The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
216 巻, 1 号
September
選択された号の論文の12件中1~12を表示しています
Review
  • Ming-Chyi Pai
    2008 年 216 巻 1 号 p. 1-5
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Psychotic features are frequently seen in dementia patients, which indeed cast a huge psychological and physical burden onto their care givers. This is especially true for delusions and hallucinations. If inquired into in greater detail, some of the delusions and even hallucinations can be found to arise from plausible origins. In this article, the author reports two dementia patients, with an attempt to link the unique psychotic features to the personal history of the individual patient. In addition to biological predisposition, the background and the personal history of each patient may play a role in the development of such psychotic features. To emphasize the background of the patients and to treat him or her as a person is also the core spirit of medical humanity, which is an issue important for dementia care. The author also discusses the two topics: visual hallucination in patients with dementia with Lewy bodies and the genetic polymorphism of dopamine D2 receptor gene in dementia patients with delusions. If clinicians spend more time to understanding the history of their patients, at least some of the need to use medical treatment can be reduced.
Regular Contributions
  • Elnur Ilham Farajov, Tetsuji Morimoto, Ulviyya Fizuli Aslanova, Naonor ...
    2008 年 216 巻 1 号 p. 7-15
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    The calcium-sensing receptor (CaSR) is known well as a sensor of extracellular calcium for regulating parathyroid hormone secretion. CaSR is located along all nephron segments in the kidney. While hypercalcemia strongly enhances urinary acidification, the relationship between CaSR and acid-base metabolism in the kidney is still uncertain. In the present study, we examined whether CaSR activation caused acid secretion in the medullary thick ascending limb (mTAL), which is one of the major nephron segments involved in both mineral and acid-base regulation. The effects of a potent calcimimetic neomycin (Neo) on intracellular pH (pHi) were analyzed in the in vitro miroperfused mouse mTALs. The mTALs were incubated with 2,7-bis-(2-carboxyethyl)-5(6)-carboxyfluoresceine-acetoxymethylester (BCECF-AM) for microfluorescent pHi measurements. In HCO3/CO2-buffered solution, the steady-state pHi was 7.17 ± 0.01 (n = 19). Basolateral Neo at 0.4 mM in basolateral side significantly alkalinized the mTAL cells to 7.28 ± 0.02 (n = 19), while Neo in the lumen had no effect on pHi. Neo in the basolateral side alkalinized the mTALs in the absence of ambient Na+ and the presence of H+-ATPase inhibitor bafilomycin in the lumen, indicating that the effect of Neo is unrelated to Na+-dependent acid-base transporters such as Na+-H+ exchangers and Na+-HCO3 cotransporter, or to luminal H+-ATPase. In contrast, the effect of Neo on pHi was inhibited by K+ removal or treatment with specific H+-K+-ATPase (HKa) inhibitors, ouabain and Sch-28080Sch-28080, in the lumen. Our results suggest that hypercalcemia induces urinary acidification partly by stimulating luminal K+-dependent H+-excretion via CaSR in mouse mTALs.
  • Mitsuyoshi Mineta, Hirotaka Sano, Ryogo Ichinose, Yoshifumi Saijo, Eij ...
    2008 年 216 巻 1 号 p. 17-24
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Supraspinatus tendon tearing is one of the most common causes of the shoulder pain and dysfunction, which often requires a surgical repair. In this situation, proximal tendon stump is usually retracted medially from its original insertion. For successful reduction of the retracted tendon stump to its original insertion, the elasticity of the tendon-muscle unit should be preserved by the time of surgery. The purpose of the present study was to clarify the chronological changes in the elasticity of the supraspinatus tendon-muscle unit after acute tendon tearing to determine the optimal timing for the surgery. Right supraspinatus tendon was detached (detached side) in 40 male Japanese white rabbits, with left shoulders served as controls (control side). Eight animals were euthanized at 3 days and 1, 2, 4, or 8 weeks after surgery. Tissue sound speed that closely correlates to its elasticity was measured with a scanning acoustic microscope. In the supraspinatus tendon, tissue sound speed at 3 days after surgery was 1691.1 m/s, compared to 1714.3 m/s at the control side, but the difference was not statistically significant at any postoperative time period up to 8 weeks. In the supraspinatus muscle, tissue sound speed was not affected at all by the detachment of the tendon. The present study indicated that the elasticity of the supraspinatus tendon-muscle unit was well preserved for 8 weeks after the detachment. In the clinical practice, the retracted supraspinatus tendon stump could be repaired without excessive tension by 8 weeks from the acute tendon tearing.
  • Tetsuharu Shinjyo, Hidemitsu Kurosawa, Jun-ichi Miyagi, Kiyoto Ohama, ...
    2008 年 216 巻 1 号 p. 25-34
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been widely studied because of its aberrant expression in human cancer. Survivin has multiple functions, including cell-cycle regulation at mitosis, inhibition of apoptosis and caspase-independent cytoprotection. Clinical studies have shown that survivin is associated with resistance to treatment and its expression is linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate survivin expression in hematopoietic cells. Here we analyzed downstream pathways of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic cells that express constitutively active Ras mutants, using signaling pathway-specific inhibitors. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases, Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin expression in Baf-3 cells. Interestingly, constitutively active Ras mutants also induced survivin in a cell cycle-dependent manner. Reporter assays of the survivin gene promoter revealed a transcriptional regulatory cis-acting region that is responsible for Ras signaling, indicating that Ras increases the transcription of the survivin gene through specific enhancer elements. These data illustrate the pathways regulating survivin expression by Ras. Ras activates the MAPK, PI3-K and mTOR pathways, and these signals enhance survivin transcription. Our data will provide the new information about mechanisms of survivin expression by Ras-signalling pathways.
  • Xian-Feng Cheng, Di Li, Min Zhuang, Zhao-Yan Chen, De-Xiang Lu, Toshio ...
    2008 年 216 巻 1 号 p. 35-45
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Kidney and prostate cancers are leading causes of death in the world, and accumulating evidence suggests that tumor suppressor gene, Krüppel-like factor 6 (KLF6), plays an important role in both the development and the progression of cancer. However, the effect of wild type KLF6 (wtKLF6) on the growth potential of renal carcinoma cells has not been examined. In the present study, we therefore introduced wtKLF6 gene into a prostatic carcinoma derived cell line, DU145, and a renal carcinoma derived cell line, OS-RC-2, and have established DU145-KLF6 and OS-RC-2-KLF6 cell lines, both of which stably over-express KLF6. Compared with vector-transfected cell lines (control cells), the wtKLF6-transfected cell lines showed the lower proliferation capacity (p < 0.01) and higher percentages of cells with apoptotic signals (p < 0.01). Moreover, the KLF6-overexpressed cell lines showed significant increases in the cell population at G0/G1 phase and significant decreases in the cell population at S and G2/M phases. There was no significant difference in the results of the cell cycle analysis between the two KLF6-overexpressed cell lines, DU145-KLF6 and OS-RC-2-KLF6. The cyclin-dependent kinase inhibitor p21 as a transcriptional target of the KLF6 gene was also studied. The expression levels of p21 mRNA and protein were up-regulated in both KLF6-overexpressed cell lines. These results indicate that the wtKLF6 gene effectively inhibited the growth of the prostatic carcinoma DU145 and renal carcinoma OS-RC-2 cell lines, probably through up-regulation of p21. Thus, KLF6 may represent a novel therapeutic target for inhibiting prostate and renal cancer.
  • Masahiro Kohno, Motohiro Takeda, Yoshimi Niwano, Rumiko Saito, Natsumi ...
    2008 年 216 巻 1 号 p. 47-52
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Early detection and optimal treatment are the most effective means to improve cancer mortality. Mass screening for cancer has yielded a marked reduction of cancer mortality in the United States. Simple and effective methods are expected for screening of malignancy. Hematoporphyrin derivatives (HPDs) are known to accumulate in cancer cells; thus, HPD has been used for local diagnosis and photodynamic therapy of cancer. The lymphocytes of cancer patients also demonstrate the active uptake of HPD and this phenomenon has been applied for the diagnosis of cancer. In the present study, we have developed a novel method for measurement of the chemiluminescence of HPD in peripheral blood lymphocytes. HPD is composed of hematoporphyrin and its oligomers. Seven cancer patients and seven controls were recruited for this study. The primary cancers included two prostate cancers (one without metastasis and the other with lung metastasis), a renal cancer, a lung adenocarcinoma with systemic metastasis, two gallbladder cancers with lung metastasis, and a colon cancer with liver metastasis. HPD in lymphocytes was measured using a highly sensitive chemiluminescence analyzer with laser light irradiation to detect photoemission by 1O2 from HPD. The intensity of chemiluminescence exhibited a linear correlation with the concentrations of HPD. In addition, the level of HPD in lymphocytes was significantly higher in cancer patients than that in healthy volunteers (p < 0.05). These results suggest that detection of the chemiluminescence of HPD in lymphocytes could be a sensitive and simple method for cancer diagnosis and screening.
  • Tomofumi Hoshino, Keiji Tabuchi, Yuki Hirose, Isao Uemaetomari, Hideka ...
    2008 年 216 巻 1 号 p. 53-59
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Acoustic injury is a common cause of hearing loss for people in industrial societies. Cyclooxygenase (COX) and lipoxygenase (LOX) are two important enzymes involved in arachidonic acid metabolism. Two COX isozymes are characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression. Although COX-1, COX-2, and LOX are expressed in cochlea, their roles played in cochlear acoustic injury have not fully been evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit either COX or LOX, or both. This study evaluated the effects of NSAIDs on the functional recovery of the cochlea after acoustic injury. Mice were exposed to a 4-kHz pure tone of 128 dB SPL (sound pressure level) for 4 hours and received one of the following drugs for two weeks after acoustic overexposure: indomethacin (COX-1 inhibitor), meloxicam, SC58125, and CAY10404 (COX-2 inhibitors), and nordihydroguaiaretic acid (LOX inhibitor). The hearing ability was evaluated using an auditory brainstem response (ABR) before and after overexposure. The ABR threshold shifts, defined as subtraction between ABR thresholds before and after overexposure, were compared among the control and the medication groups at one and two weeks after acoustic overexposure. Treatment of mice with either indomethacin or nordihydroguaiaretic acid decreased the ABR threshold shifts after overexposure, indicating that COX-1 and LOX inhibitors exhibited protective effects against acoustic injury. In contrast, COX-2 inhibitors, meloxicam, SC58125, and CAY10404, showed no noticeable effects on the ABR threshold shifts. These findings suggest that COX-1 and LOX are involved in the pathogenesis of acoustic injury in cochlea.
  • Koji Saito, Toshihiro Wagatsuma, Hiroaki Toyama, Yutaka Ejima, Kunihik ...
    2008 年 216 巻 1 号 p. 61-68
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    The function of immune system is to protect hosts from invading microorganisms by destroying infected cells while minimizing damage to tissues. Among immune cells, CD4+CD25+ regulatory T cells (Treg cells) control immune responses by limiting infectious processes. However, it remains unclear whether Treg cells are induced in systemic inflammatory response syndrome (SIRS) or infectious SIRS (i.e. sepsis). SIRS and sepsis are associated with stressful inflammatory conditions. We therefore measured CD25+ T cells and circulating CD4+ T cells, along with plasma levels of CD25, interleukin (IL)-6, and IL-10, in 20 septic patients (64 ± 11 years), 16 SIRS patients (59 ± 16 years), and control subjects: 13 elderly (60 ± 16 years) and 14 young volunteers (28 ± 3 years). Septic patients (23.3 ± 11.8%, p < 0.01) showed significantly higher percentages of CD25+ cells among CD4+ T cells (i.e. Treg cells) than did either young (10.6 ± 3.7%) or elderly volunteers (11.1 ± 3.8%). The percentages of Treg cells in septic patients were higher than those in SIRS patients (12.4 ± 6.9%, p < 0.01). Moreover, plasma levels of soluble CD25 were significantly higher in septic patients, compared to the levels in SIRS patients or volunteers (p < 0.01). No significant difference in plasma levels of IL-6 or IL-10 was found between septic patients and SIRS patients. Thus, sepsis is associated with the increased percentages of Treg cells and elevated plasma level of soluble CD25. The elevation of these parameters might be a useful marker of infections in SIRS.
  • Aya Morimoto, Rimei Nishimura, Naho Suzuki, Toru Matsudaira, Kentaro T ...
    2008 年 216 巻 1 号 p. 69-75
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Tsunan, Niigata is a non-westernized rural Japanese town, known for heavy snowfalls and as a rice-producing area, whose inhabitants have a long life expectancy. We investigated the prevalence of obesity, metabolic syndrome (MetS) and its components in Tsunan. A total of 1,155 men and women, 40-69 years of age were recruited from participants in the 2005 public-health program in Tsunan. Obesity was defined as body-mass index (BMI) ≥ 25 kg/m2. MetS was defined as BMI ≥ 25 kg/m2 as well as at least two of the following three items: (1) high glycosylated hemoglobin (HbA1c ≥ 5.5%); (2) high blood pressure (HBP: systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg), and (3) low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL). If an individual was diagnosed with diabetes, hypertension, or dyslipidemia, each item was recorded as a positive finding. The prevalence of MetS and its components among Tsunan inhabitants were compared to the results of the 2005 Japanese nationwide survey. The prevalence of MetS was 4.6% in males and 4.2% in females. The prevalence of obesity, high HbA1c, HBP, and low HDL-C were 22.1/22.2%, 13.4/16.4%, 46.6/40.0%, and 9.2/3.9% in males/females, respectively. All values were significantly lower than the national results, except for the rate of female obesity. The lower prevalence of MetS and its components in Tsunan may be due to the consumption of traditional Japanese food, which is still commonly eaten there, and the higher levels of regular physical activity of farmers.
  • Masato Tashiro, Koichi Izumikawa, Daisuke Yoshioka, Shigeki Nakamura, ...
    2008 年 216 巻 1 号 p. 77-80
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of several types of malignancy, including germ cell tumors, lymphoma, and certain types of squamous-cell carcinoma. The common adverse effect of BLM is interstitial pneumonitis, followed by pulmonary fibrosis. BLM-induced pneumonitis occurs in up to 46% of patients treated with BLM-containing chemotherapy and lung toxicity usually appears during treatment. Here we describe a patient with lung fibrosis, who presented with slow progressive breathlessness and pneumothorax more than 10 years after cessation of BLM therapy. A 15 year-old girl presented with abnormal shadows on chest X-ray. The patient had a yolk sac carcinoma in the sacral region at 1 year of age and obtained complete remission after being treated with tumor resection, radiation, and several anti-cancer drugs including BLM. There were no abnormal findings in chest X-ray until she reached 3 years of age, when she had developed respiratory distress that worsened with age. The patient had experienced an episode of pneumothorax at 13 years of age. Chest CT at the time revealed interstitial reticular opacities. Radiological findings and pathological examination of the lung tissue obtained during bullectomy with video-assisted thoracic surgery were compatible with BLM-induced pneumonitis. The present study suggests that lung fibrosis may surface more than 10 years after cessation of BLM therapy at the age of 1 year, with no chest radiographic findings 1 year after completion of chemotherapy. The use of BLM in infants requires strict supervision and observation and careful long-term follow up.
  • Yuji Suda, Akiko Tanaka, Katsutoshi Hayashi, Yuriko Shindoh, Hideya Ii ...
    2008 年 216 巻 1 号 p. 81-93
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Diagnosis of suspected cancer in the periphery of the lung is difficult. A flexible ultrathin bronchoscope has been developed for the diagnosis of peripherally located pulmonary lesions that cannot be reached with the sampling devices for standard flexible bronchoscopes. The diagnostic yield with forceps and a brush for ultrathin bronchoscopes, however, is not adequate, especially when a lesion is not exposed to the bronchial lumen. We have thus developed a novel needle-type sampling device and tested its yield in transbronchial cytology. The device consists of an elongated dental H-file (0.4 mm in diameter and 110 cm in length), a housing sheath (1.0 mm in outer diameter), and a novel handle, which enables rapid out-and-in motion of the needle. Ten consecutive patients with a peripheral pulmonary lesion who had an indication for diagnostic procedure with a flexible ultrathin bronchoscope were enrolled. The optimal bronchial route to the lesion was analyzed with virtual bronchoscopy in a data set obtained with high-resolution computed tomography, and a novel bronchial route labeling system (prior-ridge-based relative orientation nomenclature) was employed to guide insertion of the bronchoscope. Sampling with the novel needle was performed prior to use of the forceps and brush under conventional fluoroscopy. In all the cases, sampling with the needle was successful and the amount of the specimen was sufficient for cytology. Our novel sampling system with flexible ultrathin bronchoscopes may contribute to accurate and minimally invasive diagnosis of peripheral pulmonary lesions.
  • Gen-i Hazama, Yuichi Inoue, Kazushige Kojima, Toshiyuki Ueta, Kazuyuki ...
    2008 年 216 巻 1 号 p. 95-98
    発行日: 2008年
    公開日: 2008/08/22
    ジャーナル フリー
    Delayed sleep phase syndrome (DSPS) is a circadian rhythm sleep disorder with a typical onset in the second decade of life. DSPS is characterized by the sleep-onset insomnia and the difficulty in waking at the desired time in the morning. Although DSPS is associated with inability to attend school, the prevalence has been controversial. To elucidate a change in the prevalence of DSPS among young population, epidemiological survey was conducted on Japanese students. A total of 4,971 students of junior high school, senior high school, and university were enrolled in this cross sectional study in Tottori Prefecture. They answered anonymous screening questionnaire regarding school schedule, sleep hygiene and symptomatic items of sleep disorders. The prevalence of probable DSPS was estimated at 0.48% among the total subject students without gender difference. In university, the prevalence of the last year students showed the highest value (1.66%), while that of the first year students showed the lowest value (0.09%) among all school years from junior high school to university. The prevalence increased with advancing university school years. Thus, a considerable number of Japanese students are affected with DSPS. Senior students of university are more vulnerable to the disorder than younger students. Appropriate school schedule may decrease the mismatch between the individual's sleep-wake cycle and the school schedule. Promotion of a regular sleep habit is necessary to prevent DSPS among this population.
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