Vitamin K occurs in the natural world in several forms, including a plant form, phylloquinone (PK), and a bacterial form, menaquinones (MKs). In many species, including humans, PK is a minor constituent of hepatic vitamin K content, with most hepatic vitamin K content comprising long-chain MKs. Menaquinone-4 (MK-4) is ubiquitously present in extrahepatic tissues, with particularly high concentrations in the brain, kidney and pancreas of humans and rats. It has consistently been shown that PK is endogenously converted to MK-4 (refs 4-8). This occurs either directly within certain tissues or by interconversion to menadione (K(3)), followed by prenylation to MK-4 (refs 9-12). No previous study has sought to identify the human enzyme responsible for MK-4 biosynthesis. Previously we provided evidence for the conversion of PK and K(3) into MK-4 in mouse cerebra. However, the molecular mechanisms for these conversion reactions are unclear. Here we identify a human MK-4 biosynthetic enzyme. We screened the human genome database for prenylation enzymes and found UbiA prenyltransferase containing 1 (UBIAD1), a human homologue of Escherichia coli prenyltransferase menA. We found that short interfering RNA against the UBIAD1 gene inhibited the conversion of deuterium-labelled vitamin K derivatives into deuterium-labelled-MK-4 (MK-4-d(7)) in human cells. We confirmed that the UBIAD1 gene encodes an MK-4 biosynthetic enzyme through its expression and conversion of deuterium-labelled vitamin K derivatives into MK-4-d(7) in insect cells infected with UBIAD1 baculovirus. Converted MK-4-d(7) was chemically identified by (2)H-NMR analysis. MK-4 biosynthesis by UBIAD1 was not affected by the vitamin K antagonist warfarin. UBIAD1 was localized in endoplasmic reticulum and ubiquitously expressed in several tissues of mice. Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin K intake and bone health.
BackgroundAlthough numerous studies describe the clinical characteristics of idiopathic osteonecrosis of the femoral head (ONFH) in specific study populations, these have not been confirmed in countrywide studies.Questions/purposesWe therefore determined: (1) the annual number of patients seeking medical care and number of patients newly diagnosed; and (2) the distribution of the age and gender of the patients, potential causative factors, severity of the disease, and operative procedures performed.Patients and MethodsWe conducted a nationwide epidemiologic survey in 2005. The survey included all orthopaedic departments in Japan by stratified random sampling according to the number of beds.ResultsThe number of patients who sought medical care for idiopathic ONFH during 2004 was estimated to be 11,400 (95% confidence interval, 10,100–12,800). We obtained clinical information from 1502 of these patients. The peak in age distribution occurred in the 40s. Potential causative factors were systemic steroid administration (51%) and habitual alcohol use (31%). Hip replacement was the most frequently performed procedure (65%). Among patients with a history of systemic steroid administration, systemic lupus erythematosus was reported most frequently (31%) as the underlying disease. Among patients younger than 40 years, steroid use was the most prominent potential causative factor (60%), and hip replacement frequently was performed (45%). A greater proportion of patients with no history of steroid or alcohol use was observed among patients 65 years or older (41%).ConclusionsIn addition to the disease burden of idiopathic ONFH in Japan, our results confirmed the importance of developing preventive and treatment strategies, especially among the younger population.Level of EvidenceLevel IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
The present prospective study examined the association between maternal consumption of dairy products, calcium, and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16-24 months.Subjects were 763 Japanese mother-child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood.Higher maternal intake of total dairy products, milk, cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles were 0.45 (0.25-0.79), 0.50 (0.28-0.87), 0.51 (0.31-0.85), and 0.57 (0.32-0.99), respectively). When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile, children whose mothers had consumed o4.309 mg?day -1 had a significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64 (0.43-0.97) and 0.63 (0.41-0.98), respectively). Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze. Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema.
Maternal nutritional status during pregnancy is an important determinant of fetal growth. Although the effects of several nutrients and foods have been well examined, little is known about the relationship of overall maternal diet in pregnancy to fetal growth, particularly in nonWestern populations. We prospectively examined the relationship of maternal dietary patterns in pregnancy to neonatal anthropometric measurements at birth and risk of small-for-gestational-age (SGA) birth among 803 Japanese women with live-born, singleton, term deliveries. Maternal diet in pregnancy was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups (g/4184 kJ) were extracted by cluster analysis. The following three dietary patterns were identified: the 'meat and eggs' (n 326), 'wheat products', with a relatively high intake of bread, confectioneries and soft drinks (n 303), and 'rice, fish and vegetables' (n 174) patterns. After adjustment for potential confounders, women in the 'wheat products' pattern had infants with the significantly lowest birth weight (P¼ 0·045) and head circumference (P¼0·036) among those in the three dietary patterns. Compared with women in the 'rice, fish and vegetables' pattern, women in the 'wheat products' pattern had higher odds of having a SGA infant for weight (multivariate OR 5·2, 95 % CI 1·1, 24·4), but this was not the case for birth length or head circumference. These results suggest that a diet high in bread, confectioneries, and soft drinks and low in fish and vegetables during pregnancy might be associated with a small birth weight and an increased risk of having a SGA infant.
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