The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 231, Issue 2
October
Displaying 1-9 of 9 articles from this issue
Regular Contributions
  • Masayuki Hayashi, Yuko Kataoka, Yoshihisa Sugimura, Fumiko Kato, Maki ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 75-84
    Published: 2013
    Released on J-STAGE: September 28, 2013
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    The steroidogenic enzyme 21-hydroxylase is necessary for the synthesis of both glucocorticoids and mineralocorticoids. 21-hydroxylase is a cytochrome P-450 enzyme and is encoded by the gene CYP21A2. Here we report a 68-year-old phenotypically ‘male’ but genetically female patient with 21-hydroxylase deficiency (21OHD) and the concomitant virilizing adrenocortical carcinoma. This patient grew up as a male and has not encountered any episodes of adrenal insufficiency without glucocorticoid replacement in his lifetime. A chromosome test at admission, however, identified the 46, XX karyotype, and serum 17-hydroxyprogesterone and urine pregnanetriolone and 11β-hydroxyandrostendione were all elevated, consistent with 21OHD. Moreover, serum testosterone was 1.90 ng/ml, much higher than the female standard levels, and serum cortisol was 5.7 µg/ml, slightly lower than standard levels. Genetic analysis identified the patient as a heterozygote of the two pathogenic mutations in the CYP21A2 gene: IVS2-13C(A)>G and R356W. Magnetic resonance imaging (MRI) revealed the presence of left adrenal tumor measuring 6 cm, which was subsequently diagnosed as adrenocortical carcinoma based on the criteria of Weiss. Immunohistochemical analysis of the tumor specimens revealed the expression of various enzymes involved in testosterone production, including 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17,20-lyase, and 17β-hydroxysteroid dehydrogenase. Importantly, the expression of immunoreactive 21-hydroxylase was detected in these tumor cells. The levels of adrenal tumor-derived steroid metabolites were all markedly decreased following the surgery. This is the first report on a virilized 21OHD patient associated with the adrenocortical tumor that produces testosterone. Moreover, the concomitant adrenocortical tumor may ameliorate adrenocortical insufficiency by producing cortisol.
  • Kiyomi Harada, Ayako Saruwatari, Kaori Kitaoka, Wataru Aoi, Sayori Wad ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 85-91
    Published: 2013
    Released on J-STAGE: October 03, 2013
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    In Japan, the rate of low birth weight infants has increased, due to an increase in the number of women who smoke or are lean. A recent study showed that low birth weight was associated with a high adult waist-to-height ratio in adult Japanese women, but little data is available concerning children. In this cross-sectional study with 568 subjects (276 boys and 292 girls), we examined the association between birth weight and waist-to-height ratio in 7- or 8-year-old Japanese children, all born at full term. The mothers of the subjects responded to a questionnaire about the weight of the children at birth, and physical data were collected from the results of measurements conducted at each school. We divided the subjects into two groups by the median of the birth weight (3,000 g) by sex to elucidate the effects of birth weight on the waist-to-height ratio. There were 119 boys and 164 girls and 157 boys and 128 girls in the < 3,000 g and ≥ 3,000 g birth weight groups, respectively. The Mann-Whitney U test was used to compare the physical conditions in the two birth weight categories. Height was significantly lower in the birth weight < 3,000 g group among both the boys (P < 0.001) and girls (P < 0.001). The waist-to-height ratio was significantly higher in the < 3,000 g group in girls (P = 0.004), but not in the boys. Our results suggest that intrauterine environmental insults might have an effect on children, depending on sex.
