COVID-19 Cluster in the Hematology/Respirology Ward of a University Hospital during the Seventh Wave of the SARS-CoV-2 Pandemic in Japan: A Descriptive Study.

Objective Patients with hematological malignancies and solid organ tumors reportedly tend to have a more severe coronavirus disease 2019 (COVID-19) trajectory than do those with other diseases. We studied the clinical features and outcomes of nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the seventh wave of the pandemic. Methods This study retrospectively described the characteristics of COVID-19 clusters involving patients in the hematology/respirology ward of Kochi Medical School Hospital during the seventh wave of the pandemic of SARS-CoV-2. Patients A total of 40 individuals, including 25 patients and 15 healthcare workers, were studied. The diagnosis of SARS-CoV-2 infection was based on reverse transcription polymerase chain reaction performed on nasopharyngeal samples. Results Eleven patients had hematological diseases, and 14 had respiratory diseases. Most patients presented with a fever (n=19) and/or sore throat (n=10). Lower respiratory tract symptoms and pneumonia were rather infrequent, occurring in two patients. All patients received antivirals. The maximal severities were mild in 21 patients and moderate in 2. Two asymptomatic patients with SARS-CoV-2 infection did not develop symptoms of COVID-19. Cycle threshold values in nasopharyngeal samples were significantly lower in patients with COVID-19 than in those who were asymptomatic at the time of the diagnosis with SARS-CoV-2 infection. All SARS-CoV-2-infected inpatients recovered or did not develop symptoms of COVID-19. Conclusion COVID-19 vaccination, early or preemptive treatment with antivirals, and intrinsic changes in SARS-CoV-2 may have contributed to the more favorable outcomes in our series than in previously reported nosocomial clusters.

Association between Motilin Receptor Gene Haplotypes and Growth Traits in Japanese Hinai-dori Crossbred Chickens.

We previously identified quantitative trait loci (QTL) for body weight and average daily gain in a common region between ADL0198 (chr 1: 171.7 Mb) and ABR0287 (chr 1: 173.4 Mb) on chicken chromosome 1 in an F2 resource population produced by crossing low- and high-growth lines of the Hinai-dori breed. Motilin receptor (MLNR) is a candidate gene affecting growth traits in the region. In this study, we genotyped polymorphisms of the MLNR gene and investigated its association with growth traits in a Hinai-dori F2 intercross population. All the exons of the MLNR gene in the parental population were subjected to PCR amplification, nucleotide sequenced and haplotypes identified. To distinguish resultant diplotype individuals in the F2 population, a mismatch amplification mutation assay was performed. Three haplotypes (Haplotypes 1-3) were accordingly identified. Six genotypes produced by the combination of three haplotypes (Haplotype 1, 2, and 3) were examined in order to identify associations between MLNR haplotypes and growth traits. The data showed that Haplotype 1 was superior to Haplotype 2 and 3 in body weight at 10 and 14 weeks of age, average daily gain between 4 and 10 weeks, 10 and 14 weeks, and 0 and 14 weeks of age in female in F2 females. It was concluded that MLNR is a useful marker of growth traits and could be used to develop strategies for improving growth traits in the Hinai-dori breed.

Association between cholecystokinin type A receptor haplotypes and growth traits in Japanese Hinai-dori crossbred chickens.

We previously identified quantitative trait loci for body weight and average daily gain in a common region between MCW0240 (chr 4: 69.9 Mb) and ABR0622 (chr 4: 86.3 Mb) on chicken chromosome 4 in an F(2) resource population produced by crossing low- and high-growth lines of the Hinai-dori breed. Cholecystokinin type A receptor (CCKAR) is a candidate gene affecting growth traits in the region. In this study, we genotyped polymorphisms of the CCKAR gene and investigated its association with growth traits in a Hinai-dori F(2) intercross population. All the exons of the CCKAR gene in the parental population were subjected to PCR amplification, nucleotide sequenced and haplotypes identified. To distinguish resultant diplotype individuals in the F(2) population, a mismatch amplification mutation assay was performed. Five haplotypes (Haplotypes 1-5) were accordingly identified. Six genotypes produced by the combination of three haplotypes (Haplotype 1, 3, and 4) were examined in order to identify associations between CCKAR haplotypes and growth traits. The data indicate that Haplotype 1 was superior to Haplotype 3 and 4 in body weight at 10 and 14 weeks of age, average daily gain between 4 and 10 weeks, 10 and 14 weeks, and 0 and 14 weeks of age. It was concluded that CCKAR is a useful marker of growth traits and could be used to develop strategies for improving growth traits in the Hinai-dori breed.

Manganese superoxide dismutase overexpression changes plating efficiency bidirectionally according to change in redox for SaOS2 human osteosarcoma cell line.

Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that converts cytotoxic superoxide radicals into hydrogen peroxide. MnSOD activity is lower in tumor cells, and MnSOD overexpression reportedly ameliorates malignant phenotypes. We established stable MnSOD overexpressing cell lines from a human osteosarcoma cell line, SaOS2, and then investigated the effects of MnSOD overexpression on plating efficiency (PE) and the involvement of reactive oxygen species, including nitric oxide (NO) in those effects. The PE of SaOS2FM(L), a moderate MnSOD overexpression cell line, increased, while that of SaOS2FM(H), a high MnSOD overexpression cell line, decreased. Although we assessed PE using a colony-formation assay, time-lapse microscopic observation revealed that cells attached to the flasks had undergone neither apoptosis nor necrosis. Moreover, MnSOD overexpression did not affect cell doubling time. Therefore, MnSOD overexpression might correlate directly with cellular adhesion's effect on PE changes. When L-buthionine-[S,R]-sulfoximine (BSO) was administered to increase the intracellular concentration of hydrogen peroxide, the PEs of both cell lines decreased, and when hydrogen peroxide was eliminated by the administration of sodium pyruvate, only the PE of SaOS2FM(H) increased. The combination of BSO and NO (NOR4 or isosorbide 5-mononitrate) administration synergistically decreased PE in both cell lines. These findings suggest that changes in cellular adhesion properties correlate with the balance between increased hydrogen peroxide levels and decreased superoxide radical levels. This is the first report to indicate that PE and cellular adhesion properties change bidirectionally according to the levels of MnSOD overexpression: first increasing then decreasing as MnSOD activity increases. Our results indicate that PE changes might be decided by the balance between two cytotoxic compounds (decreased superoxide radical levels and increased hydrogen peroxide levels), and that NO loading and increased hydrogen peroxide synergistically reduce PE and cellular adhesion.

Cepharanthin enhances adriamycin sensitivity by synergistically accelerating apoptosis for adriamycin-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR.

Cepharanthin (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. CEP is reported to inhibit drug resistance by inhibiting P-glycoprotein, a drug efflux pump, and recently to induce apoptosis. In the present study, we examined the effects of CEP as an inhibitor of adriamycin (ADR) resistance on ADR-induced apoptosis and necrosis. First, we established p53-deficient ADR-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR. Resistant cells showed a higher level of intracellular glutathione peroxidase activity than parent cells. P-glycoprotein was overexpressed in resistant cells. The intracellular ADR level of resistant cells was lower than that of parent cells. One micro g/ml CEP eliminated the degradation of intracellular ADR of resistant cells; that is, to a level equivalent to that of the parent cells. CEP of 0.5 micro g/ml, which was not cytotoxic when used alone, significantly increased the ADR sensitivity of resistant cells, to a level similar to the parent cell level. Isosorbide 5-mononitrate, a potential nitric oxide-generation agent, combined with CEP further increased the ADR sensitivity of resistant cells, indicating a synergistic effect of CEP and isosorbide 5-mononitrate on ADR cytotoxicity. Time-lapse microscopic observation revealed that ADR dominantly induced apoptosis much more than necrosis for both parent and resistant cells, and that the use of 0.5 micro g/ml CEP with ADR synergistically accelerated apoptosis in resistant cells. Finally, we clarified the property by which CEP synergistically accelerates ADR-induced apoptosis. This property might be a new mechanism that explains how CEP overcomes ADR resistance.