Publications by authors named "Masahiro Fujita"

206 Publications

Comparison of clinical and biomechanical outcomes between the kinematic and mechanical alignment methods in total knee arthroplasty: Protocol for a multicenter randomized controlled trial.

Contemp Clin Trials Commun 2021 Jun 15;22:100775. Epub 2021 Apr 15.

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, 650-0017 Japan.

Introduction: The concept of anatomic restoration has garnered considerable interest in the form of kinematically aligned total knee arthroplasty (KA-TKA). KA-TKAs have been reported to reproduce natural alignment and kinematics. However, few randomized controlled trials (RCTs) have compared the biomechanical outcomes and the long-term clinical outcomes of KA-TKA with those of mechanically aligned TKA (MA-TKA). We aim to investigate the long-term clinical and biomechanical effects of KA-TKA and to determine whether KA-TKA or MA-TKA is more appropriate for primary TKA.

Methods: This trial will compare clinical and biomechanical outcomes of KA-TKA to those of MA-TKA. Two hundred patients will be enrolled in the RCT and randomized into KA-TKA or MA-TKA groups. Both the groups will be evaluated 1 week before the operation, on the day of the operation, 6 months after the operation, and 1, 5, and 10 years after the operation. The primary outcome is the difference between preoperative and 1-year postoperative functional activity scores of the 2011 Knee Society Score (2011 KSS) in both groups as well as the differences between the scores of both groups. The secondary outcomes will include differences in symptom, satisfaction, and expectation scores of the 2011 KSS, intraoperative kinematics evaluation, postoperative clinical outcomes and complications, pre- and postoperative gait analyses and radiograph evaluations between both KA-TKA and MA-TKA.
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http://dx.doi.org/10.1016/j.conctc.2021.100775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085889PMC
June 2021

In vitro and pilot in vivo imaging of 18 kDa translocator protein (TSPO) in inflammatory vascular disease.

EJNMMI Res 2021 May 5;11(1):45. Epub 2021 May 5.

Nuclear Medicine Department, University Hospital of Bordeaux, 33076, Bordeaux, France.

Background: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [C]-PBR28 and [F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [C]-PBR28.

Results: All in vitro sections showed specific binding of [F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [C]-PBR28 or [F]-PBR06 was negative in all participants.

Conclusion: Despite good uptake on surgical samples in vitro, [C]-PBR28 and [F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease.

Trial Registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov .
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http://dx.doi.org/10.1186/s13550-021-00786-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099943PMC
May 2021

External rotation of the tibial component should be avoided in lateral unicompartmental knee arthroplasty.

Knee 2021 Apr 16;30:70-77. Epub 2021 Apr 16.

Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Background: Lateral unicompartmental knee arthroplasty (UKA) leads to good clinical outcomes for isolated lateral osteoarthritis. However, the impact of the tibial component position on postoperative outcomes in lateral UKA is yet to be determined.

Purpose: This study investigated the influence of tibial component malposition on clinical outcomes in lateral UKA.

Materials: This was a retrospective study of 50 knees (mean age 73.5 years) who underwent lateral UKA between September 2013 and January 2019. The Oxford Knee Score (OKS), Knee Society Score - Knee (KSSK), and Knee Society Score - Function (KSSF) were evaluated. The coronal alignment, posterior slope of tibial component, tibial component rotation relative to Akagi's line (angle α), and femoral anteroposterior (AP) axis (angle β) were measured postoperatively. The average follow up period was 2.3 (range, 1-4.9) years.

Results: Clinical scores were significantly improved after lateral UKA. The mean coronal alignment was 0.9° ± 3.2° varus (range, 9.1° varus to 5.5° valgus), the mean posterior slope was 6.8° ± 3.8° (range, 0.8° to 14.8°). The mean α and β angles, were 4.1° ± 5.8° (range, -9.7° to 16.5°) and 6.7° ± 7.1° (range, -7.0° to 20.5°) external rotation. The angle α had significant negative correlations with postoperative OKS (r = -0.36), KSSK (r = -0.28), and KSSF (r = -0.39), and angle β had significant negative correlations with postoperative OKS (r = -0.34) and KSSK (r = -0.46).

Conclusion: Excessive external rotation of the tibial component could negatively influence the postoperative outcomes of lateral UKA.
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http://dx.doi.org/10.1016/j.knee.2021.03.016DOI Listing
April 2021

Comparison of plantar pressure distribution during walking and lower limb alignment between modified kinematically and mechanically aligned total knee arthroplasty.

