Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

BACKGROUND: Bortezomib is widely used for the treatment of multiple myeloma. Bone marrow stromal cells (BMSCs) endow myeloma cells with survival and growth advantages. However, the influence of bortezomib on BMSCs is not well elucidated. We examined the effects of bortezomib on the survival and growth of BMSCs in vitro. METHODS: The effects of bortezomib on the survival and proliferation of the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane cell migration was evaluated using the Transwell system. A short interfering RNA strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the migration and localization of myeloma cells, MS-5 monolayers were treated with bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma cells. RESULTS: Bortezomib inhibited BMSC proliferation in a concentration-dependent manner, and induced cellular apoptosis. Bortezomib decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment of BMSC monolayers reduced the tendency of myeloma cells to locate to positions under the monolayers. CONCLUSION: Bortezomib inhibits the survival and growth of BMSCs via downregulation of CXCL12, which may contribute to the clinical effects of this agent.
Apoptosis ; Cell Line ; Cell Movement ; Down-Regulation ; Humans ; Mesenchymal Stromal Cells* ; Multiple Myeloma ; RNA, Messenger ; RNA, Small Interfering ; Bortezomib

BACKGROUND: The C-X-C chemokine receptor 7 (CXCR7) has been shown to be a decoy receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid leukemia (AML) cells in vitro. METHODS: CXCR7 mRNA was knocked down in AML cells by using small interfering RNA (siRNA) technology, and subsequent biological alterations in the cells were evaluated in vitro. RESULTS: All AML cell lines examined in this study (U937, K562, KG1a, HL-60, and MO7e) and primary CD34+ cells obtained from patients with AML expressed CXCR7 mRNA at various levels. Western blotting showed that all AML cells produced CXCR7. Furthermore, all AML cells expressed CXCR7 in both the cytoplasm and on the cell surface at various levels. Stromal cell-derived factor-1 (SDF-1; C-X-C motif ligand 12 (CXCL12)) induced internalization of cell surface CXCR7. However, neither hypoxia nor the examined hematopoietic growth factors (interleukin-1beta (IL-1beta), IL-3, IL-6, granulocyte-colony-stimulating factor, granulocyte, macrophage-colony-stimulating factor, and stem cell factor) and proinflammatory cytokines (interferon-gamma, transforming growth factor-beta, and tumor necrosis factor-alpha) were found to alter cell surface CXCR7 expression. The transfection of AML cells with CXCR4 siRNA, but not CXCR7 siRNA, significantly impaired the CXCL12-induced transmigration of the cells. The transfection of AML cells with CXCR7 siRNA did not affect the survival or proliferation of these cells. Knockdown of CXCR7, but not CXCR4, induced the upregulation of CXCL12 mRNA expression and CXCL12 production in AML cells. CONCLUSION: CXCR7 is involved in the regulation of autocrine CXCL12 in AML cells.
Anoxia ; Apoptosis ; Blotting, Western ; Cell Line ; Cell Proliferation ; Cytokines ; Cytoplasm ; Granulocytes ; Humans ; Intercellular Signaling Peptides and Proteins ; Interleukin-3 ; Interleukin-6 ; Leukemia, Myeloid, Acute* ; Necrosis ; RNA, Messenger ; RNA, Small Interfering ; Stem Cells ; Transfection ; Up-Regulation

BACKGROUND: Complex regional pain syndrome (CRPS) is categorized into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Spinal cord stimulation (SCS) is a promising approach in the treatment of severely disabling CRPS. Patients with good responses to sympathetic block before SCS are more likely to have positive responses to SCS than those with negative responses. This study compared the effects of SCS in patients with CRPS, of SMP and SIP categories. METHODS: This was a retrospective study of 16 patients (SMP 8, SIP 8) with CRPS who had undergone trials of SCS. Eleven of the patients had permanent SCS device implants, and the pain relief levels at 1 and 6 months were recorded. RESULTS: Sixteen patients with severe, incapacitating, and therapy-resistant CRPS underwent SCS trials. Five patients (SMP 3, SIP 2) had poor pain relief during the trial despite adequate coverage. The remaining 11 patients (SMP 5, SIP 6) had permanent electrode implantation performed under local anesthesia and experienced good pain relief. The difference in VAS reduction was not significant between the two groups at the 1-month follow-up (P = 0.325) and the 6-month follow-up (P = 0.779). CONCLUSIONS: There were no statistically significant differences in VAS pain scores between the two groups. The favorable outcome in all 11 patients with only minor remaining symptoms or without remaining symptoms or severe recurrences suggests that SCS is an efficient treatment in SMP and SIP.
Anesthesia, Local ; Electrodes ; Follow-Up Studies ; Humans ; Recurrence ; Retrospective Studies ; Spinal Cord ; Spinal Cord Stimulation

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.
Barrett Esophagus ; Biopsy ; Chest Pain ; Cough ; Esophagus ; Gastroesophageal Reflux ; Heartburn ; Hoarseness ; Light ; Metaplasia ; Microscopy ; Prospective Studies ; Proton Pumps ; Sensation

BACKGROUND: Antagonists of CXC chemokine receptor 4 (CXCR4), including AMD3100, induce peripheral mobilization of hematopoietic stem cells and have been approved for clinical use. We explored whether the CXCR4 antagonists affected the survival and proliferation of myeloid leukemia cells in vitro. METHODS: The effects of CXCR4 antagonists AMD3100 and T140 on the survival and proliferation of myeloid leukemia cell lines (U937, HL-60, MO7e, KG1a, and K562) as well as CD34+ cells obtained from patients with AML and CML were analyzed by flow cytometry by using annexin V and a colorimetric cell proliferation assay. RESULTS: AMD3100, but not T140, stimulated the proliferation of leukemia cells in vitro in a dose-dependent manner for up to 5 days (~2-fold increase at a concentration of 10-5 M), which was not abrogated by pretreatment of the cells with pertussis toxin, but was attenuated by RNAi knockdown of CXCR7 transcripts. In contrast, AMD3100 induced a marked decrease in the cell numbers after 5-7 days. AMD3100, but not T140, induced phosphorylation of MAPK p44/p42. AMD3100 increased the number and size of leukemia cell colonies and reduced cell apoptosis during the first 5-7 days of incubation, but the phenomena were reversed during the later period of incubation. CONCLUSION: The effects of CXCR4 antagonists on the proliferation of myeloid leukemia cells are not uniform. AMD3100, but not T140, exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of the cells in vitro.
Annexin A5 ; Apoptosis ; Cell Count ; Cell Line ; Cell Proliferation ; Flow Cytometry ; Hematopoietic Stem Cells ; Heterocyclic Compounds ; Humans ; Leukemia ; Leukemia, Myeloid ; Oligopeptides ; Pertussis Toxin ; Phosphorylation ; Receptors, CXCR4

PURPOSE: AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist in vitro. Thus, we explored whether AMD3100 affected the survival and proliferation of myeloma cells in vitro. MATERIALS AND METHODS: The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay). RESULTS: AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions. CONCLUSION: AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling via CXCR4 in vitro.
Annexin A5 ; Apoptosis ; Cell Line ; Cell Proliferation ; Flow Cytometry ; GTP-Binding Proteins ; Hematopoietic Stem Cells ; Heterocyclic Compounds ; Humans ; Interleukin-6 ; Multiple Myeloma ; Oligopeptides ; Pertussis Toxin ; Phosphorylation

Spinal cord stimulation (SCS) has become an established clinical option for treatment of refractory chronic pain. Current hardware and implantation techniques for SCS are already highly developed and continuously improving, however equipment failures over the course of the long-term treatment are still encountered in a relatively high proportion of treated cases. Percutaneous SCS leads seem to be particularly prone to dislocation and insulation failures. We describe our experience of lead breakage in implanted SCS which was inserted to a complex regional pain syndrome patient who obtained satisfactory pain relief after the revision of SCS.
Chronic Pain ; Dislocations ; Equipment Failure ; Humans ; Spinal Cord ; Spinal Cord Stimulation

Remote ischemic preconditioning (IP), brief tolerating cycles of ischemia and reperfusion in remote non-vital organs, can reduce ischemic injury of the heart. IP induces cardiac protection by down-regulating iNOS or up-regulating eNOS. In addition, Akt has been known to protect myocardium against ischemia-reperfusion injury. This study was undertaken to observe the expression of iNOS, eNOS, Akt and phospho-Akt (p-Akt) in the rat myocardium after IP. Thirty-five weeks-old male Sprague-Dawley rats were divided into control and IP groups. The IP group was further subdivided into 3 groups based on the number of cycles of IP. For IP, left commom iliac artery was occluded 3, 6 and 10 cycles for 5 min of ischemia alternating with 5 min of reperfusion. The rat were sacrificed at 0, 3, 6, 24 and 72 hours of IP and the heart was removed. The expression of iNOS, eNOS, Akt and p-Akt in the rat myocardium was examined by immunohistochemical staining and Western blot analysis. The expression of iNOS was increased by IP and was higher in 10IP groups than 3IP and 6IP group. The expression of eNOS was increased or decreased by IP and was showed no difference with increasing episode of IP. The expression of Akt was decreased by IP at 24 and 72 hours after reperfusion, and showed no differences with increasing episode of IP. The expression of p-Akt was increased by IP and showed no difference with increasing episode of IP. These results suggest that hind limb ischemic preconditioning provides cardiac protection through up-regulation of eNOS and phosphorylation of Akt, however excessive episodes of remote preconditioning may induce the myocardial ischemic injury through overexpression of iNOS.
Animals ; Blotting, Western ; Extremities ; Heart ; Humans ; Iliac Artery ; Ischemia ; Ischemic Preconditioning ; Male ; Myocardium ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury ; Up-Regulation