caseating epithelioid cell granulomas. For pathological diagnosis, an endobronchial biopsy of normal-appearing bronchial mucosa in combination with transbronchial lung biopsy (TBLB) has been reported to be useful for sarcoidosis patients in Europe or the U.S. This is the first report assessing the utility of endobronchial biopsy for diagnosis of Japanese patients with sarcoidosis. Eighteen consecutive patients with strongly suspected sarcoidosis were evaluated by endobronchial biopsy of normal-appearing bronchial mucosa, together with TBLB and bronchoalveolar lavage. The TBLB specimens demonstrated non-caseating epithelioid cell granulomas in the lungs of 11 patients (61.1%), but not any specific findings in those of other 7 patients. In contrast, endobronchial biopsy specimens confirmed a diagnosis of sarcoidosis in only one patient that required steroid therapy for deterioration of pulmonary sarcoidosis. All 18 patients of this study, including 5 patients with pathological findings obtained from extrapulmonary sites, met the pathological or clinical diagnostic criteria. In conclusion, endobronchial biopsy of normal-appearing bronchial mucosa in combination with TBLB does not improve the diagnostic capacity for detecting sarcoidosis in Japanese patients, despite earlier reports. Thus, this method is of limited usefulness as a conventional diagnostic modality for Japanese patients with suspicious sarcoidosis. The present study also suggests the racial difference in the endobronchial involvement in pulmonary sarcoidosis.
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  • Yasushi Mariya, Genichirou Sekizawa, Yoshisuke Matsuoka, Hirobumi Seki ...
    2011 Volume 223 Issue 2 Pages 125-131
    Published: 2011
    Released on J-STAGE: February 03, 2011
    JOURNAL FREE ACCESS
    Non-small cell lung cancer (NSCLC) is characterized by brain metastases that occur in about 30 to 50% of patients. To control tumor growth potential with maintaining neurocognitive function is important in the recent radiotherapy against brain metastases. From this viewpoint, we investigated the utility of repeat stereotactic radiosurgery (SRS) with a linear accelerator in the management of brain metastases from NSCLC. Between October 1998 and May 2010, 28 patients harboring brain metastases received repeat SRS (20 men and 8 women, with the age ranged from 51 to 79). The total number of SRS sessions ranged from 2 to 5, and the total number of lesions in one patient ranged from 1 to 8. Neurological decline due to uncontrolled brain lesions was identified in 9 of 28 patients after the repeat SRS, while the remaining 19 patients showed no neurological decline. Out of the 28 patients, 18 patients died by July 1, 2010; 12 patients died of active extracranial disease and 6 patients died from progressive brain lesions, considered neurological death. The 2-year and 4-year overall survival rates were 51% and 23%, respectively, and the median survival time was 26 months. In conclusion, repeat SRS is a preferred option to manage brain metastases from NSCLC, leading to a long survival with a decreased neurological decline. Repeat SRS is promising to preserve neurocognition, because the convergent dose distribution decreases the unfavorable influences from radiation on germinal niches, thereby preserving neural stem cells that are responsible for the nervous system repair.
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  • Susumu Ogawa, Mikihito Ishiki, Kazuhiro Nako, Masashi Okamura, Miho Se ...
    2011 Volume 223 Issue 2 Pages 133-135
    Published: 2011
    Released on J-STAGE: February 04, 2011
    JOURNAL FREE ACCESS
    Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a newly developed oral hypoglycemic agent. Sitagliptin increases the level of glucagon-like polypeptide (GLP)-1 that increases insulin secretion. In addition, GLP-1 decreases salt intake and increases urinary salt excretion. Therefore, the sitagliptin treatment might lower blood pressure in hypertensive patients with type 2 diabetes. It also remains to be examined whether the reduction in blood pressure with sitagliptin treatment is related to the blood glucose improvement and the body weight decrease. To identify beneficial effects of sitagliptin treatment, we administered sitagliptin (50 mg) on alternate days to seventeen type 2 diabetes outpatients with insufficient blood glucose control (8 males and 9 females; mean age of 67.1 years). The patients were also treated with oral hypoglycemic agents and antihypertensive drugs for six months before and during the sitagliptin administration. We measured the level of hemoglobin (Hb) A1c, systolic blood pressure (SBP), and body mass index (BMI) for up to six months thereafter. Their BMIs remained unchanged. The levels of HbA1c were dropped from 6.5 ± 0.3% to 5.8 ± 0.3%, while SBP was also dropped from 130.0 ± 37.2 mmHg to 119.7 ± 9.4 mmHg. However, the degree of the decrease in HbA1c levels was not significantly correlated with that of SBP (r = 0.24). In conclusion, the present findings suggest that sitagliptin lowers SBP without reducing BMI, independent of the blood glucose reduction. The hypotensive effect is apparent with the alternate-day regimen of sitagliptin at a lower dose compared to the everyday medication.