  • Tae Hoon Kim, Tae Sung In, Hwi-young Cho
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 93-100
    Published: 2013
    Released on J-STAGE: October 05, 2013
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    Severe upper limb paresis is a major contributor to disability after stroke. This study investigated the efficacy of task-related training (TRT) with transcutaneous electrical nerve stimulation (TENS) on recovery of upper limb motor function in chronic-stroke survivors. Thirty patients with chronic stroke were randomly allocated two groups: the TRT+TENS group (n = 15) and the TRT+placebo (TRT+PLBO) group (n = 15). Patients in the TRT+TENS group received TENS stimulation (two to three times the sensory threshold), while subjects in the TRT+PLBO group received TENS without real electrical stimulation. TENS was applied to muscle belly of triceps and wrist extensors, while placebo (PLBO) stimulation was administrated without real electrical stimulation. Both interventions were given for 30 minutes per day, 5 days per week, for a period of 4 weeks. The primary outcomes were assessed with Fugl-Meyer assessment scores (FMA), Manual function test (MFT), Box and block test (BBT), and Modified Ashworth scale (MAS), each of which was performed one day before and one day after intervention. Both groups showed significant improvements in FMA, MFT, and BBT after intervention. When compared with the TRT+PLBO group, the TRT+TENS group showed significantly greater improvements in FMA (p = 0.034), MFT (p = 0.037), and BBT (p = 0.042). In MAS score, significant improvement was observed only in the TRT+TENS group (p = 0.011). Our findings indicate that TRT with TENS can reduce motor impairment and improve motor activity in stroke survivors with chronic upper limb paresis, highlighting the benefits of somatosensory stimulation from TENS.
  • Sai Luo, Lijun Hao, Xiang Li, Dongmei Yu, Zhiyong Diao, Liwen Ren, Hai ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 101-110
    Published: 2013
    Released on J-STAGE: October 08, 2013
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    Autologous fat transplantation (AFT) is a common and important operation in plastic surgery for soft tissue defects and adipose tissue-derived stem cells (ADSCs) are considered as a promising supplement to decrease absorption and subsequent side effects due to the ability of multiple differentiation and production of vascular endothelial growth factor (VEGF). The capacities of ADSCs can be further enhanced by treatment with 17-β estradiol (E2). Therefore, we hypothesized that E2 may promote the potential of ADSCs for AFT. In this study, ADSCs were extracted from three female patients by liposuction. In vitro studies showed that E2 supplementation at an optimal concentration of 10-8 M resulted in enhanced proliferation, VEGF production, and adipogenic differentiation of human ADSCs, and reduced apoptosis rate in a serum-free environment. In addition, a nude mice model of fat transplantation was utilized to demonstrate the efficacy of ADSC for survival ratio in vivo. These results using the volume of fat tissues after 12 weeks compared original volume, revealed that the addition of E2-treated ADSCs induced a significantly higher tissue survival ratio (76.9 ± 1.9%) when compared with the ADSC-free system (55.5 ± 1.5%). Furthermore, increased capillary formation stained with hematoxylin-eosin (H&E) was observed in ADSCs systems after treatment with E2. Therefore, this study demonstrated E2 could promote the capacities of ADSCs about aspects of adipogenic differentiation, growth factor secretion and apoptosis reduction in vitro, vascularization improvement in vivo, and then enhanced the survival ratio of AFT.
  • Haneul Lee, Jerrold S. Petrofsky, Michael Laymon, JongEun Yim
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 111-115
    Published: 2013
    Released on J-STAGE: October 08, 2013
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    Women have a higher risk for anterior cruciate ligament (ACL) injuries compared to men. ACL elasticity and muscle flexibility are major risk factors for knee injuries. The presence of estrogen receptors in connective tissue allows estrogen to change the mechanical properties of muscles and ligaments. Delayed onset muscle soreness (DOMS) happened when begin unaccustomed levels of exercise. Thus, the purpose of this study was to examine ACL elasticity after exercise meant to produce DOMS. As a measure of DOMS, visual analog pain scale and quadriceps strength were measured. One hundred forty healthy students (age: 25.2 ± 2.4 years, height: 165.9 ± 8.0 cm, weight: 62.5 ± 10.5 kg, BMI: 22.6 ± 3.1) participated in this investigation and were divided into two groups: men (n = 70) and women (n = 70). Visual analog pain scale, ACL elasticity, and quadriceps strength were measured before and after the intervention. Subjects participated in the same exercise to induce DOMS. To provoke DOMS, subjects accomplished squats for 5 minutes for 3 rounds. Greater ACL elasticity, greater pain on the subjective pain scale and less muscle strength were found (p < 0.001) in women compared to men before and after exercise. A greater reduction of ACL elasticity (p < 0.05) was found as a result of DOMS in women compared to men. Women are likely to have the damage to the ACL and recover slower compared to men after exercise. Thus, we suggest that women should have more time for musculoskeletal recovery after heavy exercise.
  • Hiroyuki Ida, Osamu Suyari, Mai Shimamura, Tran Tien Tai, Masamitsu Ya ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 117-125
    Published: 2013
    Released on J-STAGE: October 11, 2013
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    Heme oxygenase (HO) is a rate-limiting step of heme degradation, which catalyzes the conversion of heme into biliverdin, iron, and CO. HO has been characterized in microorganisms, insects, plants, and mammals. The mammalian enzyme participates in adaptive and protective responses to oxidative stress and various inflammatory stimuli. The present study reports that eye imaginal disc-specific knockdown of the Drosophila HO homologue (dHO) conferred serious abnormal eye morphology in adults, resulting in the generation of reactive oxygen species and apoptosis in third-instar larvae. Oxidative stress frequently induces DNA lesions that are recognized by damage sensors, including ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) proteins. The knockdown of dHO took place in G0/G1-arrested cells posterior to the morphogenetic furrow and thus prevented these cells from entering S-phase, with an increase in the level of histone H2A.V, a DNA damage marker. Moreover, the knockdown of dHO resulted in the enhancement of the rough eye phenotype in ATM-deficient flies or was lethal in ATR-deficient flies. These results indicate that dHO functions in control of the signal pathway of DNA damage. On the other hand, genetic crosses with a collection of Drosophila deficiency stocks allowed us to identify eight genomic regions, each deletion of which caused suppression of the rough eye phenotype induced by dHO knockdown. This information should facilitate the identification of HO regulators in Drosophila and clarification of the roles of HO in eye development.
  • Zhe Tang, Lan Ni, Sara Javidiparsijani, Fengqi Hu, Louis A Gatto, Robe ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 127-138
    Published: 2013
    Released on J-STAGE: October 12, 2013
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    Autophagy is a protective cellular mechanism in response to various stresses, including sepsis. Sepsis is defined as systemic inflammation by infection. Surfactant protein A and D (SP-A and SP-D) are involved in host defense, regulation of inflammation, and homeostasis, but their roles in the autophagic activity and relevant gene expression in sepsis are unclear. In this study, mice lacking SP-A and SP-D (SP-A/D KO mice) and background-matched wild-type (WT) C57BL/6 mice underwent either cecal ligation and puncture (CLP) or sham surgery. The results showed that SP-A/D KO mice had lower mortality than WT mice in CLP sepsis. Liver tissues showed marked pathological changes in both septic SP-A/D KO and WT mice 24 hrs after CLP treatment; and quantitative analysis of liver histopathology revealed significant difference between septic SP-A/D and septic WT mice. SP-A/D KO mice had higher basal and sepsis-induced level of autophagy than WT mice (p < 0.05), as judged by Western blot and electron microscopic analyses. The expression of 84 autophagy-related genes revealed differential basal and sepsis-induced gene expression between SP-A/D KO and WT mice. The expression increased in three genes and decreased in four genes in septic WT mice, as compared to septic SP-A/D KO mice (p < 0.05). Furthermore, differential responses to sepsis between SP-A/D KO and WT mice were found in six signaling pathways related to autophagy and apoptosis. Therefore, enhanced autophagic activity improves the survival of septic SP-A/D KO mice through the regulation of liver autophagy/apoptosis-related gene expression and signaling pathway activation.
