Chie Ishihara

Human peripheral eosinophils express functional interferon‐gamma receptors (IFN‐γR)

In order to determine whether or not IFN‐γR is associated with regulatory mechanisms on human eosinophil function, we examined the expression of functional IFN‐γR on human peripheral eosinophils. In this study, peripheral blood eosinophils were obtained from seven normal controls and 12 patients (bronchial asthma, n = 9, and hypereosinophilic syndrome (HES), n = 3), and the purity of eosinophils was 97.11 ± 2. 31%, n = 19. We first showed that anti‐IFN‐γR α‐chain MoAb reacted with all tested eosinophils of both normal controls and patients by flow cytometry analysis. We also showed expression of mRNA for the α‐chain of IFN‐γR in all purified eosinophils of six individuals. Further, to characterize IFN‐γR on eosinophils, we did binding experiments with 125I‐IFN‐γ on purified peripheral eosinophils. The linear Scatchard plot indicated a single type of high‐affinity binding sites (dissociation constant (Kd) = 3.89–4.95 × 10−10 M, numbers of binding sites = 183–233/cell, n = 3). To determine whether IFN‐γR on eosinophils is functional, we examined surface eosinophilic cationic protein (ECP) and CD69 induction after IFN‐γR ligation with recombinant human IFN‐γ (rhIFN‐γ) on eosinophils by flow cytometry. rhIFN‐γ stimulation significantly induced both ECP and CD69 expression on the 2–18 h‐cultured eosinophils in a dose‐dependent manner. Further, the effects of rhIFN‐γ stimulation were significantly blocked by both a neutralizing anti‐IFN‐γ MoAb and a blocking anti‐IFN‐γR MoAb. These results suggest that human peripheral eosinophils express functional IFN‐γR.

Role of JAK2 signal transductional pathway in activation and survival of human peripheral eosinophils by interferon-gamma (IFN-γ)

The purpose of this study was to determine whether the JAK pathway is involved in eosinophil activation and survival through IFN‐γ receptor signalling in human peripheral eosinophils. Eosinophils were purified from the blood of six atopic disease patients by anti‐CD16 magnetic bead‐negative selection. IFN‐γ significantly up‐regulated survival and CD69 expression in 24–48 h cultured eosinophils. Further, IFN‐γ induced tyrosine phosphorylation of JAK2 in eosinophils, as indicated by Western blot analysis. Finally, the specific JAK2 inhibitor AG‐490 inhibited the tyrosine phosphorylation of JAK2, IFN‐γ‐induced survival and CD69 expression in eosinophils. In conclusion, these results indicate that IFN‐γ induces eosinophil survival and CD69 expression through the activation of JAK2 in peripheral eosinophils, suggesting that JAK2 may play a significant role in eosinophil regulation by IFN‐γ–IFN‐γR interaction.

Signal Transduction through Interferon–Gamma Receptor on Human Eosinophils

Background: We reported on the constitutive interferon–γ receptor (IFN–γR) expression on eosinophils. But signal transduction through IFN–γR on eosinophils remains to be elucidated. In this study, we examined the involvement of the Jak/Stat pathway in the signaling of eosinophils after IFN–γR conjugation by the ligand binding. Methods: Purified peripheral eosinophils were stimulated with IFN–γ at 37°C for 1–60 min. Tyrosine phosphorylation of IFN–γR, Jak1, Jak2, and Stat1α was examined by immunoblotting. Gel–shift assay was also examined to show the formation of Stat1α–DNA complexes. Results: We show that binding of IFN–γ to human eosinophils initiated a series of events that resulted in the rapid tyrosine phosphorylation of not only the IFN–γRα chain but also Jak1, Jak2, and Stat1α. In addition, IFN–γ enhanced the DNA–binding activity of Stat1α. Conclusion: These data indicate that IFN–γ affects eosinophils through its specific receptor and utilizes the Jak/Stat pathway as its mode of signaling.

Heterogeneous Expression of Tumor Necrosis Factor-α Receptors I and II on Human Peripheral Eosinophils

Background: Expression of the tumor necrosis factor-α receptor by human eosinophils has not been determined. We examined the surface expression and mRNA for tumor necrosis factor-α receptors I and II (TNF-αRI and TNF-αRII) on peripheral eosinophils. Methods: Eosinophils were obtained from 17 asthma patients and 3 healthy volunteers. Flow cytometry was used to examine receptor expression, and the reverse transcriptase-polymerase chain reaction was used to examine receptor mRNA expression. Results: Flow cytometry revealed that 16 out of 20 subjects had eosinophils expressing TNF-αRI and 18 subjects had eosinophils expressing TNF-αRII. All eosinophils expressed at least one receptor. The mRNA for TNF-αRII was detected in all eosinophils examined, but the signals for TNF-αRI mRNA were only found in cells expressing this receptor. Conclusions: Human peripheral eosinophils show heterogeneous expression of TNF-αRI and TNF-αRII.

Predicting onset of chronic lung disease using cord blood cytokines

Applicability of cord blood interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study.

Bilateral basal ganglia infarction after mild head trauma

Head trauma can result in various cerebrovascular complications, including occlusion of the vertebral arteries, carotid arteries, and intracranial arteries due to emboli from the cervical portion of the carotid artery, vasospasm, traumatic dissection, or post-traumatic thrombosis. Although mild head trauma is not life-threatening and does not typically result in long-term disability, it can, rarely, result in occlusion of intracranial arteries without concomitant loss of consciousness. We report the case of an 11-month-old boy who developed transient neurological signs and symptoms due to bilateral infarction of the basal ganglia after mild head trauma.

Micafungin versus fluconazole for prophylaxis against fungal infections in premature infants.

We conducted a comparative clinical study to evaluate the prophylactic effects of micafungin (MCFG) and fluconazole (FLCZ) on the incidence of fungal infections in extremely low‐birthweight infants who were born at a gestational age of less than 26 weeks and weighed less than 1000 g.

Kawasaki disease presenting with macroscopic hematuria.

© 2008 Japan Pediatric Society Kawasaki disease (KD) is an acute febrile exanthematous illness and the diagnosis is made on clinical signs and symptoms. KD is caused by vasculitis of medium-sized vessels and is common in children. Multi-system organ involvement occurs, and pyuria and proteinuria are common fi ndings. A few cases of acute renal failure due to interstitial nephritis have been reported, but presentation of macroscopic hematuria with massive proteinuria is very rare. 1,2

Outcome of infants with hypoxic ischemic encephalopathy treated with brain hypothermia

The aim of this study was to determine perinatal factors associated with cerebral palsy (CP) in infants treated with brain hypothermia (BHT).

Extracorporeal membrane oxygenation in 61 neonates: Single-center experience

There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants.