Takeshi B. Sato

X-RAY STUDY OF THE HUMAN NECK MOTION DUE TO HEAD INERTIA LOADING

Presented in this study are results from x-ray analysis of live human/neck motion in sled test simulations of low-speed frontal, lateral, and rear-end vehicle impacts. The methodology used may provide insight into the mechanism of neck injuries caused by the head inertia loading. The experimental results suggest that the most significant factor of the head/neck response is the initial curvature of the cervical and thoracic spine.

MECHANISMS, TOLERANCE LIMIT CURVE AND THEORETICAL ANALYSIS IN BLOW-OUT FRACTURES OF TWO AND THREE­ DIMENSIONAL ORBITAL WALL MODELS*

According to Converse & Smith (1957), the orbital blow-out fracture is caused by a sudden increase of intraorbital pressure resulting from the application of a traumatic force to the soft tissue of the orbital area. This concept is supported by a classical experimental study by Smith (1957). His original description is as follows.

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation

Abstract Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes

Heterozygous and/or homozygous HESX1 mutations have been reported to cause isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD), in association with septo optic dysplasia (SOD). We report a novel heterozygous HESX1 mutation in a CPHD patient without SOD phenotypes. The propositus was a one-year-old Japanese girl. Shortly after birth, she was found to be hypoglycemic. She was diagnosed with central adrenal insufficiency based on low cortisol and ACTH at a time of severe hypoglycemia. Further endocrine studies indicated that the patient also had central hypothyroidism and growth hormone deficiency. Using a next-generation sequencing strategy, we identified a novel heterozygous HESX1 mutation, c.326G>A (p.Arg109Gln). Western blotting and subcellular localization revealed no significant difference between wild type and mutant HESX1. Electrophoretic mobility shift assays showed that the mutant HESX1 abrogated DNA-binding ability. Mutant HESX1 was unable to repress PROP1-mediated activation. In conclusion, this study identified Arg109 as a critical residue in the HESX1 protein and extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in HESX1. When multiple genes need to be analyzed for mutations simultaneously, targeted sequence analysis of interesting genomic regions is an attractive approach.

Neonatal case of classic maple syrup urine disease: Usefulness of 1 H-MRS in early diagnosis

We describe a male neonate with classic maple syrup urine disease (MSUD) in metabolic crisis. On day 7 of life, he was referred to hospital because of coma and metabolic acidosis with maple syrup odor. On day 4 after admission, brain magnetic resonance imaging findings were consistent with encephalopathy due to MSUD. Proton magnetic resonance spectroscopy (1H‐MRS) showed a large methyl resonance peak at 0.9 p.p.m. The diagnosis of MSUD was confirmed on low branched‐chain α‐keto acid dehydrogenase complex activity in lymphocyte. 1H‐MR spectra were obtained in 10 min, while it took at least several days to obtain the results of other diagnostic examinations. In convalescence, the peak at 0.9 p.p.m. decreased. The large methyl resonance peak at 0.9 p.p.m. in brain 1H‐MRS would be one of the earliest clues to the diagnosis of classic MSUD in the neonatal period, especially in metabolic crisis.

Congenital corneal staphyloma as a complication of Kabuki syndrome.

Kabuki syndrome has long been clinically defined based mainly on its characteristic eye features. The recent discovery of MLL2 as a causative gene of Kabuki syndrome has enabled the extreme end of the phenotype to be explored. We herein report on two patients with striking visible congenital staphyloma at birth. A diagnosis of Kabuki syndrome was subsequently made in both patients based on a constellation of characteristic eye features, cardiac abnormalities and severe developmental delay, and finally by the confirmation of MLL2 mutations. In conclusion, congenital corneal staphyloma is a complication of Kabuki syndrome with MLL2 mutations.

Association Between Graves’ Disease and Renal Coloboma Syndrome: A Case Report

Renal coloboma syndrome is an autosomal dominant condition characterized by renal lesions and optic nerve abnormalities. We report an 11-yr-old Japanese girl with familial renal coloboma syndrome, who also had Graves’ disease. Four affected family members had a previously reported heterozygous mutation (c.76dupG, p.Val26Glyfs*28) in the PAX2 gene. We hypothesized that PAX2 mutations may increase the risk of autoimmune diseases through alterations of human β-defensin 1 expression.

Mechanism of orbital blow-out fracture Experimental study by three-dimensional eye model

In order to confirm the conclusion by a previous two-dimensional eye model, the impact tests utilizing a three-dimensional eye model were carried out.Three kinds of eye models were made. Model 1 consisted of the orbital walls alone. Model 2 was the orbital walls with orbital contents, but without the eyeball. Model 3 was the orbital walls with the orbital contents and the eyeball.Three series of impact tests were performed. Test 1 tested the impact to the infraorbital margin in the eye models 1, 2 and 3, test 2 the impact to the eyeball in eye model 3, and test 3 the impact to the eyeball and infraorbital margin in the eye model 3.In order to clarify these experimental results, a numerical calculation was performed with a digital computer in the three-dimensional mathematical eye model.The following conclusion was obtained. the impact to the eyeball alone did not increase the infraorbital hydraulic pressure enough to cause the orbital floor fracture. When the impact struck the infraorbital margin, the orb...

A pediatric case of insulinoma and a novel MEN1 mutation: the efficacy of the combination therapy of diazoxide and cornstarch

Satsuki Nakano1, 2, Takeshi Sato2, Mayumi Hosokawa1, Chisato Takagi3, Fumiko Yoshida4, Tomohiro Ishii2, Seiji Sato1, and Tomonobu Hasegawa2 1 Department of Pediatrics, Saitama City Hospital, Saitama, Japan 2 Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan 3 Department of Surgery, Saitama City Hospital, Saitama, Japan 4 Department of Pediatric Surgery, Saitama City Hospital, Saitama, Japan

A pediatric case of pheochromocytoma without apparent hypertension associated with von hippel-lindau disease

Abstract. Pheochromocytomas are catecholamine-secreting tumors. These tumors are rare in children, and they may be associated with hereditary syndromes such as von Hippel-Lindau (VHL) disease. Most pediatric patients with pheochromocytoma present with sustained hypertension, while 10% to 69% of adult patients are asymptomatic. Herein, we present the case of a 12-yr-old Japanese girl with pheochromocytoma due to a germline mutation in the VHL (Arg161Gln). The only complaint was loss of weight. Pyrexia, anemia, and increases in C-reactive protein (CRP) and ferritin were observed. Abdominal ultrasonography revealed a right adrenal gland tumor. Fractionated catecholamines and metanephrines in plasma and 24-h collected urine revealed elevated levels of norepinephrine and normetanephrine. Although hypertension and tachycardia were inapparent by an ordinary physical examination, paroxysmal mild hypertension and tachycardia were identified by a thorough examination after walking and abdominal compression. Paroxysmal hypertension and tachycardia were profound during operation. In conclusion, pheochromocytoma can be a consideration in the differential diagnosis of weight loss. Hypertension and tachycardia can be inapparent and paroxysmal in pediatric patients as well as in adults; thus, thorough assessment should be repeated.