Gas-Phase Epoxidation of Propylene to Propylene Oxide on a Supported Catalyst Modified with Various Dopants

In the present study, the production of propylene oxide (PO) from propylene via gas-phase epoxidation was investigated using various catalysts. Although Ag is known to be a highly active catalyst for the epoxidation of ethylene, it was not active in the present reaction. Both Al and Ti showed high levels of activity, however, which resulted in confusion. The present study was conducted to solve such confusion. Although the employment of MCM-41 modified with Ti and/or Al was reported as an active catalyst for epoxidation, the combination resulted in the formation of PO at a less than 0.1% yield. Since this research revealed that the acidic catalyst seemed favorable for the formation of PO, versions of ZSM-5 that were both undoped and doped with Na, Ti, and Ag were used as catalysts. In these cases, small improvements of 0.67% and 0.57% were achieved in the PO yield on H‒ZSM-5 and Ti‒ZSM-5, respectively. Based on the results of the Ti-dopant and acidic catalysts, Ag metal doped on carbonate species with a smaller surface area was used as a catalyst. As reported, Ag‒Na/CaCO3 showed a greater yield of PO at 1.29%. Furthermore, the use of SrCO3 for CaCO3 resulted in a further improvement in the PO yield to 2.17%. An experiment using CO2 and NH3 pulse together with SEM and TEM examinations for Ag‒Na/CaCO3 revealed that the greatest activity was the result of the greater particle size of metallic Ag rather than the acid‒base properties of the catalysts

Retrospective Analysis of Clinical Factors Relating to the Outcome of Gemtuzumab Ozogamicin Therapy

It is difficult to predict the clinical outcome of gemtuzumab ozogamicin (GO) therapy based solely on the previously identified predictive factors. We retrospectively analyzed the relationship between clinical factors and outcomes in 12 patients with relapsed or refractory acute leukemia who received GO monotherapy. The median patient age at initial GO infusion was 56 years, and the average initial dosage was 8.1 mg/m2. Four patients (33%) achieved an overall remission (OR). The time from diagnosis to GO infusion was significantly longer in patients with OR than in patients with no remission (NR)(1747 vs. 501 days, respectively; P < 0.01). The number of karyotype abnormalities before GO infusion was significantly greater in NR patients (9.5) than in OR patients (0.5; P = 0.03). Monocyte counts in the bone marrow before GO therapy were significantly lower in OR than in NR patients (100/μL vs. 1080/μL, respectively; P = 0.048). In a multivariate analysis, monocyte count was significantly associated with overall survival (P = 0.005). CD14 expression in OR patients was lower than in NR patients, with the exception of 4 patients whose French-American-British subtypes were M4 or M5 (OR, 0.3%; NR, 2.5%; P = 0.04). NR was noted in all 6 patients who underwent allogeneic stem cell transplantation before and/or after GO infusion. Patients showing good sensitivity to conventional chemotherapy with good survival after diagnosis tend to be sensitive to GO as well. A low monocyte count in the bone marrow at infusion of GO might indicate improved efficacy of GO therapy. Further investigation is warranted for establishing appropriate patient selection and for clarifying efficient conditions for GO therapy

Chronic Orofacial Pain in Dental Patients: Retrospective Investigation over 12 years

Orofacial pain is often difficult to diagnose and treat. However, there have been few reports on the clinical observation of dental patients with orofacial pain. We retrospectively investigated the characteristics of 221 dental patients who had suffered from persistent orofacial pain. Data were collected from the outpatient medical records in our clinic over the past 12 years. More than half of the patients (53.8%) had suffered with pain for more than 6 months from pain onset until the first visit to our clinic. The main diagnoses were neuropathic pain (30.3%), myofascial pain (23.5%), psychogenic pain (20.4%), odontogenic toothache (17.2%), and others (7.7%) such as temporomandibular disorders and glossitis. The treatments included pharmacotherapy, splint therapy, and others such as nerve block, dental treatment, physiotherapy, and/or psychotherapy. Excluding the patients (52 of 221 initially enrolled patients) with unknown responses to treatment, 65.7% showed remission or a significant improvement in pain in response to treatment. Although only a small group of patients had odontogenic toothache, the rate of improvement was highest for this disorder. In conclusion, early consultation with a dentist is useful to prevent chronicity of odontogenic pain and to make a differential diagnosis in patients with orofacial pain

