The case of Kawasaki disease after rituximab infusion triggered by human anti-chimeric antibodies.

Rituximab (RTX) is an effective treatment for refractory nephrotic syndrome (NS), but may produce human anti-chimeric antibodies (HACA) which can cause severe infusion reaction or rituximab-induced serum sickness (RISS). RISS presents with a fever, rash, and arthralgia, which typically occurs 7-21 days after RTX infusion. On the other hand, Kawasaki disease (KD) also presents with fever and rash. There have been no reports of KD developed after RTX infusion. A 6-year-old girl with frequently relapsing NS was admitted to our hospital for fever and rash on day 7 after receiving RTX. Although it was suggestive of RISS at first, she also had conjunctival hyperemia, swelling, and erythema of the hands and feet, and a right coronary artery abnormality on echocardiography. Her symptoms met the diagnostic criteria of KD. We administered intravenous immunoglobulin (IVIg) (2 g/kg), and her symptoms resolved within a few days. The HACA titer determined using the serum collected at admission was very high. This is the first report of KD with a clinical course similar to RISS. It should be noted that a careful follow-up of coronary arteries should be performed in patients suspected of RISS.

NGS-based targeted resequencing identified rare subtypes of albinism: Providing accurate molecular diagnosis for Japanese patients with albinism.

Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for albinism have been identified; thus, the accurate diagnosis of albinism requires next-generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous albinism (OCA)1-4 and Hermansky-Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS-based targeted resequencing. We identified a genetic background for albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in albinism-related genes. Furthermore, most patients who were not diagnosed with albinism by the NGS analysis showed mild manifestations of albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin-color associated gene variants.

Synthesis, SAR studies, and evaluation of 1,4-benzoxazepine derivatives as selective 5-HT1A receptor agonists with neuroprotective effect: Discovery of Piclozotan.

A new series of 1,4-benzoxazepine derivatives was designed, synthesized, and evaluated for binding to 5-HT1A receptor and cerebral anti-ischemic effect. A lot of compounds exhibited nanomolar affinity for 5-HT1A receptor with good selectivity over both dopamine D2 and alpha1-adrenergic receptors. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1, 4-benzoxazepin-5(4H)-one (50: SUN N4057 (Piclozotan) as 2HCl salt) showed remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

New piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives as selective 5-HT1A receptor agonists with highly potent anti-ischemic effects.

A series of new piperidinyl- and 1,2,3,6-tetrahydropyridinyl-pyrimidine derivatives were synthesized. Among these compounds, 4-methyl-2-(1,2,3,6-tetrahydropyridin-4-yl)pyrimidine derivative 23 (SUN N5147) exhibited sub-nanomolar affinity for 5-HT1A receptor with 1000-fold selectivity over both dopamine D2 and alpha1-adrenergic receptors and remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

[Japanese radiological report creation with continuous speech recognition].

Ten Japanese radiological reports consisting of 1381 characters (681 words) were created by two board-certified radiologists who used conventional typing and a continuous speech-recognition system called AmiVoice (Advanced Media, Inc., Tokyo, Japan). The two radiologists had not had any special training prior to their use of the continuous speech-recognition system. The model of speech-to-text analysis was generated from 22,589 radiological reports (5.7 MB). Dedicated pronunciations for loan words (i.e., English words) were registered by a board-certified radiologist in consideration of variations in Japanese pronunciation. Misrecognition occurred in 40 of 1362 words, corresponding to a 97.1% rate of accuracy of recognition. The average speech recognition time per report was 31.3 sec, and the additional time required for corrections was 25.0 sec. The total speech input time of 56.2 sec was much less than the conventional input time of 142.8 sec for typing. Continuous speech recognition is faster than typing, even considering the additional time required for corrections, and is acceptable in view of the overall reduction in report turn-around time.