Mobilization of arachidonic acid between diacyl and ether phospholipids in rabbit alveolar macrophages

AbstractThe metabolism of 20:4 (arachidonic acid) in alkenylacyl, alkylacyl and diacyl lipid classes in choline glycerophospholipids (CGP) and ethanolamine glycerophospholipids (EGP) in rabbit alveolar macrophages was examined. [3H]20:4 was very rapidly incorporated into diacyl glycerophosphocholine (GPC). After the removal of free 20:4, the radioactivity was gradually lost from diacyl GPC. Concomitantly, the radioactivities in alkylacyl GPC and alkenylacyl glycerophosphoethanolamine (GPE) were increased, indicating that 20:4 was mobilized from diacyl GPC to alkylacyl GPC and alkenylacyl GPE. The mobilization was considered to be a 20:4-specific event. The gradual accumulation of 20:4 in ether phospholipids leads to a high abundance of 20:4 in these lipids. These results suggest metabolic relationships between 20:4 and ether phospholipids, including platelet-activating factor (PAF)

キーンベック病に対する手関節背側からの血管柄付骨移植術

Purpose The objective of this article is to evaluate functional and radiological outcomes of vascularized bone grafts for stage 2 and 3 Kienböck disease. The outcomes of three different donor sites via dorsal approach of the wrist were compared. Pearls and pitfalls in surgical technique were discussed. Methods There were 28 patients who underwent vascularized bone grafts, including the extensor fourth and fifth compartmental artery graft of distal radius in 8 patients, the first and second supraretinacular intercompartmental artery graft of distal radius in 12 patients, and the second dorsal metacarpal neck graft in 8 patients. Average age was 32 years, and radiological grading according to Lichtman classification was stage 2 in 8 patients, stage 3A in 10 patients, and stage 3B in 10 patients. Temporary pinning fixing the midcarpal joint was conducted for 10 weeks postoperatively. Results Follow-up periods averaged 70 months. Pain reduced in 27 patients, and visual analog scale for pain of pre- and postoperative level averaged 59 and 18. Range of wrist flexion and extension motion improved from 87 to 117 degrees, and average grip strength improved from 21 kg preoperatively to 33 kg postoperatively. Carpal height ratio had almost no change from 0.52 to 0.53. Fragmentation of necrotic bone healed in 7 of the 14 cases. Comparative analyses of functional and radiological outcomes between three donor sites found no significant difference. Conclusion Three different vascularized bone grafts from the dorsal wrist and hand area demonstrated favorable and comparable functional outcomes. It was technically important to elevate vascular bundle with surrounding retinaculum or fascia, to include sufficient periosteum, and to insert the vascularized bone as the cortex aligned longitudinally.博士（医学）・乙第1385号・平成28年11月24日最終稿掲載不可のため本文の掲載無し（国立国会図書館には送付済み

烏口突起骨端線離開の新分類：自験例9例と過去の論分のレビューから

Objectives and Design. Epiphyseal separation of the coracoid process (CP) rarely occurs in adolescents. In this retrospective case series, we reviewed the data of nine patients treated at our center and those of 28 patients reported in the literature. This injury can be classified into three types according to the injured area: Type I, base including the area above the glenoid; Type II, center including the coracoclavicular ligament (CCL); and Type III, tip with the short head of the biceps and coracobrachialis, as well as the pectoralis minor. Patients/Participants. A total of 37 patients were included in the analysis. Data on sex, age, cause and mechanism of injury, separation type, concomitant injury around the shoulder girdle, treatment, and functional outcomes were obtained. Main Outcome Measurements and Results. Type I is the most common type. The cause of injury and associated injury around the shoulder girdle were significantly different between Type I, II, and III fractures. The associated acromioclavicular (AC) dislocation and treatment were significantly different between Type I and III fractures. Our new classification system reflects the clinical features, imaging findings, and surgical management of epiphyseal separation of the CP. Type I and II fractures are mostly associated with AC dislocation and have an associated injury around the shoulder girdle. Type III fractures are typically caused by forceful resisted flexion of the arm and elbow. Although the latter are best managed surgically, whether conservative or surgical management is optimal for Type I and II fractures remains controversial. Conclusions. We noted some differences in the clinical characteristics depending on the location of injury; therefore, we aimed to examine these differences to develop a new system for classifying epiphyseal separation of the CP. This would increase the clinicians' awareness regarding this injury and lead to the development of an appropriate treatment.博士（医学）・甲第783号・令和3年3月15日Copyright © 2020 Takamitsu Mondori et al. This is an open access article distributed under the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supranuclear Melanin Caps Reduce Ultraviolet Induced DNA Photoproducts in Human Epidermis

