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Tatenobu Goto,
Mohamed Hamed Hussein,
Shin Kato,
Ghada Abdel-Hamid Daoud,
Takenori Kato,
Takahiro Sugiura,
Hiroki Kakita,
Masanori Nobata,
Michi Kamei, Haruo Mizuno,
Masaki Imai,
Tetsuya Ito,
Ineko Kato,
Satoshi Suzuki,
Noriko Okada,
Hajime Togari,
Hidechika Okada
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ABSTRACT: Background:Oxidative stress (oxidant/antioxidant imbalance) plays an important role in the pathophysiolog of neonatal sepsis. The present study evaluated whither an antisense peptide endothelin receptor antagonist ETR-P1/fl could attenuate oxidative stress in a neonatal sepsis model.Methods:Eighteen 3-day-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP) (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05mg/kg/h) of ETR-P1/fl 30 minutes after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAP), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT) and creatinine were measured before CLP and at 1, 3 and 6h after CLP.Results:CLP evoked a state of shock resulting in elevated TH, OSI and IL-6. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3h after CLP, OSI at 1 and 3h after CLP, IL-6 at 1 and 3h after CLP, and GOT at 3 and 6h after CLP compared to the CLP group.Conclusion:ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6 and GOT in a progressive neonatal sepsis CLP model.Pediatric Research (2012); doi:10.1038/pr.2012.134.
Pediatric Research 10/2012; · 2.70 Impact Factor
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ABSTRACT: Laparoendoscopic single-site surgery (LESS), a minimally invasive procedure, is gaining widespread acknowledgment in pediatric urology. We report the case of a 7-year-old girl with Turner's syndrome with 45,XO/46,XY mosaicism, for whom bilateral prophylactic gonadectomy using LESS was performed. Histopathological findings revealed bilateral streak gonads. The surgical and cosmetic outcome was excellent. Diagnostic and therapeutic laparoscopy is essential for accurate clinical management of patients with disorders of sex development. Although this is only a single case report, it supports the theory that LESS is an exceedingly practical and superior technique for such children, since it provides excellent magnification, as well as allowing normal psychological development owing to the concealed scar. Further studies and long-term follow-up are required to evaluate the benefits and limitations of applying LESS in pediatrics.
Journal of pediatric urology 03/2012; 8(4):e39-42. · 1.38 Impact Factor
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ABSTRACT: Kallmann syndrome (KS) is a genetic disorder characterized by the simultaneous occurrence of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Here, we present 3 cases of KS with detailed description. In Case 1, testicular morphology was examined by testicular biopsy, and Leydig cells were examined by immunohistochemistry using antibodies against Ad4BP/SF1. Contrary to our predictions, the present study revealed the presence of Leydig cells in the testis. Testicular morphology in the patients with KS is more varied than expected, and further investigation is required to elucidate hormonal effects on normal testicular development.
Urology 12/2011; 79(3):684-6. · 2.43 Impact Factor
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Sachiko Yamaguchi,
Mohamed Hamed Hussein,
Ghada AbdEl-Hamid Daoud,
Tatenobu Goto,
Shin Kato,
Hiroki Kakita, Haruo Mizuno,
Tetsuya Ito,
Sumio Fukuda,
Ineko Kato,
Satoshi Suzuki,
Takashi Hashimoto,
Hajime Togari
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ABSTRACT: Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.
The Tohoku Journal of Experimental Medicine 01/2011; 223(4):235-41. · 1.24 Impact Factor
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Tatenobu Goto,
Mohamed Hamed Hussein,
Shin Kato,
Ghada Abdel-Hamid Daoud,
Takenori Kato,
Hiroki Kakita, Haruo Mizuno,
Masaki Imai,
Tetsuya Ito,
Ineko Kato,
Satoshi Suzuki,
Noriko Okada,
Hajime Togari,
Hidechika Okada
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ABSTRACT: To evaluate effects of endothelin receptor antagonist ETR-P1/fl in a neonatal sepsis model.
Eighteen anesthetized and mechanically ventilated 3-day-old piglets were divided into three groups. Six piglets received cecal ligation and perforation (CLP group). Six piglets were administrated a continuous infusion of ETR-P1/fl (0.05 mg/kg/h), an antisense homology box-derived peptide with an endothelin A receptor antagonist effect, starting 30 min after CLP (ETR-P1/fl group). Six piglets acted as the sham group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, body temp (BT), serum nitrite and nitrate (NOx), tumor necrosis factor (TNF)-α, and high-mobility group box 1 (HMGB-1) were measured before CLP and at 1, 3, 6, and 9 h after CLP.
Cecal ligation and perforation exposure evoked a state of shock and showed deteriorated cardiac output, pulmonary hypertension, decreased MAP, low oxygen saturation, and base excess (BE) with elevated TNF-α, NOx, and HMGB1. ETR-P1/fl administration resulted in higher MAP at 6 and 9 h after CLP, less negative BE, lower mean pulmonary arterial pressure (mPAP)/MAP ratio at 9 h after CLP, and lower TNF-α, NOx, and HMGB-1 compared to the CLP group. BT showed no differences between the groups. Survival time in the ETR-P1/fl group was longer than in the CLP group (18.9 ± 2.3 h vs. 9.0 ± 0.8 h, p < 0.01).
ETR-P1/fl treatment significantly attenuated the elevation of NOx, TNF-α, and HMGB-1, which improved the systemic hypotension, pulmonary hypertension, and blood gases, thereby causing improvement of survival time in a progressive neonatal sepsis CLP model.
European Journal of Intensive Care Medicine 12/2010; 36(12):2132-9. · 5.17 Impact Factor
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ABSTRACT: We report our experience with laparoscopic gonadal biopsy and gonadectomy for a girl with a dicentric Y chromosome in mixed gonadal dysgenesis (MGD). A 4-year-old phenotypic girl was referred to our hospital because of slight enlargement of the clitoris. Fluorescence in situ hybridization analysis with Y chromosome-specific probes showed a karyotype with 45,XO/46,X,+idic(Y)(p11.32) and presence of the sex-determining region Y sequence. The pathologic finding by frozen section technique using laparoscopic biopsy specimens during the operation demonstrated a left streak gonad and right testis, and she was diagnosed with MGD. Finally, we performed laparoscopic bilateral gonadectomy. Laparoscopic management is a good approach for patients with sexual development disorders, including MGD because it provides minimally invasive surgery for children and enables all necessary procedures, including evaluation, biopsy, and gonadectomy, for diagnosis and treatment.
Journal of Pediatric Surgery 02/2009; 44(1):e1-3. · 1.45 Impact Factor
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ABSTRACT: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro.
We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis.
The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal.
Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.
Hormone Research 02/2009; 71(6):318-23. · 2.48 Impact Factor
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ABSTRACT: Females with salt-wasting (SW) 21-hydroxylase deficiency (21OHD) may present with mild external genitalia virilization, despite complete or almost complete enzyme inactivation. We therefore analyzed genotype/phenotype correlation in 13 Japanese female patients with SW 21OHD. Criteria for classification into the SW phenotype included history of a salt-losing crisis with documented hyponatremia, hyperkalemia, and markedly elevated plasma renin activity. Urologists and pediatricians determined the Prader genital stage and classified the location of the vaginal entrance into the common urogenital sinus as low, moderate, or high. CYP21A2 gene, coding for 21-hydroxylase, was analyzed with Southern blotting and direct sequencing. Genotypes were categorized into four mutation groups, based on the degree of enzymatic activity (N, complete enzyme inactivation; groups A, < 2%, B, 3-7%, and C > 30%). Basal androgen levels were available from only six out of thirteen patients, so we could not relate androgen levels with the severity of external genitalia virilization. We compared the degree of external genitalia virilization with genotype. The severity of external genitalia virilization varied from Prader stage 1 to 4. One patient who presented with Prader 1 had a genotype consistent with Group B. In addition, discordance between Prader classification and the location of the vaginal entrance was noted; one patient classified as Prader 4 showed low vaginal entrance, while another patient classified as Prader 3 showed high vaginal entrance. The degree of the impairment of 21-hydroxylase activity does not correlate with the severity of virilization of the external genitalia in female patients with the SW type of 21OHD.
