The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 208 , Issue 3
March
Showing 1-12 articles out of 12 articles from the selected issue
In Memoriam
Invited Review
  • Soisungwan Satarug, Muneko Nishijo, Jerome M. Lasker, Robert J. Edward ...
    2006 Volume 208 Issue 3 Pages 179-202
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Cadmium (Cd) is a metal toxin of continuing worldwide concern. Daily intake of Cd, albeit in small quantities, is associated with a number of adverse health effects which are attributable to distinct pathological changes in a variety of tissues and organs. In the present review, we focus on its renal tubular effects in people who have been exposed environmentally to Cd at levels below the provisional tolerable intake level set for the toxin. We highlight the data linking such low-level Cd intake with tubular injury, altered abundance of cytochromes P450 (CYPs) in the kidney and an expression of a hypertensive phenotype. We provide updated knowledge on renal and vascular effects of the eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and eicosatrienoic acids (EETs), which are biologically active metabolites from arachidonate metabolism mediated by certain CYPs in the kidney. We note the ability of Cd to elicit “oxidative stress” and to alter metal homeostasis notably of zinc which may lead to augmentation of the defense mechanisms involving induction of the antioxidant enzyme heme oxygenase-1 (HO-1) and the metal binding protein metallothionein (MT) in the kidney. We hypothesize that renal Cd accumulation triggers the host responses mediated by HO-1 and MT in an attempt to protect the kidney against injurious oxidative stress and to resist a rise in blood pressure levels. This hypothesis predicts that individuals with less active HO-1 (caused by the HO-1 genetic polymorphisms) are more likely to have renal injury and express a hypertensive phenotype following chronic ingestion of low-level Cd, compared with those having more active HO-1. Future analytical and molecular epidemiologic research should pave the way to the utility of induction of heme oxygenases together with dietary antioxidants in reducing the risk of kidney injury and hypertension in susceptible people.
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Regular Contributions
  • Filiz Kuralay, Emel Altekin, Ayten Sayin Yazlar, Banu Onvural, Ozhan G ...
    2006 Volume 208 Issue 3 Pages 203-212
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Percutaneous transluminal coronary angioplasty (PTCA) has been recognized as a reliable treatment procedure for acute reversible ischemia and reperfusion. Ischemic reperfusion cycle in PTCA leads to the systemic inflammation and extensive tissue injury by the production of reactive oxygen species including nitric oxide (NO) radicals. In patients with coronary artery disease, undergoing PTCA, the effects of trimetazidine (TMZ), a piperazine-derivative anti-anginal drug, were studied on several indirect markers of systemic inflammatory response: tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and NO products (nitrite and nitrate). Patients (n = 11 each group) were untreated or pre-treated with TMZ (20 mg per orally three times a day), begun three days prior to PTCA, and marker levels were measured before the start of TMZ therapy (baseline), just before PTCA (0 hr), and 4, 24, and 48 hrs after PTCA. The baseline levels of markers were not significantly different between the untreated and pre-treated patients. In contrast, all parameters were lower in the TMZ-treated group than those in the matched control group in the pre- and post-angioplasty periods. Interestingly, in the TMZ group, CRP and nitrite levels were significantly lower than in the control group at each time point of the pre- and post-angioplasty periods, but the TNF-α levels were significantly decreased only in the post-angioplasty period. Pre-procedural treatment with oral TMZ for three days significantly suppressed the elevation of inflammatory markers before and shortly after PTCA. We suggest the usefulness of TMZ in preventing inflammatory cardiovascular events after PTCA.
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  • Pengyu Cao, Shin-Ichi Toyabe, Kouhei Akazawa
    2006 Volume 208 Issue 3 Pages 213-224
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    To realize an effective cost control, a practical and accurate cost accounting system is indispensable in hospitals. In traditional cost accounting systems, the volume-based costing (VBC) is the most popular cost accounting method. In this method, the indirect costs are allocated to each cost object (services or units of a hospital) using a single indicator named a cost driver (e.g., Labor hours, revenues or the number of patients). However, this method often results in rough and inaccurate results. The activity based costing (ABC) method introduced in the mid 1990s can prove more accurate results. With the ABC method, all events or transactions that cause costs are recognized as “activities”, and a specific cost driver is prepared for each activity. Finally, the costs of activities are allocated to cost objects by the corresponding cost driver. However, it is much more complex and costly than other traditional cost accounting methods because the data collection for cost drivers is not always easy. In this study, we developed a simplified ABC (S-ABC) costing method to reduce the workload of ABC costing by reducing the number of cost drivers used in the ABC method. Using the S-ABC method, we estimated the cost of the laboratory tests, and as a result, similarly accurate results were obtained with the ABC method (largest difference was 2.64%). Simultaneously, this new method reduces the seven cost drivers used in the ABC method to four. Moreover, we performed an evaluation using other sample data from physiological laboratory department to certify the effectiveness of this new method. In conclusion, the S-ABC method provides two advantages in comparison to the VBC and ABC methods: (1) it can obtain accurate results, and (2) it is simpler to perform. Once we reduce the number of cost drivers by applying the proposed S-ABC method to the data for the ABC method, we can easily perform the cost accounting using few cost drivers after the second round of costing.
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  • Naoki Kawagishi, Kazushige Satoh, Yoshitaka Enomoto, Yorihiro Akamatsu ...
    2006 Volume 208 Issue 3 Pages 225-233
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Deoxyspergualin (DSG) is an immunosuppressive agent used to treat steroid-resistant acute rejection after kidney transplantation. But in the case of acute rejection after liver transplantation, DSG was reported effective in just a few cases. From July 1991 to November 2005, 96 patients underwent living donor liver transplantation (LDLTx) in our institution. Of them, 9 patients, including 4 ABO incompatible recipients, are presented. Rejection symptoms that did not respond to steroid pulse therapy (methylprednisolone, 10-20 mg/kg/day for 3 days) and were treated with DSG (3 or 5 mg/kg/day) for 4 to 14 days together with a maintenance dose of the steroid. Among them, five responded to treatment with DSG, two did not respond and the other two patients were not evaluated. Six of the nine patients are symptom free at present. Complications such as leukopenia and thrombocytopenia were successfully treated with granulocyte-colony stimulating factor or by platelet transfusion. No recipient died as a direct consequence of the complications induced by DSG. DSG proved effective and safe for some of the LDLTx recipients with steroid-resistant acute rejection but it was not effective for the treatment of accelerated humoral rejection in ABO incompatible recipients.
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  • Mari Sampei, Katsuyuki Murata, Miwako Dakeishi, Donald C. Wood
    2006 Volume 208 Issue 3 Pages 235-242
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Preschool children with sleep deficit may suffer from autonomic symptoms or hypotension. Heart rate variability, reflecting cardiac parasympathetic and sympathetic activities, and blood pressure were assessed to clarify the effects of nocturnal sleep duration on cardiac autonomic function in 134 preschool children aged 5 and 6 years. Parents reported their children's typical bedtimes and wake times for weekdays. In the children, the mean nocturnal sleep duration (± standard deviation) was 575 ± 42 min. The parasympathetic and sympathetic activities and systolic blood pressure (SBP) were significantly lower in the 80 children with short sleep (nocturnal sleep duration < 10 hrs) than in the 54 children with long sleep (≥ 10 hrs). Only the SBP was positively correlated with nocturnal sleep duration in the children (p < 0.001); also, short nocturnal sleep duration was significantly related to hypotension (SBP < 100 mmHg), as judged by multiple logistic regression analysis. Among the children, inverse correlations were seen between the parasympathetic activity and SBP and between the sympathetic activity and diastolic blood pressure (p < 0.05). These findings indicate that shortening of nocturnal sleep is associated with cardiac autonomic hypofunction and low SBP in preschool children. We suggest that sleep duration is an important predictor for autonomic development in childhood.
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  • Bahri Akdeniz, Özer Badak, Nezihi Baris, Özgür Aslan, & ...
    2006 Volume 208 Issue 3 Pages 243-250
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Restoration of sinus rhythm by electrical cardioversion is a therapeutic option in appropriately selected patients with atrial fibrillation. It is important to determine predictors of electrical cardioversion outcome in patients with atrial fibrillation. Predictive value of clinical and conventional echocardiographic parameters for predicting cardioversion outcome is limited. The role of left atrial appendage (LAA) function, which may reflect left atrial contractile function, for prediction of cardioversion outcome remains unclear. We conducted a single center prospective study to evaluate the role of LAA function for prediction of cardioversion success in patients with atrial fibrillation. One hundred sixty three patients with atrial fibrillation underwent transthoracic and transesophageal echocardiography (TEE) before electrical cardioversion. LAA functions, including LAA peak flow velocity, LAA area and LAA ejection fraction, were examined. Cardioversion was successful in 133 patients and unsuccessful in 30 patients. Mean LAA peak emptying flow velocity was significantly higher in the patients with successful cardioversion than in those with unsuccessful cardioversion (0.34 ± 0.14 vs 0.27 ± 0.1 m/sec; p = 0.013). At multivariate logistic regression analysis, only LAA flow velocity (> 0.28 m/sec, odds ratio = 2.8 ; p = 0.03) proved to be an independent predictor of cardioversion success. LAA area (p = 0.18) and LAA ejection fraction (p = 0.52) were not different between successful and unsuccessful cardioversion groups. Therefore, measurement of LAA flow velocity provides valuable information for prediction of cardioversion outcome in patients with atrial fibrillation before TEE guided cardioversion.
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  • A. Faruk Kiroglu, Hasmet Bayrakli, Koksal Yuca, Hakan Cankaya, Muzaffe ...
    2006 Volume 208 Issue 3 Pages 251-254
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Sildenafil citrate is an effective oral drug for erectile dysfunction. The main action of sildenafil is the enhancement of the effect of nitric oxide (NO) by inhibiting the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE-5), an enzyme responsible for degradation of cGMP. NO is also present in the nasal mucosa and is responsible for vasodilation causing congestion and nasal obstruction. The aim of this study was to detect the effect of sildenafil on nasal mucosa in terms of nasal obstruction. A total of 16 patients presented to urology clinic suffering from impotence and medicated with sildenafil were included in the study. Before and after oral administration of 50 mg sildenafil, in all of the patients the nasal patency was examined by active anterior rhinomanometry (a method of assessing nasal resistance) using air pressure of 150 Pascal. In addition, all patients were asked about their sensation of nasal patency to detect the symptomatic nasal obstruction. There was a significant decrease in nasal air flow values (cm3/s) (p < 0.05). Except for three cases, all patients indicated that they had the sensation of nasal obstruction after the use of sildenafil (p < 0.05). Nasal obstruction is a common complaint for the patients using Sildenafil.
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  • Ikuko Takahashi, Maki Utsunomiya, Kayoko Inoue, Tsutomu Takahashi, Jun ...
    2006 Volume 208 Issue 3 Pages 255-259
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Human growth is a highly complicated process, but it is obviously influenced by a genetic factor. Recent genome-wide linkage analyses suggested some genetic regions underlying stature variations. However, any specific genes underlying stature variations have not been identified. Noonan syndrome (NS) is an autosomal dominant disorder clinically characterized by short stature, minor facial anomalies, and congenital heart defects. Recently, PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) has been identified as a major responsible gene for NS, causing about half of the affected individuals. We herein report a large family demonstrating NS caused by one of the common PTPN11 mutations, c.188 A > G (Y63C). In this family, the patients were apparently healthy, but heterozygosity of the c.188 A > G (Y63C) mutation was related to growth impairment. This finding suggested that PTPN11 genetic variants contribute to adult height in the general population. However, c.188 A > G (Y63C) was not identified in 96 short individuals from the general population of 2,281 healthy adults. Thus, it is unlikely that PTPN11 is one of the genes underlying stature variations in the general population.
