Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow

Inaba, K., Inaba, M., Deguchi, M., Hagi, K., Yasumizu, R., Ikehara, S., Muramatsu, S., and Steinman, R.M. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc. Natl. Acad. Sci. USA. 90: 3038-3042, 1993https://digitalcommons.rockefeller.edu/historical-scientific-reports/1034/thumbnail.jp

Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development - granulocytes, macrophages, and dendritic cells - can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF

Effect of flow in solution on motion of steps during solution growth

金沢大学総合メディア基盤センターWe study step bunching on a vicinal face in solution growth. Assuming that steps are straight, we consider a twodimensional diffusion filed to represent a solution and a one-dimensional vicinal face. The steps are expressed as dots in the vicinal face. Taking account of a flow in a solution, we numerically solve the diffusion equation and the Navier-Stokes equation in the solution, and determine step velocities. If a flow in a solution is absent or is in the step-up direction, a vicinal face is stable. When the flow is in the step-down direction, the vicinal face is unstable and step bunching occurs. In the initial stage, small bunches are formed. Then, owing to the coalescence of small bunches, large bunches are formed. © 2011 The Physical Society of Japan

Formation of step bunches induced by flow in solution

We study the formation of step bunches induced by flow in solution during growth. In our previous study [M. Inaba and M. Sato: J. Phys. Soc. Jpn. 80 (2011) 074606], we showed that the step-down flow in solution causes bunching. In this research, we study the dependence of step behavior on some parameters. With a slow flow, the separation and coalescence between steps and bunches occur frequently during step bunching. With increasing flow rate, the frequency decreases and tight bunches are formed. The decrease in the frequency also occurs with increasing strength of the repulsion between steps. © 2012 The Physical Society of Japan

Limitations in the use of rifampicin-gelatin grafts against virulent organisms

AbstractObjective: Efficacy and duration of antibacterial activity of rifampicin-gelatin grafts against virulent organisms were evaluated in an animal model. Materials and Methods: Rifampicin-gelatin grafts were prepared with impregnation of Gelseal (Vascutek Ltd, Scotland) graft in 1 mg/mL rifampicin solution. Rifampicin-gelatin grafts (6 cm long; n = 24) and plain Gelseal grafts as controls (n = 4) were implanted into the canine abdominal aorta with inoculation of Staphylococcus epidermidis, Escherichia coli, or methicillin-resistant Staphylococcus aureus (MRSA), and the rifampicin-gelatin grafts were retrieved after 1 to 4 weeks. Disks cut from the retrieved rifampicin-gelatin grafts were placed on agar plates streaked with one of the organisms, and the graft antibacterial activity was assessed with the width of the inhibition zone. Results: In in vitro tests, initial inhibition zones (inhibition zone of 24 hours after incubation) of rifampicin-gelatin grafts against S epidermidis, MRSA, and E coli were 40.0 ± 0.3 mm, 36.0 ± 0.2 mm, and 11.8 ± 0.1 mm, respectively. In the implantation, S epidermidis -inoculated rifampicin-gelatin grafts had no findings of graft infection, and no colony growth was recognized on the plates streaked with the perigraft fluids. Initial inhibition zones of S epidermidis -inoculated rifampicin-gelatin grafts retrieved at 1 or 2 weeks were 20.1 ± 1.1 mm and 7.6 ± 1.0 mm, respectively. In E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts, all of the eight animals had perigraft abscess, and blood culture test results probed septicemia in five animals with patent grafts at death. Inhibition zones against E coli or MRSA were not formed on the plates streaked with the same organism, whereas initial inhibition zones of E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts on S epidermidis -streaked plates were 8.0 ± 0.2 mm and 18.5 ± 0.5 mm, respectively. In the MRSA group, however, recolonization of high minimal inhibitary concentration strains developed within the inhibition zones as early as 24 hours. Histologically, neither organisms nor inflammatory cells were found in S epidermidis -inoculated rifampicin-gelatin grafts and tissue ingrowth was recognized at 2 to 4 weeks, whereas E coli -inoculated and MRSA-inoculated rifampicin-gelatin grafts had aggressive neutrophil infiltration into the graft interstices, revealing establishment of uncontrollable graft infection. Conclusion: These results suggested that rifampicin-gelatin grafts are clearly valid for S epidermidis infection, whereas no efficacy was recognized against either MRSA or E coli graft infection because of early development of high minimal inhibitary concentration MRSA strains or poor susceptibility. (J Vasc Surg 2002;35:779-85.

