Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases.

Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions.

Successful management of acute graft-versus-host disease with ibrutinib during cord blood transplantation for germline -mutated acute myeloid leukemia.

Background: Acute graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with significant morbidity and mortality, and efficacy of currently available therapeutics are limited. Acute and chronic GVHD are similar in that both are initiated by antigen presenting cells and activation of alloreactive B-cells and T-cells, subsequently leading to inflammation, tissue damage, and organ failure. One difference is that acute GVHD is mostly attributed to T-cell activation and cytokine release, whereas B-cells are the key players in chronic GVHD.

Generation of reporter mice for detecting the transcriptional activity of nuclear factor of activated T cells.

Nuclear factor of activated T cells (NFAT) is a transcription factor essential for immunological and other biological responses. To develop analyzing system for NFAT activity in vitro and in vivo, we generated reporter mouse lines introduced with NFAT-driven enhanced green fluorescent protein (EGFP) expressing gene construct. Six tandem repeats of -286 to -265 of the human IL2 gene to which NFAT binds in association with its co-transcription factor, activator protein (AP)-1, was conjunct with thymidine kinase minimum promoter and following EGFP coding sequence.

Spectra and characteristics of somatic mutations induced by ionizing radiation in hematopoietic stem cells.

Spectra and frequencies of spontaneous and X-ray-induced somatic mutations were revealed with mouse long-term hematopoietic stem cells (LT-HSCs) by whole-genome sequencing of clonal cell populations propagated in vitro from single isolated LT-HSCs. SNVs and small indels were the most common types of somatic mutations, and increased up to twofold to threefold by whole-body X-irradiation. Base substitution patterns in the SNVs suggested a role of reactive oxygen species in radiation mutagenesis, and signature analysis of single base substitutions (SBS) revealed a dose-dependent increase of SBS40.

Early embryonic mutations reveal dynamics of somatic and germ cell lineages in mice.

De novo mutations accumulate with zygotic cell divisions. However, the occurrence of these mutations and the way they are inherited by somatic cells and germ cells remain unclear. Here, we present a novel method to reconstruct cell lineages.

Hodgkin Lymphoma on Hemodialysis Successfully Treated with Extended Courses of Brentuximab Vedotin.

Chemotherapy for hemodialysis (HD) patients is a challenging situation because HD patients are generally frail, and the pharmacokinetics and pharmacodynamics of most chemotherapeutics in HD patients are unknown. We report a classical Hodgkin lymphoma (cHL) patient successfully treated with 34 courses of brentuximab vedotin (BV) monotherapy, of which 30 courses were carried out during HD. Although grade 2 peripheral sensory neuropathy and one occasion of febrile neutropenia were observed, treatment was well-tolerated overall and effective.

Four new C-diterpenoid alkaloids from .

Diterpenoid alkaloids with remarkable chemical properties and biological activities are frequently found in plants of the genera , , and . Accordingly, several C-diterpenoid alkaloid components from cv. Pacific Giant, as well as their derivatives, exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines.

Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice.

The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates.

Delineation of a frequency-organized region isolated from the mouse primary auditory cortex.

The primary auditory cortex (AI) is the representative recipient of information from the ears in the mammalian cortex. However, the delineation of the AI is still controversial in a mouse. Recently, it was reported, using optical imaging, that two distinct areas of the AI, located ventrally and dorsally, are activated by high-frequency tones, whereas only one area is activated by low-frequency tones.

Expansion of stochastic expression repertoire by tandem duplication in mouse Protocadherin-α cluster.

Tandem duplications are concentrated within the Pcdh cluster throughout vertebrate evolution and as copy number variations (CNVs) in human populations, but the effects of tandem duplication in the Pcdh cluster remain elusive. To investigate the effects of tandem duplication in the Pcdh cluster, here we generated and analyzed a new line of the Pcdh cluster mutant mice. In the mutant allele, a 218-kb region containing the Pcdh-α2 to Pcdh-αc2 variable exons with their promoters was duplicated and the individual duplicated Pcdh isoforms can be disctinguished.

The alterations in neurotransmitters and their metabolites in discrete brain regions in the rats after inhalation of disinfectant, glutaraldehyde or ortho-phthalaldehyde for 4 weeks.

Glutaraldehyde (GA) and ortho-phtalaldehyde (OPA) have been widely used as major components of disinfectants in hospitals. We evaluated the alterations in GA or OPA in rats after subacute inhalation exposure by determining levels of neurotransmitters (norepinephrine [NE], dopamine [DA], DA metabolites, dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA], indoleamine serotonin [5-HT] and 5-HT metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) in discrete brain regions using high performance liquid chromatography (HPLC) equipped with an electrochemical detector. Female Wistar rats were exposed to 0, 50, 100, or 200 ppb gaseous GA or OPA by inhalation for 1 h per day, 5 d per week for 4 wk.