Case
  • Tatsuro Sasaji, Kiyotsugu Shinagawa, Shigetsune Matsuya
    Article type: Case
    2013 Volume 231 Issue 2 Pages 139-144
    Published: 2013
    Released on J-STAGE: October 17, 2013
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    Spontaneous thoracic spinal subarachnoid hemorrhage is rare, and thus no useful radiological findings for preoperative diagnosis have been reported. We experienced a patient with spontaneous thoracic spinal subarachnoid hemorrhage. A 37-year-old female presented with sudden-onset paraplegia and numbness in the trunk and bilateral lower extremities. The patient had no past history of trauma, lumbar puncture and bleeding disorder. T2-weighted sagittal magnetic resonance imaging (MRI) of the cervical and thoracic spines showed a mass occupied in the ventral space of spinal cord that was dorsally shifted. The mass extended from C6 to Th6 levels, with its largest size at Th2 level. Thoracic spine T2-weighted sagittal and axial MRI showed that the mass compressed spinal cord and was located in the intradural space. There was no spinal cord tumor and no spinal vascular malformation around the mass. Brain computed tomography (CT) showed a high-density area in the subarachnoid space, indicating the possibility of subarachnoid hemorrhage. Brain MRI showed no ruptured aneurysm. The patient was diagnosed as a spontaneous thoracic spinal subarachnoid hemorrhage and emergency surgery was selected. We performed right-side hemilaminectomy at Th1-Th6 and opened dura mater and arachnoid membrane. Hematoma was found in the ventral space of spinal cord and was removed. One year after surgery, numbness in the trunk and bilateral lower extremities had disappeared but paraplegia remained unchanged. Thoracic spine T2-weighted MRI confirmed no hematoma but showed a newly formed intradural cyst. Preoperative combination of brain CT and thoracic MRI is useful to diagnose thoracic spinal subarachnoid hemorrhage.
Regular Contributions
  • Satoru Okada, Tomomi Kiyama, Eri Sato, Yukinori Tanaka, Takefumi Oizum ...
    Article type: Regular Contributions
    2013 Volume 231 Issue 2 Pages 145-158
    Published: 2013
    Released on J-STAGE: October 19, 2013
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    Bisphosphonates (BPs) are pyrophosphate analogs. They are widely used against enhanced bone-resorption in various diseases. Nitrogen-containing BPs (N-BPs) exhibit strong anti-bone-resorptive effects but have inflammatory and necrotic side effects. The non-nitrogen-containing BPs (non-N-BPs) etidronate and clodronate lack such side effects, but their anti-bone-resorptive effects are weak. In mice, etidronate and clodronate reduce the inflammatory/necrotic effects of N-BPs, even those of zoledronate, the N-BP with the strongest anti-bone-resorptive effect yet reported and the highest risk of inflammation/necrosis. Here, to explore the mechanisms underlying this protection, we used a mouse model in which a single reagent or a mixture of two reagents was injected subcutaneously into ear-pinnas. These reagents included zoledronate, four non-N-BPs, pyrophosphate, and inhibitors of various organic-anion-transporters. Pyrophosphate and two of the four non-N-BPs (not etidronate or clodronate) had inflammatory/necrotic effects. These effects were reduced by etidronate and clodronate, but not by phosphonoformate, an inhibitor of two of the three known phosphate-transporter families. Phosphonoformate reduced the inflammatory/necrotic effects of zoledronate, but not those of pyrophosphate or of non-N-BPs. Conversely, pyrophosphate, at non-inflammatory/necrotic concentrations, reduced the inflammatory/necrotic effects of non-N-BPs, but not those of zoledronate. The efficacies of the protective effects against the inflammatory/necrotic effects of zoledronate were clodronate > etidronate > phosphonoformate. These findings suggest that (i) the N-BP zoledronate may enter soft-tissue cells via phosphonoformate-inhibitable phosphate-transporters, (ii) other phosphate-transporters may carry pyrophosphate and inflammatory/necrotic non-N-BPs into such cells, and (iii) etidronate and clodronate inhibit all these transporters, and they ameliorate the side effects of zoledronate by inhibiting phosphonoformate-inhibitable phosphate-transporters.
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