J Biomech 2021 May 13;120:110379. Epub 2021 Mar 13.

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Electronic address:

Lower extremity alignment is very important after total knee arthroplasty (TKA). This study aimed to compare the plantar pressure distribution while walking and the overall limb alignment, including the hindfoot, between kinematically (KA) and mechanically aligned (MA) TKA. The plantar pressure distribution was investigated using a pressure plate during walking and one-leg standing among four groups: patients one year after KA-TKA (KA group; n = 25), patients one year after MA-TKA (MA group, n = 25), patients with osteoarthritis (OA) undergoing non-surgical care (OA group, n = 25), and healthy controls (Healthy group; n = 25). Conventional and true mechanical axes (the line from the femoral head to the lowest point of the calcaneus) were evaluated on unipedal standing long-leg radiographs in the KA, MA, and OA groups. Results were compared using analysis of variance. The OA group showed a lateral loading pattern in the mid- and rearfoot, while the MA group showed a medial rearfoot loading pattern during walking. On the contrary, the KA and Healthy groups showed an almost equal pressure distribution between the medial and lateral rearfoot. Moreover, although both mechanical axes in the KA group passed through the knee more medially, a more neutral alignment was achieved in the true mechanical axis compared to that in the MA group. KA-TKA results in more neutral weight-bearing through the true mechanical axis and allows patients to walk while maintaining medial and lateral rearfoot pressure more evenly than MA-TKA.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110379DOI Listing
May 2021

Neuroinflammation is highest in areas of disease progression in semantic dementia.

Brain 2021 Apr 6. Epub 2021 Apr 6.

Nantz National Alzheimer Center, Stanley H. Appel Department of Neurology, Houston Methodist Research Institute, Weill Cornell Medicine, Houston, TX, USA.

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 pathologic process in semantic variant primary progressive aphasia, should be further studied as a possible therapeutic target to slow disease progression.
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http://dx.doi.org/10.1093/brain/awab057DOI Listing
April 2021

Cryopreserved human adipose-derived stromal vascular fraction maintains fracture healing potential via angiogenesis and osteogenesis in an immunodeficient rat model.

Stem Cell Res Ther 2021 Feb 4;12(1):110. Epub 2021 Feb 4.

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-chou, 650-0017, Kobe, Japan.

Background: Novel therapeutic strategies for the healing of nonunion, which has serious effects on the quality of life of patients, are needed. We evaluated the therapeutic effect of local transplantation of human stromal vascular fraction (SVF) cells on fracture healing in a rat non-healing fracture model and compared the effects between freshly isolated (F) and cryopreserved (C)-SVFs.

Methods: Non-healing fracture model was induced in the femur of female immunodeficient rats (F344/N Jcl rnu/rnu) with cauterizing periosteum. Immediately after the creation of non-healing fracture, rats received local transplantation of F and C-SVFs suspended in phosphate-buffered saline (PBS) or the same volume of PBS without cells using the same scaffold as a control group. During 8 weeks post-surgery, radiologic, histological, immunohistochemical, and biomechanical analyses were performed to evaluate fracture healing. The comparison of radiological results was performed with a chi-square test, and the multiple comparisons of immunohistochemical, histological, and biomechanical results among groups were made using a one-way analysis of variance. A probability value of 0.05 was considered to denote statistical significance.

Results: At week 8, in 60% of animals receiving F-SVF cells and in 50% of animals receiving C-SVF cells, the fracture radiologically healed with bone union whereas nonunion was observed in the control group. The healing potential was also confirmed by histological and biomechanical assessments. One of the mechanisms underlying healing involving intrinsic angiogenesis/osteogenesis was enhanced in F- and C-SVF groups compared with that in the control group. Human cell-derived vasculogenesis/osteogenesis, which was also confirmed in an in vitro differentiation assay, was also enhanced in the F- and C-SVF groups compared with that in the control groups and could be another mechanism for healing.

Conclusions: SVF cells can enhance bone healing and cryopreserved cells have almost equal potential as fresh cells. SVF cells can be used for improving nonunion bone fracture healing as an alternative to other mesenchymal stem cells and the effect of SVF cells can be maintained under cryopreservation.
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http://dx.doi.org/10.1186/s13287-021-02182-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863470PMC
February 2021

Electrochemical Impedimetric Study of Non-Watson-Crick Base Pairs of DNA.

