1.Transforming Growth Factor-β Induces Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells through Partial Activation of p38 and p44/42 Mitogen-Activated Protein Kinases
Yuta GOTO ; Kenji KATO ; Kiyoshi YAGI ; Yohei KAWAGUCHI ; Hiroki YONEZU ; Tomoko KOSHIMAE ; Yuko WAGURI-NAGAYA ; Hideki MURAKAMI ; Nobuyuki SUZUKI
Asian Spine Journal 2023;17(6):997-1003
Methods:
HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively.
Results:
TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation.
Conclusions
Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.
2.Real-world efficacy and safety of bevacizumab single-maintenance therapy following platinum-paclitaxel chemotherapy plus bevacizumab in patients with advanced cervical cancer
Saki KOTAKA ; Eiji KONDO ; Yosuke KAWAI ; Kota OKAMOTO ; Yasuyuki KISHIGAMI ; Takaharu YAMAWAKI ; Kenji NAGAO ; Toru HIRATA ; Shiro SUZUKI
Journal of Gynecologic Oncology 2023;34(5):e60-
Objective:
Bevacizumab maintenance therapy following platinum-based combination chemotherapy for metastatic, recurrent, or persistent cervical cancer is not recommended as standard therapy. This pilot study aimed to evaluate the efficacy and safety of bevacizumab maintenance therapy and the contribution of the platinum-free interval to the efficacy of subsequent chemotherapy for advanced cervical cancer.
Methods:
We retrospectively identified 115 patients with metastatic, recurrent, or persistent cervical cancer treated with platinum-paclitaxel chemotherapy plus bevacizumab at 7 institutions between 2015 and 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients who received bevacizumab maintenance therapy and those who did not. We also analyzed the adverse events associated with bevacizumab and survival time from the start of subsequent chemotherapy in both groups.
Results:
Following platinum-paclitaxel plus bevacizumab chemotherapy, 34 patients received bevacizumab maintenance therapy and 81 patients did not. Of the 115 patients, 56 received chemotherapy for subsequent relapse. Although bevacizumab maintenance therapy prolonged PFS (median of 16.0 months vs. 9.0 months, p=0.041), significant differences were not observed in OS (p=0.374). Furthermore, bevacizumab maintenance therapy did not prolong OS and PFS after the start of subsequent chemotherapy (p=0.663 and p=0.136, respectively). Bevacizumab maintenance therapy significantly increased hypertension (p=0.035) and proteinuria (p=0.005) but did not cause complications leading to death.
Conclusion
Bevacizumab single-maintenance therapy for advanced cervical cancer can be considered in selected cases, such as those with acceptable bevacizumab-related side effects. The outcomes of our study will likely contribute to decision-making regarding practical treatment strategies.
3.Segmental Arteries and Veins at Higher Lumbar Levels Can Intersect the Adjacent Caudal Intervertebral Disc in the Anterior Part of the Spinal Column: A Cadaveric Analysis
Kiyoshi YAGI ; Nobuyuki SUZUKI ; Jun MIZUTANI ; Kenji KATO ; Akira KONDO ; Yuya WASEDA ; Yuta GOTO ; Hideki MURAKAMI
Asian Spine Journal 2022;16(1):1-8
Methods:
Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column.
Results:
The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively.
Conclusions
The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.
4.p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells Stimulated by Tumor Necrosis Factor-α
Kiyoshi YAGI ; Yuta GOTO ; Kenji KATO ; Nobuyuki SUZUKI ; Akira KONDO ; Yuya WASEDA ; Jun MIZUTANI ; Yohei KAWAGUCHI ; Yuji JOYO ; Yuko WAGURI-NAGAYA ; Hideki MURAKAMI
Asian Spine Journal 2021;15(6):713-720
Methods:
HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction.
Results:
TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs.
Conclusions
This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.
5.Acetabular Morphology in Patients with Developmental Dysplasia of the Hip with High Dislocation
Kenji TATEDA ; Satoshi NAGOYA ; Daisuke SUZUKI ; Ima KOSUKEGAWA ; Toshihiko YAMASHITA
Hip & Pelvis 2021;33(1):25-32
Purpose:
The current study aimed to investigate the morphology of the true acetabulum in developmental dysplasia of the hip (DDH) with high dislocation. A secondary was to evaluate the acetabular cup placement in patients with high dislocation who were treated with total hip arthroplasty (THA).
Materials and Methods:
Using a retrospective design, 23 hips with DDH with high dislocation in patients who were treated with THA were included in this study. We measured the depth, width and thickness of the anterior and posterior walls of the original acetabulum using preoperative computed tomography images and investigated the cup size applied in these cases.