The Tohoku Journal of Experimental Medicine 08/2008; 215(4):341-8. · 1.24 Impact Factor
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ABSTRACT: Loss-of-function mutations in the thyrotropin receptor (TSHR) gene were described as a syndrome characterized by thyroid hyposensivity to biologically active TSH, ranging from euthyroid to severe hypothyroidism. In Japanese, a common mutation in the TSHR gene is R450H, which demonstrated moderately impaired receptor function. We studied six subjects of Japanese origin whose major abnormality was persistent hyperthyrotropinemia by genetic sequence analysis of the TSHR gene. Three subjects were homozygous for the R450H mutation, whereas the three remaining subjects were single heterozygous. Homozygous subjects displayed mild hypothyroidism confirmed by moderately elevated basal TSH levels and excessive TSH response to TRH administration. Heterozygous subjects also demonstrated fully or partially compensated hypothyroidism, but less severe than that of homozygous subjects. More frequent involvement of the R450H mutation in the TSHR gene in Japanese was identified. In addition, a good correlation between phenotype and genotype was demonstrated in respect to biochemical analysis and drug dosage. Our observations showed clinical significance of heterozygosity associated with compensated hypothyroidism in spite of only mildly impaired receptor function.
Endocrine 01/2007; 30(3):383-8. · 1.42 Impact Factor
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Hiromichi Taneichi,
Hirokazu Kanegane,
Takeshi Futatani,
Keisuke Otsubo,
Keiko Nomura,
Yuya Sato,
Asahito Hama,
Seiji Kojima,
Urara Kohdera,
Takahide Nakano, [......],
Yoko Inoh,
Junji Kamizono,
Naoto Adachi,
Yuko Osugi, Haruo Mizuno,
Noriko Hotta,
Hiroshi Yoneyama,
Eiji Nakashima,
Shiro Ikegawa,
Toshio Miyawaki
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ABSTRACT: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and skeletal abnormalities. SBDS was identified as a causative gene for SDS in 2003, and genetic analyses of SDS have been performed. We performed genetic analysis of 13 Japanese patients with presumed SDS and found that 10 of them had SBDS mutations. Most patients had recurrent mutations (181-184TA-->CT and 258+2T-->C); however, 2 patients had unique mutations (259-1G-->A and 428C-->G). Although genetic analysis is useful for definitive diagnosis and for genetic counseling of SDS patients and families, SDS appears to be a genetically heterogeneous disorder. In addition, presumed SDS patients without SBDS mutations may be included in other disorders.
International Journal of Hematology 07/2006; 84(1):60-2. · 1.27 Impact Factor
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ABSTRACT: We describe two cases of increases in serum creatine kinase (CK) concentrations in children undergoing treatment of Graves' disease with antithyroid medications. Presenting complaints consisted of myalgias and muscle cramping in both patients, and increases in serum CK levels were noted 1 mo after initiation of antithyroid drugs. Both patients were euthyroid at the time of CK elevation. While the mechanisms for this process are not clear, it is likely that the acute decrease of thyroid hormones in tissues following a state of chronic hyperthyroidism may result in relative hypothyroid states and subsequent alterations in CK concentrations. CONCLUSION: Although this side effect has been reported in adults, it is a novel finding in children. Clinicians should be aware of the rare potential for elevations in serum CK when initiating treatment for Graves' disease in children.
Acta Paediatrica 03/2006; 95(2):243-5. · 2.07 Impact Factor
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ABSTRACT: Familial glucocorticoid deficiency (FGD) is characterized clinically by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but not with mineralcorticoid deficiency. Excessive growth was described previously in some patients with FGD, many of whom were shown to have mutations in the ACTH receptor gene. The mechanisms responsible for their excessive growth are unknown. We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD. No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature (+ 2.41S.D.) and advanced bone age (10 years 9 months) when she was 4 years 9 months old. Her plasma ACTH level had been elevated until then (124-2,684 pg/ml). Moreover, plasma estradiol was elevated for her age (21.3 pg/ml), and it decreased in response to the dexamethasone suppression test (from 25.4 to 6.9 pg/ml). Elevated plasma estradiol was apparently related to the increase in plasma ACTH and played a major role in excessive growth in this patient. On the other hand, the genetic analysis showed that the other two patients who were siblings were homozygous for the R137W mutation. Clinically, they responded well to hydrocortisone replacement therapy with almost normal plasma ACTH levels. Although all patients with the R137W mutation reported previously were tall, our patients were of normal height. We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation, but also from the action of elevated plasma ACTH.
The Tohoku Journal of Experimental Medicine 03/2005; 205(2):123-31. · 1.24 Impact Factor
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ABSTRACT: Congenital nephrogenic diabetes insipidus (NDI) is characterized by the insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge of this disease is based largely on case reports. For this study, we investigated the clinical findings of eight patients in terms of age at onset, age at diagnosis, main complaint, results of physical examination, the diagnosis, the effect of treatment, kidney function, and presence or absence of gene defects. The main complaints of all eight cases at initial examination were unknown fever, failure to thrive, and short stature. Polyuria and polydipsia are not always the chief complaints with congenital NDI. In one case, diabetes insipidus could be diagnosed based only on the results of a 5% hypertonic saline test. In six cases, we found abnormalities in the V2 receptor gene. Initially, trichlormethiazide therapy was shown to have a significant effect on polyuria; however, this effect decreased over time. In one patient with partial NDI, the addition of trichlormethiazide twice a day to 1-desamino-8-D-arginine vasopressin increased urine osmolality in the morning and caused nocturia to disappear. Results of 99mTc-diethylenetriamine pentaacetic acid kidney scintigraphy revealed a slight decrease in glomerular filtration rate in three patients. No patient experienced serious renal dysfunction.
Endocrine 07/2004; 24(1):55-9. · 1.42 Impact Factor
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Pediatrics International 05/2004; 46(2):181-3. · 0.63 Impact Factor
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ABSTRACT: To clarify the pathogenesis of transient hyper-17alpha-hydroxyprogesteronemia, we initiated a laboratory investigation in a pre-term infant with persistently high serum 17alpha-hydroxyprogesterone (17-OHP) until 2 months of age.
Serum 17-OHP level was measured by high-performance liquid chromatography and radioimmunoassay, and gene analysis of CYP21A2 (21-hydroxylase) was performed.
Serum 17-OHP level on the 29th day of life was 25.4 ng/ml, and the urinary steroid profile showed low pregnanetriolone. Gene analysis of 21-hydroxylase disclosed no mutation, and 17-OHP normalized by 3 months of age without specific treatment.
Transient elevations in 17-OHP, which do not appear related to cross-reactions with products of a residual fetal adrenal cortex, may occur in the first few months of life.
Hormone Research 02/2004; 61(5):242-5. · 2.48 Impact Factor
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ABSTRACT: To clarify whether combination treatment with desmopressin (DDAVP) and thiazide was clinically effective in a patient with congenital nephrogenic diabetes insipidus (CNDI), we evaluated the treatment in a 7-year-old boy with CNDI who had demonstrated a partial response to DDAVP.
Both volume of urine and the presence of nocturia were determined during treatment.
Neither the usual therapy of a low-salt diet and a thiazide nor intranasal therapy with a large dose of DDAVP was effective. However, combination treatment resulted in a decrease in urinary volume and the disappearance of nocturia.
DDAVP coupled with thiazide may be useful for CNDI in patients who have shown a partial response to DDAVP.
Hormone Research 02/2003; 59(6):297-300. · 2.48 Impact Factor
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ABSTRACT: Pregnancies with fetuses affected with the Bartter syndrome, an autosomal recessive disorder of hyperreninism and hyperaldosteronism, are complicated by early onset of polyhydramnios which results in preterm deliveries. We have assessed biochemical changes in amniotic fluid and the mother's blood with a view to early diagnosis. Aldosterone levels of both amniotic fluid and the mother's blood were found to be increased at 27 weeks of gestation, while electrolyte levels did not differ significantly from those reported earlier for controls. After birth the baby suffered from polyuria with hyponatremia, hypomagnesemia and hypercalciuria which could be controlled by treatment with sodium chloride and magnesium. Elevated aldosterone thus might be a useful marker for early diagnostic purposes.
Fetal Diagnosis and Therapy 20(6):481-4. · 1.05 Impact Factor
