Hiroko Kodama

Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans Cinnamon rat

BACKGROUND AND AIMS Large-scale epidemiological studies have shown that drinking more than two cups of coffee per day reduces the risks of hepatitis and liver cancer. However, the heterogeneity of the human genome requires studies of experimental animal models with defined genetic backgrounds to evaluate the coffee effects on liver diseases. We evaluated the efficacy of coffee consumption with one of experimental animal models for human disease. METHOD We used the Long Evans Cinnamon (LEC) rat, which onsets severe hepatitis and high incidence of liver cancer, due to the accumulation of copper and iron in livers caused by the genetic mutation in Atp7B gene, and leading to the continuous oxidative stress. We determined the expression of inflammation related genes, and amounts of copper and iron in livers, and incidence of the pre-neoplastic foci in the liver tissue of LEC rats. RESULTS Coffee administration for 25 weeks delayed the occurrence of hepatitis by two weeks, significantly improved survival, reduced the expression of inflammatory cytokines, and reduced the incidence of small pre-neoplastic liver foci in LEC rats. There was no significant difference in the accumulation of copper and iron in livers, indicating that coffee administration does not affect to the metabolism of these metals. These findings indicate that drinking coffee potentially prevents hepatitis and liver carcinogenesis through its anti-inflammatory effects. CONCLUSION This study showed the efficacy of coffee in the prevention of hepatitis and liver carcinogenesis in the LEC model.

Low serum biotin in Japanese children fed with hydrolysate formula

Given that nutritional biotin deficiency in Japanese infants has been reported, a straightforward method for estimating biotin level is needed. The biotin content in infant formula, breast milk, and the sera of infants fed with various types of formula were measured using avidin‐binding assay.

Low serum biotin levels in Japanese children fed with hydrolysate formulas

Given that nutritional biotin deficiency in Japanese infants has been reported, a straightforward method for estimating biotin level is needed. The biotin content in infant formula, breast milk, and the sera of infants fed with various types of formula were measured using avidin‐binding assay.

Standard values for the urine HVA/VMA ratio in neonates as a screen for Menkes disease

BACKGROUND Menkes disease is a lethal disorder associated with copper metabolism. Although early treatment with copper-histidine injections can improve outcomes, early diagnosis is difficult because the clinical features of Menkes disease are subtle or do not manifest in affected neonates. Previous report stated that the low activity of dopamine β-hydroxylase, a copper-dependent enzyme, leads to increases in the urine homovanillic acid/vanillylmandelic acid (HVA/VMA) ratios in patients with Menkes disease, and indicated that a urine HVA/VMA ratio cut-off value of >4 is useful in screening for Menkes disease. METHODS We examined the standard values of the urine HVA/VMA ratio in unaffected neonates and assessed its use as a screening parameter for Menkes disease among neonates. In total, 112 neonates, aged between 1 and 6 days, were enrolled in the study and were classified into 2 groups based on their urine HVA/VMA ratios: high (>4) and low (⩽ 4). RESULTS Multivariate logistic analysis revealed that mechanical ventilation was an independent risk factor for a high urine HVA/VMA ratio (odds ratio: 21.94; 95% confidence interval: 2.82-247.03; p=0.004). The mean urine HVA/VMA ratio was 2.47 ± 0.67 among 92 neonates who did not receive mechanical ventilation. CONCLUSION This study established standard values for the urine HVA/VMA ratio in newborn babies that could be useful in screening for Menkes disease among neonates.

Recent Trends of Trace Element Studies in Clinical Medicine in Japan

The deficiency or excess intake of trace elements, including zinc, copper, selenium and iodine, has often been reported. Zinc deficiency is often observed in infants fed breast milk with low zinc concentration, individuals administered chelating medicines, athletes and patients with diabetes mellitus, hepatic cirrhosis or nephrosis syndrome. Menkes disease is associated with severe copper deficiency, and there is no effective treatment. Deficiencies of selenium and iodine are observed in patients who receive special formulas of milk and enteral formula with low selenium and iodine concentrations, respectively. In contrast, neonatal transient hypothyroidism due to excess intake of iodine in pregnant women has also reported in Japan. It is expected that collaborative studies by researchers and clinicians will contribute to clarify the detail mechanism, diagnosis and treatment of these abnormalities.

