The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
212 巻, 4 号
August
選択された号の論文の11件中1~11を表示しています
Regular Contributions
  • Edward J. Land, Christopher A. Ramsden, Patrick A. Riley
    2007 年 212 巻 4 号 p. 341-348
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Tyrosinase is a copper-containing mono-oxygenase, widely distributed in nature, able to catalyze the oxidation of both phenols and catechols to the corresponding ortho-quinones. Tyrosinase is characterised by a hitherto unexplained irreversible inactivation which occurs during the oxidation of catechols. Although the corresponding catechols are formed during tyrosinase oxidation of monophenols, inactivation in the presence of monophenolic substrates is minimal. Previous studies have established the kinetic features of the inactivation reaction which is first-order in respect of the enzyme concentration. The inactivation reaction exhibits the same pH-profile and saturation properties as the oxidation reaction, classing the process as a mechanism-based suicide inactivation. The recent elucidation of the crystallographic structure of tyrosinase has stimulated a new approach to this long-standing enigma. Here we report the results of an investigation of the tyrosinase-catalysed oxidation of a range of hydroxybenzenes which establish the structural requirements associated with inactivation. We present evidence for an inactivation mechanism based on catechol hydroxylation, with loss of one of the copper atoms at the active site. The inactivation mechanism involves two linked processes occurring in situ: (a) catechol presentation resulting in α-oxidation, and (b) deprotonation of an adjacent group. On the basis of our experimental data we believe that a similar mechanism may account for the inhibitory action of resorcinols.
  • Jiunn Diann Lin, Hsiang-Lin Wan, Jer-Chuan Li, Chung-Ze Wu, Shi-Wen Ku ...
    2007 年 212 巻 4 号 p. 349-357
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.
  • Aleš Zák, Eva Tvrzická, Marek Vecka, Marie J&aacu ...
    2007 年 212 巻 4 号 p. 359-371
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Metabolic syndrome (MS) is defined by the clustering of several components (MSC), which include abdominal fat accumulation, impaired glucose homeostasis, hypertriglyceridemia, lowered high-density lipoprotein cholesterol, increased blood pressure, and hyperuricemia. Metabolic syndrome is also accompanied by increased oxidative stress and inflammation as well as by altered composition of esterified fatty acids (FA). Therefore, we have investigated 210 men (categorized into six groups with increasing number of MSC) to find trends in the extent of oxidative stress, FA pattern and frequency of pathological alleles of the selected candidate genes for lipid metabolism. Increasing number of MSC was connected with the raised serum glucose and insulin, increased concentrations of conjugated dienes in low-density lipoprotein (all p < 0.0001), and high frequency of e2 and e4 alleles of the apolipoprotein E gene (p < 0.005). However, the last significance was lost after the adjustment for age. The incidence of 54Thr allele for intestinal isoform of the fatty acid-binding protein (FABP-2) gene was comparable in all groups. The most important findings were the raised content of saturated FA and the increased activities of Δ9 and Δ6 desaturases (all p < 0.0001), and the decreased content of polyunsaturated FA n-6 family and the decreased activity of Δ5 desaturase (both p < 0.001) in connection with increasing number of MSC. In conclusion, the severity of MS is connected with the progression of oxidative stress and the unfavorable changes in the FA composition. These changes are independent of the studied gene polymorphisms.
  • Harushi Yoshida, Terumi Ayuse, Satoru Ishizaka, Shingo Ishitobi, Tomoy ...
    2007 年 212 巻 4 号 p. 373-378
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    The gag reflex is a somatic natural response in which the body attempts to eliminate instruments or agents from the oral cavity by muscle contraction. Some patients suffered from such severe retching that behavioral techniques did not sufficiently reduce gagging in dentistry. In these patients, pharmacological management was thought to be the last alternative to eliminate the reflex. However, the potential of intravenous (IV) sedation as a way to overcome problems in gagging management during prosthodontic (prosthetic) therapy has not been sufficiently explored. We examined the benefit of IV sedation to facilitate prosthodontic treatment for problematic gagging patients intolerable to dental therapy. The subjects were 10 severely retching patients (7 males and 3 females) who received prosthodontic or restorative therapy under propofol IV sedation. The number, location and prognosis of dentures/restorations were reviewed retrospectively. Eight dentures (3 removable and 5 fixed partial dentures) and 22 restorations (18 crowns and 4 inlays) were seated successfully in the oral cavity without serious complications related to IV sedation. The restored teeth were located predominantly in the posterior regions. Throughout the observation period of at least 6 months, no symptoms of postoperative pain or swelling were found. Five of the 10 patients showed improved tolerance to oral inspection, indicating a behavioral adjustment to dental care. In prosthodontic treatment extended to the posterior regions, propofol IV sedation proved useful in managing reflex control.
  • Li-Qiang Qin, Yuan Wang, Jia-Ying Xu, Takashi Kaneko, Akio Sato, Pei-Y ...
    2007 年 212 巻 4 号 p. 379-387
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl3) and carbon tetrachloride (CCl4). The CYP2E1 content was significantly increased in 15 kcal-food and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl3 and CCl4, the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl3 was cleared by hepatic metabolism about 8-10 times faster than that of CCl4. Similarly, the areas under the blood concentration-time curve of CCl4 was as much as twice that of the corresponding CHCl3. In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl4 or CHCl3 was augmented by, at least in part, CYP2E1 induction and GSH depletion.
  • Kiyoto Shiga, Takenori Ogawa, Shun Sagai, Kengo Kato, Toshimitsu Kobay ...
    2007 年 212 巻 4 号 p. 389-396
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    The incidence of oral cancer is increasing all over the world and tongue cancer is the most common type of oral cancer. However, standard treatment strategy for early stage tongue cancer has not yet been determined. To assess the appropriate therapy including elective neck dissection, a retrospective chart review of the patients were performed. Thirty-one patients with T1 or T2 tongue carcinomas were surgically treated in our hospital from 2001 through 2005. Twenty-one out of these patients were diagnosed as N0 by physical and diagnostic examinations. Three of 6 patients with T2N0 tumors who had undergone only partial glossectomy had recurrent tumors in the neck and died of disease. The disease-free survival rates at 40 months by Kaplan-Meier analysis were 100% and 60% for T1N0 and T2N0 patients, respectively, with a median follow-up time of 27 months for surviving patients. The depth of the tumor invasion and diameter of the tumors were analyzed. There was a significant difference between the frequency of nodal metastasis in patients with tumor less than 4 mm in depth and patients with tumors more than 4 mm in depth. These data indicate that elective neck dissection should be considered for treating patients with T2N0 tongue cancer because of the poorer prognosis of the patients if they did not undergo elective neck dissection, and that the depth of the tumor invasion is a critical factor for lymph node metastasis and preoperative evaluation of it might be an effective tool for the selection of the therapy.
  • Mehmet Yokusoglu, Oral Nevruz, Oben Baysan, Mehmet Uzun, Sait Demirkol ...
    2007 年 212 巻 4 号 p. 397-402
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Autonomic function is impaired in anemic patients with various etiologies such as vitamin B12 deficiency, sickle cell trait, and thalassemia major. However, there are insufficient data about autonomic functions in patients with iron deficiency anemia, the leading cause for anemia in the general population. In the present study we aimed to investigate the autonomic status in iron deficiency anemia by analyzing the heart rate variability (HRV). Age- and gender-matched 43 patients with iron deficiency anemia and 39 healthy subjects were undertaken into 24-hr Holter monitoring for assessing the HRV. We used serum levels of iron, iron binding capacity, C-reactive protein, vitamin B12, and folate to exclude other causes of anemia. While age, gender, vitamin B12 and folate levels were not different between the groups, HRV values were lower in patients with iron deficiency anemia compared to control group, which reflects parasympathetic withdrawal. Blood hemorheological factors such as decreased viscosity and/or altered red cell deformability may be responsible for this decreased parasympathetic activity. However, these components do not display remarkable contribution in iron deficiency anemia. Therefore, we speculated a probable link between anemia and the accentuated sympathetic activity that may be triggered by hypoxia sensed through carotid bodies. Despite lacking adequate convincing evidence concerning exact mechanism of carotid body activation, it is assumed as due either to hypoxia-related mitochondrial respiratory chain inhibition or potassium channel suppression that leads to intracellular calcium accumulation. In conclusion, the present study demonstrates an altered autonomic balance in patients with true iron deficiency anemia.
  • Hitoshi Niikura, Atsuko Katahira, Hiroki Utsunomiya, Tadao Takano, Kiy ...
    2007 年 212 巻 4 号 p. 403-413
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Radical hysterectomy has been performed for invasive cervical cancer, and autonomic nerve-sparing procedures have been developed to preserve bladder function. To perform and improve the nerve-sparing radical hysterectomy, it is important to understand anatomy of the intra pelvic fasciae, specially vesico-uterine ligament (VUL), because most of injuries to the nerves occurred during incision of the VUL in radical hysterectomy procedures. The objectives of the present study were to provide histological understanding of major structures found in nerve-sparing radical hysterectomy. Serial macroscopic slices (15-20 mm thick) from five female pelves were trimmed and prepared for paraffin-embedded histology. We noted an anatomical entity as “the visceroparietal fascial bridge”, which corresponds with the macroscopically identified arcus tendineus fasciae pelvis. A histologically identifiable neurovascular pedicle to the bladder neck corresponded with the deep portion of VUL. These findings could help better preservation of autonomic nerves during radical hysterectomy and improve patient's quality of life after the operation. Translation of surgical anatomy into anatomic terminology enables us to have fruitful discussions with persuasive power by excluding any bias from individual surgeons.
