Journal of Nippon Medical School
Online ISSN : 1347-3409
Print ISSN : 1345-4676
ISSN-L : 1345-4676
74 巻, 3 号
選択された号の論文の13件中1~13を表示しています
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Review
  • Akihito Nakai
    2007 年 74 巻 3 号 p. 190-201
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Recirculation following 30 minutes of intrauterine ischemia due to uterine artery occlusion has previously been found to be accompanied by delayed deterioration of the cellular bioenergetic state and of mitochondrial function in the fetal rat brain. The objective of this study was to assess whether the delayed deterioration is due to the activation of mitochondrial permeability transition (MPT), which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in the fetal rat brain were examined at the end of 30 minutes of intrauterine ischemia and after 1, 2, 3 or 4 hours of recirculation. Cyclosporin A (CsA), a potent and specific MPT blocker, or vehicle was given 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of the cellular bioenergetic state and mitochondrial activities 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. Both the deterioration and swelling were prevented by CsA. The present study indicates that treatment with CsA improves recovery of energy metabolism and inhibits mitochondrial swelling following transient intrauterine ischemia in the fetal brain. The results suggest that mitochondria and MPT may be involved in the development of ischemic brain damage in the immature rat.
  • Hiroki Yamaguchi
    2007 年 74 巻 3 号 p. 202-209
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Dyskeratosis congenita (DKC) is a bone marrow failure (BMF) with characteristic physical anomalies, and is typically diagnosed in childhood. Some forms of DKC are known to be caused by mutations occurring in DKC1, telomerase RNA component (TERC), and telomerase reverse transcriptase (TERT). These genes are the main constituents of the telomerase complex that plays a role in replicating telomeres and stabilizing them against shortening. Mutations in these genes could shorten telomeres and impair the proliferative capacity of hematopoietic stem cells, eventually causing DKC. Recently, mutations in TERC and TERT have been reported in some cases of aplastic anemia (AA) and myelodysplastic syndrome (MDS). These cases are considered to be atypical forms of DKC that develop slowly in adulthood without characteristic physical anomalies. Genetic tests are essential in diagnosing this late-presenting DKC and determining the appropriate treatment. This article reviews mutations in the telomerase complex and their connections with DKC and bone marrow failures.
Original
  • Narumi Tsuboi, Taiji Nishimura, Haiwen Chen, Yoshihiko Norose, Masumi ...
    2007 年 74 巻 3 号 p. 210-216
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    In our continuing investigation of the significance of leukocytosis in prostatic fluid (PF), the relation of leukocytosis in PF to that in selected sections of prostate with significant inflammation was studies with whole-mount specimens obtained at radical prostatectomy from 12 patients with prostate cancer. Although leukocytosis was observed both in PF and in prostate tissue in all 12 patients, there was no correlation between the leukocyte count in PF and the intensity of inflammation. However, the ratio of macrophages among leukocytes in PF correlated with the number of ducts filled with macrophages in prostate tissue (p=0.0481). This finding was consistent with our previous finding that activation of macrophages in PF reflects active inflammation in prostate tissue. Further studies are needed to clarify the roles of macrophages and whole leukocytes in PF and prostate tissue.
  • Cai Li, Akihiko Gemma, Yuji Minegishi, Kuniko Matsuda, Yoko Seike, Rin ...
    2007 年 74 巻 3 号 p. 217-222
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    The primary aim of this in vitro simulation study was to evaluate the utility of gene expression profile analysis in predicting the effect of varying drug combinations for the treatment of lung cancer. Using 10 human cancer cell lines, we focused our gene expression analysis on a cohort of candidate sensitivity-prediction factors, previously reported using cDNA filter arrays, with a view to predicting the ability of a set of anti-cancer drugs commonly used to treat lung cancer, namely cisplatin, 5-fluorouracil (5FU), SN38, docetaxel, gemcitabine, and vinorelbine. Altered expression of genes for glutathione-S-transferase-pi, uridine phosphorylase, O-6-methylguanine-DNA methyltransferase, and multidrug resistance 1 was identified in lung cancer cell lines. Drug sensitivity testing, in the form of methylthiotetrazol analysis, was performed using these six anti-cancer drugs against the panel of 10 lung cancer cell lines. We compared the predicted chemosensitivity based on the gene expression pattern of 19 well-known sensitivity-related genes with the cytotoxic activity of each of these anti-cancer drugs. Molecular profiling data predicted resistance to CDDP in LK-2 cells, 5FU in LK-2, PC7, A549, NCI-N231, Lu135 cells, irinitecan in PC9 cells, and VNR in PC7 cells. However, the prediction efficacy (number of predicted inactive drugs by gene expression analysis/number of inactive drugs by methylthiotetrazol assay) was 21.6% (8 of 37). No false-positive findings in relation to sensitivity-related genes were obtained on the basis of this molecular analysis. Thus, prediction of sensitivity to lung cancer by molecular analysis appears possible. With elucidation of additional drug sensitivity factors, selection of appropriate anticancer drugs by gene expression profiling may make it possible to increase the response rate in lung cancer chemotherapy.