Melanin can form supranuclear caps in human epidermis, suggesting that intracellular melanin reduces ultraviolet transmission to underlying cell nuclei and inhibits the formation of ultraviolet induced DNA photoproducts. The purpose of this study was to determine the photoprotective effect of epidermal melanin. We irradiated normal human skin explants with ultraviolet B and determined the formation of cyclobutane pyrimidine dimers and (6–4)photoproducts in individual epidermal cells by indirect immunofluorescence and by laser cytometry using monoclonal antibodies specific for cyclobutane dimers or for (6–4)photoproducts. We found that epidermal cells with supranuclear melanin caps had significantly less DNA photoproducts (both types) than epidermal cells without supranuclear melanin caps. Moreover, the protection factor against both types of photolesions correlated with melanin concentration in epidermal cells. These results indicate that melanin reduces ultraviolet induced DNA photoproducts in human epidermis in a concentration dependent manner

頚椎症性脊髄症症例における頚椎アライメント評価 : 坐位頚椎レントゲンと立位全脊椎レントゲンは等しく有用か?

Study Design: Retrospective review of medical charts and radiographic data. Objectives: We aimed to clarify the differences in cervical alignment findings between sitting cervical lateral radiographs and standing whole-spine lateral radiographs with clavicle positioning in cervical spondylotic myelopathy (CSM) patients. Methods: We retrospectively evaluated the radiographs of 50 consecutive patients who underwent cervical surgery for CSM in our hospital. Cervical sagittal alignment was evaluated based on the C0-2 angles and C2-7 Gore and Cobb angles. Head position was evaluated in terms of the center of gravity of the head to C7 (CGH-C7) angle and the McGregor angle (ie, the angle between the McGregor line and a horizontal line). The T1-slope was also evaluated. Results: The mean values of the CGH-C7 angle and T1-slope were significantly lower, while the mean value of the McGregor angle was significantly higher on whole-spine lateral radiographs with clavicle positioning than on sitting cervical lateral radiographs. The mean values of the C0-2 and C2-7 angles did not differ significantly between the 2 radiographic positioning approaches. Conclusions: Using whole-spine lateral radiographs with clavicle positioning may result in a significantly lower T1-slope and a posterior tilt of the head. In the absence of a compensatory change in cervical alignment, clavicle positioning may force patients to adopt an upward gazing position of the head. These compensatory mechanisms should be considered while evaluating cervical alignment on whole-spine lateral radiographs with clavicle positioning. Surgical planning should take into account the effect of posture on the radiographic appearance of cervical alignment.博士（医学）・甲第702号・平成31年3月15日© The Author(s) 2018. Creative Commons Non Commercial No Derivs CC BY-NC-ND: This article is distributed under the terms of the Creative Commons Attribution-Non Commercial-NoDerivs 4.0 License (http://www.creativecommons.org/licenses/by-nc-nd/4.0/) which permits non-commercial use, reproduction and distribution of the work as published without adaptation or alteration, without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage)

Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

クローン性造血の臨床予後への影響を解明 --遺伝子変異とコピー数異常の統合的な知見--. 京都大学プレスリリース. 2021-07-09.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11, 234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH

Evolutionary histories of breast cancer and related clones

乳がん発生の進化の歴史を解明 --ゲノム解析による発がんメカニズムの探索--. 京都大学プレスリリース. 2023-07-28.Tracking the ol' mutation trail: Unraveling the long history of breast cancer formation. 京都大学プレスリリース. 2023-08-31.Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1, 2, 3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves