Energy spectrum measurement of scattered X-rays during IVR procedure.

With the increase of the number of interventional radiology (IVR) procedures, the occupational exposure of operators and medical staff has attracted keen attention. The energy of scattered radiation in medical clinical sites is important for estimating the biological effects of occupational exposure. Recent years have seen many reports on the dose of scattered radiation by IVR, but few on the energy spectrum. In this study, the energy spectrum of scattered X-rays was measured by using a cadmium telluride (CdTe) semiconductor detector during IVR on several neurosurgical and cardiovascular cases. The cumulated spectra in each case were compared. The spectra showed little changes among neurosurgical cases and relatively large changes among cardiovascular cases. This was assumed to be due to the change of X-ray tube voltage and tube angle was larger in cardiovascular cases. The resulting energy spectra will be essential for the assessment of detailed biological effects of occupational exposure.

Photoswitchable molecular glue for RNA: reversible photocontrol of structure and function of the ribozyme.

Single-stranded RNA folds into a variety of secondary and higher-order structures. Distributions and dynamics of multiple RNA conformations are responsible for the biological function of RNA. We here developed a photoswitchable molecular glue for RNA, which could reversibly control the association of two unpaired RNA regions in response to light stimuli. The photoswitchable molecular glue, NCTA, is an RNA-binding ligand possessing a photoisomerizable azobenzene moiety. Z-NCTA is an active ligand for the target RNA containing 5'-WGG-3'/5'-WGG-3' (W = U or A) site and stabilizes its hybridized state, while its isomer E-NCTA is not. Photoreversible isomerization of NCTA enabled control of the secondary and tertiary structure of the target RNA. The RNA-cleaving activity of hammerhead ribozyme, where appropriate RNA folding is necessary, could be reversibly regulated by photoirradiation in cells treated with NCTA, demonstrating precise photocontrol of RNA structure and function by the photoswitchable molecular glue.

Actin filaments accumulated in the nucleus remain in the vicinity of condensing chromosomes in the zebrafish early embryo.

In the cytoplasm, filamentous actin (F-actin) plays a critical role in cell regulation, including cell migration, stress fiber formation, and cytokinesis. Recent studies have shown that actin filaments that form in the nucleus are associated with diverse functions. Here, using live imaging of an F-actin-specific probe, superfolder GFP-tagged utrophin (UtrCH-sfGFP), we demonstrated the dynamics of nuclear actin in zebrafish (Danio rerio) embryos. In early zebrafish embryos up to around the high stage, UtrCH-sfGFP increasingly accumulated in nuclei during the interphase and reached a peak during the prophase. After nuclear envelope breakdown (NEBD), patches of UtrCH-sfGFP remained in the vicinity of condensing chromosomes during the prometaphase to metaphase. When zygotic transcription was inhibited by injecting α-amanitin, the nuclear accumulation of UtrCH-sfGFP was still observed at the sphere and dome stages, suggesting that zygotic transcription may induce a decrease in nuclear F-actin. The accumulation of F-actin in nuclei may contribute to proper mitotic progression of large cells with rapid cell cycles in zebrafish early embryos, by assisting in NEBD, chromosome congression, and/or spindle assembly.

Relationships among hip instability, iliofemoral ligament, and pain in patients with developmental dysplasia of the hip.

BACKGROUND: To evaluate the relationships among hip instability, pain, and morphology of the iliofemoral ligament (ILFL) in patients with developmental dysplasia of the hip (DDH) using ultrasonography (US). METHODS: We reviewed 86 patients (109 hips) with DDH (Group D), 40 patients (46 hips) with borderline hip dysplasia (BDDH) (Group B) and 20 patients (23 hips) without hip pain and bony abnormality (control group). Group D was classified into three subgroups-the severe (group SP), moderate (group MP), and none/mild (group NMP) hip pain groups-using the visual analogue scale (VAS). For evaluating hip instability and ILFL morphology, the distance between the anterior edge of the anterior inferior iliac spine (AIIS) and the horizontal line to the femoral head, and ILFL thickness were measured using US. The difference between the distance in the neutral position and Patrick position was calculated and defined as the femoral head translation distance (FTD). RESULTS: FTD and ILFL thickness in group D were significantly larger than those in the control group and group B (P < 0.05). There was a significant positive correlation between FTD and ILFL thickness in three groups (r = 0.57, P < 0.05; r = 0.55, P < 0.05; r = 0.62, P < 0.05, respectively). FTD and ILFL thickness in group SP were significantly larger than those in group NMP (P < 0.05). FTD and ILFL thickness in group D had significantly negative correlations with the lateral center edge (r = -0.54, P < 0.05; r = -0.40, P < 0.05, respectively) and vertical-center-anterior angle (r = -0.51, P < 0.05; r = -0.43, P < 0.05, respectively). CONCLUSIONS: Acetabular bony deficiency, especially in the anterior and lateral region can result in antero-posterior hip instability, leading to thickened ILFL and hip pain, even in patients with BDDH. These findings may facilitate our understanding and treatment of patients with DDH. When hip instability is suspected, hip US examination may help confirm the diagnosis and assist in providing objective clinical diagnostic evidence.

Evaluation of antero-posterior instability of the hip using modified Lequesne's false profile view.

BACKGROUND: Accurate evaluation of hip instability is critical for the diagnosis and successful treatment of developmental dysplasia of the hip (DDH). However, dynamic evaluation of hip instability is not well established. This study aimed to use the lateral view from a radiograph to evaluate dynamic antero-posterior hip instability in patients with DDH. METHODS: Seventy-four patients (92 hips) with DDH (DDH group) and 46 patients (59 hips) without hip pain and DDH (Control group) were examined. A false profile view (FPV) according to Lequesne was taken at standard and 90° flexion with the hip of interest defined as functional FPV; the translation of the center of the femoral head (CFH) obtained from the functional FPV was measured. As a validation test, we measured the anterior translation of the CFH using ultrasonography (US). RESULTS: There was a significant difference between the two groups in the translation of the CFH (p < 0.01). The degree of CFH translation depended on the severity of DDH (lateral center edge angle, r = -0.56, p < 0.01; vertical center anterior margin angle, r = -0.57, p<0.01) and lateralization of the femoral head (head lateralization index, r = 0.54, p < 0.01). There was a significant correlation between functional FPV and US measurements (r = 0.71, p < 0.01). CONCLUSION: The present study confirmed that antero-posterior hip instability in DDH patients can be detected using functional FPV. Our novel measurement, as a new method for assessing hip instability, may be useful for evaluating hip dynamic instability in diagnosing the etiology, and determining and evaluating the treatment for DDH at lower cost and improved accessibility.

Safety and efficacy of high-dose cytarabine MEAM therapy and other treatments for auto-peripheral blood stem cell transplantation: A retrospective comparative study.

AIM: The MEAM regimen consisting of ranimustine (MCNU), etoposide (ETP), cytarabine (Ara-C), and melphalan (MEL) is widely used before auto-peripheral blood stem cell transplantation (auto-PBSCT) for malignant lymphoma in Japan. The MEAM regimen generally consists of 200-400 mg/m2 for 4 days, but we decided to increase the dosage of Ara-C from the standard to 2 g/m2 for 2 days with the aim of increasing drug transferability to the central nervous system. We evaluate the safety and therapeutic efficacy of high-dose Ara-C MEAM therapy. METHODS: The high-dose Ara-C MEAM protocol consisted of MCNU 300 mg/m2 on day -7, ETP 200 mg/m2 on days -6, -5, -4, -3 and Ara-C 2 g/m2 on day -4 -3, and MEL 140 mg/m2 on day -2. We retrospectively analyzed 37 cases of malignant lymphoma at our institution between May 2014 and July 2020. RESULTS: All patients got engraftment and there were no cases of treatment-related mortality. In all cases, the 3-year overall survival (OS) and progression-free survival (PFS) after transplantation were 80.6% and 65.7%, respectively. Twenty-one cases of diffuse large B-cell lymphoma recurrence, for which there is proven usefulness of auto-PBSCT, showed good results after transplantation, with the 3-year OS and PFS after transplantation being 100% and 74.3%, respectively. CONCLUSION: The safety and efficacy of high-dose Ara-C MEAM therapy were demonstrated, but the expected therapeutic effect on central nervous system lesions could not be fully evaluated owing to the small number of cases.