Nutritional Status of Japanese Women of Childbearing Age and the Ideal Weight Range for Pregnancy

According to the recent 2015 Nutrition Survey, the prevalence of being underweight (Body Mass Index, BMI <18.5 kg/m2) among women in their 20s is 22.3%. Women of childbearing age tend to have a lower intake of protein and their total energy intake is lower than the requirements established by the 2015 Dietary Reference Intakes for Japanese. There is a growing body of evidence showing that underweight women tend to bear small babies and that these babies have an increased risk of diabetes or cancer in their adulthood. In order to prevent Japanese women from bearing small babies, the literature has suggested that women of childbearing age should be encouraged to remain at a normal weight before pregnancy. For optimal weight gain during pregnancy, existing guidelines recommend different ranges of weight gain based on prepregnancy BMI. Owing to the absence of official GWG recommendations in Asian countries, including China and Taiwan, the US Institute of Medicine (IOM) guidelines are generally followed. However, Asian women are smaller and experience lower weight gains; therefore, excessive weight gain may lead to harmful events including macrosomia, preterm birth, preeclampsia, gestational diabetes, pregnancy-induced hypertension, and short- and long-term postpartum weight retention. Thus, an accurate GWG range should be determined for Asian women. We introduce one epidemiological study in which the optimal weight gain range was investigated by analyzing receiver-operating characteristic curves together with potential research ideas in this field with the aim of encouraging young researchers to solve this public health problem affecting mothers and children.

Sexual precocity in a girl with early-onset Graves’ disease

Abstract. We describe the case of a girl diagnosed with Graves’ disease (GD) at 2 yr of age, who developed early puberty. Preoperative examination for craniosynostosis revealed thyrotoxicosis. While she was tall and her bone age was advanced at GD onset, her linear growth attenuated after commencement of anti-thyroid treatment. However, at approximately 6 yr of age, breast budding was recognized. Hormonal analysis revealed pubertal levels of LH response to a GnRH stimulation test and serum E2. Gonadal suppression therapy with GnRH agonist was initiated, and her adult stature slightly exceeded the genetic potential. Although accelerated growth and skeletal maturation are often reported to occur at GD onset in prepubertal patients, early puberty is unusual, and this is the first reported case of sexual precocity in a girl with GD.

A Novel Two-Nucleotide Deletion in the ATP7A Gene Associated With Delayed Infantile Onset of Menkes Disease

BACKGROUND Determining the relationship between clinical phenotype and genotype in genetic diseases is important in clinical practice. In general, frameshift mutations are expected to produce premature termination codons, leading to production of mutant transcripts destined for degradation by nonsense-mediated decay. In X-linked recessive diseases, male patients with frameshift mutations typically have a severe or even lethal phenotype. PATIENT We report a case of a 17-month-old boy with Menkes disease (NIM #309400), an X-linked recessive copper metabolism disorder caused by mutations in the ATP7A copper transporter gene. He exhibited an unexpectedly late onset and experienced milder symptoms. STUDY AND RESULT His genomic DNA showed a de novo two-nucleotide deletion in exon 4 of ATP7A, predicting a translational frameshift and premature stop codon, and a classic severe phenotype. Characterization of his ATP7A mRNA showed no abnormal splicing. CONCLUSION We speculate that translation reinitiation could occur downstream to the premature termination codon and produce a partially functional ATP7A protein. Study of the childs fibroblasts found no evidence of translation reinitiation; however, the possibility remains that this phenomenon occurred in neural tissues and influenced the clinical phenotype.