The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 231, Issue 3
November
Displaying 1-12 of 12 articles from this issue
Regular Contributions
  • Maiko Kaga, Tadashi Matsuda, Tatsuya Watanabe, Sachiko Onodera, Shinpe ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 159-164
    Published: 2013
    Released on J-STAGE: October 23, 2013
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    In extremely low birth weight (ELBW) infants, systemic hypotension is associated with poor neurological outcomes as a result of cerebral hypoperfusion. Treatment with arginine vasopressin (AVP) has been shown to increase blood pressure (BP) and urine output in ELBW infants suffering from refractory hypotension. The purpose of this study was to clarify whether low doses of AVP increased renal blood flow (RBF) in ELBW infants. We retrospectively analyzed data from the medical charts describing nine AVP infusions at 0.3-0.8 mU/kg/min in four ELBW infants. The median gestational age was 23 (22.5-23.5, interquartile range) weeks, and the median birth weight was 466 (414-563) g. Changes in the heart rate, BP, urine output, and RBF velocity patterns in response to the AVP infusions were compared using statistical analyses. The AVP infusion caused significant increases in systolic BP from 44 (41.0-47.0) to 50 (42.5-55.5) mmHg, diastolic BP from 17 (15.0-26.5) to 31 (28.5-33.0) mmHg, mean BP from 26 (24.5-30.5) to 36 (34.5-40.5) mmHg, and urine output from 1.4 (0.2-2.5) to 2.8 (1.0-8.6) mL/kg/hr. We also observed significant decreases in the resistance index from 1.0 (0.96-1.0) to 0.8 (0.71-0.91) and peak systolic flow velocity in the renal artery from 40 (27.2-50.6) to 28 (16.0-28.9) cm/s after AVP infusions. AVP infusions at 0.3-0.8 mU/kg/min in ELBW infants appeared to significantly increase the RBF by inducing renal vascular dilation and increasing the BP. Increasing the RBF most likely induces an increase in the glomerular filtration rate, resulting in the diuretic effect of AVP.
Case
  • Jong-Ho Lee, Jeonghwan Lee, Jin Suk Han
    Article type: Case
    2013 Volume 231 Issue 3 Pages 165-169
    Published: 2013
    Released on J-STAGE: October 25, 2013
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    Gitelman’s syndrome is an autosomal recessive salt-losing tubulopathy showing hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis and hyperreninemic hyperaldosteronism. This syndrome is caused by mutations in the SLC12A3 gene that encodes sodium-chloride cotransporter expressed at the apical membrane of renal distal convoluted tubule. Symptoms and renal outcomes of Gitelman’s syndrome are, in general, mild and benign, and renal insufficiency from Gitelman’s syndrome associated with long-standing hypokalemia and volume depletion is extremely rare. Herein, we report a 27-year-old male patient with Gitelman’s syndrome who manifested renal failure, hypokalemia, severe metabolic alkalosis and altered mentality. About one year ago, the patient had been transferred to Seoul National University Hospital, because of unsolved hypokalemia, and was diagnosed as Gitelman’s syndrome by clinical features and genetic analysis of the SLC12A3 gene. The patient carries a missense mutation at one allele of SLC12A3 gene (c.781C>T, p.Arg261Cys). His mother is also heterozygous for the same mutation and she had a history of hypokalemia. On this admission, the patient had recurrent bouts of vomiting induced by psychiatric eating disorder and showed severe volume depletion with hypotension, azotemia and metabolic alkalosis. Intense hydration therapy and emergency hemodialysis transiently improved his fluid-electrolyte imbalance and renal function. However, renal dysfunction progressively deteriorated despite the medical treatment. Our findings suggest that even in Gitelman’s syndrome, constant monitoring for volume status and other comorbid conditions should be employed to prevent progressive renal injury.
Regular Contributions
  • Lin-Chung Woung, Pai-Huei Peng, Chih-Ching Liu, Ching-Yao Tsai, Kai-Ch ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 171-177
    Published: 2013
    Released on J-STAGE: October 29, 2013
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    Patients with optic neuritis (ON) are at an increased risk of developing multiple sclerosis (MS), an illness that may result in physical dysfunction and short life expectancy. Information on the conversion rate to MS of patients with ON is essential in determining the impact of ON on the incidence of MS. Previous Taiwanese studies on the risk of MS in patients with ON were all hospital based, thereby limiting the generalizability of the findings. We aimed to estimate the risk of MS in patients with ON using a nationally representative sample. A cohort of 2,741 patients who sought outpatient care for ON in 2000 was identified from Taiwan’s National Health Insurance claims. The control group consisted of 27,330 age- and sex-matched subjects randomly selected from all beneficiaries in 2000. The person-year approach with Poisson assumption was used to estimate the incidence rate of MS from 2000 to 2008. The relative risk of outpatient visit or hospitalization for MS was estimated using the Cox proportional hazard model. The incidence rates of MS in the ON and control groups were 25.6 and 0.4, respectively, per 10,000 person-years; these values represent a relative risk estimate of 30.84 (95% confidence interval: 14.48 to 65.73) after the potential confounders were considered. Female or younger patients with ON were associated with a significantly elevated risk of developing MS. This study found that Taiwanese patients with ON are at a substantially high relative risk of developing MS. In addition to patients with ON, female and younger people should also receive intensive neurological care to further reduce their risk of developing MS.
  • Yasushi Kudo, Sachiko Hayashi, Emiko Yoshimura, Masashi Tsunoda, Akizu ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 179-186
    Published: 2013
    Released on J-STAGE: October 31, 2013
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    Prevention is better than cure. Public health plays an important role in promoting prevent medicine. To obtain the abilities to provide appropriate nursing services, learning public health is necessary for students who want to become registered nurses. When teachers teach public health to nursing students, it is important to motivate them to learn it. Therefore, we investigated the reasons for the lack of motivation to learn public health by conducting a questionnaire survey. The subjects were female nursing students in 29 vocational schools in Kanagawa and Chiba prefectures of Japan that allow graduation after a 3-year study period. We asked the students whether or not they had completed the subject of public health and analyzed those students who answered affirmatively. We analyzed 1,553 respondents whose average age was 22.6 ± 5.2 years (range, 18 to 45). Using factor analysis, we discovered the 5 reasons that lead to the lack of nursing students’ motivation to learn public health: “Difficulties acquiring knowledge of public health,” “Inappropriate attitudes of public health teachers,” “Thinking lightly about the national examination in the field of public health,” “Lack of understanding the importance of learning public health,” and “Future plans that do not specialize in public health.” Using multiple linear regression analysis, these 5 reasons were significant predictors for the lack of students’ motivation. Older students also had significantly less motivation to learn public health than did younger students. When teachers instruct their students, they should teach public health better with the present knowledge.
  • Tsuguya Fukui, Osamu Takahashi, Mahbubur Rahman
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 187-191
    Published: 2013
    Released on J-STAGE: November 01, 2013
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    During 1991-2000, Japan contribution to the top general medicine journals was very small although the contribution to the top basic science journals was sizeable. However, it has not been examined whether the contribution to the top general medicine and basic science journals has changed during the last decade (2001-2010). The objective of this study was to compare Japan representation in high-impact general medicine and basic science journals between the years 1991-2000 and 2001-2010. We used PubMed database to examine the frequency of articles originated from Japan and published in 7 high-impact general medicine and 6 high-impact basic science journals. Several Boolean operators were used to connect name of the journal, year of publication and corresponding authors’ affiliation in Japan. Compared to the 1991-2000 decade, Japan contribution to the top general medicine journals did not increase over the 2001-2010 period (0.66% vs. 0.74%, P = 0.255). However, compared to the same period, its contribution to the top basic science journals increased during 2001-2010 (2.51% vs. 3.60%, P < 0.001). Japan representation in basic science journals showed an upward trend over the 1991-2000 period (P < 0.001) but remained flat during 2001-2010 (P = 0.177). In contrast, the trend of Japan representation in general medicine journals remained flat both during 1991-2000 (P = 0.273) and 2001-2010 (P = 0.073). Overall, Japan contribution to the top general medicine journals has remained small and unchanged over the last two decades. However, top basic science journals had higher Japan representation during 2001-2010 compared to 1991-2000.
  • Fumihiko Suzuki, Satoru Nagase, Kichiya Suzuki, Etsuko Oba, Eri Hiroki ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 193-199
    Published: 2013
    Released on J-STAGE: November 07, 2013
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    Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ-positive UPSC and 80% of 14-3-3σ-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC.