Anal Sci 2021 May 22;37(5):765-771. Epub 2021 Jan 22.

Bioengineering Laboratory, RIKEN Cluster for Pioneering Research.

Electrochemical impedance spectroscopy (EIS) was used to detect non-Watson-Crick base pairs of DNA. Thiol-modified DNA as a probe and mercaptohexanol (MCH) were co-immobilized to form a DNA/MCH mixed self-assembled monolayer on a gold electrode surface and then hybridized with complementary DNAs. The DNA layers were measured by the EIS method and interpreted by equivalent circuits. Every terminal base mismatch of the DNA duplex brought about an increase in the charge-transfer resistance (R), unlike the case with a fully matched DNA duplex. The value of R was highly sensitive to the number of base mismatches for both unpaired and overhang DNA at the terminal. For internal base mismatches, however, no significant increase in R was observed. These experimental results proved that the charge transfer of redox molecules to the electrode surface is largely hindered by an end fraying motion due to base unpairing and dangling overhang. EIS was able to detect these steric properties of DNA strands. Furthermore, an electrode modified with G-quadruplex (G4) DNA demonstrated the influences of bulkiness and loop structure on the accessibility of the redox probe to the electrode.
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http://dx.doi.org/10.2116/analsci.20SCP21DOI Listing
May 2021

[Laparoscopic Local Resection for Duodenal Gastrointestinal Stromal Tumor Located in the Third Portion Using Kocher's Maneuver-A Case Report].

Gan To Kagaku Ryoho 2020 Dec;47(13):2144-2146

Dept. of Surgery, Fujita Health University.

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.
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December 2020

[Vacuolar myelopathy after allogeneic bone marrow transplantation in a patient with acute lymphoblastic leukemia].

Rinsho Ketsueki 2020 ;61(11):1625-1627

Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital.

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.
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http://dx.doi.org/10.11406/rinketsu.61.1625DOI Listing
February 2021

Preoperative Condition of the Patellofemoral Joint Does Not Negatively Impact Surgical Outcomes of Lateral Unicompartmental Knee Arthroplasty in the Short Term.

J Knee Surg 2020 Oct 27. Epub 2020 Oct 27.

Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Chuo-Ku, Kobe, Hyogo, Japan.

The relationship between patellofemoral joint (PFJ) degeneration and clinical outcomes following lateral unicompartmental knee arthroplasty (UKA) has not been well described thus far. This study aimed to investigate the relationship between the preoperative PFJ condition and postoperative outcomes and the changes in lower-limb and PFJ alignment after lateral UKA. This was a retrospective study including 54 patients (mean age 72.9 years) who underwent lateral UKA for isolated lateral knee osteoarthritis at our institution between March 2013 and January 2019. The Oxford Knee Score (OKS), the Knee Society Score-Knee (KSSK), and Knee Society Score-Function (KSSF), the degree of degeneration, tilting angle and lateral shift of the PFJ, and the hip-knee-ankle angle (HKA) were evaluated pre- and postoperatively. The average follow-up period was 2.8 (range 1-6.1) years. There was a significant improvement in the OKS, KSSK, and KSSF after lateral UKA. Preoperative degeneration of the PFJ did not correlate with the recovery of clinical scores. The degeneration, tilting angle, and lateral shift of the PFJ did not significantly progress following lateral UKA. The HKA was improved after lateral UKA, and there was no correlation between the HKA change and PFJ condition. Postoperative severe valgus knee alignment was associated with a greater tilting angle. Preoperative degeneration of the PFJ did not have a negative impact on postoperative outcomes, and no short-term changes in the degeneration, tilting angle, and lateral shift of the PFJ were observed. Correction of knee-joint alignment did not have a negative impact on the condition of the PFJ.
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http://dx.doi.org/10.1055/s-0040-1718606DOI Listing
October 2020

[Dose Verification for Respiratory-gated VMAT-SBRT Using Real-time Tumor Tracking System].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(7):674-688

Department of Radiology, Kakogawa Central City Hospital.

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.
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http://dx.doi.org/10.6009/jjrt.2020_JJRT_76.7.674DOI Listing
September 2020

Meningitis and bacteremia by nonhemolytic Group B Streptococcus strain: A whole genome analysis.

Microbiol Immunol 2020 Sep 21;64(9):630-634. Epub 2020 Jul 21.

Gunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi, Gunma, Japan.

Group B streptococcus (GBS) is a leading cause of neonatal infections. Most isolates are β-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.
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http://dx.doi.org/10.1111/1348-0421.12826DOI Listing
September 2020

First-in-human evaluation of [C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain.

Eur J Nucl Med Mol Imaging 2020 12 12;47(13):3143-3151. Epub 2020 May 12.

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA.

Purpose: This study assessed whether the newly developed PET radioligand [C]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 (V) were assessed. Correlation analyses were conducted between brain regional V and COX-1 transcript levels provided in the Allen Human Brain Atlas.

Results: In the brain, [C]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. V values showed excellent test-retest variability (range 6.0-8.5%) and good reliability (intraclass correlation coefficient range 0.74-0.87). V 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 V. Significant correlation was observed between V and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [C]PS13 binding reflects actual COX-1 density in the human brain.

Conclusions: These results from the first-in-human evaluation of the ability of [C]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.
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http://dx.doi.org/10.1007/s00259-020-04855-2DOI Listing
December 2020

PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study.

J Neuroinflammation 2020 May 2;17(1):140. Epub 2020 May 2.

National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.

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 [C]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 [C]PS13.

Results: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BP) of [C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [C]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 BP (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 [C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [C]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 [C]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.
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http://dx.doi.org/10.1186/s12974-020-01804-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195739PMC
May 2020

PET Imaging of Phosphodiesterase-4 Identifies Affected Dysplastic Bone in McCune-Albright Syndrome, a Genetic Mosaic Disorder.

J Nucl Med 2020 11 13;61(11):1672-1677. Epub 2020 Apr 13.

Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland; and.

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the gene, which encodes the 3',5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the mutation during embryogenesis, the tissues involved, and the role of Gα in the affected tissues. The Gα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS but not in humans with fibrous dysplasia. PET imaging of PDE4 with C-()-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. C-()-rolipram whole-body and brain PET scans were performed on 6 individuals with MAS (3 for brain scans and 6 for whole-body scans) and 9 healthy controls (7 for brain scans and 6 for whole-body scans). C-()-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in C-()-rolipram uptake was noted between participants with MAS and healthy controls. This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected-a finding that could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with C-()-rolipram to indirectly measure increased cAMP pathway activation in human disease.
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http://dx.doi.org/10.2967/jnumed.120.241976DOI Listing
November 2020

Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model.

J Orthop Res 2020 10 15;38(10):2157-2169. Epub 2020 Apr 15.

Department of Orthopaedic Surgery, Kobe University School of Medicine, Kobe, Japan.

Eicosapentanoic acid (EPA) is an antioxidant and omega-3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of ~3 weeks. Therefore, this study aimed to clarify the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten-week-old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 µL corn oil, EPA injection alone (EPA-I): DMM + 2 µL corn oil + 125 μg/μL EPA, Gel: DMM + gelatin hydrogels, and EPA-G: DMM + 125 μg/μL EPA-incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix-metalloproteinases-3 (MMP-3), MMP-13, interleukin-1β (IL-1β), p-IKK α/β, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA-G than in EPA-I. MMP-3-, MMP-13-, IL-1β-, and p-IKK α/β-positive cell ratio was significantly lower in EPA-G than in EPA-I. However, CD86- and CD163-positive cell ratio was not significantly different between EPA-I and EPA-G. The average-sum F4/80 score of macrophage in EPA-G was significantly lower than that in EPA-I. EPA-incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra-articular administration of controlled-release EPA can be a new therapeutic approach for treating OA.
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http://dx.doi.org/10.1002/jor.24688DOI Listing
October 2020

Sciatic Nerve Palsy following Curved Periacetabular Osteotomy.

Case Rep Orthop 2020 19;2020:8569285. Epub 2020 Mar 19.

Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-Cho, Chuo-Ku, Kobe, Hyogo 650-0017, Japan.

Curved periacetabular osteotomy (CPO) is used for the treatment of dysplastic hips. Previous studies have reported satisfying outcomes and low rate of severe complications associated with this procedure; however, no case of postoperative sciatic nerve palsy has been reported. In this study, we describe a case of postoperative sciatic nerve palsy following CPO due to nerve strangulation by scar tissue without direct injury. A female patient had severe buttock pain and posterior leg numbness after she underwent left-side CPO. Postoperative magnetic resonance imaging showed that the sciatic nerve was strangulated by the surrounding soft tissue. There was no bone fragment, active infection, bone necrosis, tumor, or spine disease. Therefore, we diagnosed nerve palsy by soft tissue strangulation, and revision surgery was indicated. During revision surgery, the sciatic nerve was observed to be strangulated by the scarring soft tissue, and the nerve had no mobility. After detachment, the pain and numbness disappeared. Direct injury of the sciatic nerve should not be caused by CPO; however, there is a possibility of postoperative sciatic nerve palsy due to the scarring soft tissue. Early diagnosis and appropriate treatment are important for optimal postoperative clinical outcomes.
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http://dx.doi.org/10.1155/2020/8569285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106866PMC
March 2020

Author Correction: Concyclic CH-π arrays for single-axis rotations of a bowl in a tube.

Nat Commun 2020 Mar 31;11(1):1699. Epub 2020 Mar 31.

Department of Chemistry, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-15286-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109097PMC
March 2020

Discovery, Radiolabeling, and Evaluation of Subtype-Selective Inhibitors for Positron Emission Tomography Imaging of Brain Phosphodiesterase-4D.

ACS Chem Neurosci 2020 05 8;11(9):1311-1323. Epub 2020 Apr 8.

National Institute of Mental Health, Bethesda, Maryland 20892-9663, United States.

We aimed to develop radioligands for PET imaging of brain phosphodiesterase subtype 4D (PDE4D), a potential target for developing cognition enhancing or antidepressive drugs. Exploration of several chemical series gave four leads with high PDE4D inhibitory potency and selectivity, optimal lipophilicity, and good brain uptake. These leads featured alkoxypyridinyl cores. They were successfully labeled with carbon-11 ( = 20.4 min) for evaluation with PET in monkey. Whereas two of these radioligands did not provide PDE4D-specific signal in monkey brain, two others, [C]T1660 and [C]T1650, provided sizable specific signal, as judged by pharmacological challenge using rolipram or a selective PDE4D inhibitor (BPN14770) and subsequent biomathematical analysis. Specific binding was highest in prefrontal cortex, temporal cortex, and hippocampus, regions that are important for cognitive function. [C]T1650 was progressed to evaluation in humans with PET, but the output measure of brain enzyme density () increased with scan duration. This instability over time suggests that radiometabolite(s) were accumulating in the brain. BPN14770 blocked PDE4D uptake in human brain after a single dose, but the percentage occupancy was difficult to estimate because of the unreliability of measuring . Overall, these results show that imaging of PDE4D in primate brain is feasible but that further radioligand refinement is needed, most likely to avoid problematic radiometabolites.
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http://dx.doi.org/10.1021/acschemneuro.0c00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444660PMC
May 2020

Evolution and Diversity of the Wild Rice Oryza officinalis Complex, across Continents, Genome Types, and Ploidy Levels.

Genome Biol Evol 2020 04;12(4):413-428

National Institute of Genetics, Mishima, Japan.

The Oryza officinalis complex is the largest species group in Oryza, with more than nine species from four continents, and is a tertiary gene pool that can be exploited in breeding programs for the improvement of cultivated rice. Most diploid and tetraploid members of this group have a C genome. Using a new reference C genome for the diploid species O. officinalis, and draft genomes for two other C genome diploid species Oryza eichingeri and Oryza rhizomatis, we examine the influence of transposable elements on genome structure and provide a detailed phylogeny and evolutionary history of the Oryza C genomes. The O. officinalis genome is 1.6 times larger than the A genome of cultivated Oryza sativa, mostly due to proliferation of Gypsy type long-terminal repeat transposable elements, but overall syntenic relationships are maintained with other Oryza genomes (A, B, and F). Draft genome assemblies of the two other C genome diploid species, Oryza eichingeri and Oryza rhizomatis, and short-read resequencing of a series of other C genome species and accessions reveal that after the divergence of the C genome progenitor, there was still a substantial degree of variation within the C genome species through proliferation and loss of both DNA and long-terminal repeat transposable elements. We provide a detailed phylogeny and evolutionary history of the Oryza C genomes and a genomic resource for the exploitation of the Oryza tertiary gene pool.
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http://dx.doi.org/10.1093/gbe/evaa037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531200PMC
April 2020

Second-look arthroscopic findings of cartilage and meniscus repair after injection of adipose-derived regenerative cells in knee osteoarthrits: Report of two cases.

Regen Ther 2019 Dec 24;11:212-216. Epub 2019 Aug 24.

Department of Orthopaedic Surgery and Joint Surgery Centre, Takatsuki General Hospital, 1-3-13, Kosobe-Cho, Takatsuki City, Osaka 561-1115, Japan.

Background: The purpose of this study was to use second-look arthroscopic findings and clinical assessment to determine outcome in two cases of knee osteoarthritis treated by intra-articular knee injection of adipose-derived regenerative cells (ADRCs).

Case Presentation: This study involved two patients who received ADRC therapy for knee osteoarthritis and completed the six-month post-treatment follow-up period. For each treatment, 130 mL of subcutaneous adipose tissue was harvested using tumescent liposuction technique and manual aspiration of tissue from the thigh using a suction cannula under local anesthesia in the operating room. The adipose tissue harvested was processed using the Celution® Centrifuge in a dedicated cell processing room. The ADRCs were injected into the articular cavity of both knees for one patient and into a single affected knee in the second patient (three joints). Pain and knee function were assessed using a Visual Analogue Scale (VAS) and the Knee Outcome in Osteoarthritis Score (KOOS) respectively. The cartilage defect was assessed by direct visualization (arthroscopy). No serious adverse events were reported throughout follow-up. Pain and knee function were significantly improved from baseline in all treated knees at one, three and six months after ADRCs. At six-months after ADRCs treatment, the second-look arthroscopy showed that almost all the cartilage defect areas were covered by regenerated cartilage, some cartilage fibrillation area was reduced, and meniscus tear areas were repaired.

Conclusions: Cartilage and meniscus repair were observed six-months after ADRCs therapy under second-look arthroscopy. It was shown that a single administration of ADRCs might be effective as a treatment for knee osteoarthritis.
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http://dx.doi.org/10.1016/j.reth.2019.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715888PMC
December 2019

Successful hematopoietic stem-cell mobilization with plerixafor plus granulocyte-colony stimulating factor in multiple myeloma patients treated with pomalidomide.

Int J Hematol 2019 Jul 13;110(1):115-118. Epub 2019 Apr 13.

Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.

Autologous stem-cell transplantation is an effective procedure for the treatment of multiple myeloma, and involves the collection of hematopoietic stem cells (HSCs). However, in some patients, HSCs in the bone marrow fail to mobilize. Pomalidomide upregulates CXCR4 in hematopoietic stem cells, in a manner similar to that of lenalidomide, and is, thus, likely to have a negative impact on hematopoietic stem-cell mobilization in multiple myeloma patients. Here, we report the two cases in which hematopoietic stem cells were mobilized using plerixafor plus granulocyte-colony stimulating factor after exposure to lenalidomide and pomalidomide. Use of plerixafor with a sufficient washout period may lead to successful mobilization following pomalidomide use, although further study of this potential use is needed.
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http://dx.doi.org/10.1007/s12185-019-02622-0DOI Listing
July 2019

Innovative technique of minimally invasive closed reduction for impacted femoral neck fractures (MICRIF).

J Orthop Surg (Hong Kong) 2019 Jan-Apr;27(1):2309499019832418

2 Department of Orthopedics, Konan Hospital, Kobe, Japan.

The moment arm of gluteus medius proportionated to distance from femoral head tends to be decreased postoperatively in valgus-impacted femoral neck fractures treated by in situ internal fixation. The aim of this article is to introduce a new gentle technique to correct the deformity. The innovative technique of Minimally Invasive Closed Reduction for Impacted Femoral neck fractures (MICRIF) mainly focused to disimpact valgus neck fractures into anatomical position. Patients were positioned on the fracture table to fix the hip joint in abduction and internal rotation. A 2.4-mm diameter Kirschner wire was inserted a few centimetres outside the iliac crest piercing the acetabular beak to enter the femoral head, followed by repositioning of the lower extremity from abduction into neutral. This method provides satisfactory anatomical reduction. Thereafter, a surgical implant was applied to osteosynthesize the reduced fracture. This simple technique effectively provides anatomical reduction in valgus impacted femoral neck fracture.
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http://dx.doi.org/10.1177/2309499019832418DOI Listing
April 2020

Potential of Oryza officinalis to augment the cold tolerance genetic mechanisms of Oryza sativa by network complementation.

Sci Rep 2018 11 5;8(1):16346. Epub 2018 Nov 5.