Total expression and dual gene-regulatory mechanisms maintained in deletions and duplications of the Pcdha cluster.

The clustered protocadherin-alpha (Pcdha) genes, which are expressed in the vertebrate brain, encode diverse membrane proteins whose functions are involved in axonal projection and in learning and memory. The Pcdha cluster consists of 14 tandemly arranged genes (Pcdha1-Pcdha12, Pcdhac1, and Pcdhac2, from 5' to 3'). Each first exon (the variable exons) is transcribed from its own promoter, and spliced to the constant exons, which are common to all the Pcdha genes.

DNA polymerase delta is required for early mammalian embryogenesis.

Background: In eukaryotic cells, DNA polymerase delta (Poldelta), whose catalytic subunit p125 is encoded in the Pold1 gene, plays a central role in chromosomal DNA replication, repair, and recombination. However, the physiological role of the Poldelta in mammalian development has not been thoroughly investigated.

Methodology/principal Findings: To examine this role, we used a gene targeting strategy to generate two kinds of Pold1 mutant mice: Poldelta-null (Pold1(-/-)) mice and D400A exchanged Poldelta (Pold1(exo/exo)) mice.

[Facial edema and pruritus after intravenous injection of midazolam].

Midazolam is a short-acting benzodiazepine commonly used for conscious sedation for a variety of procedures. Severe adverse reactions, including respiratory depression, respiratory arrest, and anaphylactoid reaction, have been described by manufacturers. We report a patient who developed facial edema after iv injection of midazolam during caesarian section.

Invasion and spread of equine herpesvirus 9 in the olfactory pathway of pigs after intranasal inoculation.

The neuropathogenesis of equine herpesvirus 9 (EHV-9) in pigs was investigated by intranasal inoculation of the virus together with intramuscular administration of dexamethasone (DM). All infected pigs developed characteristic meningo-encephalitis, accompanied by basophilic intranuclear inclusion bodies in the neuronal cells. One non-DM-treated and two DM-treated pigs had prominent malacic lesions in the rhinencephalon.

Brain lesions and transmission of experimental equine herpesvirus type 9 in pigs.

We demonstrated that pigs are susceptible to acute infection by equine herpesvirus type 9 (EHV-9). Six 8-week-old SPF pigs were inoculated intranasally and four were inoculated orally with different doses of EHV-9, and observed for 6 days. Although neurological signs did not develop in any of the infected pigs, the six intranasally infected pigs and one of the orally infected pigs developed lesions of encephalitis consisting of neuronal necrosis, neuronophagia, and intranuclear inclusion bodies, distributed mainly in the rhinencephalon.

Structure-activity relationship and conformational analysis of monoglycosylceramides on the syngeneic mixed leukocyte reaction.

We examined effects of alpha-, beta-galactosylceramides (CalCers) and alpha-, beta-glucosylceramides (GlcCers) on the syngeneic mixed leukocyte reaction (MLR) using spleen cells (responder cells) and dendritic cells (DC, stimulator cells). The DC pretreated with these alpha-monoglycosylceramides markedly stimulated the proliferation of spleen cells, in contrast to the little stimulatory effects produced by the DC pretreated with the corresponding beta-anomers. In addition, when we compared the effects of alpha-GalCer derivatives on the syngeneic MLR, it appeared that the 2"- and 3-hydroxyl groups in alpha-GalCers play a critical role in their stimulation of the MLR response.

Immunohistochemical demonstration of spread of Aujeszky's disease virus to the porcine central nervous system after intestinal inoculation.

Aujeszky's disease virus (ADV) was injected into the duodenal lumen of eight specific pathogen-free pigs aged 5 weeks. The infected pigs did not show any diarrhoea or nervous symptoms, but they developed characteristic necrotizing enteritis and myenteric plexitis, accompanied by follicular necrosis in the Peyer's patches. ADV antigen was detected in the submucosa of the dome area of Peyer's patches, lymphatic follicles, Meissner's and Auerbach's plexuses, solar ganglia and thoracic spinal ganglia.

Effects of alpha- and beta-galactosylated C2-ceramides on the immune system.

In contrast to the immunosuppressive effects of C2-ceramide (C2-Cer), alpha-galactosylceramides with ceramides having more than 10 carbons in fatty acid chains have immunostimulatory activities. We therefore synthesized alpha- and beta-galactosylated C2-Cers in order to examine their effects on the immune system. beta-Galactosylated C2-Cer and C2-Cer suppressed the allogeneic mixed leukocyte reaction (MLR) responses, but alpha-galactosylated C2-Cer stimulated the MLR response.