  • Gabriela Vázquez-Armenta, Natalia González-Leal, Mayra J Vázquez-de la ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 201-209
    Published: 2013
    Released on J-STAGE: November 07, 2013
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    An adequate immune and antioxidant response is a key to the resolution of sepsis. Heme oxygenase-1 (HMOX1) is a stress protein with a polymorphic (GT)n repeat in its gene promoter that regulates its expression in response to oxidative injury, such as that present in sepsis. HMOX1 is the rate-limiting enzyme of heme degradation, and the heme breakdown products, CO, Fe, and bilirubin, are considered to be biologically active metabolites with direct or indirect antioxidant and anti-inflammatory properties. In this study, we investigated the inflammatory and antioxidant response and the relationship with the HMOX1 levels and HMOX1 polymorphism in Mexican septic pediatric patients. In a case-control pilot study, we enrolled 64 septic patients and 72 hospitalized control patients without a diagnosis of sepsis. DNA extracted from buffy coat was genotyped for HMOX1 (GT)n polymorphism by PCR and markers of antioxidant and inflammatory status were quantified in plasma by analysis of the oxygen radical absorbance capacity (ORAC), protein carbonyl (PC), interleukin (IL) 6, IL10, and HMOX1 levels. In septic children, oxidative and inflammatory markers were elevated, and HMOX1 levels were positively correlated with IL10 levels. Genotypic and allelic distribution of HMOX1 polymorphism showed no difference between groups. HMOX1 short-allele septic carriers (< 25 GT repeats) presented favorable ORAC, PC and IL10 levels. This study confirms that an active response against pediatric sepsis involves the expression of HMOX1 and IL10, suggesting that the high antioxidant status associated with HMOX1 short-allele septic carriers might provide a beneficial environment for sepsis resolution.
  • Kentaro Tamaki, Nobumitsu Tamaki, Yoshihiko Kamada, Kano Uehara, Minor ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 211-216
    Published: 2013
    Released on J-STAGE: November 09, 2013
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    Less invasive procedures are currently required to examine the axillary lymph node status. Shear wave elastography with acoustic radiation force impulse provides objective and reproducible quantification of the intrinsic property of the soft tissue. In this study, we measured shear wave velocity of the axillary lymph nodes of patients with breast cancer using Virtual Touch Tissue Quantification (VTTQ). The degree of lymph node metastasis was evaluated by measuring the expression level of cytokeratin 19 (CK19) mRNA, a specific marker for breast cancer cells. The one-step nucleic acid amplification (OSNA) was used to determine the copy number of CK19 mRNA in 149 lymph node specimens of 149 primary breast cancer patients. Axillary lymph node status according to OSNA (copy number/μl) were categorized as 0-249 copies (−), 250-5,000 copies (+), and copy number > 5,000 (++). A category (−) represents no metastasis in the axillary lymph node. There were 121 patients with OSNA−, 9 with OSNA+ and 19 with OSNA++. The average velocities according to OSNA categories were 1.64 ± 0.42 m/second for OSNA−, 2.25 ± 0.78 m/second for OSNA+, and 2.79 ± 0.98 m/second for OSNA++. There were significant differences in the shear wave velocity between OSNA− and OSNA+ (P = 0.040) or OSNA++ (P < 0.001). The most optimal cutoff velocity to distinguish benign from metastasis is 1.44 m/second, as determined using the receiver operating characteristic method. The shear wave velocity measured with VTTQ could provide clinically useful information about axillary lymph node metastasis in patients with primary breast cancer.
  • Siti Safiah Mokhtar, Paul M. Vanhoutte, Susan W.S. Leung, Mohd Imran Y ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 217-222
    Published: 2013
    Released on J-STAGE: November 13, 2013
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    Diabetic endothelial dysfunction is characterized by impaired endothelium-dependent relaxation. In this study, we measured the expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostacyclin synthase (PGIS), and prostacyclin receptor (IP) in subcutaneous arteries of type-2 diabetic and non-diabetic patients. Subcutaneous arteries were dissected from tissues from seven diabetics (4 males and 3 females) and seven non-diabetics (5 males and 2 females) aged between 18 to 65 years, who underwent lower limb surgical procedures. Diabetics had higher fasting blood glucose compared to non-diabetics, but there were no differences in blood pressure, body mass index and age. Patients were excluded if they had uncontrolled hypertension, previous myocardial infarction, coronary heart disease, renal or hepatic failure and tumor. The relative expression levels of eNOS, COX-1, COX-2, PGIS and IP receptor were determined by Western blotting analysis, normalized with the β-actin level. Increased expression of COX-2 was observed in subcutaneous arteries of diabetics compared to non-diabetics, whereas the expression levels of eNOS and PGIS were significantly lower in diabetics. There were no significant differences in expression levels of COX-1 and IP receptor between the two groups. Immunohistochemical study of subcutaneous arteries showed that the intensities of eNOS and PGIS staining were lower in diabetics, with higher COX-2 staining. In conclusion, type-2 diabetes is associated with higher COX-2 expression, but lower eNOS and PGIS expression in subcutaneous arteries. These alterations may lead to impaired endothelium-dependent vasodilatation, and thus these proteins may be potential targets for protection against the microvascular complications of diabetes.
  • Takatoshi Iida, Haruka Tohara, Satoko Wada, Ayako Nakane, Ryuichi Sanp ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 223-228
    Published: 2013
    Released on J-STAGE: November 15, 2013
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    Swallowing disorders are common in the elderly, and aging is a factor that affects swallowing function. The elevation of the hyoid bone is important for swallowing and is controlled by the suprahyoid muscles. The hyoid and laryngeal elevation allows the bolus to enter the esophagus. The suprahyoid muscles, therefore, play an important role in swallowing. The effects of aging on suprahyoid muscle strength are unclear. In this study, we analyzed the effects of aging on suprahyoid muscle strength by comparing the jaw opening functions of healthy adults and elderly adults. The subjects were 150 healthy volunteers consisting of 76 adults aged < 70 years (38 men and 38 women; mean age, 48.8 ± 13.8 years; range, 23-69) and 74 elderly adults aged > 70 years (37 men and 37 women; mean age, 78.1 ± 4.8 years; range, 70-92). The jaw opening force (JOF) was measured with a jaw opening sthenometer and compared between the healthy adult and elderly groups. The mean JOF of healthy adults was about 10 kg in men and about 6 kg in women, which was significantly greater than the mean JOF of the healthy elderly subjects (about 7 kg in men and about 4 kg in women). The JOF of the men was significantly greater than that of the women in the healthy adult and elderly groups. We thus propose that aging decreases the strength of suprahyoid muscles in healthy adults. The swallowing function may decrease even in healthy adults, aged over 70 years.
Case
  • Yasuhiro Nakamura, Motonobu Nishimura, Takashi Terano, Keely M McNamar ...
    Article type: Case
    2013 Volume 231 Issue 3 Pages 229-234
    Published: 2013
    Released on J-STAGE: November 16, 2013
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    POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is potentially fatal multisystem disorder but its renal complication has often been overlooked because renal involvement is not necessarily included in the diagnostic criteria of POEMS. This report documents the patient with POEMS syndrome with long-term renal histopathological changes evaluated by renal biopsy. A 32-year-old Japanese woman presented with symptoms consistent with POEMS syndrome associated with proteinuria and IgA-λ type monoclonal gammopathy. Initial renal biopsy for confirmation of diagnosis revealed the proliferation of glomerular capillary loops located in the expanded mesangial matrices associated with glomerular enlargement. Electron microscopy examination of the renal biopsy revealed the presence of double contoured glomerular basement membrane containing peculiar fibrillary structure. The patient was therefore initially diagnosed as membranoproliferative glomerulonephritis (MPGN)-like lesion without any significant immunoglobulins and complements deposition. The patient was subsequently admitted to hospital on five occasions due to renal dysfunction and anasarca for the next four years of her clinical course. The severity of anasarca was correlated mainly with serum titer of vascular endothelial growth factor (VEGF) during this period. Acute renal failure occurred at the last admission and the second biopsy was performed. An increased mesangial matrix and frequent global sclerosis of the glomeruli with arteriolosclerosis was noted in this second biopsy compared to the first one. These findings of renal biopsies suggest that the glomerular microangiopathy of POEMS syndrome may occur in the context of systemic capillary leak syndrome superimposed on chronic endothelial injury.
Regular Contributions
  • Manabu Matsumoto, Satoshi Yasuda, Shunichi Miyazaki, Yu Kataoka, Hiros ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 3 Pages 235-242
    Published: 2013
    Released on J-STAGE: November 15, 2013
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    Ghrelin is a novel growth hormone-releasing peptide isolated from the stomach and possesses various cardioprotective effects, including energy balance improvement and regulation of autonomic nervous system activity. We investigated the changes in serum ghrelin levels and its association with cardiac function and myocardial infarct size in patients with acute myocardial infarction (AMI). Forty-seven consecutive patients were divided into the following 4 groups: 16 patients with AMI, 12 patients with unstable angina pectoris (UAP), 13 patients with stable angina pectoris (SAP), and 6 control patients. Serum levels were measured with the ELISA kit. Compared to the control (72 ± 26 fmol/mL), SAP (69 ± 47 fmol/mL), and UAP (72 ± 31 fmol/mL) groups, serum ghrelin levels on admission were significantly lower in the AMI group (27 ± 12 fmol/mL, P < 0.01). After admission, the serum ghrelin level gradually increased (30 ± 15 fmol/mL on day 2 and 39 ± 18 fmol/mL on day 7) and became significantly higher on day 14 (49 ± 28 fmol/mL, P < 0.01), compared to the level on admission. In patients with AMI, the ratio of day 14 to admission serum ghrelin levels, an index of AMI-related acute changes in ghrelin, correlated positively with peak creatine phosphokinase levels (R = 0.72, P < 0.01) and the double products (R = 0.60, P < 0.01) and inversely with left ventricular ejection fraction (R = −0.53, P < 0.05). In conclusion, serum ghrelin levels are significantly decreased in association with myocardial infarct size and cardiac function.
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