Department of Plant and Soil Science, 219 Experimental Sciences Building, Texas Tech University, Lubbock, TX, 79409, USA.

Oryza officinalis is an accessible alien donor for genetic improvement of rice. Comparison across a representative panel of Oryza species showed that the wild O. officinalis and cultivated O. sativa ssp. japonica have similar cold tolerance potentials. The possibility that either distinct or similar genetic mechanisms are involved in the low temperature responses of each species was addressed by comparing their transcriptional networks. General similarities were supported by shared transcriptomic signatures indicative of equivalent metabolic, hormonal, and defense status. However, O. officinalis has maintained an elaborate cold-responsive brassinosteroid-regulated BES1-network that appeared to have been fragmented in O. sativa. BES1-network is potentially important for integrating growth-related responses with physiological adjustments and defenses through the protection of photosynthetic machinery and maintenance of stomatal aperture, oxidative defenses, and osmotic adjustment. Equivalent physiological processes are functional in O. sativa but their genetic mechanisms are under the direct control of ABA-dependent, DREB-dependent and/or oxidative-mediated networks uncoupled to BES1. While O. officinalis and O. sativa represent long periods of speciation and domestication, their comparable cold tolerance potentials involve equivalent physiological processes but distinct genetic networks. BES1-network represents a novel attribute of O. officinalis with potential applications in diversifying or complementing other mechanisms in the cultivated germplasm.
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http://dx.doi.org/10.1038/s41598-018-34608-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218501PMC
November 2018

Imaging of renal cell carcinoma in patients with acquired cystic disease of the kidney: comparison C-choline and FDG PET/CT with dynamic contrast-enhanced CT.

Jpn J Radiol 2019 Feb 30;37(2):165-177. Epub 2018 Oct 30.

Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Purpose: To evaluate renal cell carcinoma (RCC) findings in acquired cystic disease of the kidney (ACDK) shown by C-choline and FDG PET/CT, and contrast-enhanced CT.

Materials And Methods: Six ACDK patients with 7 RCCs underwent C-choline and FDG PET/CT, and contrast-enhanced CT before nephrectomy. Findings obtained with 3 imagings were evaluated and sensitivity detecting RCC was compared using 3-point grading scale (negative, equivocal, positive). The equivocal scale used for SUVmax ranged from 2.0 to 3.0 for PET/CT and a peak enhancement value ranging from 20 to 30 HU was used for CT.

Result: The histopathologic subtypes of 7 RCCs were clear-cell (n = 4) and ACD-associated RCC (n = 3). The negative/equivocal/positive grading results were 0/0/7 for C-choline-PET/CT, 0/3/4 for FDG-PET/CT, and 2/2/3 for CT. Three equivocal cases by FDG-PET/CT were 2 clear-cell RCCs and 1 ACD-associated RCC. CT of 3 ACD-associated RCCs showed negativity for 2 and equivocality for 1. Sensitivity defining equivocal interpretation as negative for C-choline-PET/CT, FDG-PET/CT, and CT was 100% (7/7), 57.1% (4/7), and 42.9% (3/7).

Conclusion: C-choline-PET/CT was more sensitive to detect RCC in ACDK as compared to FDG-PET/CT and contrast-enhanced CT in our series. FDG-PET/CT may be limited for detecting clear-cell RCC, while CT may have difficulty with detection of ACD-associated RCC.
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http://dx.doi.org/10.1007/s11604-018-0789-1DOI Listing
February 2019

Concyclic CH-π arrays for single-axis rotations of a bowl in a tube.

Nat Commun 2018 09 17;9(1):3779. Epub 2018 Sep 17.

Department of Chemistry, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.

The hydrogen bond is undoubtedly one of the most important non-covalent interactions. Among the several types of the hydrogen bonds, the CH-π interaction is a relatively new notion that is being recognised in chemistry and biology. Although the CH-π hydrogen bond and conventional hydrogen bonds share common features such as directionality, this weak interaction has played a secondary role in molecular recognition. In this study, we have devised a host-guest complex that is assembled solely by the CH-π hydrogen bonds. Multivalent interactions of a bowl-shaped hydrocarbon with its peripheral hydrogen atoms are made possible via CH-π hydrogen bonds by adopting a tubular hydrocarbon as a host for their enthalpy-driven complexation. Concyclic arrays of weak hydrogen bonds further allow dynamic rotational motions of the guest in the host. Solid-state analysis with crystallographic and spectroscopic methods reveal a single-axis rotation of the bowl in the tube.
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http://dx.doi.org/10.1038/s41467-018-06270-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141547PMC
September 2018

Next-generation DNA sequencing analysis of two Streptococcus suis ST28 isolates associated with human infective endocarditis and meningitis in Gunma, Japan: a case report.

Infect Dis (Lond) 2019 Jan 15;51(1):62-66. Epub 2018 Aug 15.

b Gunma Prefectural Institute of Public Health and Environmental Sciences , Maebashi-shi , Japan.

Streptococcus suis (S. suis) is an important emerging zoonotic agent. Here, we report two cases of S. suis infection in pig farmers in Gunma Prefecture, Japan. We conducted a high-resolution molecular epidemiologic analysis on the basis of whole-genome sequencing data of each isolate using next-generation sequencing (NGS). NGS analysis revealed that the two S. suis clinical isolates were belonged to serotype 2 ST28. Phylogenetic analysis showed that two isolates were closely related to S. suis strains isolated from pigs in Japan at least until 1995. Since 41 nucleotide substitutions were found between the two strains, these strains might be derived from the same genetic lineage but distinct sporadic cases. NGS analysis is a powerful diagnostic tool for analysing bacterial infections. The database is more fulfilling, and more detailed analysis will become possible in the near future. Attention should be paid to S. suis infections, especially if the patient works on a livestock farm.
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http://dx.doi.org/10.1080/23744235.2018.1490813DOI Listing
January 2019

PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects.

EJNMMI Res 2018 Jul 3;8(1):57. Epub 2018 Jul 3.

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Building 10, CRC Room 6-5340, 10 Center Drive, Bethesda, MD, 20892, USA.

Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using C-PBR28. Total distribution volume (V, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression.

Results: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen's d = 0.64, p = .038, 95% CI 0.04-1.24) and ACC (d = 0.60, p = .049, 95% CI 0.001-1.21), though these comparisons missed the corrected threshold for statistical significance (α = .025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers.

Conclusions: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.
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http://dx.doi.org/10.1186/s13550-018-0401-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029989PMC
July 2018

Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys.

J Nucl Med 2018 12 29;59(12):1907-1912. Epub 2018 Jun 29.

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.

This study assessed whether the newly developed PET radioligands C-PS13 and C-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of C-MC1 was not observed in any organ except the ovaries and possibly kidneys. The findings suggest that C-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.
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http://dx.doi.org/10.2967/jnumed.118.211144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278897PMC
December 2018

Assessment of tumor response to chemoradiotherapy and predicting prognosis in patients with head and neck squamous cell carcinoma by PERCIST.

Ann Nucl Med 2018 Aug 1;32(7):453-462. Epub 2018 Jun 1.

Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.

Purpose: To evaluate therapeutic response to chemoradiotherapy and prediction of recurrence and death in patients with head and neck squamous cell carcinoma (HNSCC) using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST).

Materials And Methods: Forty-two patients (mean 63.4, range 20-79 years) with nasopharyngeal (n = 10), oropharyngeal (n = 13), hypopharyngeal (n = 11), or laryngeal (n = 8) cancer underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and approximately 3 months (mean 95.0, range 70-119 days) after undergoing concurrent chemoradiotherapy. The effect of PERCIST regarding progression-free survival (PFS) and overall survival (OS) was examined using log-rank and Cox methods.

Results: Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease shown by PERCIST were seen in 30 (71.4%), 9 (21.4%), 3 (7.1%), and 0 patients, respectively. Fourteen (33.3%) developed recurrent disease (median follow-up 27.2, range 8.7-123.1 months) and 9 (21.4%) died (median follow-up 43.6, range 9.6-132.6 months). Furthermore, 4 (13.3%) of 30 patients with CMR developed recurrence, while 7 (77.8%) of 9 with PMR and all 3 (100%) with SMD developed recurrence. Two (6.7%) of 30 patients with CMR, 4 (44.4%) of 9 with PMR, and all 3 (100%) with SMD died. Patients who achieved CMR showed significantly longer PFS and OS as compared to those who did not (PMR and SMD) (both, p < 0.0001).

Conclusion: PERCIST is useful for evaluating therapeutic response to chemoradiotherapy and predicting recurrence and death in HNSCC patients.
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http://dx.doi.org/10.1007/s12149-018-1267-7DOI Listing
August 2018