  • Kazuyuki Daitoku, Kazuhiko Seya, Ken-Ichi Furukawa, Shigeru Motomura
    2007 年 212 巻 4 号 p. 415-422
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    It is important to accurately and conveniently assess the effects of L- and N-type Ca2+ channel blocking drugs, which are commonly used for treatment of hypertension, but no method is available to simultaneously assess the effects of them in the same preparation. We have therefore designed an ex vivo method to measure the changes in contractile response of anterior papillary muscle of right ventricle and myocardial interstitial norepinephrine (NE) level using canine blood-perfused papillary muscle preparations. Papillary muscle-developed tension (PMDT) induced by an electronic stimulator was measured with force transducer. Myocardial interstitial NE effluent was collected by microdialysis fiber, which was implanted at the base of the papillary muscle, and measured with high performance liquid chromatography. Cilnidipine, a typical L- and N-type Ca2+ channel blocker, was used to prove the efficiency of this method. First, to assess the effects of drugs on L-type Ca2+ channel, the changes in basal PMDT were measured. Cilnidipine and nicardipine, a selective L-type Ca2+ channel blocker, but not omega-conotoxin GVIA (ω-CTX), a selective N-type Ca2+ channel blocking peptide, decreased basal PMDT dose-dependently. Second, to assess the effects of drugs on N-type Ca2+ channel, the changes in PMDT and myocardial interstitial NE level by intracardiac sympathetic ganglion stimulation were measured. Cilnidipine and ω-CTX, but not nicardipine, dose-dependently reduced sympathomimetic increases in PMDT and myocardial interstitial NE level. These results indicate that our method is efficient to assess the effects of various L- and N-type Ca2+ channel blocking drugs in the same papillary muscle preparation.
  • Umit Dincer, Engin Cakar, M. Zeki Kiralp, Erkan Bozkanat, Hilmi Kilac, ...
    2007 年 212 巻 4 号 p. 423-430
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Rheumatic diseases are chronic inflammatory diseases which cause mild to severe functional loss and disability due to articular and extra-articular manifestations. One common form -ankylosing spondylitis (AS)- affects mainly the axial skeleton and sacroiliac joints, and certain extra-articular organs. The pulmonary involvement is a known manifestation of AS and emerges either in the form of interstitial lung disease or in the form of restricted pulmonary functions. The aim of this study is to determine the pulmonary functions in AS patients and to assess its relationship with quality of life, functionality and disease activity. Thirty-six AS patients and 34 healthy volunteers were recruited for the study. A detailed examination, pulmonary function tests, smoking inquiry and quality of life questionnaire were performed on all participants. Also patients were requested to complete functionality and disease activity indexes. The outcomes showed that 15 (41.7%) AS patients had pulmonary involvement: twelve patients with restrictive patterns, one with obstructive pattern, and two with both restrictive and obstructive patterns. Decreased forced expiratory volume in one second was associated with deteriorated functionality (p < 0.05). Decreased chest expansion was also accompanied with decreased forced vital capacity (p < 0.05). There was no statistically significant difference between the smoking and non-smoking patients in regard to disease activity, functionality and pulmonary function test variables (p > 0.05). In conclusion, the pulmonary involvement is common in AS and might have disturbed functionality and the quality of life in AS patients.
  • Yumiko Oka, Yasuhiko Hirabayashi, Tomonori Ishii, Reiko Takahashi, Tak ...
    2007 年 212 巻 4 号 p. 431-437
    発行日: 2007年
    公開日: 2007/07/27
    ジャーナル フリー
    Hyperhomocysteinemia has been reported as one of the risk factors for vascular damage. Homocysteine induces endoplasmic reticulum (ER) stress in vascular endothelial cells, which is followed by production of homocysteine-induced ER protein (Herp). Herp has been thought to have a protective role against ER stress and inhibition of apoptosis, but the details are still obscure. To detect Herp protein precisely, we established a murine hybridoma clone producing an anti-human Herp monoclonal antibody (mAb), named HT2. The specific binding of HT2 mAb to Herp was confirmed by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In ELISA, HT2 mAb was able to bind to Herp in a dose-dependent manner, and its binding was interrupted by recombinant Herp. In Western blot analysis, a 54-kDa band corresponding to Herp was detected with HT2 mAb in the membrane fraction of untreated HeLa cells, and its expression was remarkably increased in ER-stressed HeLa cells that had been treated with homocysteine, thapsigargin, or 2-mercaptoethanol. Importantly, the signal was eliminated by absorption of HT2 mAb with recombinant Herp prior to incubation with the blotted membrane. Immunofluorescence microscopy revealed that HT2 mAb stained the perinuclear cytoplasm of ER-stressed HeLa cells, which was similar to the staining pattern with anti-KDEL (Lys-Asp-Glu-Leu) mAb that recognizes the ER. In contrast, untreated HeLa cells were weakly stained with HT2 mAb. Thus, the HT2 mAb is useful in the quantitative and/or qualitative detection of Herp and to study the role of Herp at a variety of pathological states.
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