We previously reported that a human carbonyl reductase 1 (CBR1) DNA-dendrimer complex could potentially be used in gene therapy for peritoneal metastasis of ovarian cancer. The aims of the current study were to make exosomes which overexpressed CBR1 and to examine the antiproliferative effect of using the CBR1overexpressing exosomes on ovarian cancer cells. Endometrial stromal cells (fibroblasts) were transfected with CBR1 DNA by using Lipofectamine, the highest expression level of CBR1 was produced from the cells transfected under the condition of Lipofectamin 24 μl/DNA 36 μg for 48 h. Exosomes were purified from culture supernatants by exoEasy Maxi Kit. Western blot showed that CBR1 notably expressed in exosomes extracted from the stromal cells transfected with CBR1 DNA. Proliferation of ovarian cancer cell line was significantly inhibited by adding CBR1overexpressing exosomes compared to proliferation of those cells in which exosomes without CBR1 DNA were added. We obtained the evidence that CBR1-overexpressing exosomes could function in carrying CBR1 DNA into ovarian cancer cells. Results suggested that exosomes are a useful tool of gene delivery and that a gene therapy of combining CBR1 DNA and exosomes may be promoted in the treatment of advanced and recurrent ovarian cancers with peritoneal dissemination. Hirosaki Med.J. 71:120―130,2021
Background: The Duffy antigen receptor for chemokines (DARC) is expressed on RBCs and is a non-signaling receptor for multiple chemokines. In the previous study, we had shown that DARC-affinity chemokines are stored in the RBCs. However, the fate of intracellularly stored chemokines has yet to be investigated. This study investigated whether RBCs retain the ability to accumulate these chemokines as they age. Methods: Peripheral blood from five healthy volunteers were collected, and then transferred to hematocrit capillary tubes. After centrifugation, the RBC layer was divided to compare the top, upper, middle and bottom fractions. HbA1c, eotaxin-1 and RANTES were measured in each fraction. Results: HbA1c increased significantly from the top fraction to the bottom fraction. Eotaxin-1 decreased significantly from the top fraction to the bottom fraction. RANTES exhibited a similar decrease, although no significant differences were observed. Eotaxin-1 showed a negative correlation (r = -0.51, p = 0.03) with HbA1c. Although not statistically significant, RANTES showed a decreasing tendency (r = -0.40, p = 0.08) with the increase of HbA1c levels. These results indicate that RANTES and eotaxin-1 decrease rather than increase with RBC aging. Conclusion: Eotaxin-1 and RANTES stored in RBCs tended to decrease as RBCs age. Hirosaki Med.J. 71:113―119,2021
Objectives: To clarify the relationship between trunk range of motion (ROM) and back extensor strength (BES) for postural alignment in community-dwelling older adults. Methods: Postural alignment in the sagittal plane (thoracic kyphosis angle, lumbar lordosis angle, sacral inclination angle, overall inclination angle, knee flexion angle), trunk ROM, and BES were measured in 52 subjects. We analyzed the relationship between trunk ROM and BES for each of the postural alignment variables and the group of postural alignment variables. Results: After adjusting for age, body mass index (BMI), and 5-repetition sit-to-stand test (SS-5), all postural alignment variables except for the sacral inclination angle were affected by the thoracolumbar ROM. The postures with decreased lumbar lordosis, forward-tilted trunk, and knee flexion were influenced by lumbar ROM, age, BMI, and SS-5. The postures with increased thoracic kyphosis, lumbar lordosis, and sacral forward tilt were affected by only thoracolumbar ROM. Conclusions: Postural alignment was related to trunk ROM, but there was not enough evidence to say that it is related to BES. Depending on postural characteristics, there may be no relationship with BES. Hirosaki Med.J. 70:109―118,2020
In kidney transplantation, stable hemodynamics is essential to preserve graft function. We used ketamine as an anesthetic because of its sympathomimetic properties. On the other hand, ketamine has several adverse effects, such as prolonged emergence from anesthesia or psychological reactions. Altered ketamine pharmacokinetics was previously reported in rabbits with renal insufficiency, but no study has examined human living kidney transplantation, which has the potential to cause renal insufficiency in the donor and recipient. Therefore, we evaluated ketamine pharmacokinetics in the donor and recipient of living kidney transplantation in various situation including ABO blood type-compatible and -incompatible transplantation. Materials and Methods: We examined the ketamine pharmacokinetics in donors (n=8), and ABO blood type -compatible (n=8) and -incompatible (n=8) recipients of living kidney transplantation. We also measured the estimated glomerular filtration ratio (eGFR), blood urea nitrogen (BUN), and serum creatinine in these patients. Results: The time course of changes in the ketamine level after stopping ketamine administration did not differ between the donors and recipients. We also found that the eGFR in recipients gradually improved 48 h after the kidney transplantation. No patient developed ketamine-related adverse effects or allograft rejection. Conclusion: We conclude that ketamine can be safely applied as an adjuvant with intravenous anesthesia during ABO blood type-compatible and -incompatible living kidney transplantation. Hirosaki Med.J. 70:156―162,2020
The treatment of esophageal achalasia using peroral endoscopic myotomy (POEM) is a standard technique that is less invasive than other techniques. There have been no previous reports of using transthoracic ultrasonography to detect complications with POEM. We report the case of a 29-year-old male patient with esophageal achalasia who underwent POEM. The procedure was repeatedly interrupted due to hypercapnia and hemodynamic instability. Even after a peritoneal puncture to release abdominal distention, improvement of his respiratory condition was limited. The patient emerged promptly from general anesthesia but developed tachypnea. Using transthoracic ultrasonography we diagnosed left pneumothorax. He was admitted to the intensive care unit, and the trachea was extubated without any invasive intervention 6 hours later. We treated a patient who required mechanical ventilation due to hypercapnic respiratory failure after undergoing POEM and found that transthoracic ultrasonography may be useful to detect pneumothorax in such cases. Hirosaki Med.J. 70:172―176,2020
Background Combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) is mostly performed for patients with aortic stenosis (AS) and coronary artery disease (CAD). Objectives We aim to clarify that combined operation of AVR and CABG with adequate perioperative cardiac protection does not increase operative and postoperative risk. Methods A total of 217 patients who underwent AVR for aortic stenosis alone or combined AVR and CABG from 1/2002 to 12/2015 were recruited. The aortic valve alone group (group A) had 164 patients, with an average age of 71.6± 8.1 years. The combined operation group (group C) consisted of 54 patients, with an average age of 73.5±8.5 years. Aortic valve area and pressure gradient showed no significant differences between the two groups. In group C, an average of 2±0.8 vessels had CAD. Cold crystalloid cardioplegia according to left ventricular mass ± a terminal hot shot was used for all patients. Distal graft anastomosis was done after cardiac arrest and cardioplegia (1.5-fold normal) was injected additionally from the graft with severe proximal obstruction of the right coronary artery. Results Group C included more patients with diabetes mellitus (DM, 43.4% vs. 26.8%) and low left ventricular ejection fraction (LVEF<50%, 33.96% vs. 16.46%) than group A. On the other hand, the incidence of atrial fibrillation (AF, 3.77% vs. 13.41%) was significantly less in group C than in group A. Although cardiac arrest time was longer in group C, postoperative CPK-MB was not significantly elevated, except in 4 patients. Postoperative data showed no significant differences between the two groups. Conclusions In our department, satisfactory clinical outcomes were obtained with combined operation AVR and CABG. Sufficient myocardial protection had an important effect on clinical outcomes. Hirosaki Med.J. 70:99―108,2020
Background: We previously reported that ST-segment elevation myocardial infarction (STEMI) patients with large residual thrombus burden after thrombectomy before stent implantation had more severe microvascular dysfunction, and greater myocardial damage compared with those with small residual thrombus. However, clinical significance of residual thrombus after stent implantation in STEMI patients is unclear. Aims: This study aimed to evaluate the incidence of thrombus by optical coherence tomography (OCT) after stent implantation, and to investigate its clinical impact in STEMI patients. Methods and Results: A total of 180 STEMI patients within 12 hours after onset of symptoms were studied. Patients were divided into two groups according to OCT findings after stent implantation: thrombus group (n = 73) and nonthrombus group (n = 107). Peak CPK levels were greater in thrombus group than in non-thrombus group with close to significance (3649 {1752-7053} versus. 2563 {1201-4282} IU/L, p = 0.053). Thrombus after stent implantation was independently associated with peak CPK levels by a stepwise multivariate analysis. Conclusions: Residual thrombus on OCT after stent implantation was detected in 41% of STEMI patients. The residual thrombus was associated with greater myocardial damage assessed by peak CPK levels, indicating clinical impact of OCT-detected thrombus in STEMI patients. Hirosaki Med.J. 70:139―147,2020
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