Mutation Analysis of the IL36RN Gene in 14 Japanese Patients with Generalized Pustular Psoriasis

Generalized pustular psoriasis (GPP) is a rare, potentially life threatening, and aggressive form of psoriasis, which is characterized by sudden onset with repeated episodic skin inflammation leading to pustule formation. Familial GPP is known to be caused by recessively inherited mutations in the IL36RN gene, which encodes interleukin 36 receptor antagonist (IL‐36Ra). In this article, we performed mutation analysis of the IL36RN gene in 14 Japanese patients with GPP, and identified mutations in two of these patients analyzed. One patient was compound heterozygous for mutations c.115+6T>C and c.368C>G (p.Thr123Arg), whereas the other carried compound heterozygous mutations c.28C>T (p.Arg10*) and c.115+6T>C in the IL36RN gene. Expression studies using total RNA from the patients’ skin revealed that the mutation c.115+6T>C resulted in skipping of exon 3, leading to a frameshift and a premature termination codon (p.Arg10Argfs*1). The protein structure analysis suggested that the missense mutation p.Thr123Arg caused misfolding and instability of IL‐36Ra protein. In vitro studies in cultured cells showed impaired expression of the p.Thr123Arg mutant IL‐36Ra protein, which failed to antagonize the IL‐36 signaling pathway. Our data further underscore the critical role of IL36RN in pathogenesis of GPP.     

Gross anatomical study of bilateral megaureters associated with renal pelvis dilatation and a giant urinary bladder: an adult cadaver with a brief review of the literature

Although bilateral megaureters are not an infrequent occurrence in the urinary tract, bilateral megaureters associated with bilateral renal pelvis dilatation and a giant urinary bladder appear to be rare. In this paper, a cadaver case of an adult Japanese male with bilateral megaureters is described. In addition to describing and illustrating this case, the anatomy and etiology of these anomalous structures is discussed with a brief review of the literature.     

Regional differences in facial skin blood flow responses to the cold pressor and static handgrip tests

We have previously reported the unique regional responses of facial skin blood flow (SkBF) to oral application of the basic tastes without simultaneous systemic circulatory changes. In the present study, we determined whether a systemic circulatory challenge due to sympathetic activation induces regional differences in facial SkBF by observing the responses in facial SkBF and blood pressure to a 2-min cold pressor test (CPT) and static handgrip exercise (HG) by right hand in 20 healthy subjects. The CPT significantly increased SkBF in the forehead, eyelid, cheek, upper lip and lower lip by 6 ± 2 to 8 ± 2  % (mean ± SEM) as compared to resting baseline, with a significant simultaneous increase (13 ± 2 %) in mean arterial pressure (MAP), whereas it significantly decreased the SkBF in the nose by 5 ± 2 %. The HG significantly increased SkBF in the forehead, cheek and lower lip by 6 ± 3 to 10 ± 3 %, with a significant simultaneous increase in MAP (13 ± 2 %), while it induced no significant change in the other regions. Increases in SkBF were greater in the right than left cheek during CPT. These results demonstrate that a systemic circulatory challenge via sympathetic activation elicits regional differences in the facial SkBF response.     

Longest neurite‐specific activation of Rap1B in hippocampal neurons contributes to polarity formation through RalA and Nore1A in addition to PI3‐kinase

In a developing nervous system, axon‐dendrite formation is instructed by extrinsic cues, and the mechanism whereby a developing neuron interprets these cues using intracellular signaling is particularly important. Studies using dissociated hippocampal neurons have identified many signaling pathways underlying neuronal polarization. Among the components of these pathways, Rap1B is essential for axon specification in hippocampal cultures. However, spatiotemporal regulation of Rap1B activity in polarizing neurons and how it affects neuronal polarization remain unclear. Herein, we investigated spatiotemporal activity‐change of Rap1B and its target molecules in hippocampal neurons. FRET imaging showed that specific activation of Rap1B was observed at the tip of a future axon. To dissect downstream signaling, we used three effector mutants of Rap1B. Expression of Rap1B‐G12V/E37G and G12V/Y40C mutants resulted in supernumerary axons. The targets of Rap1B‐G12V/E37G were RalA and Nore1A, whereas Rap1B‐G12V/Y40C activated PI3‐kinase. RalA was activated in the tip of stage 3 axons, and RalA‐S28N expression reduced the fraction of neurons with supernumerary axons induced by Rap1B‐G12V/E37G. Furthermore, Nore1A depletion reduced the number of cells without axons. These results indicate that specific activation of Rap1B contributes to neuronal polarization via interaction with RalA and Nore1A in addition to PI3‐kinase.     

Single serum cortisol values at 09:00 h can be indices of adrenocortical function in children with Kawasaki disease treated with intravenous immunoglobulin plus prednisolone

Combination treatment with intravenous immunoglobulin (IVIG) plus prednisolone is effective for prevention of cardiovascular complications in children with Kawasaki disease (KD). However, administration of prednisolone for approximately 20 d in this regimen causes adrenocortical suppression in a high proportion of treated children. To establish a simple method to screen for this suppression, we performed a prospective study on 72 children with KD treated with this regimen in our institution from February 2012 to March 2014. By performing ROC analysis of 21 initial patients treated between February and June 2012, a serum cortisol value at 09:00 h of 5 mcg/dL was established as a threshold for intact adrenocortical function, which is equivalent to a peak serum cortisol value of higher than 15 mcg/dL in the CRH stimulation test. Then, we applied this screening test to 51 subsequent patients treated between July 2012 and March 2014. Approximately 90% of the patients with morning serum cortisol values above 5 mcg/dL 2 to 6 mo after the cessation of initial prednisolone treatment had peak serum cortisol values exceeding 15 mcg/dL, suggesting the efficacy of this approach.     

Stenosing ureteritis in Henoch–Schönlein purpura: Report of two cases

Stenosing ureteritis (SU), a rare complication of Henoch–Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early‐stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non‐specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.     

The effect of heel elevation in Parkinsonian gait

The effect of heel elevation of shoes in Parkinson's disease was analyzed by using two gait measurement systems. The heel elevation brought about some improvement of walking in the patients with Parkinson's disease with shortening of a stride period, a step period and the transition time of the plantar pressure peak from heel contact to toe off. After measurement study of the gait, all the patients answered the best heel height of shoes was higher than that of their casual footwear or the same. This simple treatment method may be also effective for fall prevention in patients with Parkinson's disease, and further investigation with follow-up observations should be necessary to verify the effect.