  • Ryouhei Futami, Masao Miyashita, Tsutomu Nomura, Hiroshi Makino, Takes ...
    2007 年 74 巻 3 号 p. 223-229
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Objectives: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis. We evaluated the changes in serum levels of VEGF following major surgical trauma and postoperative inflammatory complications.
    Materials and Methods: The serum concentration of VEGF was measured with enzyme-linked immunosorbent assay in 41 patients with esophageal cancer who underwent right transthoracic esophagectomy with extensive lymphadenectomy and in 13 patients with gallstones who underwent less-invasive laparoscopic cholecystectomy for comparison. Serum and plasma samples were obtained before the operation and on postoperative days (PODs) 1, 7, 14, 21, and 28. The changes in serum VEGF levels were compared among groups categorized by age, sex, blood loss volume during operation, amount of transfusion, pathological stage of the tumor, and postoperative inflammatory complications. The correlation between serum VEGF levels and inflammatory factors, such as peripheral blood cell count, interleukin-6 (IL-6), C-reactive protein (CRP), and severity of postoperative inflammatory complications, was also investigated. Furthermore, because platelets are a potential source of serum VEGF, platelet-poor plasma (PPP) was prepared from plasma samples, and the VEGF concentration in PPP was measured to compare with those in sera.
    Results: Serum VEGF levels increased significantly postoperatively. After reaching maximal levels on POD 14, VEGF levels gradually decreased until POD 28. The increase in the tranthoracic esophagectomy group was approximately twice that in laparoscopic cholecystectomy group on POD 14. Serum VEGF levels were not correlated with sex, age, blood loss, amount of transfusion, or tumor stage. However, serum VEGF levels were significantly higher in patients with postoperative inflammatory lung complications than in patients without such complications, and the maximal level of serum VEGF correlated with the severity of postoperative lung complications. However, there were no significant correlations between the increase in the level of serum VEGF and that of serum IL-6 or CRP. The increase of platelet counts in the peripheral blood correlated with that of the serum VEGF level, and VEGF levels in PPP were significantly lower than those in sera.
    Conclusions: Serum VEGF levels increased in the angiogenesis phase of wound healing following major surgical injury. Platelets are a potential source of increased serum VEGF levels, whereas inflammatory lung complications might also be related to increased serum VEGF levels.
  • Masataka Akimoto, Toshiyuki Oka, Koichiro Oki, Hiko Hyakusoku
    2007 年 74 巻 3 号 p. 230-235
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    The concentration of mechanical stress in soft tissue can cause or worsen pressure sores. We have previously reported the results of analysis of stress concentration in soft tissue using a finite element model. In the present study, we hypothesized that even if a cushion pad was thin, it would effectively reduce horizontal loads that can increase stress concentration in soft tissue. To our knowledge, there have been no previous reports describing stress distribution in soft tissue attached to a thin cushion pad with a horizontal load. In the present study, we performed mechanical analysis of a model of a human seated on a thin cushion pad with a range of hardness values (i.e., Young's module). Two-dimensional finite element models were used to perform this analysis. Loads were applied at the upper edge of the model as oblique compulsory displacement. In all of the cushion pad models, the peak value of effective stress was less than that of the control model without a cushion pad. Also, the peak value of effective stress decreased as Young's module of the cushion pad decreased. These results suggest that use of a thin cushion pad is an effective way to prevent the development of pressure sores.
Report on Experiments and Clinical Cases
  • Shigeki Kushimoto, Yasushi Shibata, Yuichi Koido, Makoto Kawai, Hiroyu ...
    2007 年 74 巻 3 号 p. 236-240
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Markers of inflammation, such as C-reactive protein (CRP) and white blood cell count, have, because of their low specificity, proven far from ideal in identifying patients with sepsis. Procalcitonin (PCT) has been shown to be a useful marker for differentiating patients with bacterial infection from other acute inflammatory conditions. Corticosteroid therapy has been demonstrated to be effective for treating patients with septic shock, late-phase acute respiratory distress syndrome (ARDS), or functional adrenal insufficiency, and the use of corticosteroid in critical illness has recently increased. It is also well established that corticosteroid modulate inflammatory variables in acute inflammatory conditions. The purpose of this study was to evaluate the clinical usefulness of PCT measurement for assessing the severity of bacterial infection in patients requiring corticosteroid therapy.
    Materials and Methods: Six patients with confirmed bacterial infectious diseases or suspected infectious diseases and requiring corticosteroid therapy were enrolled in the study. Levels of PCT and CRP were measured. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score were calculated to evaluate the severity of sepsis.
    Results: 1) There was no significant correlation between the serum concentration of PCT and the plasma level of CRP in patients requiring corticosteroid therapy. 2) The PCT concentration was significantly correlated with the SOFA score (R2=0.467, p<0.0001) and the APACHE II score (R2=0.308, p=0.0003). However, no significant correlations was found between the CRP concentration and the SOFA score (R2=0.054, p=0.15) or the APACHE II score (R2=0.043, p=0.20). 3) Data sets were divided into two groups: septic shock and non-septic shock. No significant differences were present in CRP levels between the groups. However, significant differences were apparent in PCT concentrations (p<0.001).
    Conclusion: PCT can be a more sensitive and useful marker than CRP for evaluating the severity and progression of sepsis in patients requiring corticosteroid therapy. Further studies are needed to confirm these results in larger groups of patients.
  • Satoshi Mizutani, Takeshi Shioya, Kentaro Maejima, Masanori Yoshino, O ...
    2007 年 74 巻 3 号 p. 241-245
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    We conducted a clinicopathological study of cases of gastric carcinoma with pyloric stenosis and examined treatment outcomes and the prognosis of cases of stage IV gastric carcinoma with pyloric stenosis and the validity of gastrectomy as palliative surgery in these cases. The outcomes of 49 surgeries for gastric carcinoma with pyloric stenosis were compared with those of 671 surgeries for gastric carcinoma without pyloric stenosis. The diagnosis of pyloric stenosis was confirmed with both upper gastrointestinal endoscopy and an upper gastrointestinal barium series. The frequency of pyloric stenosis in patients with gastric carcinoma was 7.3%. Serosal invasion was observed in about 70% of all cases. Of these cases, 53.1% were classified as stage IV. The resection rate was 73.5%, and the resection was classified as curative in 44.9% of cases. The incidence of complications after surgery in cases of stage IV gastric carcinoma was 47.1%. The median survival time was significantly greater in patients undergoing resection group than in those not undergoing resection (p=0.025). Most patients with gastric cancer and pyloric stenosis can be considered to have stage IV disease, which is associated with high rates of morbidity and mortality; thus, prevention of complications, and therefore, avoidance of gastrectomy is recommended in such patients. Nonetheless, in this study, gastrectomy was shown to improve prognoses in these patients.
Case Reports
  • Masao Ogata, Kentaro Maejima, Naoto Chihara, Satoshi Mizutani, Osamu K ...
    2007 年 74 巻 3 号 p. 246-250
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    We report on two patients with gastric tumors (early cancer and adema) and diabetes mellitus who were treated with argon plasma coagulation (APC) therapy. Case 1. A 78-year-old woman visited the Nippon Medical School Musashi Kosugi Hospital because of epigastric pain. An early gastric cancer (IIc) in the anterior wall of the gastric antrum was diagnosed on the basis of the results of a gastric endoscopy examination. The patient had had diabetes mellitus for 18 years and had injected insulin (NovoRapid 30 Mix®, 72 units/day) by herself everyday for 10 years. Case 2. A 61-year-old man was referred to our hospital because of a gastric tumor. A gastric adenoma in the anterior of the gastric antrum was diagnosed on the basis of the results of a gastric endoscopy examination. The patient had had diabetes mellitus for 12 years and had been taking oral medication for 2 years. Endoscopic APC was performed in both patients to remove the gastric tumors. These patients have been well for 28 months and 30 months, respectively, after undergoing APC treatment. APC therapy appears to be a safe and useful treatment for patients with diabetes and gastric mucosal lesions.
