A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy

BACKGROUND: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS). METHODS: Neuroimaging was performed at the first episode of lethargy. For (1)H-MRS, locations were placed in the semioval center and the basal ganglia. Quantification of metabolite concentrations were derived using the LCModel. We confirmed the diagnosis subsequently by enzyme and molecular studies, which involved direct DNA sequence analysis and the development of a novel multiplex ligation-dependent probe amplification test. RESULTS: (1)H-MRS analysis revealed an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the results of quantitative (1)H-MRS and clinical findings, GABA-T deficiency was suspected and confirmed in cultured lymphoblasts. Molecular studies of the GABA-T gene revealed compound heterozygosity for a deletion of one exon and a missense mutation, 275G>A, which was not detected in 210 control chromosomes. CONCLUSIONS: Our results suggest that excessive prenatal GABA exposure in the central nervous system (CNS) was responsible for the clinical manifestations of GABA transaminase deficiency. Our findings suggest the dual nature of GABA as an excitatory molecule early in life, followed by a functional switch to an inhibitory species later in development. Furthermore, quantitative (1)H-MRS appears to be a useful, noninvasive tool for detecting inborn errors of GABA metabolism in the CNS

4-Hydroxyderricin inhibits osteoclast formation and accelerates osteoblast differentiation

4-Hydroxyderricin (4-HD) is a major polyphenol of Angelica keiskei (Japanese name Ashitaba), exhibiting anti-allergic, anti-diabetic, anti-oxidant, and antitumor effects. The present study was designed to evaluate the effects of 4-HD on bone formation and maintenance by using cultured osteoclasts and osteoblasts. 4-HD did not affect cell proliferation of stromal ST2 cells and preosteoblast MC3T3-E1 cells at concentrations of 1–10 μM. This compound inhibited the formation of multinucleated osteoclasts from mouse splenic cells, and we identified a molecular pathway of osteoclast differentiation mediated by 4-HD, which led to inhibition of the expression of receptor activator of nuclear factor-κB ligand and macrophage-colony stimulating factor in ST2 cells. By contrast, 4-HD enhanced indices of osteoblast differentiation, such as alkaline phosphatase activity and calcium deposition by osteoblastic MC3T3-E1 cells, at concentrations of 1–10 μM. Furthermore, we found that 4-HD at 1 μM attenuated H2O2 levels in MC3T3-E1 cells. Our findings indicate that 4-HD may have critical effects on bone formation and maintenance

Cigarette smoking and tooth loss experience among young adults: a national record linkage study

<p>Abstract</p> <p>Background</p> <p>Various factors affect tooth loss in older age including cigarette smoking; however, evidence regarding the association between smoking and tooth loss during young adulthood is limited. The present study examined the association between cigarette smoking and tooth loss experience among adults aged 20–39 years using linked data from two national databases in Japan.</p> <p>Methods</p> <p>Two databases of the National Nutrition Survey (NNS) and the Survey of Dental Diseases (SDD), which were conducted in 1999, were obtained from the Ministry of Health, Labor and Welfare with permission for analytical use. In the NNS, participants received physical examinations and were interviewed regarding dietary intake and health practices including cigarette smoking, whereas in the SDD, participants were asked about their frequency of daily brushing, and received oral examinations by certified dentists. Among 6,805 records electronically linked via household identification code, 1314 records of individuals aged 20 to 39 years were analyzed. The prevalence of 1+ tooth loss was compared among non-, former, and current smokers. Multiple logistic regression models were constructed including confounders: frequency of tooth brushing, body mass index, alcohol consumption, and intake of vitamins C and E.</p> <p>Results</p> <p>Smoking rates differed greatly in men (53.3%) and women (15.5%). The overall prevalence of tooth loss was 31.4% (31.8% men and 31.1% women). Tooth loss occurred more frequently among current smokers (40.6%) than former (23.1%) and non-smokers (27.9%). Current smoking showed a significant association with 1+ tooth loss in men (adjusted OR = 2.21 [1.40–3.50], P = 0.0007) and women (1.70 [1.13–2.55], P = 0.0111). A significant positive exposure-related relationship between cigarette smoking status and tooth loss was observed (P for trend < 0.0001 and 0.0004 in men and women, respectively). Current smoking was also associated with the prevalence of decayed teeth (1.67 [1.28–2.20], P = 0.0002).</p> <p>Conclusion</p> <p>An association between cigarette smoking and tooth loss was evident among young adults throughout Japan. Due to limitations of the available variables in the present databases, further studies including caries experience and its confounders should be conducted to examine whether smoking is a true risk of premature tooth loss in young adults.</p

Transient ischemic attack-like episodes without stroke-like lesions in MELAS.

A stroke-like episode is a core symptom in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Proton magnetic resonance spectroscopy (1H-MRS) is useful in the diagnosis of mitochondrial diseases. We report an 8-year-old girl with MELAS, presenting with a seizure and blindness. 1H-MRS showed a strikingly elevated lactate peak in the right occipital region, where no abnormal signals appeared on either T2-W or diffusion-weighted MRI. She recovered completely within a day. We describe this mild clinical condition with abnormal lactate peak in normal-appearing gray matter as a transient ischemic attack-like episode in MELAS