Investigating the subchondral trabecular bone microstructure in patients with osteonecrosis of the femoral head using multi-detector row computed tomography.

OBJECTIVES: To analyse the microstructural changes of subchondral trabecular bone in patients with osteonecrosis of the femoral head (ONFH) using multi-detector row computed tomography (MDCT). METHODS: We retrospectively investigated 76 hips in 50 patients diagnosed with ONFH between 2017 and 2021. Groups 1, 2, 3, and 4 comprised hips without ONFH, ONFH without femoral head collapse (FHC), ONFH with mild collapse (<2 mm), and ONFH with severe collapse (>2 mm), respectively. All patients underwent MDCT, and the subchondral trabecular bone microstructure was assessed. Regions of interests were set at the lateral boundary of the femoral head necrotic lesion and centre of the acetabular weight-bearing portion. RESULTS: In both the femoral head and the acetabular regions, there were significant differences in Groups 2 and 3 compared to Group 1, with increased volumetric bone mineral density and apparent bone volume fraction, and more plate-like with increased connectivity, indicating that osteosclerotic changes were occurring. CONCLUSIONS: In both the femoral head and the acetabular regions, osteosclerotic changes of subchondral trabecular bone microstructure were present before FHC.

The impact of increasing femoral offset and stem anteversion on postoperative dislocation in bipolar hemiarthroplasty.

BACKGROUND: Femoral offset and anteversion have been reported to affect the incidence of dislocation following bipolar hemiarthroplasty, although the magnitudes of contributions of the femoral offset and stem anteversion on dislocation, both singly and in combination is not fully understood. METHODS: Using the CT data of 61 patients (61 hips), including 30 male and 31 female who underwent bipolar hemiarthroplasty, three-dimensional dynamic motion analysis was performed using a modular implant that enabled adjustment of femoral offset and stem anteversion independently. The pattern of impingement and relationship between femoral offset/stem anteversion and range of motion were evaluated using the software. FINDINGS: We found that a higher femoral offset and stem anteversion correlate with a greater range of motion of flexion and internal rotation. Furthermore, an increased femoral offset has a great effect on increasing range of motion of flexion than stem anteversion, and increased both femoral offset and stem anteversion have fewer effect on the flexion, whereas increasing stem anteversion has a great impact on internal rotation than offset, especially in the case with lower femoral anteversion. However, a higher stem anteversion decrease the range of motion of external rotation, whereas a higher femoral offset leads to an increased range of motion of external rotation. INTERPRETATION: We demonstrated that both a higher femoral offset and stem anteversion substantially affected the range of motion in flexion, internal rotation and external rotation. However, these are not independent, but rather mutually confounding, the surgeons should consider retaining femoral/anterior offset in bipolar hemiarthroplasty.

Multiple Preprocessing Hybrid Level Set Model for Optic Disc Segmentation in Fundus Images.

The accurate segmentation of the optic disc (OD) in fundus images is a crucial step for the analysis of many retinal diseases. However, because of problems such as vascular occlusion, parapapillary atrophy (PPA), and low contrast, accurate OD segmentation is still a challenging task. Therefore, this paper proposes a multiple preprocessing hybrid level set model (HLSM) based on area and shape for OD segmentation. The area-based term represents the difference of average pixel values between the inside and outside of a contour, while the shape-based term measures the distance between a prior shape model and the contour. The average intersection over union (IoU) of the proposed method was 0.9275, and the average four-side evaluation (FSE) was 4.6426 on a public dataset with narrow-angle fundus images. The IoU was 0.8179 and the average FSE was 3.5946 on a wide-angle fundus image dataset compiled from a hospital. The results indicate that the proposed multiple preprocessing HLSM is effective in OD segmentation.

Development of a novel scorpionate ligand with 6-methylpyridine and comparison of the structural and electronic properties of nickel(II) complexes with related tris(azolyl)borates.

A novel anionic tridentate borate ligand with a 6-methylpyridyl donor, TpyMe, has been synthesized. Comparison of the molecular structures and reactivities of nickel(II)-bromido complexes with tris(azolyl)borate ligands composed of pyridyl, pyrazolyl, or oxazolinyl donors indicates the characteristic sterically demanding nature and strong electron donating ability of TpyMe.

Associations between implant alignment or position and patient-reported outcomes after total hip arthroplasty.

BACKGROUND: We aimed to evaluate the associations between implant alignment/position and patient-reported outcomes following total hip arthroplasty using CT-based simulation software. METHODS: We reviewed hips of 137 patients (27 males, 110 females, mean age: 67.3 years old) who underwent total hip arthroplasty. Radiographic evaluations were based on the software for evaluation of the parameters related to implant alignment/position and femoral/3-dimensional offset using post-operative CT data. Pre-operative and one-year post-operative patient-reported outcomes using Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire scores were evaluated. FINDINGS: The total and movement scores of normal combined anteversion and stem anteversion angle groups were significantly higher than those of lower and higher groups. The pain and movement scores of decreased femoral offset group were significantly lower than those of restored and increased femoral offset group. There were no significant differences in all scores in cup inclination and anteversion angle, stem coronal alignment, and 3-dimensional femoral offset among groups. Moreover, investigation of the associations between combined anteversion angle/stem anteversion/femoral offset and movement scores revealed that combined anteversion angle and stem anteversion were significantly associated with the movement that needs deep hip flexion and occasionally deep abduction, and high femoral offset was also associated with the movement that needs deep hip flexion. INTERPRETATION: Surgeons should consider the stem anteversion, stem sagittal alignment, and combined anteversion, in addition to the femoral offset to achieve patient's post-operative satisfaction, although the surgeon may have a relatively larger choice for the implant positioning, especially on the cup side.

NPM1-mutation-based measurable residual disease assessment after completion of two courses of post-remission therapy is a valuable clinical predictor of the prognosis of acute myeloid leukemia.

Recent studies have reported that measurable residual disease (MRD) analysis using NPM1 mutations helps determine whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in acute myeloid leukemia (AML) patients. However, the optimal timing and cutoff value for measuring MRD using genomic DNA remain undetermined. This study aimed to investigate the optimal timing and cutoff value to ascertain the value of NPM1 mutation in MRD assessment. NPM1-mutated MRD was quantified by real-time polymerase chain reaction of bone marrow samples from 56 patients with NPM1-positive AML who achieved hematological remission. The area under the receiver-operating characteristic curve was greatest when MRD was assessed after two courses of post-remission therapy with a cutoff value of 0.010% (specificity, 68.4%; sensitivity, 87.0%). Patients whose MRD was below the cutoff value throughout the course of treatment had significantly better overall survival and relapse-free survival rates. Of the 33 patients who did not undergo transplantation during the first remission, all of the 11 who were never MRD-negative at any point experienced a relapse. Evaluating MRD with a cutoff value of 0.010% after two courses of post-remission therapy helps predict prognosis and determine the indication for allo-HSCT.

Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia.

Mutations of CCAAT/enhancer-binding protein alpha (CEBPAmu) are found in 10% to 15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (P < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .026). Multivariate analysis of 744 patients aged ≤70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio, 0.3287; P < .001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA-mutated AML.

miR-23a/b clusters are not essential for the pathogenesis of osteoarthritis in mouse aging and post-traumatic models.

Osteoarthritis (OA), the most prevalent aging-related joint disease, is characterized by insufficient extracellular matrix synthesis and articular cartilage degradation and is caused by various risk factors including aging and traumatic injury. Most microRNAs (miRNAs) have been associated with pathogenesis of osteoarthritis (OA) using in vitro models. However, the role of many miRNAs in skeletal development and OA pathogenesis is uncharacterized in vivo using genetically modified mice. Here, we focused on miR-23-27-24 clusters. There are two paralogous miR-23-27-24 clusters: miR-23a-27a-24-2 (miR-23a cluster) and miR-23b-27b-24-1 (miR-23b cluster). Each miR-23a/b, miR-24, and miR-27a/b is thought to function coordinately and complementary to each other, and the role of each miR-23a/b, miR-24, and miR-27a/b in OA pathogenesis is still controversial. MiR-23a/b clusters are highly expressed in chondrocytes and the present study examined their role in OA. We analyzed miRNA expression in chondrocytes and investigated cartilage-specific miR-23a/b clusters knockout (Col2a1-Cre; miR-23a/bflox/flox: Cart-miR-23clus KO) mice and global miR-23a/b clusters knockout (CAG-Cre; miR-23a/bflox/flox: Glob-miR-23clus KO) mice. Knees of Cart- and Glob-miR-23a/b clusters KO mice were evaluated by histological grading systems for knee joint tissues using aging model (12 and/or 18 month-old) and surgically-induced OA model. miR-23a/b clusters were among the most highly expressed miRNAs in chondrocytes. Skeletal development of Cart- and Glob-miR-23clus KO mice was grossly normal although Glob-miR-23clus KO had reduced body weight, adipose tissue and bone density. In the aging model and surgically-induced OA model, Cart- and Glob-miR-23clus KO mice exhibited mild OA-like changes such as proteoglycan loss and cartilage fibrillation. However, the histological scores were not significantly different in terms of the severity of OA in Cart- and Glob-miR-23clus KO mice compared with control mice. Together, miR-23a/b clusters, composed of miR-23a/b, miR-24, miR-27a/b do not significantly contribute to OA pathogenesis.

Preoperative T2 mapping MRI of articular cartilage values predicts postoperative osteoarthritis progression following rotational acetabular osteotomy.

AIMS: Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI. METHODS: We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head. RESULTS: There were 16 patients with postoperative OA progression. The T2 values of the centre to the anterolateral region of the acetabulum and femoral head in the OA progression cases were significantly higher than those in patients without OA progression. The preoperative T2 values in those regions were positively correlated with the narrowed joint space width. The receiver operating characteristic analysis revealed that the T2 value of the central portion in the acetabulum provided excellent discrimination, with OA progression patients having an area under the curve of 0.858. Furthermore, logistic regression analysis showed T2 values of the centre to the acetabulum's anterolateral portion as independent predictors of subsequent OA progression (p < 0.001). CONCLUSION: This was the first study to evaluate the relationship between intra-articular degeneration using T2 mapping MRI and postoperative OA progression. Our findings suggest that preoperative T2 values of the hip can be better prognostic factors for OA progression than radiological measures following RAO. Cite this article: Bone Joint J 2021;103-B(9):1472-1478.

Three-dimensional analysis of the cortical contact state of short and conventional stems in different stem positions in total hip arthroplasty.

BACKGROUND: Despite the increasing use of short cementless stems in total hip arthroplasty, their potential benefits have yet to be confirmed. We evaluated the cortical contact state of short and conventional stems in different femoral canal types and stem positions using a CT-based 3-dimensional templating software. METHODS: We reviewed 153 hips in 153 patients, grouped according to femoral canal type-normal (68), champagne-flute (41), and stove-pipe canal (44). We investigated the influence of stem position on the contact state by evaluating three situations of stem anteversion (original anteversion, +5°anteverted, and +5°retroverted), three stem positions, neutral +2°extended, and +2°flexed positions using Taperloc Complete MicroplastyⓇ stem. FINDINGS: The contact values of all zones between both stems in all canal types exhibited no significant differences. The values in zones 1, 2, 6, and 7 of both stems in 5° retroverted and anteverted, 2° extended and flexed positions were not significantly different compared to those of the neutral position. However, the values in zones 3, 4, and 5 of both stems were significantly greater compared to those of the neutral position in 2° extended and flexed positions; these values were also significantly larger in all canal types for the conventional stem. INTERPRETATION: We demonstrated that the short and conventional stems can achieve the same proximal cortical contact in any femoral canal, regardless of the stem position. However, extended and flexed stem positions increase the distal contact, especially in conventional stems. Furthermore, the distal contact increases for the retroverted stem insertions.

Combination Cancer Therapy of a Del1 Fragment and Cisplatin Enhanced Therapeutic Efficiency In Vivo.

BACKGROUND/AIM: Combination cancer therapy is currently under investigation. This study examined the effect of cancer combination therapy using the E3 and C1 (E3C1) domains of developmental endothelial locus-1 (Del1) and cisplatin (CDDP) in murine transplanted tumors. MATERIALS AND METHODS: Mice with transplanted tumors (A431, SCCKN or SCC-4 cells) were injected intraperitoneally with CDDP and injected locally with nonviral plasmid vectors encoding E3C1. Histochemical analysis of the transplanted tumors was then performed to assess the effects on prognosis. RESULTS: The CDDP+E3C1 injected group had reduced tumor growth and longer survival compared to the CDDP injected group. In addition, cell death was observed in the tumor of the CDDP+E3C1 group.. Furthermore, angiogenesis and increased blood vessels were observed together with stromal development. CONCLUSION: The CDDP+E3C1 treatment resulted in improved survival and poor tumor stromal development in mice with transplanted tumors.

An epidermal growth factor motif of developmental endothelial locus 1 protein inhibits efficient angiogenesis in explanted squamous cell carcinoma in vivo

ABSTRACT Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have long-term effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis. (REV INVEST CLIN. 2021;73(1):39-51)

Live-cell epigenome manipulation by synthetic histone acetylation catalyst system.

Chemical modifications of histones, such as lysine acetylation and ubiquitination, play pivotal roles in epigenetic regulation of gene expression. Methods to alter the epigenome thus hold promise as tools for elucidating epigenetic mechanisms and as therapeutics. However, an entirely chemical method to introduce histone modifications in living cells without genetic manipulation is unprecedented. Here, we developed a chemical catalyst, PEG-LANA-DSSMe 11, that binds with nucleosome's acidic patch and promotes regioselective, synthetic histone acetylation at H2BK120 in living cells. The size of polyethylene glycol in the catalyst was a critical determinant for its in-cell metabolic stability, binding affinity to histones, and high activity. The synthetic acetylation promoted by 11 without genetic manipulation competed with and suppressed physiological H2B ubiquitination, a mark regulating chromatin functions, such as transcription and DNA damage response. Thus, the chemical catalyst will be a useful tool to manipulate epigenome for unraveling epigenetic mechanisms in living cells.

Presence of Promyelocytes in Peripheral Blood as a Novel Predictor of Optimal Timing for Single-Step Peripheral Blood Stem Cell Collection.

BACKGROUND: Because peripheral blood stem cell (PBSC) collection places a burden on the patient and should ideally be completed in a single procedure, a convenient clinical predictive factor is needed. METHODS: This retrospective study included 72 patients who underwent autologous PBSC collection. A median volume of 3.9 × 106 CD34-positive cells/kg (range: 0.3-47.4 × 106 cells/kg) was collected on the first day. We defined failure as inability to collect 2.0 × 106 cells/kg on the first day. PBSC collection was classified as failed (n = 25, 34.7%) and successful (n = 47, 65.3%), and patient clinical characteristics were analyzed. RESULTS: The success group had significantly more cases in which a differential white blood cell count in peripheral blood on the day of PBSC collection detected promyelocytes (n = 34 [72.3%] vs. n = 11 [44.0%] in the failure group; P = 0.008). Sixty-two patients underwent autologous PBSC transplantation (median number of transplanted cells, 5.6 × 106/µL; range: 1.60-47.4 × 106 cells/µL). Among transplanted patients, the success and failure groups did not significantly differ in relation to the interval until neutrophil, platelet, or red blood cell engraftment. CONCLUSION: The presence of promyelocytes in peripheral blood may be a useful indicator of the optimal timing for single-step PBSC collection.