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1.
Osteoarthritis Cartilage ; 32(1): 28-40, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37648149

ABSTRACT

OBJECTIVE: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles in mammalian cell differentiation and development. In this study, we investigated the function of KLF15 in the progression of osteoarthritis (OA). METHODS: 0Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male wild-type control (WT) mice and cartilage-specific KLF15 knockout (KO) mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining were performed. Morphological changes were measured using microcomputed tomography. Six mice from each group were analyzed (total number of mice analyzed: 60). In vitro, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blot analyses were performed. RESULTS: KLF15 KO DMM mice exhibited significant cartilage degradation compared to WT mice. According to the Osteoarthritis Research Society International cartilage OA-histopathology scoring system, the mean sum score in KLF15 KO mice was significantly higher than that in WT mice at 8 weeks after surgery. Immunohistochemistry results revealed KLF15 KO mice exhibited reduced peroxisome proliferator-activated receptor gamma (PPARγ) expression, increased pIKKα/ß, a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) 5, and Matrix metalloproteinases (MMP13) expression, and reduced Forkhead box O (FOXO1) and Light chain 3B (LC3B) expression. Inhibition of PPARγ phosphorylation accelerated the effects of interleukin (IL) 1ß-treatment in both KLF15 KO and WT chondrocytes, and activation of PPARγ expression canceled the IL1ß-induced catabolic effects. CONCLUSION: Our results indicated that the OA phenotype of KLF15 KO DMM mice was influenced by reduced PPARγ expression, including enhanced pIKKα/ß, ADAMTS5, and MMP13 expression, reduced autophagy, and increased apoptosis. KLF15 regulation may constitute a possible therapeutic strategy for the treating OA.


Subject(s)
Cartilage, Articular , Osteoarthritis , Animals , Male , Mice , Cartilage, Articular/pathology , Chondrocytes/metabolism , Disease Models, Animal , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/pharmacology , Mammals/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Mice, Knockout , Osteoarthritis/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , X-Ray Microtomography
2.
Mol Psychiatry ; 27(3): 1362-1372, 2022 03.
Article in English | MEDLINE | ID: mdl-35022529

ABSTRACT

The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.


Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Brain , Depressive Disorder, Major/genetics , Disks Large Homolog 4 Protein/genetics , Humans , Mood Disorders , RNA, Messenger
3.
Chem Rec ; 23(8): e202200287, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36782072

ABSTRACT

A zwitterion is a neutral compound that has both a cation and an anion in the same molecule. Quaternary ammonium cations are frequently used for zwitterions. Zwitterions with quaternary ammonium cations are also common in biological molecules, such as phospholipids, which are the main components of cell membranes. Chemically, they have broad applicability because they are dielectric, non-volatile, and highly polar compounds with a large dipole moment. In addition, after salt addition, ion exchange does not occur in the presence of zwitterions. Owing to these characteristics, zwitterions have been applied as novel electrolyte materials targeting high ionic conductivity. In this review, application of zwitterions and their polymers for Li-ion batteries is addressed.

4.
Langenbecks Arch Surg ; 408(1): 364, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37725176

ABSTRACT

PURPOSE: Postoperative diarrhea (PD) remains one of the significant complications. Only a few studies focused on PD after minimally invasive surgery. We aimed to investigate PD after minimally invasive gastrectomy for gastric cancer. METHODS: A total of 1476 consecutive patients with gastric cancer undergoing laparoscopic or robotic gastrectomy between 2009 and 2019 at our institution were retrospectively reviewed. PD was defined as continuous diarrhea for ≥ 2 days, positive stool culture, or positive clostridial antigen test. The incidence, causes, and related clinical factors were analyzed. RESULTS: Of the 1476 patients, the median age was 69 years. Laparoscopic and robotic approaches were performed in 1072 (72.6%) and 404 (27.4%), respectively. Postoperative complications with Clavien-Dindo classification grade of ≥ IIIa occurred in 108 (7.4%) patients. PD occurred in 89 (6.0%) patients. Of the 89 patients with PD, Clostridium difficile, enteropathogenic Escherichia coli, and methicillin-resistant Staphylococcus aureus were detected in 24 (27.0%), 16 (33.3%), and 7 (14.6%) patients, respectively. Multivariate analysis revealed that age ≥ 75 years (OR 1.62, 95% CI [1.02-2.60], p = 0.042) and postoperative complications (OR 6.04, 95% CI [3.54-10.32], p < 0.001) were independent risk factors for PD. In patients without complications, TG (OR 1.88) and age of ≥ 75 years(OR 1.71) were determined as independent risk factors. CONCLUSION: The incidence of PD following minimally invasive gastrectomy for gastric cancer was 6.0%. Older age and TG were obvious risk factors in such a surgery, with the latter being a significant risk even in the absence of complications.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Stomach Neoplasms , Humans , Aged , Stomach Neoplasms/surgery , Clinical Relevance , Incidence , Retrospective Studies , Diarrhea , Gastrectomy/adverse effects , Postoperative Complications/epidemiology
5.
Arch Orthop Trauma Surg ; 143(6): 3621-3627, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36125537

ABSTRACT

INTRODUCTION: Bone mineral density is important in detecting implant loosening after total hip arthroplasty. The Polarstem can improve postoperative bone mineral density changes, but no information exists on the influence of postoperative stem alignment. Therefore, we investigated the relationship between bone mineral density change and stem alignment following total hip arthroplasty using a cementless Polarstem. MATERIALS AND METHODS: This retrospective study included 42 patients (50 hips) who underwent total hip arthroplasty using a cementless Polarstem. Bone mineral density around the stem was measured according to the established Gruen zone classification using dual-energy X-ray absorptiometry. Measurements were performed 2 months postoperatively (baseline) and 6, 12, 18, and 24 months postoperatively. Bone mineral density changes at each follow-up were calculated as (bone mineral density at follow-up/at 2 weeks) × 100 (%). The stem varus, anterior tilt, and anteversion angles were measured using computed tomography. The correlation coefficient between bone mineral density changes and stem alignment were investigated. RESULTS: The 24-month postoperative bone mineral density increased in zones 4 (106.0%) and 5 (107.3%) and decreased in zones 1 (89.6%) and 7 (90.6%). The mean stem varus angle, anterior tilt, and anteversion error were - 0.3° ± 1.8°, 1.9° ± 2.2°, and 6.8° ± 5.4°. Negative correlations were observed between the stem varus angle and 24-month postoperative bone mineral density change in zone 1 (r = - 0.34, p = 0.02), and the stem anteversion error and 24-month postoperative bone mineral density change in zone 1 (r = - 0.48, p < 0.01) and zone 7 (r = - 0.31, p = 0.03). CONCLUSIONS: The cementless Polarstem may have a positive effect on postoperative bone mineral density in the distal femur. However, varus malalignment and anteversion error of the stem could have a negative influence on the bone mineral density changes in the proximal femur.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Bone Density , Retrospective Studies , Absorptiometry, Photon , Femur/diagnostic imaging , Femur/surgery , Prosthesis Design
6.
Arch Orthop Trauma Surg ; 143(12): 7229-7235, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37479832

ABSTRACT

INTRODUCTION: The aim of this study is to compare the accuracy of acetabular cup positioning between the accelerometer-based navigation system and the augmented reality-based navigation system during THA in the supine position. MATERIALS AND METHODS: This retrospective study included 66 patients (70 hips) who underwent THA using two types of portable navigation system, Hip Align or AR-Hip, in the spine position. The absolute difference between the intraoperative navigation record and postoperative measurement using computed tomography data was evaluated. Preoperative clinical factors that decreased the accuracy of cup positioning by ≥ 3° were analyzed via multiple logistic regression analyses. RESULTS: The average absolute error of inclination was 2.8 ± 2.6° in Hip Align and 2.7 ± 1.8° in AR-Hip, and absolute anteversion error was 2.5 ± 2.0° in Hip Align and 2.6 ± 2.2° in AR-Hip, and there was no significantly different between the two navigation systems. There was a significant association between the absolute measurement error (≥ 3°) of cup inclination and patients' BMI in the Hip Align group [odds ratio (OR) 1.350; 95% confidence interval (CI) 1.035-1.760; p = 0.027], but not in the AR-Hip group. CONCLUSIONS: The accuracy of the acetabular cup positioning between the Hip Align and AR-Hip showed no difference during THA in the spine position. The high BMI could have negative influence on the accuracy of cup positioning in THA using Hip Align, thus AR-Hip could be designable for obesity patients.


Subject(s)
Arthroplasty, Replacement, Hip , Augmented Reality , Hip Prosthesis , Surgery, Computer-Assisted , Humans , Arthroplasty, Replacement, Hip/methods , Supine Position , Retrospective Studies , Acetabulum/surgery , Surgery, Computer-Assisted/methods
7.
J Cell Physiol ; 237(9): 3627-3639, 2022 09.
Article in English | MEDLINE | ID: mdl-35766589

ABSTRACT

The adipose-derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose-derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases-3 (TIMP-3), and matrix metalloproteinases-13 (MMP-13) messenger RNA (mRNA) expression levels were evaluated using reverse-transcription polymerase chain reaction, and the transforming growth factor-ß (TGF-ß) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre-treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP-3 expression were higher in the SVF group than in the ADSC group and controls, while MMP-13 expression was the highest in the ADSC group and the lowest in the controls. TGF-ß levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti-inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti-inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF-ß-induced Smad2/3 phosphorylation.


Subject(s)
Chondrocytes , Tissue Inhibitor of Metalloproteinase-3 , Chondrocytes/metabolism , Collagen/metabolism , Humans , Macrophages/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction , Smad2 Protein/metabolism , Stromal Vascular Fraction , Tissue Inhibitor of Metalloproteinase-3/genetics , Transforming Growth Factor beta/metabolism
8.
Langmuir ; 38(16): 4870-4878, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35422119

ABSTRACT

G-quadruplex (G4) DNA-functionalized gold nanoparticles (AuNPs) were fabricated for a new sensing platform for a biomolecule, thrombin. Thrombin-binding aptamer (TBA), which forms a highly ordered G4 structure, was immobilized on AuNPs. The particles were induced to aggregate by binding of thrombin to G4 DNA. Thrombin was thus detected by the color change of the colloidal system from red to purple-blue. The aggregation was not due to the bridging between the particles through thrombin but to the reduction in steric repulsion attributable to the mobility and flexibility of G4 DNA. The change in the colloidal stability was quick and the bathochromic peak shift varied with the concentration of thrombin. The sensor showed a high specificity to the thrombin target over major proteins in human serum. The detection sensitivity and analytical performance were successfully tuned for an on-demand sensor with a linearity of 10.0-40.0 nM. The limits of detection and of quantification were 3.6 and 10.7 nM, respectively.


Subject(s)
G-Quadruplexes , Metal Nanoparticles , DNA , Gold/chemistry , Humans , Metal Nanoparticles/chemistry , Thrombin/chemistry
9.
Clin Exp Rheumatol ; 40(11): 2060-2070, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35084317

ABSTRACT

OBJECTIVES: To investigate the cell types that undergo apoptosis in TNF-α inhibitor (TNFI)- and IL-6 inhibitor (IL-6I)-treated synovia of RA patients, and to observe and compare histological changes in them. METHODS: Synovial tissue was collected during total knee arthroplasty from 20 RA patients who were divided into three groups based on RA treatment received: conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs, control group), TNFI, or IL-6I. Tissue samples were subjected to haematoxylin and eosin staining, terminal deoxynucleotidyl transferase fluorescein-deoxyuridine triphosphate nick end labelling (TUNEL), immuno-histochemistry (IHC) and immunofluorescence staining for, respectively, histopathological assessment, apoptosis detection and IHC evaluation and scoring. RESULTS: TUNEL-positive cells were detected surrounding the discoid fibrosis unique to the TNFI group, while those in the IL-6I group were distributed widely, especially surrounding the blood vessels. IHC revealed that in TNFI-treated tissue, CD86- and CD80-positive cells were detected only in the lining and sublining layer, while CD163- and CD206-positive cells were detected more broadly; in the IL-6I-treated tissue, all four were detected widely but their levels were lower than in the control group. Immunofluorescence also revealed macrophages mainly were the apoptotic cells in the lining and sublining layers of TNFI group. TUNEL Expression levels of CD20- and CD3-positive cells were remarkably lower in the IL-6I group, compared with the control and TNFI groups. CONCLUSIONS: TNFIs and IL-6Is target different action sites and synovial cell types, resulting in histopathological features of synovium distinct from one another.


Subject(s)
Arthritis, Rheumatoid , Interleukin-6 , Synovial Membrane , Tumor Necrosis Factor Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Interleukin-6/antagonists & inhibitors , Synovial Membrane/pathology , Tumor Necrosis Factor Inhibitors/therapeutic use
10.
Brain ; 144(5): 1565-1575, 2021 06 22.
Article in English | MEDLINE | ID: mdl-33824991

ABSTRACT

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. We also tested the hypothesis that inflammation, by providing non-specific binding targets, could explain the 18F-flortaucipir signal in semantic variant primary progressive aphasia. Eight amyloid-PET-negative patients with semantic variant primary progressive aphasia underwent 11C-PBR28 and 18F-flortaucipir PET. Healthy controls underwent 11C-PBR28 PET (n = 12) or 18F-flortaucipir PET (n = 12). Inflammation in PET with 11C-PBR28 was analysed using Logan graphical analysis with a metabolite-corrected arterial input function. 18F-flortaucipir standardized uptake value ratios were calculated using the cerebellum as the reference region. Since monoamine oxidase B receptors are expressed by astrocytes in affected tissue, selegiline was administered to one patient with semantic variant primary progressive aphasia before repeating 18F-flortaucipir scanning to test whether monoamine oxidase B inhibition blocked flortaucipir binding, which it did not. While 11C-PBR28 uptake was mostly cortical, 18F-flortaucipir uptake was greatest in the white matter. The uptake of both tracers was increased in the left temporal lobe and in the right temporal pole, as well as in regions adjoining the left temporal pole such as insula and orbitofrontal cortex. However, peak uptake of 18F-flortaucipir localized to the left temporal pole, the epicentre of pathology, while the peak of inflammation 11C-PBR28 uptake localized to a more posterior, mid-temporal region and left insula and orbitofrontal cortex, in the periphery of the damage core. Neuroinflammation, greatest in the areas of progression of the pathological process in semantic variant primary progressive aphasia, should be further studied as a possible therapeutic target to slow disease progression.


Subject(s)
Aphasia, Primary Progressive/pathology , Brain/pathology , Inflammation/pathology , Aged , Aphasia, Primary Progressive/diagnostic imaging , Brain/diagnostic imaging , Disease Progression , Female , Humans , Inflammation/diagnostic imaging , Male , Middle Aged , Positron-Emission Tomography/methods
11.
Gan To Kagaku Ryoho ; 49(13): 1820-1822, 2022 Dec.
Article in Japanese | MEDLINE | ID: mdl-36733010

ABSTRACT

A 46-year-old man was referred to further treatment for a 20 mm submucosal tumor at the gastric angle found during a medical check-up. Endoscopic ultrasonography and chest abdominal contrast-enhanced CT revealed the tumor was located at the 4th(proper muscular)layer of the posterior wall of the gastric antrum and slightly enhanced. No metastasis was found. Although a biopsy failed to reveal an accurate diagnosis, GIST was clinically suspected. A robotic distal gastrectomy was planned to manage the residual gastric stricture. The intraoperative findings indicated possible passage of the remnant stomach; therefore, local resection was performed. The patient's postoperative course was uneventful, and he was discharged on postoperative day 9. A histopathological examination confirmed the diagnosis of a PAS-positive, S100-positive granular cell tumor with no nuclear atypia. These findings suggest that use of the robotic approach could help determine the stomach resection extent.


Subject(s)
Gastric Stump , Granular Cell Tumor , Robotics , Stomach Neoplasms , Humans , Male , Middle Aged , Gastrectomy , Granular Cell Tumor/diagnostic imaging , Granular Cell Tumor/surgery , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Robotic Surgical Procedures
12.
Gan To Kagaku Ryoho ; 49(13): 1862-1864, 2022 Dec.
Article in Japanese | MEDLINE | ID: mdl-36733024

ABSTRACT

A 79-year-old male presented with epigastric discomfort and appetite loss. A type 1 advanced gastric tumor was detected by upper gastrointestinal endoscopy. Contrast-enhanced CT revealed a 7 cm mass with contrast effect at the greater curvature of the lower body of the stomach. No distant metastases were found. Staging laparoscopy confirmed gastric cancer with single giant lymph node metastasis, which was resectable, although the metastatic node possibly invaded the transverse colon. We performed total gastrectomy and partial colectomy. Pathological examination revealed the tumor was pT3N1; the mass was #4sa lymph node metastasis of gastric cancer. The postoperative course was uneventful. No tumor recurrence has been found for 12 months postoperatively.


Subject(s)
Laparoscopy , Stomach Neoplasms , Male , Humans , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Lymphatic Metastasis , Neoplasm Recurrence, Local/surgery , Lymph Node Excision , Gastrectomy , Lymph Nodes/pathology
13.
Gan To Kagaku Ryoho ; 49(13): 1867-1869, 2022 Dec.
Article in Japanese | MEDLINE | ID: mdl-36733026

ABSTRACT

A 78-year-old male who had received laparoscopic total gastrectomy for upper gastric cancer 30 months ago(pT3N0, pStage ⅡB)was referred for further treatment for a 30-mm in size mass at the splenic hilum. The mass was suspected of lymph node metastasis was suspected. Two courses of SOX therapy failed to achieve the tumor response. Since there was no other metastasis, surgical treatment was indicated. Robot distal pancreatectomy with splenectomy was performed. There was no finding of peritoneal metastasis during the operation. The operative time was 384 min, the blood loss 22 mL, respectively. The postoperative course was uneventful, and he was discharged on the 12th postoperative day. The histopathological examination found that the resected mass was pancreatic metastasis of gastric cancer. Despite 3 courses of SOX therapy after the operation, the tumor recurred at the liver and paraaortic lymph nodes 2 months later. The second-line ramucirumab plus paclitaxel was started and has continued for 11 months with partial response. Although oncological benefit of surgical resection for isolated metastasis of gastric cancer, including pancreatic metastasis, was unclear, the robotic approach for such an atypical case was safe and feasible, leading to smooth initiation of postoperative systemic therapy.


Subject(s)
Pancreatic Neoplasms , Robotic Surgical Procedures , Robotics , Stomach Neoplasms , Male , Humans , Aged , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Pancreatectomy , Lymph Node Excision , Neoplasm Recurrence, Local/surgery , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Gastrectomy
14.
J Neuroinflammation ; 17(1): 140, 2020 May 02.
Article in English | MEDLINE | ID: mdl-32359360

ABSTRACT

BACKGROUND: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success. METHODS: The novel PET tracer [11C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [11C]PS13. RESULTS: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BPND) of [11C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [11C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BPND (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [11C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [11C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor. CONCLUSIONS: Taken together, these results indicate that [11C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912428. Registered April 11, 2019.


Subject(s)
Cyclooxygenase 2/analysis , Inflammation/diagnostic imaging , Positron-Emission Tomography/methods , Pyrimidines , Radiopharmaceuticals , Adult , Animals , Arthritis, Rheumatoid/diagnostic imaging , Brain/diagnostic imaging , Female , Humans , Macaca mulatta , Middle Aged
15.
Eur J Nucl Med Mol Imaging ; 47(13): 3143-3151, 2020 12.
Article in English | MEDLINE | ID: mdl-32399622

ABSTRACT

PURPOSE: This study assessed whether the newly developed PET radioligand [11C]PS13, which has shown excellent in vivo selectivity in previous animal studies, could be used to quantify constitutive levels of cyclooxygenase-1 (COX-1) in healthy human brain. METHODS: Brain test-retest scans with concurrent arterial blood samples were obtained in 10 healthy individuals. The one- and unconstrained two-tissue compartment models, as well as the Logan graphical analysis were compared, and test-retest reliability and time-stability of total distribution volume (VT) were assessed. Correlation analyses were conducted between brain regional VT and COX-1 transcript levels provided in the Allen Human Brain Atlas. RESULTS: In the brain, [11C]PS13 showed highest uptake in the hippocampus and occipital cortex. The pericentral cortex also showed relatively higher uptake compared with adjacent neocortices. The two-tissue compartment model showed the best fit in all the brain regions, and the results from the Logan graphical analysis were consistent with those from the two-tissue compartment model. VT values showed excellent test-retest variability (range 6.0-8.5%) and good reliability (intraclass correlation coefficient range 0.74-0.87). VT values also showed excellent time-stability in all brain regions, confirming that there was no radiometabolite accumulation and that shorter scans were still able to reliably measure VT. Significant correlation was observed between VT and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [11C]PS13 binding reflects actual COX-1 density in the human brain. CONCLUSIONS: These results from the first-in-human evaluation of the ability of [11C]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation. CLINICAL TRIAL REGISTRATION: NCT03324646 at https://clinicaltrials.gov/ . Registered October 30, 2017. Retrospectively registered.


Subject(s)
Brain , Positron-Emission Tomography , Animals , Brain/diagnostic imaging , Brain/metabolism , Cyclooxygenase 1/metabolism , Humans , Radiopharmaceuticals , Reproducibility of Results
16.
Microbiol Immunol ; 64(9): 630-634, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32484984

ABSTRACT

Group B streptococcus (GBS) is a leading cause of neonatal infections. Most isolates are ß-hemolytic, and their activity is considered to be pivotal for GBS pathogenicity. We report a case of a neonate with meningitis caused by nonhemolytic GBS. The patient developed meningitis 3 days after birth. Genotyping was performed and the characteristics of the strain (GCMC97051) identified by whole genome sequence using next generation sequencing. GCMC97051 possesses genetic alterations such as disruption of cylA by IS1381A insertion and a frameshift mutation in cylE, resulting in a lack of hemolysis. Thus, nonhemolytic GBS can retain the potential to cause invasive infections.


Subject(s)
Genome, Bacterial , Meningitis, Bacterial/diagnosis , Streptococcal Infections/diagnosis , Streptococcus agalactiae/genetics , Child, Preschool , Hemolysin Proteins/genetics , Humans , Male , Meningitis, Bacterial/microbiology , Phylogeny , Streptococcal Infections/microbiology , Streptococcus agalactiae/classification , Streptococcus agalactiae/isolation & purification , Virulence Factors/genetics , Whole Genome Sequencing
17.
Rinsho Ketsueki ; 61(11): 1625-1627, 2020.
Article in Japanese | MEDLINE | ID: mdl-33298658

ABSTRACT

Vacuolar myelopathy (VM) is known to be a neurological complication in patients with acquired immunodeficiency syndrome (AIDS). In autopsy-based studies, VM was reported in approximately 20-50% of patients with AIDS. It manifests in various says, mainly presenting as a painless spastic paraparesis with a sensory ataxia. We present a rare case of VM after bone marrow transplantation (BMT) in a patient without AIDS. A 50-year-old man developed weakness in the lower legs, leg muscle atrophy, and difficulty in walking 86 days after BMT. The patient died from septic shock on day 309. The autopsy revealed intralamellar vacuolation in the spinal white matter, which was compatible with VM.


