Successful Treatment of Cisplatin Overdose with Plasma Exchange

Accidental cisplatin overdose has been occurring with an increasing frequency due to expanding usage of the agent. However, the optimal strategy to treat such patients remains to be established. Here, we report a case of large cisplatin overdose, successfully managed by plasma exchange, intravenous hydration, granulocyte colony-stimulating factor (G-CSF) administration, and other supportive care. A 67-year-old man with esophageal carcinoma received a large cisplatin overdose of 240 mg/m2, when he received adjuvant therapy following subtotal esophagectomy. On day 4, he experienced frank cisplatin toxicities and emergency plasma exchange was initiated. With 7 cycles of plasma exchange, the cisplatin concentration decreased from 2,350 to 110 ng/mL. Severe bone marrow suppression with high fever ensued on day 10, which was successfully treated with G-CSF and antibiotics. Despite moderate hearing sense reduction, he recovered without significant complications. Immediate plasma exchange with hydration and other care was efficacious in quickly lowering cisplatin concentrations

Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys

ヒト・サルの胎児卵巣から原始卵胞を体外で作出することに成功. 京都大学プレスリリース. 2022-08-01.New egg recipe to boost fertility research. 京都大学プレスリリース. 2022-08-14.In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates

Recurrent Erythema Nodosum in a Child with a SHOC2 Gene Mutation

We report the case of a 6-year-old male who developed recurrent erythema nodosum (EN) at the age of 3 years. The patient exhibited hypertelorism, low-set ears, micrognathia, moderate intellectual disability, thin long fingers, loose anagen hair, and prominent palmoplantar wrinkles. A heterozygous single nucleotide variant in the SHOC2 gene (c.4 A > G, p.S2G) was identified. Patients with a SHOC2 mutation exhibit a unique combination of ectodermal abnormalities including darkly pigmented skin and loose anagen hair. This report is the first to describe EN in a patient with SHOC2 mutation, and to examine the patient’s hair using scanning electron microscopy. We hypothesize that the RAS/MAPK pathway is associated with the pathogenesis of cutaneous lesions in patients with SHOC2 mutations via autoinflammation and disturbance of epithelial stem cells

ZGLP1 is a determinant for the oogenic fate in mice

生殖細胞が卵母細胞へと分化する仕組みを解明. 京都大学プレスリリース. 2020-02-14.Mammalian sexual reproduction relies on the dichotomy of male and female germ cell development. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate in mice. ZGLP1 acts downstream of bone morphogenetic protein (BMP), but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to the oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine

Successful Treatment of Cisplatin Overdose with Plasma Exchange

Accidental cisplatin overdose has been occurring with an increasing frequency due to expanding usage of the agent. However, the optimal strategy to treat such patients remains to be established. Here, we report a case of large cisplatin overdose, successfully managed by plasma exchange, intravenous hydration, granulocyte colony-stimulating factor (G-CSF) administration, and other supportive care. A 67-year-old man with esophageal carcinoma received a large cisplatin overdose of 240 mg/m 2 , when he received adjuvant therapy following subtotal esophagectomy. On day 4, he experienced frank cisplatin toxicities and emergency plasma exchange was initiated. With 7 cycles of plasma exchange, the cisplatin concentration decreased from 2,350 to 110 ng/mL. Severe bone marrow suppression with high fever ensued on day 10, which was successfully treated with G-CSF and antibiotics. Despite moderate hearing sense reduction, he recovered without significant complications. Immediate plasma exchange with hydration and other care was efficacious in quickly lowering cisplatin concentrations