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  • Ping Chen, Yaozong Yuan, Shiwen Wang, Leheng Zhan, Jiayu Xu
    2006 Volume 208 Issue 3 Pages 261-266
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Previous studies have shown that matrix metalloproteinase 9 (MMP-9) degrades basement membrane components in inflammation, but the change of serum MMP-9 level in the progression of acute pancreatitis remains unclear. The aim of our study was to assess the value of MMP-9 as a prognostic marker in acute pancreatitis. The prospective study included 10 patients with severe acute pancreatitis (SAP) and 10 patients with mild acute pancreatitis. The study also enrolled 10 healthy individuals as control. The serum MMP-9 level, serum C-reactive protein (CRP) level, serum tumor necrosis factor α (TNF-α) level and acute physiology and chronic health evaluation (APACHE) II score were measured at 1 hr and 48 hrs after admission. APACHEII scores and serum MMP-9, TNF-α and CRP levels were significantly increased in patients with SAP compared to those with mild acute pancreatitis and control subjects at 1 hr after admission (p < 0.01). When the states of illness were improved, the levels of the above-mentioned markers were decreased in patients with SAP at 48 hrs after admission (1 hr vs 48 hrs, p < 0.01 or p < 0.05). Furthermore, significant positive correlation was found between serum MMP-9 level and serum TNF-α level, serum CRP level or APACHEII score in patients at 1 hr after admission (MMP-9/TNF-α, r = 0.956; MMP-9/CRP, r = 0.935; MMP-9/APACHE II score, r = 0.957; p < 0.01). These results suggest that MMP-9 is involved in the deterioration of SAP and serum MMP-9 level is a valuable assessment marker for the severity of SAP.
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  • Yuhong Wang, Rie Takai, Hidekatsu Yoshioka, Komei Shirabe
    2006 Volume 208 Issue 3 Pages 267-274
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    To understand the development of serotonergic neurons in vertebrates, we used zebrafish as a model system. In this study we cloned two cDNAs (complementary DNAs) coding for serotonin transporter (SERT) from the zebrafish, named serta and sertb. The serta cDNA encodes a protein of 693 amino acids and showed high level of sequence identity with rat and human SERTs. In situ hybridization showed serta to be expressed in raphe nuclei, ventral posterior tuberculum and pineal organ. The expression of serta in raphe and ventral posterior tuberculum overlapped with the location of serotonin and expression of tryptophan hydroxylase, which is a key enzyme for serotonin synthesis. In the pineal organ serta is expressed in the cells in the vicinity of tryptophan hydroxylase-positive cells. We also cloned another zebrafish serotonin transporter, sertb, and found to be expressed in the medulla oblongata and in the inner nuclear layer of retina. The existence of two sert genes in the zebrafish genome indicates the gene was duplicated in the process of evolution as can be seen in other genes in the teleosts including zebrafish. The expression of the serta cDNA in cultured cells conferred a serotonin transport activity, thus indicating the validity of the cloned cDNA. We have established the expression system of zebrafish serotonin transporter in the cell culture in the present study, which is useful for the pharmacological analysis to determine the important residues for the interaction with serotonin and inhibitors. The expression system in the cell culture can be used to determine the effective concentration of inhibitors and addictive drugs. These information might be useful to evaluate the effect of those chemicals on serotonin neuron development and behavior of the animal.
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Case Report
  • Masahito Hatori, Mika Watanabe, Hideyoshi Kotake, Shoichi Kokubun
    2006 Volume 208 Issue 3 Pages 275-281
    Published: 2006
    Released: February 24, 2006
    JOURNALS FREE ACCESS
    Enchondromas are the most common benign cartilaginous bone tumors arising in the medullary cavity of the small bones of the hand. In contrast, chondrosarcomas, commonly occurring in the pelvis and proximal femur and humerus, are very uncommon at this site. We report an unusual case of chondrosarcoma arising in the ring finger proximal phalanx with its radiological and histological features and reviewed the literature. The patient was an 80-year-old man whose chief complaint was swelling and pain for seven years. The findings of cortical irregular thickening by plain radiography and computed tomography and soft tissue extension by magnetic resonance imaging suggested the tumor was chondrosarcoma rather than a common enchondroma. Thorough curettage and artificial bone grafting was performed because of the age of the patient, his senile dementia and the strong desire of the patient and his family. Histological examination revealed that the tumor was composed of polygonal cells with eosinophilic cytoplasm proliferating in the chondromatous matrix with partially myxoid changes. Nuclear irregularity, binucleated cells, bone permeation and encasement were observed and the tumor was diagnosed as grade 2 chondrosarcoma. The tumor recurred five months after surgery. Amputation of the ring finger including the distal part of the 4th metacarpal was performed. At two years after surgery, the patient was free from recurrence or lung metastasis. In conclusion, details of radiological as well as pathological findings are essential for differential diagnosis between benign enchondroma and chondrosarcoma in the hand. Chondrosarcoma of the hand requires a prompt and more radical treatment than enchondroma. Wide excision is recommended to avoid local recurrence or metastasis.
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