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  • Yuan Liang, Jia-Li Liu, Yan Wu, Zhen-Yong Zhang, Rong Wu
    2011 Volume 223 Issue 2 Pages 137-144
    Published: 2011
    Released on J-STAGE: February 04, 2011
    JOURNAL FREE ACCESS
    Esophageal cancer (EC) is one of the most common cancers worldwide with 5-year survival rate less than 10%. However, there is a lack of specific genetic markers that could help better understanding the mechanisms of esophageal carcinogenesis, improving the detection rate of EC, and distinguishing histological types. Cyclooxygenase-2 (COX-2) as an inducible enzyme in cancer development and progression is involved in esophageal carcinogenesis. A large number of studies have demonstrated a strong association between COX-2 polymorphisms and EC risk. However, the overall results are still controversial. This controversy may be partly due to the mix-up of esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The aim of this study was to investigate the association between COX-2 polymorphisms and susceptibility to ESCC or EAC by conducting a meta-analysis. Seven studies were retrieved reporting a total of 1450 ESCC patients, 523 EAC patients, and 2663 cancer-free control subjects. Five COX-2 polymorphisms were addressed, including -765G>C (rs20417), -1195G>A (rs689465), -1290A>G (rs689466), -8473T>C (rs5275) and -1759G>A (rs3218625). Meta-analysis results showed that the -765C allele is significantly associated with the susceptibility to both ESCC and EAC especially in Asian populations. In addition, there was a significant association between the -8473C allele and the susceptibility to EAC in Caucasian populations. In conclusion, our meta-analysis suggests that the -765C allele of the COX-2 gene might be a potential risk factor for both ESCC and EAC especially in Asian populations, while the -8473C allele might be a risk factor for EAC in Caucasian populations.
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  • Sang-Heon Kim, Jin Hyeok Jeong, Hyun Jung Kwak, Sung Heon Song, Tae Hy ...
    2011 Volume 223 Issue 2 Pages 145-151
    Published: 2011
    Released on J-STAGE: February 05, 2011
    JOURNAL FREE ACCESS
    Upper airway cough syndrome (UACS), the most common cause of prolonged cough, is diagnosed based on clinical findings without specific diagnostic test. The concentration of nitric oxide in nasal cavity air (nNO) is influenced by allergic rhinitis and/or sinusitis, both of which are common causes of UACS. We measured nNO levels in patients with UACS and those with other causes. We also examined the usefulness of measuring nNO for differentiating patients with sinusitis from those without sinusitis. The study included 93 adult patients with prolonged cough lasting more than threeweeks. Etiologies of cough were identified and nNO was measured at the initial investigation. UACS was diagnosed in 58 patients (62.4%), and sinusitis was identified in 11 (19.0%) of the 58 patients with UACS. Levels of nNO in UACS did not differ from non-UACS etiologies (316.2 ± 129.2 vs. 334.9 ± 88.2 ppb; p = 0.452), suggesting that the measurement of nNO could not discriminate UACS from other etiologies of prolonged cough. However, patients with sinusitis showed significantly decreased nNO levels (190.1 ± 114.8ppb) compared with patients with UACS without sinusitis (345.7 ± 114.6ppb; p<0.001) and non-UACS patients (334.9 ± 88.2 ppb; p<0.001). In a receiver operating characteristic curve analysis for the diagnosis of sinusitis in prolonged cough, the best sensitivity (73.2%) and specificity (81.8%) were obtained with a nNO cutoff value of 279.0 ppb. These findings imply that the measurement of nNO could be useful for diagnosis of prolonged cough associated with sinusitis.
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