LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.
ADAM Proteins/*metabolism ; Antigens, CD9/genetics/*metabolism ; Cell Line, Tumor ; Humans ; LDL-Receptor Related Proteins/genetics/*metabolism ; Leukocytes/*metabolism ; Macrophages/metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Proteolysis

In this study, we implemented a health education course, comprising lectures, cooking lessons, and group discussions for household cooks, that addressed the need for continued reduction of table salt intake and evaluated the effects from participants’ narratives. After the health education course, participants reported continuing to make the following efforts: planning dishes that have a milder yet still delicious taste, evaluating the amount of salt, refraining from highly salty dishes, and continuing to reduce salt use when cooking. The reasons participants continued to reduce table salt use included wanting to live a healthy life, understanding how to reduce salt in dishes, learning to reduce salt consumption, learning to check the amount of salt in dishes, learning that low-salt cooking is easy, learning that unseasoned dishes can be delicious, and feeling the benefits of reduced salt intake. Participants learned that low-salt cooking is easy and how to determine the amount of salt from set values, which were effective for their continued reduction of salt intake. Moreover, our study shows that continuous support is important until individuals become accustomed to milder tastes.

STUDY DESIGN: Multicenter, prospective study. PURPOSE: To investigate the effects of diabetes mellitus (DM) on surgical outcomes in patients with cervical myelopathy. OVERVIEW OF LITERATURE: To date, few studies have investigated the influence of postoperative blood glucose or glycated hemoglobin (HbA1c) levels on surgical outcomes. METHODS: The participants were patients who underwent surgery for the treatment of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament. The 61 cases were evaluated preoperatively and 1 year postoperatively using the Japanese Orthopaedic Association (JOA) scores and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The study variables included fasting blood glucose and HbA1c levels measured preoperatively and at 1 week, 4 weeks, and 1 year postoperatively; the F-wave conduction velocity, latency, rate of occurrence, and M-wave latency in the ulnar and tibial nerves were measured preoperatively and at 1 year postoperatively. The patients were divided into a group without diabetes (N group, 42 patients) and a group with diabetes (DM group, 19 patients). We then assessed the associations between the surgical outcomes and each of the study variables. RESULTS: JOA scores significantly improved in both groups; however, no significant between-group differences were found. There was no significant improvement in the JOACMEQ scores, which assessed cervical function, upper and lower limb function, and bladder function in both groups. We then subdivided the DM group into those with a good control of HbA1c after 1 year (DMG group, 12 patients) and those with HbA1c deterioration after 1 year (DMB group, seven patients), prior to comparing the surgical outcomes. The JOACMEQ scores for upper and lower limb function significantly improved in the DMG group (p<0.01). Compared with the DMB group, there were no significant increases in upper or lower limb function scores in the DMG group. CONCLUSIONS: Poor glycemic control might prevent postoperative functional recovery of the spinal cord.
Asian Continental Ancestry Group ; Blood Glucose ; Diabetes Mellitus ; Electromyography ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Longitudinal Ligaments ; Lower Extremity ; Neck ; Prospective Studies ; Spinal Cord ; Spinal Cord Compression ; Spinal Cord Diseases ; Tibial Nerve ; Treatment Outcome ; Urinary Bladder