The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
221 巻, 3 号
July
選択された号の論文の12件中1~12を表示しています
Regular Contributions
  • Satoshi Yamanouchi, Daisuke Kudo, Tomoyuki Endo, Yuka Kitano, Yotaro S ...
    2010 年 221 巻 3 号 p. 175-180
    発行日: 2010年
    公開日: 2010/05/26
    ジャーナル フリー
    Stroke volume is mainly determined by preload, afterload and contractility. Accordingly, measuring cardiac preload provides essential information for treatment of hemodynamically unstable patients. Hemodynamic monitoring is widely used to measure cardiac preload, but the monitoring method is time-consuming and invasive. It is therefore important to establish a simple and non-invasive test for monitoring cardiac preload. Brain natriuretic peptide (BNP), which lowers systemic vascular resistance, is synthesized as proBNP in response to myocardial wall stretch, and blood BNP has been used as an indicator of preload. Here, we measured blood level of N-terminal proBNP (NT-proBNP), which is generated during processing of proBNP, because NT-proBNP is stable and easily measured at the bedside. To assess the correlation between blood NT-proBNP and preload, we also measured the global end-diastolic volume index (GEDVI) that reflects the cardiac preload. GEDVI was calculated with the volumes in all chambers of the heart at the time of end-diastole. Eight male patients (57.6 ± 25.3 years old) with high volume load (1,000 ml within 4 hours) were included in the present study: 3 subjects with burn, 3 subjects with sepsis, a patient with alcoholic ketoacidosis and a resuscitated patient. Blood levels of NT-proBNP were 1,316.3 ± 1,154.5 pg/ml (47 blood samples from the eight patients; the normal range, < 125 pg/ml). Notably, the increase in the NT-proBNP levels was associated with the increased GEDVI (r = 0.61, p < 0.0001). Therefore, blood NT-proBNP may be a good indicator of cardiac preload in patients with high volume load.
  • Hirokazu Arai, Atsuko Noguchi, Ryoji Goto, Takefumi Matsuda, Hatsushi ...
    2010 年 221 巻 3 号 p. 181-185
    発行日: 2010年
    公開日: 2010/05/29
    ジャーナル フリー
    Premature infants with intrauterine growth restriction (IUGR) are at greater risk for an adverse perinatal outcome. IUGR affects hepatocyte function, but the histopathological changes in the postnatal liver are not well known. We report a male infant with severe IUGR. His mother was transferred to our hospital at 26 weeks of gestation because of preterm labor and severe IUGR. An emergency cesarean section was carried out because of a non-reassuring fetal status. The birth weight of the infant was 332 g. He showed congestive heart failure and marked hepatomegaly from birth. After 1 week, blood examinations showed hyperbilirubinemia with high direct bilirubin. Because of liver dysfunction, he received the minimal total parenteral nutrition for 7 days. After 1 month, he progressively developed ascites and coagulopathy, and died 3 months after birth. Liver autopsy showed diffuse perisinusoidal fibrosis. Fibrosis was also prominent around the central vein. Immunohistochemical study revealed many α-smooth muscle actin-positive cells, which represent activated hepatic stellate cells, and a few transforming growth factor-β1-positive cells in the perisinusoidal fibrotic area. These results indicate that the infant developed chronic (end stage) liver failure by 3 months of age. We excluded congenital infection, metabolic syndrome and citrin deficiency. It is therefore conceivable that intrauterine cardiac failure may be responsible for liver fibrosis. Early detection of liver dysfunction soon after birth is a key to predict the prognosis of severe IUGR in preterm infants.
  • Duc-Cuong Le, Truong-Minh Pham, Yoshihisa Fujino, Tatsuhiko Kubo, Shin ...
    2010 年 221 巻 3 号 p. 187-190
    発行日: 2010年
    公開日: 2010/05/29
    ジャーナル フリー
    Breast cancer is one of the leading causes of death among women in Japan. Its mortality rate has been increased in recent years. However, there has been no study examining the changes in premature mortality in Japanese women. In the present study, using two health indicators, years of life lost (YLL) and average of years of life lost (AYLL), we estimated the premature mortality due to breast cancer in Japan during the period from 1995 to 2006. YLL indicates how many years that life of a patient was shortened with the presence of cancer, and AYLL provides an average loss of expected years of life among these deceased persons. Results showed an increase in total YLL due to this condition from 204,840.6 years in 1995 to 255,046.9 years in 2006. In each calendar year, YLL remained the highest in the group aged 50-59 years, accounting for 32%-36% of annual YLL. In contrast, we found a decrease in AYLL of breast cancer from 26.4 years in 1995 to 22.8 years in 2006; namely, breast cancer patients who died in 2006 lived an average 3.6 years longer than those who died in 1995. In conclusion, we show the decrease in AYLL of breast cancer deaths, despite the increase in total numbers of annual YLL during the study period. Thus, women with breast cancer have benefited from postponement of the deaths in 2006, compared to those in 1995, which may be related to the improvements in medical health care or appropriate prevention.
  • Tomohiro Hori, Toshiyuki Fukao, Hironori Kobayashi, Takahide Teramoto, ...
    2010 年 221 巻 3 号 p. 191-195
    発行日: 2010年
    公開日: 2010/06/10
    ジャーナル フリー
    Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 μmol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as C16, C18, C18:1 and C18:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L-carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients.
  • Yuji Ota, Atsushi Masamune, Kazuo Inui, Kiyoshi Kume, Tooru Shimosegaw ...
    2010 年 221 巻 3 号 p. 197-201
    発行日: 2010年
    公開日: 2010/06/10
    ジャーナル フリー
    Chronic pancreatitis (CP) is a progressive inflammatory disease that eventually results in the impairment of exocrine and endocrine functions of the pancreas. Recent studies have shown an association between mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene and CP. SPINK1 provides the first line of defense against prematurely activated trypsinogen by physically blocking the active site of trypsin. The IVS3+2T>C (c.194+2T>C) mutation is a loss-of-function splicing mutation; it affects the consensus splicing donor site in intron 3 and may cause the skipping of the entire exon 3, where the trypsin-binding site is located. We report here three CP patients carrying this mutation in a homozygous form, with no noticeable family history of pancreatitis. The first patient is a 25-year-old male with juvenile-onset idiopathic CP. He suffered from repeated attacks of pancreatitis since 5 years old and underwent pancreatico-jejunostomy. He complained of epigastralgia, and was diagnosed as obstructive pancreatitis in the area of the accessory pancreatic duct. The second patient is a 75-year-old male with alcoholic CP. He did not have apparent attacks of pancreatitis, but had numerous calcifications throughout the pancreas and confirmed exocrine failure and diabetes mellitus. The last patient is a 44-year-old female with late-onset idiopathic CP. She suffered from repeated attacks of pancreatitis since 32 years old. She had numerous stones in the main pancreatic duct in the pancreas head and confirmed exocrine failure. The clinical courses of these patients are apparently different, indicating the phenotypic variability of the SPINK1 IVS3+2T>C mutation-associated CP.
  • Jie Cheng, Hongbo Yu, Simin Deng, Guofang Shen
    2010 年 221 巻 3 号 p. 203-209
    発行日: 2010年
    公開日: 2010/06/10
    ジャーナル フリー
    Mid-gestational mammalian skin has unique capacity to heal without scar. Fetal skin undergoes phenotypic transition from scarless healing to scar repairing during embryonic development. However, the molecular mechanisms underlying the scarless phenotype and phenotypic transition remain largely unknown. MicroRNAs (miRNAs) are a novel class of small regulatory RNAs emerged as post-transcriptional gene repressors and play essential roles in diverse pathophysiological processes including skin morphogenesis and pathogenesis. Here, we performed a genome-wide miRNA profiling to identify the differentially expressed miRNAs between mid-gestational (E16 day) and late-gestational (E19 day) mouse skin, corresponding to scarless and scarring phenotype, respectively. Two miRNAs (miR-29b and miR-29c) with highest fold changes were further validated independently by real-time RT-PCR. Functional annotations of putative targets of differentially expressed miRNAs via bioinformatics approaches revealed that these predicted targets, including Smads, β-catenin and Ras, were significantly enriched and involved in several signaling pathways important for scarless wound healing. In addition, Dicer, one of the key RNase III responsible for miRNA biogenesis and functions, was found to be up-regulated in the E19 fetal skin as compared with the E16 counterpart. Taken together, our results identified differentially expressed miRNAs between mid-and late-gestational fetal skin that correlated with phenotypic transition from scarless to scarring repair during skin development. Our bioinformatics' analysis suggests that miRNAs might contribute to this phenotypic transition probably by affecting multiple target genes and signaling pathways.
  • Guizhou Ma, Danqing Yu, Zhixiong Cai, Chumin Ni, Ronghe Xu, Bin Lan, P ...
    2010 年 221 巻 3 号 p. 211-219
    発行日: 2010年
    公開日: 2010/06/12
    ジャーナル フリー
    Contrast-induced nephropathy (CIN) is a complex syndrome of acute kidney injury induced by exposure to intravascular contrast media. CIN occurs frequently in patients undergoing urgent percutaneous coronary intervention (PCI) and is associated with poor outcomes, making it a major challenge faced by interventional cardiologists. It has been suggested that female sex is a risk factor for development of CIN following PCI. However, no data exist in the literature concerning the risks of postmenopausal women with acute myocardial infarction (AMI) developing CIN after undergoing urgent PCI. To explore the incidence, risk factors and in-hospital outcomes of CIN in this special population, we analyzed 69 postmenopausal women with AMI treated with urgent PCI. CIN was defined as a relative increase of > 25% or an absolute increase of ≥ 0.5 mg/dL in serum creatinine concentration from the baseline value 72 h after exposure to contrast medium. We found 1) the incidence of CIN was 37.68%; 2) patients with CIN had worse in-hospital outcomes, including longer hospital stay and more in-hospital adverse events; and 3) in multivariate logistic analysis, independent risk factors for CIN included a longer menopausal duration and the implantation of an intra-aortic balloon pump (an indirect indicator of hemodynamic instability). These results indicate that CIN is a frequent complication associated with worse in-hospital outcomes in postmenopausal women with AMI who are undergoing urgent PCI, particularly those with longer menopausal duration and hemodynamic instability. It is therefore necessary to pay more attention to preventive strategies for renal protection in this special population.
  • Naoki Yotsumoto, Michiko Takeoka, Minesuke Yokoyama
    2010 年 221 巻 3 号 p. 221-227
    発行日: 2010年
    公開日: 2010/06/12
    ジャーナル フリー
    Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN−/−) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN−/− group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN−/− mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN−/− mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.
  • Yuko Nakajima, Yutaka Horiuchi, Hiroshi Kamata, Masayoshi Yukawa, Masa ...
    2010 年 221 巻 3 号 p. 229-235
    発行日: 2010年
    公開日: 2010/06/17
    ジャーナル フリー
    Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.
  • Akiko Kojo, Kentaro Yamada, Kin-Ya Kubo, Anzu Yamashita, Toshiharu Yam ...
    2010 年 221 巻 3 号 p. 237-243
    発行日: 2010年
    公開日: 2010/06/23
    ジャーナル フリー
    Occlusal disharmony is induced by various conditions such as the loss of teeth and inappropriate vertical dimension of crowns, bridges, or dentures. Occlusal disharmony sometimes causes indefinite complaint syndromes, which may be associated with astrocytic hypertrophy and the reduction of numbers of neuronal somata and their dendritic spines in the hippocampus. Microglia monitors the condition of neurons and responds to their degeneration accompanying with astrocytes. However, the effect of occlusal disharmony on the microglia has not yet been investigated. We artificially increased the occlusal vertical dimension by placing dental resin on the upper molars in mice and immunohistochemically investigated the effects of the increase in the vertical dimension on microglia of the hippocampal formation using an antibody against ionized calcium-binding adaptor molecule 1 (Iba-1), a marker protein for microglia. We measured the area occupied by Iba-1-immunoreactive microglia in the hippocampal CA1 region and dentate gyrus 1, 3, and 5 days after increasing the vertical dimension, and compared it with that of control mice. The hippocampal CA1 region contains vulnerable neurons and the dentate gyrus durable neurons. We found that the areas occupied by microglia in the hippocampal CA1 region increased, with the peak on the third day after increasing the vertical dimension, and it gradually declined by the fifth post-operative day. However, such an increase of the area occupied by microglia was not seen in the dentate gyrus. In conclusion, abnormal mastication may activate microglia in the area harboring vulnerable neurons, but not in the area harboring durable neurons.
  • Shoichi Asaoka, Yoko Komada, Kazuhiko Fukuda, Tatsuki Sugiura, Yuichi ...
    2010 年 221 巻 3 号 p. 245-249
    発行日: 2010年
    公開日: 2010/06/26
    ジャーナル フリー
    University students show delayed sleep-wake patterns, i.e., later bed- and rise-times, and this pattern is known to be associated with various malfunctions. There may be a variety of daily activities associated with their delayed sleep patterns, such as watching TV. However, it is unclear to what extent each activity possesses an impact on their sleep patterns. The purpose of this study was to determine the daily activities associated with delayed bedtime in Japanese university students who live with or without their families. Three hundred and thirty-one participants were required to record the timing and duration of their sleep and daily activities, and the data from the 275 students (160 men and 115 women; 19.01 ± 1.66 years) who completely filled forms were used for analysis. The results of multiple regression analyses suggested that interpersonal communication late at night is one of the major factors leading to the delayed bedtime of students living away from home. Among those living with their families, indoor activities such as watching TV and using the Internet were related to their delayed bedtimes. Attending classes and having a morning meal were related to the earlier bedtimes of the students living away from home, but there were no activities associated with those of the students living with their families. These results suggest that ensuring attendance at morning classes and having appropriate mealtimes, as well as restricting the use of visual media and socializing activities at night, are necessary for preventing late bedtimes in university students.
  • Yasuyuki Egami, Masami Nishino, Masayuki Taniike, Nobuhiko Makino, Hir ...
    2010 年 221 巻 3 号 p. 251-255
    発行日: 2010年
    公開日: 2010/06/26
    ジャーナル フリー
    Atrial fibrillation (AF) is the most common arrhythmia, and renin-angiotensin system blockade (RAS-B) may be favorable for AF because of its effect on cardiac remodeling. However, effects of RAS-B on AF in hypertensive patients are controversial. Thus, in this study, we investigated the long-term effects of RAS-B on cardiac remodeling and rhythm control after electrical cardioversion for hypertensive patients with persistent AF. We studied 27 consecutive hypertensive patients with persistent AF (duration > one week) who received electrical cardioversion and once recovered to sinus rhythm. Blood pressure of the patients was controlled by medication including RAS-B. The patients were divided into those who were pre-treated with RAS-B (n = 10) for at least two months before electrical cardioversion and those without RAS-B (n = 17). We performed echocardiography before electrical cardioversion and 3 years after electrical cardioversion in all patients and compared the differences in echocardiographic cardiac remodeling parameters, including left atrial dimension, left ventricular end-diastolic dimension and left ventricular ejection fraction. The AF recurrence-free ratio during the follow-up period was significantly higher in the RAS-B group than in the non-RAS-B group, judged by Kaplan-Meier analysis (60 vs. 24%, P = 0.01). All cardiac remodeling parameters in the RAS-B group showed better values than those in non-RAS-B group (each parameter, P < 0.05), supporting the beneficial effects of RAS-B on AF in hypertensive patients. In hypertensive patients with AF, pre-treatment with RAS-B before electrical cardioversion can prevent cardiac remodeling for 3 years and maintain sinus rhythm.
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