Search

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data. In this article, the reliability of our data was evaluated by principal component analysis (PCA) and association analysis for hematological and biochemical traits by using genome-wide SNP data. PCA of the SNPs showed that all the samples were collected from the Japanese population and that the samples were separated into two major clusters by birthplace, Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs that have been reported to be associated with 18 hematological and biochemical traits in genome-wide association studies (GWAS), the associations of 56 SNPs were replicated using our data base. Statistical power simulations showed that the sample size of the JPDSC control database is large enough to detect genetic markers having a relatively strong association even when the case sample size is small. The JPDSC database will be useful as control data for conducting PGx studies to explore genetic markers to improve the safety and efficacy of drugs either during clinical development or in post-marketing. [ABSTRACT FROM AUTHOR]

Significance: This biomarker study explored HER2 expression levels and immune cell characteristics that may affect response to T-DXd using tumor tissue samples collected from clinical trial participants. The results suggest that HER2 expression levels and tumor characteristics before the initiation of T-DXd may correlate with the efficacy of the drug., (©2024 The Authors; Published by the American Association for Cancer Research.)

The patient was a 33 year female. In 2001, she was diagnosed with systemic lupus erythematosus (SLE) and treated with prednisolone and ciclosporin. In May 2006, she noticed slight muscle weakness in the bilateral lower limbs. In July of the same year, she experienced gait difficulty and was admitted to our hospital because of fatigue, appetite loss, fever and disorientation. Soon afterwards, she had a fit of general convulsion and suffered from urinary retention and fecal incontinence. A brain magnetic resonance image revealed atrophy of the thoracic cord in T2 weighted images, and cerebrospinal fluid examination showed high total protein and interleukin-6 concentration, indicating complication of lupus myelitis as well as cerebral involvement. Steroid pulse and oral prednisolone treatment resulted in ameriolation of cerebral complications such as disorientation and convulsion, but muscle weakness and paresthesia in the lower limbs and urinary retention persisted. Cyclophosphamide pulse therapy was started and resulted in a marked recovery from muscle weakness, paresthesia and urinary retention, and she could discharge. We conclude that steroid and cyclophosphamide pulse therapy for a SLE patient with CNS lupus and lupus myelitisis is effective for ameriolation of symptoms such as disorientation, convulsion, urinary retension, fecal incontinence, muscle weakness and paresthesia in the lower limbs as well as elevated level of serum anti-ribosomal P antibody.

The conversions of hexahydroxo rhenium cluster complexes [Re6Q8(OH)6]4- (Q=S, Se) in aqueous solutions in a wide pH range were investigated by chemical methods and spectroscopic measurements. Dependences of the spectroscopic and excited-state properties of the solutions on pH have been studied in detail. It has been found that a pH decrease of aqueous solutions of the potassium salts K4[Re6Q8(OH)6].8H2O (Q=S, Se) results in the formation of aquahydroxo and hexaaqua cluster complexes with the general formula [Re6Q8(H2O)n(OH)6-n]n-4 that could be considered as a result of the protonation of the terminal OH- ligands in the hexahydroxo complexes. The compounds K2[Re6S8(H2O)2(OH)4].2H2O (1), [Re6S8(H2O)4(OH)2].12H2O (2), [Re6S8(H2O)6][Re6S6Br8].10H2O (3), and [Re6Se8(H2O)4(OH)2] (4) have been isolated and characterized by X-ray single-crystal diffraction and elemental analyses and infrared (IR) spectroscopy. In crystal structures of the aquahydroxo complexes, the cluster units are connected to each other by an extensive system of very strong hydrogen bonds between terminal ligands.