Mast Cell Infiltration is Associated with Myelofibrosis and Angiogenesis in Myelodysplastic Syndromes

Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by persistent peripheral cytopenia with morphological and functional abnormalities of hematopoietic cells. Mast cells infiltrate into or around tumor tissues and play a role in remodeling of the stromal microenvironment, contributing to tumor progression. Increased mast cell numbers are associated with fibrosis, angiogenesis and a poor prognosis in human carcinomas. The aim of this study was to determine whether mast cell infiltration contributes to myelofibrosis or angiogenesis in myelodysplastic syndromes. We evaluated the correlation between mast cell density and the extent of myelofibrosis and angiogenesis in myelodysplastic syndromes. Fifty bone marrow biopsies taken from patients with a diagnosis of myelodysplastic syndromes were examined. Grading of myelofibrosis was evaluated by silver impregnation staining. Mast cell density and microvessel density were evaluated by immunohistochemistry. Human mast cells have been divided into two phenotypes. We designated a tryptase-positive mast cell as MCT and a chymase-positive mast cell as MCTC. Microvessels were identified by CD34-positive endothelial cells. Microvessel density and the extent of myelofibrosis were significantly greater in patients with high MCT and MCTC density compared to those with low MC density. Based on this, we suggest that the presence of high mast cell numbers is associated with myelofibrosis and angiogenesis in myelodysplastic syndromes

Allergic Reactions to Local Anesthetics in Dental Patients: Analysis of Intracutaneous and Challenge Tests

Some dental patients have histories of adverse reactions to local anesthesia. The aim of the present study was to investigate the frequency of allergy to local anesthetics of dental patients who had histories of adverse reactions to local anesthesia based on the results of allergy tests in our institute over a period of 5 years. We investigated the past medical records of dental patients retrospectively, and twenty patients were studied. Three of the 20 showed a positive or false-positive reaction in the intracutaneous test, and one patient showed a false-positive reaction in the challenge test. Our results suggest that the frequency of allergy to local anesthetics is low even if patients have histories of adverse reactions to local anesthesia. However, allergy tests of local anesthetics should be performed in patients in whom it is uncertain whether they are allergic

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Phosphatidylinositol 3-kinase inhibitors, Wortmannin or LY294002, inhibited accumulation of p21 protein after γ-irradiation by stabilization of the protein

AbstractExpression of the cyclin kinase inhibitor, p21, is regulated both transcriptionally and posttranscriptionally by the ubiquitin-proteasome degradation pathway. Recently, we reported that DNA damage is required for efficient p21 expression by demonstrating that enhanced p21 mRNA expression induced by DNA damage results in increased p21 protein, but enhanced p21 mRNA without DNA damage does not. In addition, we demonstrated that DNA damage suppressed the ubiquitination of p21. In this study, we analyze the link between p21 stabilization and DNA damage. Enhanced p21 protein expression in ML-1 cells resulting from 15 Gy γ-irradiation was diminished by Wortmannin or LY294002 pretreatment of cells. However, the levels of p21 mRNA were not affected by inhibitor pretreatment. Wortmannin or LY294002 pretreatment reduces p53 expression after γ-irradiation to a lesser degree than that of p21. In addition, we examined the involvement of DNA-PK, whose activity is inhibited by Wortmannin or LY294002, in p21 stabilization using the SCID fibroblast cell line and a DNA-PK targeting ML-1 cell line. Accumulation of p21 protein by γ-irradiation was similar to that of DNA-PK intact cells and was reduced by Wortmannin or LY294002 pretreatment. Involvement of another DNA damage detecting enzyme, the ATM gene product, whose activity is also inhibited by Wortmannin or LY294002, was evaluated. ATM deficient cells induced p21 after γ-irradiation, γ-irradiation-induced p21 protein was diminished by pretreatment of cells with Wortmannin or LY294002. We conclude that the p21 stabilization mechanism functions after γ-irradiation, was sensitive to Wortmannin or LY294002, and required neither DNA-PK nor ATM gene product for activity