Subject(s)
Graft vs Host Disease , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Spinal Cord Diseases , Bone Marrow Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Spinal Cord Diseases/etiology
18.
Gan To Kagaku Ryoho ; 47(13): 2144-2146, 2020 Dec.
Article in Japanese | MEDLINE | ID: mdl-33468888

ABSTRACT

Duodenal gastrointestinal stromal tumor(GIST)are relatively rare. Here, we report a case of a duodenal GIST located in the third portion that was successfully treated via laparoscopic local resection using the Kocher maneuver. A 49-year-old woman with a high BMI of 43.4 kg/m2 was diagnosed with a 20 mm duodenal submucosal tumor in the third portion that was suspected to be a GIST; subsequently, she underwent laparoscopic local resection. After mobilization from the first to third portion of the duodenum using the Kocher maneuver, local resection using a linear stapler was completed. The surgery time was 152 minutes, and the estimated blood loss was approximately zero. The postoperative course was uneventful, and she was discharged on the 7th postoperative day. The pathological diagnosis was ultra-low-grade GIST. This procedure can be a useful option for obese patients with good operative field of view.


Subject(s)
Digestive System Surgical Procedures , Duodenal Neoplasms , Gastrointestinal Stromal Tumors , Laparoscopy , Duodenal Neoplasms/surgery , Duodenum , Female , Gastrointestinal Stromal Tumors/surgery , Humans , Middle Aged
19.
Article in Japanese | MEDLINE | ID: mdl-32684560

ABSTRACT

Recently, the introduction of various novel technologies in clinical settings has improved the accuracy of radiation therapy. Stereotactic body radiation therapy (SBRT) involves the delivery of an accurate radiation dose to the tumor with a minimal impact on normal tissues using various measures to address changes in the tumor position due to respiratory displacement. The SyncTraX FX4 real-time tumor tracking system (Shimadzu Corporation) introduced in our hospital tracks the actual tumor location by radioscopically monitoring a metallic marker that is placed in the vicinity of the tumor. However, there have been no reports yet on respiratory-gated volumetric modulated arc therapy (VMAT)-SBRT using a real-time tumor tracking system. This study aimed to develop an irradiation procedure for respiratory-gated VMAT-SBRT using a real-time tumor tracking system and to evaluate radiation doses therein. In this study, we found that absolute doses with respiratory gating did not deviate by more than ±1.0% from those without respiratory gating. In addition, the pass rate in gamma analysis using GAFCHROMIC EBT3 was ³95% with the pass criteria in dose difference, distance to agreement, and threshold being 2%, 2 mm, and 10%, respectively. Furthermore, a trajectory log file analysis did not reveal any significant error causes. Thus, these data indicate that respiratory-gated VMAT-SBRT can be applied clinically.


Subject(s)
Neoplasms , Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
20.
Phys Chem Chem Phys ; 20(16): 10978-10991, 2018 Apr 25.
Article in English | MEDLINE | ID: mdl-29620779

ABSTRACT

A zwitterion, an ion pair where cation and anion are covalently tethered, is known to be a type of salt. These ions have not been recognised as interesting, but they are physicochemically unique and fascinating ions. In the present review, some functional zwitterions derived from ionic liquids are mentioned to emphasise the usefulness of the tethering of the component cations and anions of ionic liquids. Basic properties, advantages and disadvantages after the functional design of zwitterions, and some applications are summarised.

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