Progressive external ophthalmoplegia (PEO) is one of a number of major types of mitochondrial disorders. Most sporadic PEO patients have a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in ...the mitochondria in skeletal muscles. We herein analyzed mtDNA deletions using sub-cloning and Sanger sequencing of PCR products in a 31-year-old Japanese man with multiple symptoms, including PEO, muscle weakness, hearing loss, leukoencephalopathy and hypogonadism. A large number of multiple deletions was detected, as well as four kinds of deletion breakpoints identified in different locations, including m.3347_12322, m.5818_13964, m.5829_13964 and m.5837_13503.
Escherichia coli has dispensable genome regions and eliminating them may improve cell use by reducing unnecessary metabolic pathways and complex regulatory networks. Although several strains with ...reduced genomes have already been constructed, there have been no reports of strains constructed with deletions assayed for influence on growth. To retain robust growth and fundamental metabolic pathways, the growth of each deletion strain and combination effects of deletions were checked using M9 minimal medium. Then a new strain, MGF-01, with a 1 Mb reduced genome was constructed by integrating deletions that did not affect growth. MGF-01 grew as well as the wild type in the exponential phase and continued growing after the wild type had entered the stationary phase. The final cell density of MGF-01 was 1.5 times higher than that of the wild-type strain. Using MGF-01 as a production host, a 2.4-fold increase in l-threonine production was achieved.
Abstract A 26-year-old woman with psychomotor developmental delay since late infancy showed rapid deterioration of her psychomotor abilities at the 11 years of age. She had gained the ability to ...verbally express herself and perform motor activities such as running and dancing in early childhood, but she lost the ability to verbally communicate and was unable to walk independently after this period. She also presented with dystonia in the right extremities, which markedly fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC (p.P399QfsX4) near the 3′-terminal of the coding region. The phenotype of this patient corresponds to the rare, unestablished variant of “late childhood deterioration” in MECP2-related disorders. For the first time, MECP2 mutation was confirmed to be the genetic basis of this condition.
Secondary prevention with medications is essential for the better prognosis of patients who have experienced cardiovascular events. We aimed to evaluate the use of guideline-based medications for ...secondary prevention in older adults in the community settings after discharge following percutaneous coronary intervention (PCI). A retrospective cohort study was conducted using anonymized claims data of older beneficiaries in a suburban city of Japan between April 2012 and March 2015. The prescriptions of antiplatelets, statins, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARB), and β-blockers were evaluated for 3 months before and after the month in which the participants underwent PCI. Multivariable logistic regression analysis was conducted to evaluate the associations of age (“pre-old” group 63-72 years vs. “old” group ≥ 73 years) and sex with the prescriptions, adjusting for whether a participant was followed-up by the PCI-performing hospital. Of 815 participants, 59.6% constituted the old group and 70.9% were men. The prescription rates for antiplatelets, statins, ACEi/ARB, and β-blockers after discharge were 94.6%, 65.0%, 59.3%, and 32.9%, respectively. The adjusted analysis indicated that statins were less likely to be prescribed for the old group (adjusted odds ratio aOR, 0.70; 95% confidence interval CI, 0.51-0.95; p = 0.023) and for men (aOR, 0.64; 95% CI, 0.45-0.89; p = 0.008). β-blockers were more likely to be prescribed for men (aOR, 1.66; 95% CI, 1.17-2.33; p = 0.004). Our results suggest the potential for improvements in secondary prevention by increasing the prescription rates of guideline-based medications in this population.
To clarify the characteristics of possible synergestic mitochondrial DNA (mtDNA) mutations associated with Leber's hereditary optic neuropathy (LHON), we analyzed the entire nucleotide sequences of ...mitochondrial genome of two Japanese patients from independent pedigrees harboring the 11778 mtDNA mutation, and compared their sequences with those of 47 disease and 6 normal controls. We have detected several unique mutations in the mtDNA in addition to the 11778 mutation. Two nucleotide substitutions, an A-to-G transition at position 856 in the 12S rRNA gene and an A-to-G transition at 14692 in the T psi C loop of the tRNA(Glu) gene, occurred at highly conserved sites among various species. These mutations in combination with the 11778 mutation might synergetically contribute to the pathogenesis of LHON.
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