Assignment of CPS1, OTC, CRYD2, ARG2 and ASS genes to the chicken RH map

An attempt was made to assign five genes, CPS1, OTC, ASS, CRYD2, and ARG2, to chicken chromosomes (GGA) by radiation-hybrid mapping. OTC was assigned to GGA1; ARG2 to GGA5; CPS1 to GGA7; and CRYD2 to GGA19. ASS was not, however, assigned to a specific chromosomal position

Lung stereotactic body radiation therapy for elderly patients aged >= 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study

Background Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. Methods We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan–Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values  Results Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5–95.7) months. The median age was 82.9 (range 80.0–94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5–71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. Conclusions SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC

Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage III non-small-cell lung cancer: a retrospective analysis

We intended to investigate whether muscle and adipose masses were associated with prognosis among patients with stage III non-small-cell lung cancer (NSCLC) who were undergoing chemoradiotherapy (CCRT). We retrospectively explored data of patients with stage III NSCLC who underwent definitive CCRT (>= 60 Gy) between January 2004 and March 2018 at our hospital. We examined the relationship of overall survival (OS) with body mass index (BMI), skeletal muscle index (SMI), psoas muscle index (PMI), visceral adipose tissue index (VAI), subcutaneous adipose tissue index (SAI), and visceral-to-subcutaneous adipose tissue area ratio (VSR) using log-rank tests for the univariate analysis and Cox proportional hazard models for the multivariate analysis. Overall, 16, 32, and 12 patients had stage IIIA, IIIB, and IIIC NSCLC, respectively. The total radiotherapy dose ranged from 60 Gy/30 fractions to 66 Gy/33 fractions. In the univariate analysis, the performance status (PS), BMI, and SMI were associated with OS, whereas the PMI, VAI, SAI, and VSR were not. In the multivariate analysis, the PS and SMI were associated with OS. The hazard ratios and 95% confidence intervals were 2.91 and 1.28-6.64 for PS, and 2.36 and 1.15-4.85 for SMI, respectively. The 1, 3, and 5-year OS rates were 92.1%, 59.6%, and 51.0% in patients with high SMI, and 63.6%, 53.8%, and 17.9% in patients with low SMI, respectively. The SMI correlated with prognosis in our study population, whereas adipose mass did not. Therefore, sarcopenia should be considered while predicting the OS in such patients

Clinical Outcome of Palliative Concurrent Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-small Cell Lung Cancer

Palliative concurrent chemoradiotherapy (CCRT) is often administered to patients with stage III non-small cell lung cancer (NSCLC). We investigated the clinical outcomes of patients receiving palliative CCRT for NSCLC. Data of patients with NSCLC who underwent palliative CCRT (n=16), preoperative CCRT plus surgery (n=97), or definitive CCRT (n=48) were evaluated. In all groups, the concurrent chemotherapy regimens consisted of cisplatin and docetaxel. Rates of local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and prognosis were compared. The 2-year rates of LC, DMFS, PFS, and OS in 16 patients who underwent palliative CCRT were 44.4%, 12.5%, 12.5%, and 18.8%, respectively. Univariate analysis showed that palliative CCRT was associated with poor LC (p<0.001), DMFS (p<0.001), PFS (p<0.001), and OS (p<0.001) outcomes in patients who completed CCRT as a preoperative treatment and poor LC (p=0.01), DMFS (p=0.003), PFS (p=0.04), and OS (p=0.004) outcomes in patients who were considered for definitive CCRT. Although there were some long-term survivors, the clinical outcomes of palliative CCRT were significantly inferior to those of the ideal treatments. Therefore, careful determination of the appropriate treatment indications and further studies are warranted

Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer

The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them

Full-Length Sequence of Mouse Acupuncture-Induced 1-L (Aig1l) Gene Including Its Transcriptional Start Site

We have been investigating the molecular efficacy of electroacupuncture (EA), which is one type of acupuncture therapy. In our previous molecular biological study of acupuncture, we found an EA-induced gene, named acupuncture-induced 1-L (Aig1l), in mouse skeletal muscle. The aims of this study consisted of identification of the full-length cDNA sequence of Aig1l including the transcriptional start site, determination of the tissue distribution of Aig1l and analysis of the effect of EA on Aig1l gene expression. We determined the complete cDNA sequence including the transcriptional start site via cDNA cloning with the cap site hunting method. We then analyzed the tissue distribution of Aig1l by means of northern blot analysis and real-time quantitative polymerase chain reaction. We used the semiquantitative reverse transcriptase-polymerase chain reaction to examine the effect of EA on Aig1l gene expression. Our results showed that the complete cDNA sequence of Aig1l was 6073 bp long, and the putative protein consisted of 962 amino acids. All seven tissues that we analyzed expressed the Aig1l gene. In skeletal muscle, EA induced expression of the Aig1l gene, with high expression observed after 3 hours of EA. Our findings thus suggest that the Aig1l gene may play a key role in the molecular mechanisms of EA efficacy

Whole Genome Sequencing of Influenza A and B Viruses With the MinION Sequencer in the Clinical Setting: A Pilot Study

Introduction: Whole genome sequencing (WGS) of influenza viruses is important for preparing vaccines and coping with newly emerging viruses. However, WGS is difficult to perform using conventional next-generation sequencers in developing countries, where facilities are often inadequate. In this study, we developed a high-throughput WGS method for influenza viruses in clinical specimens with the MinION portable sequencer.Methods: Whole genomes of influenza A and B viruses were amplified by multiplex RT-PCR from 13 clinical specimens collected in Tokyo, Japan. Barcode tags for multiplex MinION sequencing were added with each multiplex RT-PCR amplicon by nested PCR with custom barcoded primers. All barcoded amplicons were mixed and multiplex sequencing using the MinION sequencer with 1D2 sequencing kit. In addition, multiplex RT-PCR amplicons generated from each clinical specimen were sequenced using the Illumina MiSeq platform to validate the performance of MinION sequencer. The accuracy, recall, and precision rates of MinION sequencing were calculated by comparing the results of variant calling in the Illumina MiSeq platform and MinION sequencer.Results: Whole genomes of influenza A and B viruses were successfully amplified by multiplex RT-PCR from 13 clinical samples. We identified 6 samples as influenza type A virus H3N2 subtype and 7 as influenza B virus Yamagata lineage using the Illumina MiSeq platform. The overall accuracy, recall, and precision rates of the MinION sequencer were, respectively 99.95%, 89.41%, and 97.88% from 1D reads and 99.97%, 93.28%, and 99.86% from 1D2 reads.Conclusion: We developed a novel WGS method for influenza A and B viruses. It is necessary to improve read accuracy and analytical tools in order to better utilize the MinION sequencer for real-time monitoring of genetic rearrangements and for evaluation of newly emerging viruses

Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

新型コロナウイルスを中和するアルパカ抗体 --マウス実験で有効性を確認--. 京都大学プレスリリース. 2023-02-17.BACKGROUND: SARS-CoV-2 Omicron variants are highly resistant to vaccine-induced immunity and human monoclonal antibodies. METHODS: We previously reported that two nanobodies, P17 and P86, potently neutralize SARS-CoV-2 VOCs. In this study, we modified these nanobodies into trimers, called TP17 and TP86 and tested their neutralization activities against Omicron BA.1 and subvariant BA.2 using pseudovirus assays. Next, we used TP17 and TP86 nanobody cocktail to treat ACE2 transgenic mice infected with lethal dose of SARS-CoV-2 strains, original, Delta and Omicron BA.1. RESULTS: Here, we demonstrate that a novel nanobody TP86 potently neutralizes both BA.1 and BA.2 Omicron variants, and that the TP17 and TP86 nanobody cocktail broadly neutralizes in vitro all VOCs as well as original strain. Furthermore, intratracheal administration of this nanobody cocktail suppresses weight loss and prolongs survival of human ACE2 transgenic mice infected with SARS-CoV-2 strains, original, Delta and Omicron BA.1. CONCLUSIONS: Intratracheal trimerized nanobody cocktail administration suppresses weight loss and prolongs survival of SARS-CoV-2 infected mice

Dose-Volume Parameters Predict Radiation Pneumonitis after Surgery with Induction Concurrent Chemoradiotherapy for Non-small Cell Lung Cancer

To clarify the relationship between dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) after surgery in cases of non-small cell lung cancer (NSCLC) treated with induction concurrent chemoradiotherapy (CCRT). Patients with NSCLC treated with induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 2.0 Gy fractions once daily for a total of 46 Gy) before surgery were reviewed. We calculated the percentage of lung volume receiving at least 20 Gy (V20) and the mean lung dose (MLD) for the total lung volume and the lung remaining after resection. Factors affecting the incidence of RP at grade 2 or higher (≥ G2 RP) were analyzed. Eighteen of 49 patients (37%) experienced ≥G2 RP. The V20 and MLD for the lung remaining after resection (V20r and MLDr) were significant predictors according to the multivariate analysis (p=0.007 and 0.041, respectively). The incidence of ≥G2 RP was 8% in patients with V20r<10%, and 13% in patients with MLDr<5.6 Gy, respectively. The optimal approach to reduce the rate of postoperative RP in patients with induction CCRT for NSCLC is to keep the V20r below 10% and/or the MLDr below 5.6 Gy in the radiotherapy planning

Evaluation of PRNP Expression Based on Genotypes and Alleles of Two Indel Loci in the Medulla Oblongata of Japanese Black and Japanese Brown Cattle

BACKGROUND: Prion protein (PrP) level plays the central role in bovine spongiform encephalopathy (BSE) susceptibility. Increasing the level of PrP decreases incubation period for this disease. Therefore, studying the expression of the cellular PrP or at least the messenger RNA might be used in selection for preventing the propagation of BSE and other prion diseases. Two insertion/deletion (indel) variations have been tentatively associated with susceptibility/resistance of cattle to classical BSE. METHODOLOGY/PRINCIPAL FINDINGS: We studied the expression of each genotype at the two indel sites in Japanese Black (JB) and Japanese Brown (JBr) cattle breeds by a standard curve method of real-time PCR. Five diplotypes subdivided into two categories were selected from each breed. The two cattle breeds were considered differently. Expression of PRNP was significantly (p<0.0001) greater in the homozygous deletion genotype at the 23-bp locus in JB breed. Compared to the homozygous genotypes, the expression of PRNP was significantly greater in the heterozygous genotype at the 12-bp locus in JB (p<0.0001) and in JBr (p = 0.0394) breeds. In addition, there was a statistical significance in the PRNP levels between the insertion and the deletion alleles of the 23-bp locus in JB (p = 0.0003) as well as in JBr (p = 0.0032). There was no significance in relation to sex, age, geographical location or due to their interactions (p>0.05). CONCLUSION: Our results suggest that the del/del genotype or at least its del allele may modulate the expression of PRNP at the 23-bp locus in the medulla oblongata of these cattle breeds