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To detect and track structural changes in atomic nuclei, the systematic study of nuclear levels with firm spin-parity assignments is important. While linear polarization measurements have been applied to determine the electromagnetic character of gamma-ray transitions, the applicable range is strongly limited due to the low efficiency of the detection system. The multi-layer Cadmium-Telluride (CdTe) Compton camera can be a state-of-the-art gamma-ray polarimeter for nuclear spectroscopy with the high position sensitivity and the detection efficiency. We demonstrated the capability to operate this detector as a reliable gamma-ray polarimeter by using polarized 847-keV gamma rays produced by the [Formula: see text]([Formula: see text]) reaction. By combining the experimental data and simulated calculations, the modulation curve for the gamma ray was successfully obtained. A remarkably high polarization sensitivity was achieved, compatible with a reasonable detection efficiency. Based on the obtained results, a possible future gamma-ray polarimetery is discussed., (© 2024. The Author(s).)

Although novel techniques for avoiding incontinence during robot-assisted radical prostatectomy have been developed, long-term oncological outcomes are unknown. The objective of this study was to determine the long-term oncological outcomes and functional outcomes of novel nerve-sparing robot-assisted radical prostatectomy with endopelvic fascia preservation for a single surgeon. Data from 100 patients who underwent structure-preserving prostatectomies performed by a single surgeon were retrospectively analyzed. The median console time was 123 min. Bilateral nerve-sparing was performed in 43% of patients underwent, and 57% underwent unilateral nerve-sparing surgery. Most patients (96%) reached complete pad-zero urinary continence by one year after surgery. Satisfactory erectile function was achieved in 97% of patients who underwent bilateral nerve-sparing surgery, and 80% of patients who underwent unilateral nerve-sparing surgery. The surgical margin was positive for 25% of patients, and the biochemical recurrence-free rate at 5 years was 77%. The cancer-specific survival rate was 100% during the median follow-up period of 4.5 years. Clavien-Dindo grade III complications occurred in 1% of cases. The outcomes for novel nerve-sparing robot-assisted radical prostatectomy with endopelvic fascia preservation were similar to previously reported oncological outcomes, with satisfactory functional outcomes. This operative method may be useful for patients who are eligible for nerve-sparing surgery., (© 2024. The Author(s).)

It has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find factors that could be useful biomarkers for the diagnosis. A single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro-granulomas was also evaluated. The frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p = 0.00112). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p < 0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than those in AIH or DILI patients (p < 0.05). We demonstrated that the pre-existing ANA and characteristic liver histology including CD8 + cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy., (© 2022. The Author(s).)

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (-6.6 mmHg) and sham control (-6.5 mmHg) groups (difference: -0.1, 95% confidence interval -5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: -1.8 mmHg [p = 0.488] and -2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. CLINICAL TRIAL REGISTRATION: NCT02918305 ( http://www.clinicaltrials.gov )., (© 2021. The Author(s).)

Gland macrophages are primed for gland development and functions through interactions within their niche. However, the phenotype, ontogeny, and function of steady-state salivary gland (SG) macrophages remain unclear. We herein identified CD11c + and CD11c - subsets among CD64 + macrophages in steady-state murine SGs. CD11c - macrophages were predominant in the SGs of embryonic and newborn mice and decreased with advancing age. CD11c + macrophages were rarely detected in the embryonic period, but rapidly expanded after birth. CD11c + , but not CD11c - , macrophage numbers decreased in mice treated with a CCR2 antagonist, suggesting that CD11c + macrophages accumulate from bone marrow-derived progenitors in a CCR2-dependent manner, whereas CD11c - macrophages were derived from embryonic progenitors in SGs. CD11c + and CD11c - macrophages strongly expressed colony-stimulating factor (CSF)-1 receptor, the injection of an anti-CSF-1 receptor blocking antibody markedly reduced both subsets, and SGs strongly expressed CSF-1, indicating the dependency of SG resident macrophage development on CSF-1. The phagocytic activity of SG macrophages was extremely weak; however, the gene expression profile of SG macrophages indicated that SG macrophages regulate gland development and functions in SGs. These results suggest that SG CD11c + and CD11c - macrophages are developed and instructed to perform SG-specific functions in steady-state SGs., (© 2022. The Author(s).)

Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies. In local skin, epidermal Langerhans cells (LCs) and/or dermal dendritic cells (DCs) uptake antigens and migrate to draining lymph nodes (LNs). However, the subsets of antigen-presenting cells that contribute to Ni presentation have not yet been identified. In this study, we analyzed the Ni-binding capabilities of murine DCs using fluorescent metal indicator Newport Green. Elicitation of Ni allergy was assessed after intradermal (i.d.) injection of Ni-treated DCs into ear pinnae of Ni-sensitized mice. The Ni-binding capabilities of MHC class II hi CD11c int migratory DCs were significantly stronger than those of MHC class II int CD11c hi resident DCs and CD11c int PDCA1 + MHC class II int B220 + plasmacytoid DCs. Migratory DCs in skin-draining and mandibular LNs showed significantly stronger Ni-binding capabilities than those in mesenteric and medial iliac LNs. An i.d. injection of IL-1β induced the activation of LCs and dermal DCs with strong Ni-binding capabilities. Ni-binding LCs were detected in draining LNs after i.d. challenge with IL-1β and Ni. Moreover, an i.d. injection of Ni-treated DCs purified from skin-draining LNs elicited Ni-allergic inflammation. These results demonstrated that migratory DCs in skin-draining LNs have strong Ni-binding capabilities and elicit Ni allergy.

The ultimate goal of periodontal disease treatment is the reorganization of functional tissue that can regenerate lost periodontal tissue. Regeneration of periodontal tissues is clinically possible by using autogenic transplantation of MSCs. However, autologous MSC transplantation is limited depending on age, systemic disease and tissue quality, thus precluding their clinical application. Therefore, we evaluated the efficacy of allogeneic transplantation of adipose-derived multi-lineage progenitor cells (ADMPC) in a micro-mini pig periodontal defect model. ADMPC were isolated from the greater omentum of micro-mini pigs, and flow cytometry analysis confirmed that the ADMPC expressed MSC markers, including CD44 and CD73. ADMPC exhibited osteogenic, adipogenic and periodontal ligament differentiation capacities in differentiation medium. ADMPC showed high expression of the immune suppressive factors GBP4 and IL1-RA upon treatment with a cytokine cocktail containing interferon-γ, tumor necrosis factor-α and interleukin-6. Allogeneic transplantation of ADMPC in a micro-mini pig periodontal defect model showed significant bone regeneration ability based on bone-morphometric analysis. Moreover, the regeneration ability of ADMPC by allogeneic transplantation was comparable to those of autologous transplantation by histological analysis. These results indicate that ADMPC have immune-modulation capability that can induce periodontal tissue regeneration by allogeneic transplantation.

By combining a bolometer detector with an imaging-type interferometer, an inexpensive, easy-to-handle wide-field mid-infrared hyperspectral imaging apparatus was produced. We measured the distributions of four types of thin adhesive layers on an aluminium plate and analysed the results using correlation coefficients to visualise the distribution of various adhesives that cannot be discerned by the naked eye or conventional methods such as visible/near-infrared spectroscopic/fluorescent photography. The measurement wavelength range, obtained spectrum's wavenumber resolution, and measurement time was 8-14 μm, about 9 cm -1 , and about 30 s, respectively. Using conventional methods, adhesives could not be distinguished from the others. By using this method, we found that adhesives could be precisely distinguished by setting an appropriate threshold value for the correlation coefficient. Thus, our approach can accurately measure the spatial distribution of different types of adhesive that cannot be discriminated by conventional methods.

Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD.

CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells' tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.

Transcription factors with a basic helix-loop-helix (HLH) motif have been shown to be crucial for various cell differentiation processes during development of multicellular organisms. Id proteins inhibit the functions of these transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. Members of the Id family also promote cell proliferation, implying a role in the control of cell differentiation. Here we show that Id2 is indispensable for normal development of mice. Id2-/- mice lack lymph nodes and Peyer's patches. However, their splenic architecture is normal, exhibiting T-cell and B-cell compartments and distinct germinal centres. The cell population that produces lymphotoxins, essential factors for the development of secondary lymphoid organs, is barely detectable in the Id2-/- intestine. Furthermore, the null mutants show a greatly reduced population of natural killer (NK) cells, which is due to an intrinsic defect in NK-cell precursors. Our results indicate that Id2 has an essential role in the generation of peripheral lymphoid organs and NK cells.

The synthesis and in vitro antimicrobial activity of a new penem antibiotic, sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-ca rbo xylate (1), are reported. The MIC values of 1 are compared with those of some related 2-haloalkylthio penems prepared in this work, and also Sch 29482 and thienamycin.

The effect of cefmetazole on the growth together with the release of cellular lipoteichoic acid from cefazolin-resistant strains of Staphylococcus aureus was compared with that of cefazolin, cefotiam, cefoxitin and cefuroxime. Bacteriolytic actions were measured by turbidity and bactericidal actions were followed by viable cell count. Release of cellular lipoteichoic acid was measured by the radioactivity in the supernatant of the cultures. Cefmetazole exerted more potent effects on the bacterial growth and induced more marked release of cellular lipoteichoic acid from resistant strains as compared with other beta-lactams.

5"-Amino-3',4'5"-trideoxybutirosin A (4) was synthesized by two routes starting from the known tri-O-acetyl-tetra-N-benzyloxycarbonyl-3",5"-O-cyclohexylidene-3',4'-di-O-mesylbutirosin A (5). Introduction of amino function at C-5" was carried out by displacement of 5"-tosyloxy group with sodium azide either before or after 3',4'-deoxygenation. Compound 4 shows outstanding activities against strains including Pseudomonas aeruginosa and Escherichia coli which are highly resistant to butirosin and 5"-amino-5"-deoxybutirosin A (2).

The pharmacokinetics and metabolic fate of cefmetazole (CS-1170, CMZ) were studied in cynomolgus monkeys by means of combination of radio- and bioassay techniques and that of three radioactive drugs labeled at the different moiety of the molecule. The plasma level of radioactivity after intramuscular injection of cefmetazole[methoxyl-14C] (50 mg/kg) reached the maximum level (185 microgram/ml) after 10 minutes and declined with a half-life of about 48 minutes. In the thin-layer chromatography of the plasma extracts, a single radioactive spot was detected corresponding to unchanged cefmetazole. Repeated intravenous administration for one and two weeks showed no effect on the plasma levels and half-lives. More than 75% of the intravenous or intramuscular dose was recovered in the urine by both radio- and bioassay, the most part being excreted during the first 3 hours period. On the TLC of urine, 93--97% was detected as unchanged cefmetazole. In the bile, the most part (less than 80%) was detected as unchanged cefmetazole. In the feces, about 15% of the dose was recovered, in which 30--40% was detected as intact cefmetazole. The metabolic fate of [3-35S] and [7-35S]cefmetazole was described and discussed. The whole-body autoradiography in the monkeys was also presented.

The synthesis and the biological properties of orally active cephalosporin esters are described. 3-Methoxymethyl cephem derivatives having a 2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamide function at C-7 (1) showed good activity against a wide variety of bacteria including some beta-lactamase producing species. The prodrug type esters of 1 exhibited a good urinary recovery after oral administration to mice and 1-(isopropoxycarbonyloxy)ethyl ester (2a, CS-807) has been pre-clinically tested as an orally active cephem prodrug.

3-beta-Alanyloxymethyl, 3-glycyloxymethyl and 3-methyl derivatives of 6-(1-hydroxyethyl)-carbapenems, (VIIa, VIIb and VIII), and 3-methyl-6-(1-hydroxyethyl)carbapenam (IX) were synthesized from 3-(1-tert-butyldimethylsilyloxyethyl)-4-(3-chloro-2-oxopropyl) -2-azetidinone (I). The antibacterial activities of these compounds proved that the delta 2 double bond was essential for the appearance of bioactivity, whereas the amino group on the C-3 side chain was not necessary.

The synthesis and in vitro antimicrobial activity of a new synthetic carbapenem, (5R,6S)-6-[(R)-1-hydroxyethyl]-2-[(S)-1-acetimidoylpyrrolidin -3-ylthio]-1-carbapen-2-em-3-carboxylic acid (RS-533), are described. The MIC values of related penems and carbapenems are also given for comparison with those of the new carbapenem.