| 1. |
- Yamada, K., et al.
(författare)
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Long-term outcome of targeted therapy for low back pain in elderly degenerative lumbar scoliosis
- 2021
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 30, s. 2020-2032
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Treatment of low back pain (LBP) associated with elderly degenerative lumbar scoliosis (DLS) remains controversial. We have developed percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) targeting to the intervertebral vacuum as a minimally invasive surgery. The present study compared the long-term clinical outcomes of PIPI to that of nonoperative treatment. Methods Patients with de novo DLS, aged >= 65 years, who had LBP with visual analog scale (VAS) of >= 50 for >= 6 months with intervertebral vacuum on computed tomography and bone marrow edema (BME) on magnetic resonance imaging were included. The clinical outcomes were evaluated using VAS and the Oswestry Disability Index (ODI) at baseline, 1, 6, 12, 24 months, and at the final follow-up. The course of BME was also evaluated. Results One hundred and one patients underwent PIPI and 61 received nonoperative treatment. The mean follow-up duration after PIPI and nonoperative treatment was 63.7 +/- 32.4 and 43.9 +/- 20.9 months, respectively. VAS and ODI after PIPI were significantly improved compared to post-nonoperative treatment. BME decreased substantially in the PIPI group and it was significantly correlated with VAS and ODI improvement. Following PIPI, LBP recurred in 28 patients (35%). LBP recurrence was identified at the same level of PIPI in 10 patients, at the adjacent level of PIPI in 11 patients, and at the non-adjacent level of PIPI in seven patients. Eighteen patients underwent additional PIPIs, and both VAS and ODI were significantly improved after additional PIPIs. Conclusion Bone marrow lesions of the endplate are strongly associated with the presence of LBP. PIPI can be considered as an effective, safe and repeatable treatment for LBP in elderly DLS patients.
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| 2. |
- Chen, Y. H., et al.
(författare)
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Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
- 2023
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
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| 3. |
- Nakamae, T., et al.
(författare)
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Percutaneous Intervertebral-Vacuum Polymethylmethacrylate Injection for Foraminal Stenosis with Degenerative Lumbar Scoliosis
- 2022
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Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750. ; 165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Percutaneous intervertebral-vacuum polymethylmethacrylate injection (PIPI) is a minimally invasive procedure for low back pain in elderly patients with degenerative lumbar scoliosis (DLS). Patients with DLS often have radiculopathy as a result of foraminal stenosis in addition to low back pain. The purpose of this study was to evaluate the clinical and radiologic results of PIPI for foraminal stenosis with radiculopathy in elderly patients with DLS. Methods: We included patients with de novo DLS aged 65 years or older who underwent PIPI. The presence of an intervertebral vacuum on computed tomography and bone marrow edema on magnetic resonance imaging was required for inclusion. The intersegmental radiologic parameters on plain radiographs and computed tomography and the extent of bone marrow edema on magnetic resonance imaging were measured. The clinical outcomes were evaluated using the visual analog scale (VAS) and Oswestry Disability Index (ODI). Results: We enrolled 40 patients with DLS who underwent PIPI. There were 16 men and 24 women, and the mean age was 79.0 ± 6.3 years. The mean foraminal height and extent of bone marrow edema showed a significant increase and reduction, respectively, after PIPI (P < 0.05). VAS score for radiculopathy and ODI significantly improved after PIPI (P < 0.01). The minimum clinically important differences in VAS score for radiculopathy and ODI at the final follow-up were 73.9% and 63.6%, respectively. Conclusions: PIPI is a minimally invasive procedure not only for low back pain but also for radiculopathy in elderly patients with DLS. It leads to intervertebral stabilization and indirect decompression of the foramen. © 2022
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| 4. |
- Nishikawa, H., et al.
(författare)
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The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer
- 2004
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Ingår i: Gynecol Oncol. - : Elsevier BV. - 0090-8258. ; 92:3, s. 881-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the contribution of cathepsin B and cystatin C to the mechanisms of invasion by ovarian cancer. MATERIALS AND METHODS: Using surgical materials from patients with ovarian cancer, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis were performed using antibodies against cathepsin B or cystatin C. Serum levels of cathepsin B and cystatin C in patients with benign and malignant ovarian lesions were determined by enzyme-linked immunosorbent assay (ELISA). An invasion assay using an ovarian cancer cell line was performed by addition of cystatin C or specific inhibitors of cathepsin B. RESULTS: While immunohistochemical staining of cathepsin B and cystatin C was evident in cancer cells and associated stromal tissue, this was not the case in benign tumors. The malignancies were also found to be positive for cathepsin B and cystatin C by SDS-PAGE and Western blotting analysis. No significant difference in serum cathepsin B levels was observed between patients with benign and malignant disease. However, the concentration of cystatin C in cases with ovarian cancer was significantly higher in benign cases (P<0.0001) and in healthy controls (P<0.0001). Invasion by cancer cells was dose-dependently suppressed by cystatin C and cathepsin B inhibitors. CONCLUSION: The results provided convincing evidence that cathepsin B and cystatin C may contribute to the mechanisms of invasion of ovarian cancer.
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| 5. |
- Aoyama, K., et al.
(författare)
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Cleavage of integrin by mu-calpain during hypoxia in human endometrial cells
- 2004
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Ingår i: Am J Reprod Immunol. - 1046-7408. ; 52:6, s. 362-9
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: The distribution and activation of mu-calpain and possible cleavage of integrin in human endometrial cells under hypoxic condition were investigated. METHOD OF STUDY: Human endometrial epithelial and stromal cells were subjected to hypoxia, and subsequently used for immunostaining and western blot analysis. RESULTS: The proform of mu-calpain was detected in the cytoplasm of normal cells, and displayed a substantial decrease after hypoxia. Conversely, the active form of mu-calpain was not detected in normal cells, but was abundant after hypoxia. The cytoplasmic domain of integrin beta3 was also detected in the cytoplasm of endometrial cells. Western blot analysis confirmed that both the proform of mu-calpain and the integrin beta3 cytoplasmic domain decreased during hypoxia. CONCLUSIONS: Mu-calpain is activated in human endometrial cells during hypoxia and that subsequent cleavage of the integrin beta3 cytoplasmic domain may give some adverse effects to the function of human endometrium.
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| 6. |
- Nakanishi, T., et al.
(författare)
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Role of cathepsins and cystatins in patients with recurrent miscarriage
- 2005
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Ingår i: Mol Hum Reprod. - 1360-9947. ; 11:5, s. 351-5
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Tidskriftsartikel (refereegranskat)abstract
- In the implantation, trophoblasts penetrate maternal decidua by secreting proteases. It has been reported that cathepsins are highly expressed in the mouse villi, and play an important role in normal embryonal growth and decidualization. In this study, we evaluated cathepsins and their endogenous inhibitors, cystatins, in tissue and serum of patients with recurrent miscarriage. Decidua and villi were surgically collected from 22 patients and 12 healthy women. Immunohistochemistry was performed with antibodies against cathepsins, stefin A (cystatin A), stefin B (cystatin B) and cystatin C. The concentrations of cathepsins, stefins and cystatin C were measured by Enzyme-linked immunosorbent assay. In addition, we measured the serum level of cystatin C in 85 Japanese women with recurrent miscarriage. Staining of cathepsin B, D, H, L, stefin B and cystatin C was observed in the cytoplasm of epithelial cells in decidua. Stefin A was expressed on the surface of the trophoblast. The concentration of cathepsin B and H in patients' decidua was significantly higher than in control individuals. The serum level of cystatin C was significantly lower in patients than in control individuals. Our findings suggest that the regulation of the cathepsin-cystatin system may play an important role in patients with recurrent miscarriage.
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