  • Ryouhei Futami, Kimiyoshi Shimanuki, Atsushi Sugiura, Yoshikazu Tsuchi ...
    2007 年 74 巻 3 号 p. 251-256
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Recurrence at the site of a stapled anastomosis is generally believed to result from the luminal implantation of viable cancer cells during stapling. We report a case in which colon cancer recurred twice at the site of a stapled anastomosis, despite povidone iodine (PVP-I) lavage consisting of an enema with 5% PVP-I solution before the operation and intraoperative lavage of the rectal remnant and the descending colon with a 10% PVP-I solution. Three months after sigmoidectomy to resect a carcinoma of the sigmoid colon, a circular anastomotic recurrence was found at the suture line after anastomosis with a stapler. However, 11 months after the subsequent resection and reanastomosis to remove the first anastomotic recurrence, another anastomotic recurrence was found. We performed abdominoperineal resection for the second recurrence at the site of the stapled anastomosis. Suture-line recurrence could not be prevented in the present case despite lavage with a PVP-I solution for prophylaxis.
  • Hideki Kogo, Hiroshi Yoshida, Yasuhiro Mamada, Nobuhiko Taniai, Koichi ...
    2007 年 74 巻 3 号 p. 257-260
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    We report a case of splenic abscess that was successfully treated with percutaneous ultrasound-guided drainage and without splenectomy. A 40-year-old woman was admitted to Nippon Medical School Hospital because of pyrexia and left upper quadrant pain, which had persisted despite antibiotic treatment. On admission, computed tomography demonstrated a low-density area in the spleen, which had been been seen on computed tomography 3 months earlier. Ultrasonography demonstrated a hypoechoic area in the spleen. Initial laboratory tests revealed a serum C-reactive protein concentration of 19.7 mg/dl and a white blood cell count of 15,800 /μl. The serum glucose concentration was 267 mg/dl, and the glycolated hemoglobin value was 7.7%. A splenic abscess was diagnosed and was treated with percutaneous drainage. Milky yellow fluid was obtained, and the patients left upper quadrant abdominal pain and pyrexia resolved. A culture of the drainage fluid yielded Escherichia coli. The drainage catheter was removed 12 days after insertion. The patient was discharged 6 days later. The splenic abscess has not recurred during 3 months of follow-up. Our results suggest that ultrasound-guided percutaneous drainage is a safe and effective alternative to surgery for the treatment of splenic abscess and allows preservation of the spleen.
  • Tatsuya Nomoto, Takehiro Seta, Koichi Nomura, Yukihiro Shikama, Tadash ...
    2007 年 74 巻 3 号 p. 261-264
    発行日: 2007年
    公開日: 2007/07/12
    ジャーナル フリー
    Recently, an outbreak of acute encephalopathy associated with Sugihiratake mushroom ingestion has been reported in northern Japan. Patients with chronic kidney diseases are thought to be at risk for severe encephalopathy following Sugihiratake mushroom ingestion. We report a case of encephalopathy associated with Sugihiratake mushroom ingestion in a patient with diabetic nephropathy. Brain magnetic resonance imaging showed discriminative intensity in the medial temporal lobe, claustrum, and insula cortex bilaterally. Cerebrospinal fluid examination revealed mildly elevated protein and marked elevation of myelin basic protein without pleocytosis. Twenty-five days after admission, these signal-intensity changes had markedly improved, and the patient was discharged without sequelae. Although the exact mechanism of this acute encephalopathy remains undetermined, demyelination is believed to be a possible associated pathological change. In cases of encephalopathy of undetermined cause with distinct magnetic resonance findings, Sugihiratake mushroom intoxication should be considered in areas where ingestion of this mushroom is common.
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