Results:
The mean depth and width of the acetabulum was 18.4 and 16.2 mm proximal end, 18.4 and 24.3 mm in the middle, and 15.8 and 27.6 mm at the distal part. Mean thickness of the anterior and posterior walls was 10.9 and 23.9 mm at the proximal end, 10.3 and 22.2 mm in the middle, and 10.9 and 22.7 mm at the distal part. A 42-mm cup was using in one hip, a 46-mm cup in three hips, a 48-mm cup in 13 hips, and a 50-mm cup in six hips.
Conclusion
In patients with Crowe IV DDH, the morphology of the acetabulum comprises a triangle that broadens from proximal to distal points, with a relatively thick posterior wall. Reaming the acetabulum posteriorly and inferiorly may enable the placement of a relatively larger cup to achieve stable fixation.
6.Attitude Survey about Adverse Drug Reactions Relief System for Pharmacists of Insurance Dispensing Pharmacies and Examination of Its Problems
Shigeo AKIYAMA ; Nobuyuki DOI ; Miyoko ASANO ; Shigeyasu FUKUZUMI ; Shingo TAKAHASHI ; Katsutoshi SUZUKI ; Kenji OGAWA ; Etsuko MIYAMOTO
Japanese Journal of Drug Informatics 2020;22(2):101-107
Objectives: “Adverse Drug Reaction Relief System” (hereinafter called the Relief System) has been established to provide prompt relief to patients experiencing health damage caused by adverse drug reactions. Since 2018, the Relief System has required community pharmacies that acquire additional points as local support system to actively report adverse drug reactions. Here, we investigated the recognition and utilization of the relief system among community pharmacists.Method: A questionnaire survey was conducted among community pharmacists between August 1 and September 30, 2019.Results: The survey achieved a response rate of 58.1%. The recognition rates of the relief system and Pharmaceuticals and Medical Devices Agency (PMDA) as its application destination were 98.9 and 74.5%, respectively. Of the community pharmacists, 2.6% had experience in utilizing the relief system; and 8.8% did not want to recommend the utilization of the relief system for patients mainly because of the “low recognition of the system” and “the complicated and troublesome preparation of the necessary documents such as medical certificates.” The community pharmacists who acquire additional points as local support system, compared with those who do not, achieved significantly higher rates in two items, including that for preparation of the documented procedures pertaining to adverse drug reactions.Conclusion: Despite the high recognition of the relief system among community pharmacists, the percentage of pharmacists with experience in actually utilizing the relief system and applying to the PMDA was low. One reason that the use of the relief system was not widespread was the low recognition particularly of the destination and procedures of reports on adverse drug reactions. In the future, educational campaigns to improve pharmacists’ comprehension of the relief system will be needed. Moreover, pharmacists must play a central role in enhancing the recognition of the public relief system and promoting medical safety.
7.The Promoting Effect on the Gastric Emptying Function of Hangeshashinto was Confirmed by CT Images in Radiation therapy. A Case Report on Stomach Malignant Lymphoma with Dyspepsia
Kenji SUZUKI ; Satoshi SEKI ; Tetsuya KAWATA ; Katsurou ITOH
Kampo Medicine 2020;71(4):390-393
A 75-year-old woman visited a hospital complaining of nausea and anorexia. She was diagnosed with stomach malignant lymphoma, and 6 courses of R-CHOP therapy were performed. Since complete remission was obtained, consolidation radiotherapy was decided. When performing radiation therapy on the stomach, it is desirable to carry it out in an empty stomach. For this reason, it is necessary to skip meals before irradiation. However, in this case, scar stenosis remained in gastric vestibular, and there was always a complaint of stomach discomfort. The treatment plan CT was taken without meals, and full stomach was observed. The patient was judged to be unavoidable due to an organic passage disorder, and a treatment plan was made with a full stomach, and radiotherapy was started. However, she was administered hangeshashinto from the first day of radiation therapy, and stomach discomfort quickly improved. CT was performed again, confirming that the stomach volume was reduced. In this case, in addition to scar stenosis in the stomach, it seems that functional dyspepsia was also involved. It is considered that the promoting effect on gastric emptying function of hangeshashinto was confirmed by CT images.
8.Postoperative Radiographic Early-Onset Adjacent Segment Degeneration after Single-Level L4–L5 Posterior Lumbar Interbody Fusion in Patients without Preoperative Severe Sagittal Spinal Imbalance
Yuji MATSUOKA ; Kenji ENDO ; Hidekazu SUZUKI ; Yasunobu SAWAJI ; Hirosuke NISHIMURA ; Taichiro TAKAMATSU ; Osamu KOJIMA ; Kazuma MURATA ; Takeshi SEKI ; Shinji HORIE ; Takamitsu KONISHI ; Kengo YAMAMOTO
Asian Spine Journal 2018;12(4):743-748
STUDY DESIGN: Retrospective study. PURPOSE: To investigate the relationship between preoperative total spinal sagittal alignment and the early onset of adjacent segment degeneration (ASD) after single-level posterior lumbar interbody fusion (PLIF) in patients with normal sagittal spinal alignment. OVERVIEW OF LITERATURE: Postoperative early-onset ASD is one of the complications after L4–L5 PLIF, a common surgical procedure for lumbar degenerative disease in patents without severe sagittal imbalance. A better understanding of the preoperative characteristics of total spinal sagittal alignment associated with early-onset ASD could help prevent the condition. METHODS: The study included 70 consecutive patients diagnosed with lumbar degenerative disease who underwent single-level L4–L5 PLIF between 2011 and 2015. They were divided into two groups based on the radiographic progression of L3–L4 degeneration after 1-year follow-up: the ASD and the non-ASD (NASD) group. The following radiographic parameters were preoperatively and postoperatively measured: sagittal vertebral axis (SVA), thoracic kyphosis (TK), lumbar lordosis, pelvic tilt, and pelvic incidence (PI). RESULTS: Eight of the 70 patients (11%) experienced ASD after PLIF (three males and five females; age, 64.4±7.7 years). The NASD group comprised 20 males and 42 females (age, 67.7±9.3 years). Six patients of the ASD group showed decreased L3–L4 disc height, one had L3–L4 local kyphosis, and one showed both changes. Preoperative SVA, PI, and TK were significantly smaller in the ASD group than in the NASD group (p <0.05). CONCLUSIONS: A preoperative small SVA and TK with small PI were the characteristic alignments for the risk of early-onset ASD in patients without preoperative severe sagittal spinal imbalance undergoing L4–L5 single-level PLIF.
Animals
;
Female
;
Follow-Up Studies
;
Humans
;
Incidence
;
Kyphosis
;
Lordosis
;
Male
;
Retrospective Studies
9.Oxidized human serum albumin as a possible correlation factor for atherosclerosis in a rural Japanese population: the results of the Yakumo Study.
Ryosuke FUJII ; Jun UEYAMA ; Arisa AOI ; Naohiro ICHINO ; Keisuke OSAKABE ; Keiko SUGIMOTO ; Koji SUZUKI ; Nobuyuki HAMAJIMA ; Kenji WAKAI ; Takaaki KONDO
Environmental Health and Preventive Medicine 2018;23(1):1-1
BACKGROUND:
The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population.
METHODS:
We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA).
RESULTS:
We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA).
CONCLUSIONS
We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.
Adult
;
Aged
;
Aged, 80 and over
;
Atherosclerosis
;
epidemiology
;
etiology
;
Biomarkers
;
Carotid Intima-Media Thickness
;
statistics & numerical data
;
Cross-Sectional Studies
;
Female
;
Humans
;
Japan
;
epidemiology
;
Male
;
Middle Aged
;
Oxidation-Reduction
;
Risk Factors
;
Serum Albumin
;
metabolism
;
Serum Albumin, Human
;
metabolism
10.Successful Repair of Traumatic Tricuspid Regurgitation
Satoru SHIRAIWA ; Yoshihiro HONDA ; Kenji SAKAKIBARA ; Masatake KATSU ; Shigeaki KAGA ; Shoji SUZUKI ; Hiroyuki NAKAJIMA
Japanese Journal of Cardiovascular Surgery 2018;47(3):128-132
A 62-year-old man was referred to our hospital because of dyspnea. Electrocardiogram showed chronic atrial fibrillation and echocardiogram revealed severe tricuspid regurgitation. His history included a motorbike accident at age 17, and a heart murmur was pointed out in the following year. He developed paroxysmal atrial fibrillation when he was 45 years old. Heart failure was not controlled by medication and tricuspid valve repair was indicated. At surgery, the anterior leaflet of tricuspid valve was widely prolapsed due to chordal rupture. We performed chordal reconstruction with 4 expanded polytetrafluoroethylene (CV-5®) sutures, and ring annuloplasty. Furthermore, a small fenestration at the tricuspid annulus was noticed and was closed with a direct suture. The biatrial modified Maze procedure was performed subsequently. The patient is doing well without TR recurrence, and restored sinus rhythm is maintained. We report successful repair of traumatic tricuspid regurgitation.


Result Analysis
Print
Save
E-mail