High accumulation of plasminogen and tissue plasminogen activator at the flow surface of mural fibrin in the human arterial system

AbstractPurpose: We assessed the fibrinolytic activity of the organized mural thrombus lining of aneurysms and prosthetic grafts. Methods: Between May 1995 and April 1998, the full-thickness mural thrombi of aneurysms and the pseudointima lining of vascular grafts were obtained from 12 patients, ranging from 55 to 78 years in age, who underwent elective surgery. These included five aortic arch aneurysms, four abdominal aortic aneurysms, and three patent synthetic vascular grafts. The specimens were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot and immunohistochemistry for human plasmin/plasminogen, tissue plasminogen activator (tPA), and fibrin degradation product (D-dimer). Results: In the SDS-PAGE/immunoblot, 25- and 27-kd bands appeared specifically in experimental fibrin plates after limited digestion by plasmin and were also recognized in the mural thrombi. The presence of bands at 25 and 27 kd, which were most prominent in sections near the flow surface layer, was consistent with the hypothesis that the mural fibrin was digested by the endogenous plasmin. Apparent immunoreactivity was found at the flow surface of the masses at a thickness of 10 to 400 μm, suggesting the presence of a plasminogen and tPA-rich layer, with D-dimer as a consequential product of fibrinolysis. Conclusion: The hypothesis that fibrin surfaces in the arterial system acquire fibrinolytic activity because of digestion by circulating endogenous plasmin was confirmed; this may contribute to the antithrombogenicity of these flow surfaces. (J Vasc Surg 2000;32:374-82.

An evolutionary ‘intermediate state’ of mitochondrial translation systems found in Trichinella species of parasitic nematodes: co-evolution of tRNA and EF-Tu

EF-Tu delivers aminoacyl-tRNAs to ribosomes in the translation system. However, unusual truncations found in some animal mitochondrial tRNAs seem to prevent recognition by a canonical EF-Tu. We showed previously that the chromadorean nematode has two distinct EF-Tus, one of which (EF-Tu1) binds only to T-armless aminoacyl-tRNAs and the other (EF-Tu2) binds to D-armless Ser-tRNAs. Neither of the EF-Tus can bind to canonical cloverleaf tRNAs. In this study, by analyzing the translation system of enoplean nematode Trichinella species, we address how EF-Tus and tRNAs have evolved from the canonical structures toward those of the chromadorean translation system. Trichinella mitochondria possess three types of tRNAs: cloverleaf tRNAs, which do not exist in chromadorean nematode mitochondria; T-armless tRNAs; and D-armless tRNAs. We found two mitochondrial EF-Tu species, EF-Tu1 and EF-Tu2, in Trichinella britovi. T.britovi EF-Tu2 could bind to only D-armless Ser-tRNA, as Caenorhabditis elegans EF-Tu2 does. In contrast to the case of C.elegans EF-Tu1, however, T.britovi EF-Tu1 bound to all three types of tRNA present in Trichinella mitochondria. These results suggest that Trichinella mitochondrial translation system, and particularly the tRNA-binding specificity of EF-Tu1, could be an intermediate state between the canonical system and the chromadorean nematode mitochondrial system

Proton beam therapy with concurrent chemotherapy is feasible in children with newly diagnosed rhabdomyosarcoma

BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS. MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients’ clinical information was collected by retrospective medical record review. RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent. CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity

Regulation of Ripening in Grapes by Hormone Treatments (Agriculture)

GA処理による無核デラウェアプドウを用い, オーキシン(IAA, NAA, 2,4-D, 2,4,5-T), GA, BA, CEPAおよびABA処理が果実の成熟におよぼす影響について調査した。その結果, GAおよびBA処理は発育第I期と第III期では果実の成熟にほとんど影響をおよぼさなかったが, 第II期ではわずかに成熟を抑制することが認められた。オーキシン処理は果実の成熟を著しく抑制し, その効果はveraisonの直前処理で最も大きいことが認められた。また, オーキシンによる成熟遅延効果は用いたオーキシンの作用性の順になっているように思われた。CEPA処理は第I期および第II期では成熟を抑制することが認められ, 第III期でも成熟を促進することはなかった。いっぼう, ABAはveraison前の2週間以内に処理した場合, 明らかに果実の成熟を促進することが認められた。このABAによる成熟促進効果は2,4-Dにより部分的に打消された。これらのことから, ブドウ果実の成熟にはオーキシンとABAのバランスが関与しているように思われた。Auxin (IAA, NAA, 2,4-D, 2,4,5-T), GA, BA, CEPA and ABA were applied to the cluster of Delaware grapes at different stages during their development, and the effects on the ripening were followed by measuring changes in the fructose content of berries. GA and BA slightly delayed the ripening of grapes when applied immediately before veraison, but no effects were observed when applied at stages I and III. Auxin greatly delayed the ripening of grapes, and the greatest response to auxin was obtained by the application immediately before veraison. The effect became successively greater in the order of IAA, NAA, 2,4-D and 2,4,5-T. It seems, therefore, that auxin is prominent as a ripening retardant in grape berries. CEPA not only had almost no effect on the ripening even when applied at stage III, but also delayed the ripening at stages I and II. ABA clearly hastened the ripening of grapes when treated within two weeks before veraison, and its effect was partly reversed by 2,4-D. The data lead to the conclusion that an auxin-ABA relationship may be involved in the regulation of the ripening of grape berries

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BackgroundCryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce.MethodsThe YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible.ResultsA total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months.ConclusionsThe incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article