The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
236 巻, 3 号
July
選択された号の論文の10件中1~10を表示しています
Regular Contribution
  • Kazushige Goto, Takuma Morishima, Kazumichi Kurobe, Zhong Huang, Futos ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 163-168
    発行日: 2015年
    公開日: 2015/06/12
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    Hypoxia itself stimulates glucose uptake mediated by a mechanism independent of insulin. However, whether moderate hypoxia causes similar metabolic effect in humans remains unclear. The present study aimed to determine glycemic regulation following glucose load at a simulated moderate altitude of 2,500 m. Eight healthy young males (mean ± standard error: 24 ± 1 years; 171.3 ± 1.6 cm; 66.9 ± 3.7 kg; 22.8 ± 1.0 kg/m2) consumed 75 g of glucose solution under either hypobaric condition (560 mmHg) or normobaric condition (745 mmHg). In the hypobaric chamber, the oxygen partial pressure is proportionally reduced with a reduction of atmospheric pressure, consequently leading to the hypoxic condition. Plasma glucose and serum insulin concentrations increased significantly following glucose load in both conditions (P < 0.05). However, no significant interaction (condition × time) or main effect for condition was observed. There were no significant differences in serum glycerol, plasma epinephrine, or plasma norepinephrine concentrations between the two conditions. No significant differences between the conditions were observed in changes in VO2 or VCO2. However, the hypobaric condition showed significantly higher respiratory exchange ratio (VCO2/VO2) at 90 and 120 min following glucose load (P < 0.05 vs. normobaric condition), suggesting that carbohydrate oxidation following glucose load was enhanced in moderate hypobaric hypoxia. In conclusion, acute exposure to moderate hypobaric hypoxia significantly augmented carbohydrate oxidation following the glucose load, without affecting glucose or insulin responses. Thus, a short-time exposure to moderate hypobaric hypoxia may be beneficial for people with impaired glucose tolerance.
Commentary
  • Masaru Seguchi, Noriko Furuta, Seiji Kobayashi, Kazuhiro Kato, Kouji S ...
    原稿種別: Commentary
    2015 年 236 巻 3 号 p. 169-174
    発行日: 2015年
    公開日: 2015/06/12
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    The shortage of medical workforce in rural areas is a global long-standing problem. Due to the severity of shortages in the medical workforce, Mie prefectural government has collaborated with a medical school and the municipal governments to increase the rural medical workforce. Since 2010, this collaboration has led to an annual lecture series on rural practice for medical students. We distributed questionnaires at the beginning and end of the lecture series to examine the effect of this program. The questionnaire consisted of two parts that included an understanding of rural practice and the motivation to work in rural areas. The lecture series significantly improved the responses to the following questions “Rural practice is interesting” (p < 0.001), “Rural practitioners can deliver adequate medical care” (p < 0.01), “Rural practitioners cannot go back to urban areas” (p < 0.001), “I want to be a rural practitioner” (p < 0.001), “Healthcare facilities in rural areas have been developed” (p < 0.001), “Rural practitioners can be a specialist” (p < 0.001), and “Rural residents can be served adequate healthcare service” (p < 0.01). The percentage of students who desired to work in rural areas increased significantly (11.1% vs. 23.9%, p = 0.04). A lecture series on rural practice enhanced the motivation of medical students and their interest in a rural career. While collaboration between the local government and medical school rarely occurs in planning medical education programs, this approach may offer a promising way to foster local health professionals.
Regular Contribution
  • Dong Ho Shin, Eun Jung Kim, Samuel Lee, Soo Jin Kim, Jieun Oh
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 175-183
    発行日: 2015年
    公開日: 2015/06/16
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    Urinary tract infection (UTI) is the most common bacterial infection encountered in kidney transplant recipients. Graft pyelonephritis (GPN) is associated with acute kidney injury and renal allograft scarring. However, the influence of GPN on renal allograft outcome in kidney transplant recipients remains controversial. Two hundred sixty-five kidney transplant recipients were evaluated for the impact of early-onset GPN on renal allograft functions between January 2001 and December 2011. Early-onset GPN was defined as the first GPN episode occurring within 6 months after kidney transplantation. Thirty recipients (11.3%) were diagnosed with early-onset GPN. During the mean follow-up period of 69.1 ± 28.9 months, 56 (21.1%) recipients showed renal allograft outcomes of a > 30% reduction in the estimated glomerular filtration rate (eGFR) over 2 years. The poor outcome was significantly more frequent in the early-onset GPN group (13 patients; 43.3%) than in those without early-onset GPN (43 patients; 18.3%) (P = 0.002). Moreover, the linear mixed model revealed a significant difference in the eGFR decline rate over time between the two groups (P < 0.001). Kaplan-Meier analysis showed that renal allograft event-free survival was significantly lower in the early-onset GPN group (P = 0.006). Multivariate Cox regression analyses revealed that early-onset GPN was independently predictive of poor renal allograft outcomes (hazard ratio, 1.96; 95% confidence interval, 1.02-3.77; P = 0.04). In conclusion, early-onset GPN is independently associated with impaired renal functions in kidney transplant recipients. Thus, early-onset GPN could be a predictor for long-term outcome of renal allografts.
  • Ja-Young Jeon, Keon-Young Kim, Bong-Sik Kim, Ju-Yang Jung, Hyoun-Ah Ki ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 185-191
    発行日: 2015年
    公開日: 2015/06/16
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    Systemic lupus erythematosus (SLE) is chronic autoimmune disease with various autoantibodies, which are involved in tissue damage. Fc gamma receptors (FcγRs) bind the constant region of the immunoglobulin G and transmit stimulatory or inhibitory signal to immune cells. The FcγR genes map to 1q23, a susceptible locus for SLE. We have screened single nucleotide polymorphisms (SNPs) in one of FcγR gene, FcγRIIB, which is the only inhibitory receptor, after considering gene map and reported SNPs. There were 3 SNPs in FcγRIIB: 10849 T>C (rs1050501) in exon 5 and 10950 T>G (rs6666965) and 11045 G>T (rs12117530) in intron 5 in Koreans. The frequency of the minor allele (T) of rs12117530 was significantly higher in SLE patients (50 patients, 20.4%) than healthy controls (17 patients, 12%, p = 0.041). Leukopenia occurred more frequently in SLE patients carrying the minor allele (T) of rs12117530 (p = 0.032). Among 5 haplotypes, the frequency of decreased complement was significantly lower in SLE patients with haplotype 1 [TTG] (p = 0.045). Nephritis, lymphopenia and anti-dsDNA antibody were significantly less frequent in SLE patients with haplotype 2 [TGG] (p = 0.046, p = 0.018, p = 0.002, respectively). The frequency of thrombocytopenia and anti-dsDNA antibody was significantly higher in SLE patients with haplotype 3 [CTG] (p < 0.001, p = 0.04, respectively). These data reveal that genetic polymorphisms within FcγRIIB are associated with disease susceptibility and phenotypes of SLE in Koreans. Furthermore, FcγRIIB rs12117530 polymorphism (T allele) may be an important risk factor in SLE.
Case
  • Kae Tanaka, Hiroyuki Harada, Kou Kayamori, Ken Omura
    原稿種別: Case
    2015 年 236 巻 3 号 p. 193-198
    発行日: 2015年
    公開日: 2015/06/16
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    Immunoglobulin G4-related disease (IgG4-RD) is a systemic condition accompanied by tumefactive lesions, dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis in various organs, and, frequently, elevated serum IgG4 levels. Chronic sclerosing sialadenitis (also termed Küttner’s tumor) is thought to be a lesion of IgG4-RD; thus, IgG4-related sialadenitis may be the initial symptom of IgG4-RD. We herein report a 64-year-old Japanese female with IgG4-related chronic sclerosing sialadenitis of the right submandibular gland and retroperitoneal fibrosis, who subsequently developed tubulointerstitial nephritis and pancreatitis. She was referred to our Department for treatment of swelling of the right submandibular gland; preoperative imaging studies suggested a malignant tumor. We extirpated the submandibular glands bilaterally and diagnosed IgG4-related chronic sclerosing sialadenitis pathologically. Subsequently, the patient’s serum IgG4 concentration increased, and lesions in the retroperitoneum, kidney, and pancreas were confirmed by imaging. Although the radiological characteristics of these lesions mimicked malignancy, steroid treatment was commenced based on the pathology of the submandibular gland and elevated serum IgG4 level. This caused the lesions to disappear, indicating that the patient had experienced IgG4-related retroperitoneal fibrosis, tubulointerstitial nephritis, and pancreatitis. No relapse was detected for 4 years 8 months after surgery. A pathological diagnosis is crucial to exclude the possibility of malignancy and to make treatment decisions when lesions are evident in other organs. In addition, periodic evaluation of the serum IgG4 concentration and imaging of the whole body are warranted in long-term follow-up.
Regular Contribution
  • Tibor Stracina, Iva Slaninova, Hana Polanska, Martina Axmanova, Veroni ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 199-207
    発行日: 2015年
    公開日: 2015/06/19
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    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.
  • Chunyang Zhang, Yan Zhu, Yan Zhang, Lianru Gao, Ningkun Zhang, Huasong ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 209-217
    発行日: 2015年
    公開日: 2015/06/24
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    Radiation-induced lung injury (RILI) limits the benefits of radiotherapy in patients with lung cancer. Radiation-induced differentiation of lung fibroblasts to myofibroblasts plays a key role in RILI. Recent studies have shown that mesenchymal stem cells (MSCs) can protect against lung fibrosis and that Wnt/β-catenin signaling is involved in fibrotic processes. In the present study, we explored the therapeutic potential of human umbilical cord MSCs (HUMSCs) for preventing radiation-induced differentiation of human lung fibroblasts (HLFs) to myofibroblasts. There are two advantages in the use of HUMSCs; namely, they are easily obtained and have low immunogenicity. Irradiated HLFs were co-cultured with HUMSCs. Expression of α-smooth muscle actin (α-SMA), a myofibroblast marker, was measured by Western blot analysis and immunohistochemistry. Irradiation (X-rays, 5 Gy) induced the differentiation of HLFs into myofibroblasts, which was inhibited by co-culture with HUMSCs. Irradiation also caused activation of the canonical Wnt/β-catenin signaling in HLFs, as judged by increased phosphorylation of glycogen synthase kinase 3β, nuclear accumulation of β-catenin, and elevated levels of Wnt-inducible signaling protein-1 (WISP-1) in the conditioned medium. However, co-culture with HUMSCs attenuated the radiation-induced activation of the Wnt/β-catenin signaling. We also measured the expression of FRAT1 that can enhance the Wnt/β-catenin signaling by stabilizing β-catenin. Co-culture with HUMSCs decreased FRAT1 protein levels in irradiated nHLFs. Thus, co-culture with HUMSCs attenuated the radiation-induced activation of Wnt/β-catenin signaling in HLFs, thereby inhibiting myofibroblastic differentiation of HLFs. Wnt/β-catenin signaling is a potential therapeutic target for limiting RILI in patients receiving radiotherapy for lung cancer.
  • Lei Cong, Wei-bo Wang, Qi Liu, Jia-jun Du
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 219-224
    発行日: 2015年
    公開日: 2015/06/24
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    Vitamin D is a potential protective agent against cancer, and its activity is mediated mainly by vitamin D receptor (VDR). The FokI polymorphism (rs10735810) represents a T-to-C transition (ATG to ACG) in exon 2 of the VDR gene, and this ATG represents the translation-initiation codon, encoded by the f allele. The FokI polymorphism results in the generation of a protein shortened by three amino acids, translated from the downstream ATG codon (the F allele). We investigated the relationship between the FokI polymorphism and gastric cancer in a Chinese Han population. A total of 187 patients and 212 healthy controls were enrolled. The FokI polymorphism was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. The f allele frequency was higher in patients than that in controls (51.6% and 43.6%, P < 0.05). Multivariate logistics regression analysis revealed patients with the f allele (Ff + ff) showed a higher risk of gastric cancer [odds ratio (95% confidence interval) 2.73 (1.13~4.32)]. Patients with the f allele (Ff + ff) also presented a poorly differentiated type of gastric cancer (P < 0.05) and higher levels of C-reactive protein on admission than the FF group (5.5 ± 2.4 mg/L vs. 3.4 ± 1.3 mg/L, P < 0.05). Here, we show an association between the VDR FokI polymorphism and the susceptibility to gastric cancer, which may be helpful for early detection of high-risk individuals with the f allele for gastric cancer. Conversely, the F allele may be a protective factor against gastric cancer.
  • Takehiro Suzuki, Hiroaki Yamaguchi, Motoi Kikusato, Tetsuro Matsuhashi ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 225-232
    発行日: 2015年
    公開日: 2015/06/26
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    Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, indole-3-acetic acid. Importantly, MA-5 improved the survival of fibroblasts established from patients with mitochondrial diseases under the stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis and stroke-like episodes), Leber’s hereditary optic neuropathy, and Kearns-Sayre syndrome. The improved survival was associated with the increased cellular ATP levels. Moreover, MA-5 increased the survival of mitochondrial disease fibroblasts even under the inhibition of the oxidative phosphorylation or the electron transport chain. These data suggest that MA-5 could be a therapeutic drug for mitochondrial diseases that exerts its effect in a manner different from anti-oxidant therapy.
  • Mitsuhiko Nanno, Takuya Sawaizumi, Norie Kodera, Yuji Tomori, Shinro T ...
    原稿種別: Regular Contribution
    2015 年 236 巻 3 号 p. 233-240
    発行日: 2015年
    公開日: 2015/07/02
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    Carpal tunnel syndrome (CTS) is the most common peripheral compression neuropathy of the upper extremity. Repetitive wrist and finger motion has been suggested as a major factor of pathogenesis of CTS. However, little is known about the pathomechanics of CTS. We aimed to evaluate the movement of the median nerve in the carpal tunnel during wrist and finger motions using transverse ultrasound in 21 patients with CTS (5 men and 16 women with mean age 69.0 years). We examined quantitatively the median nerve location as a coordinate within the carpal tunnel at varied wrist positions with all fingers full extension and flexion respectively in the affected and unaffected sides. We thus found that at all wrist positions during finger motion, the median nerve moved significantly more ulnopalmarly in the affected side compared to the unaffected side (p < 0.05). Especially, at the wrist palmar-flexion position as a provocative test, the nerve moved significantly (p < 0.05) the most ulnopalmarly among all wrist positions in the affected side. The nerve was the most strongly compressed against the transverse carpal ligament by the flexor tendons. Additionally, the displacement amount of the nerve in the dorsal-palmar direction was significantly smaller in the affected side than in the unaffected side. These findings indicate that such a pattern of nerve movement has the potential to distinguish affected from unaffected individuals. This ultrasound information could be useful in better understanding of the pathomechanics of CTS, and in further improvement of diagnosis and treatment for CTS.
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