The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
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Invited Review for the 100th Anniversary of the TJEM
  • Kazutaka Nanba, Amy R. Blinder, William E. Rainey
    2021 Volume 253 Issue 4 Pages 217-232
    Published: 2021
    Released: April 09, 2021
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    The human adrenal cortex is a complex endocrine organ that produces mineralocorticoids, glucocorticoids and androgens. These steroids are produced in distinct cell types located within the glomerulosa, fasciculata and reticularis of the adrenal cortex. Abnormal adrenal steroidogenesis leads to a variety of diseases that can cause hypertension, metabolic syndrome, infertility and premature adrenarche. The adrenal cortex can also develop steroid-producing adenomas and rarely adrenocortical carcinomas. In vitro cell culture models provide important tools to study molecular and cellular mechanisms controlling both the physiologic and pathologic conditions of the adrenal cortex. In addition, the presence of multiple steroid-metabolizing enzymes within adrenal cells makes it a model for defining possible endocrine disruptors that might block these enzymes. The regulation and dysregulation of human adrenal steroid production and cell division/tumor growth can be studied using freshly isolated cells but this requires access to human adrenal glands, which are not available to most investigators. Immortalized human adrenocortical cell lines have proven to be of considerable value in studying the molecular and biochemical mechanisms controlling adrenal steroidogenesis and tumorigenesis. Current human adrenal cell lines include the original NCI-H295 and its substrains: H295A, H295R, HAC13, HAC15, HAC50 and H295RA as well as the recently established MUC-1, CU-ACC1 and CU-ACC2. The current review will discuss the use of primary cultures of fetal and adult adrenal cells as well as adrenocortical cell lines as in vitro models for the study of human adrenal physiology and pathophysiology.

Regular Contribution
  • Takehiro Hashimoto, Daisuke Shiojiri, Norio Ohmagari
    Type: Regular Contribution
    2021 Volume 253 Issue 4 Pages 233-239
    Published: 2021
    Released: April 02, 2021
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    Blood culture tests have a major role in rapid and accurate diagnosis and selection of optimal antibiotic treatment for infectious diseases. The true-positive and contamination rates of blood cultures are performance indicators for the practice of blood culture. However, the optimal number of blood cultures has not been adequately elucidated. We aimed to assess the validity of the number of blood cultures obtained in the hospital. We conducted a retrospective study of blood cultures collected from hospitalized patients between 2010 and 2014 at a tertiary care hospital in Japan and assessed the validity of the number of blood cultures per 1,000 admissions as an indicator for the optimal practice of obtaining blood culture, considering the average length of stay. We also investigated the validity of true-positive and contamination rates of blood cultures in the hospital. The number of blood cultures in this study ranged from 28.6 to 56 per 1,000 patient-days and from 404.4 to 894.6 per 1,000 admissions. The median true-positive and contamination rates of blood cultures per year was 10.1% and 2.8%, respectively. The median contamination rate of blood cultures in a community-acquired group was significantly higher than that in a hospital-acquired group (4.1% vs. 1.9%, p = 0.029). We conclude that there is a possibility that the number of blood cultures per 1,000 admissions is a more appropriate factor to evaluate than per patient-days. Moreover, the true-positive and contamination rates of blood cultures in our hospital are valid.

  • Shiroh Tabata, Fumika Kaneda, Kazunori Ohwada, Toshiro Nishiyama, Hiro ...
    Type: Regular Contribution
    2021 Volume 253 Issue 4 Pages 241-248
    Published: 2021
    Released: April 06, 2021
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    Dialysis-related amyloidosis (DRA) is characterized by the deposition of amyloid consisting of beta2-microglobulin in the musculoskeletal system, causing carpal tunnel syndrome, destructive spondyloarthropathy, and/or bone cysts. Increased cystic radiolucency of the bones and tendon thickening due to inflammation are common findings in DRA. We have developed a new dialysis method, extended-hours hemodialysis without dietary restrictions for the aim of improving both hypertension and malnutrition. We retrospectively evaluated the clinical effects of dialysis time on the risk for developing of DRA. The study subjects were all of the 30 patients who had received this treatment for more than 11 years. They were divided into two groups according to the weekly dialysis hours: 15 patients ≥ 16.5 hours/week (L-group) and 15 patients ≤ 15.5 hours/week (S-group). Plain x-ray imaging and ultrasonography were used to assess cystic radiolucency of the bones and thickness/diameter of the soft tissues. The proportion of the carpal bone cystic radiolucency was lower in the L-group. The severity of median nerve compression at the wrist was significantly less in the L-group (right hand: p = 0.0082, left hand: p = 0.0137). Multivariate regression analysis showed that dialysis time was a predictor of median nerve compression (β = −0.559, p = 0.005). In conclusion, extended-hours hemodialysis without dietary restrictions contributes to lower the risk for developing of DRA at the wrist. We therefore propose that extended-hours hemodialysis without dietary restrictions is a preferred method which maintains the patients’ quality of life compared with the conventional hemodialysis method.

  • Jingshu Da, Xiaoqian Wang, Lu Li, Yan Xu
    Type: Regular Contribution
    2021 Volume 253 Issue 4 Pages 249-259
    Published: 2021
    Released: April 09, 2021
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    Bacterial infection contributes to tumor development and malignant progression. Fusobacterium nucleatum (F. nucleatum) is reported to promote oral squamous cell carcinoma. However, molecular bases of F. nucleatum regulating oral cancer cells have not been fully elucidated. We report here that F. nucleatum down-regulates p53 and E-cadherin via the Wnt/NFAT pathway to promote cisplatin-resistance and migration in oral squamous carcinoma cells. We pretreated Cal-27 and HSC-3 cells with F. nucleatum and the survival rates against cysplatin (Cis-diamminedichloroplatinum, CDDP) were significantly higher in treated cells. The expressions of migration and apoptosis-related proteins like E-cadherin and p53 were lower in western blot analysis. We observed that F. nucleatum was an activator of the Wnt/NFAT pathway. The expression levels of the Wnt pathway gene wnt5a and Nuclear factors of activated T cells 3 (NFATc3) were notably higher in treated cells. With the inhibition effect of NFAT-inhibitory peptide VIVIT, the expressions of E-cadherin and p53 in response to F. nucleatum infection were up-regulated reversely. We concluded that F. nucleatum might promote cisplatin-resistance and migration of oral squamous cell carcinoma cells through the Wnt/NFAT pathway.

Case
  • Takashi Aki, Ko Hashimoto, Hiroaki Uozumi, Masahiro Saito, Ko Sugawara ...
    Type: Case
    2021 Volume 253 Issue 4 Pages 261-267
    Published: 2021
    Released: April 15, 2021
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    Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.

  • Mina Chishiki, Hayato Go, Kisei Endo, Nahoko Katayama Ueda, Hiroki Tak ...
    Type: Case
    2021 Volume 253 Issue 4 Pages 269-273
    Published: 2021
    Released: April 22, 2021
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    Streptococcus agalactiae or group B streptococcus (GBS) is a pathogen that causes severe neonatal infections, resulting in sepsis, pneumonia, and meningitis. Neonatal GBS meningitis has a poor neurological prognosis and a high mortality rate. GBS disease is classified as early- and late-onset if the onset age is 0-6 and 7-89 days after birth, respectively. There is currently no effective preventive strategy against late-onset GBS (LOGBS) disease. Here, we report a case of female infant with LOGBS meningitis who recovered from the septic shock by two exchange transfusions (ExTs) but still experienced severe neurological sequela. She was born at a gestational age of 39 weeks via caesarian section due to oligohydramnios and had fever 11 days after birth. GBS was detected in her cerebrospinal fluid (CSF) and blood but not in the vaginal or breast-milk cultures of the mother. The patient was treated with intravenous antibiotic administration; however, she suddenly developed pulseless ventricular tachycardia and asystole the next day. Her heart rate was normalized via cardiopulmonary resuscitation. We also performed two ExTs, and she recovered from the septic shock. Cytokine-profile analysis revealed that the serum and CSF levels of various pro-inflammatory and anti-inflammatory cytokines were elevated before the ExTs, after which the serum levels of several of these cytokines decreased. Two ExTs were effective in saving the life of the patient but did not improve the neurological prognosis. Given that neonatal GBS meningitis has high fatality and sequela rates; thus, it is necessary to establish a preventive strategy.

Regular Contribution
  • Naoto Nishizaki, Taiki Shima, Akiko Watanabe, Kaoru Obinata, Toshiaki ...
    Type: Regular Contribution
    2021 Volume 253 Issue 4 Pages 275-281
    Published: 2021
    Released: April 24, 2021
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    Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.

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