DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5–1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3′-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.     

Local Shwartzman activity of lipopolysaccharides from several selected strains of suspected periodontopathic bacteria

Lipopolysaccharides (LPSs) were isolated from Fusobacterium species, Bacteroides species, Actinobacillus actinomycetemcomitans and Escherichia coli by the phenol water procedure, and their capacity to induce the local Shwartzman reaction was determined. Preparatory and provoking injections of homologous LPS preparations caused LPSs from E. coli and F. nucleatum to induce a hemorrhagic necrosis, indicating a typical Shwartzman reaction. On the other hand, LPSs from A. actinomycetemcomitans and B. gingivalis induced a weak inflammatory lesion, but no necrotic lesion. The provoking activities of LPSs from F. nucleatum and A. actinomycetemcomitans in inducing an inflammatory lesion were comparable to that of LPS from E. coli , but the activity of LPS from B. gingivalis was low. The preparatory activities of LPSs from B. gingivalis and B. oralis in inducing an inflammatory lesion were comparable to those of LPSs from F. nucleatum, F. necrophorum and A. actinomycetemcomitans .     

Recent studies on insect hormone metabolic pathways mediated by cytochrome P450 enzymes

In insects molting and metamorphosis are primarily under the control of two insect hormones, ecdysone and juvenile hormone (JH). Physiological and biochemical studies of insect hormone metabolic pathways suggested the involvement of P450 (CYP) enzymes in the pathways, but molecular details of the enzymes were unclear. In recent years, the genome information and studies using molecular biology and genetics have allowed us to understand enzymes in the ecdysteroid and JH metabolic pathways. Genome sequencing has been accomplished in several insect species, and has shown the presence of 36-180 CYP enzymes. To date, six and one CYP enzymes have been revealed in the biosynthesis and inactivation pathways of 20-hydroxyecdysone (20E), respectively. In the 20E biosynthetic pathway, correlation among the enzymes, substrates and metabolites is elucidated in the late steps, but the enzyme(s) and intermediates in the early steps have not been fully understood and are referred to as the 'Black Box'. The gene expression of some CYP enzymes in the 20E biosynthesis is modulated by neuropeptides and JH. Furthermore, involvement of a CYP enzyme is found in both JH biosynthesis and inactivation pathways. Thus, recent studies have shown the importance of CYP enzymes in insect hormone metabolisms.     

Acquired factor V inhibitor responsive to corticosteroids in a patient with double cancers

A 70-year-old woman suffering from HCV-related liver cirrhosis was admitted for abnormal bleeding. Laboratory findings included PT at 46.6 sec, APTT at >212 sec, factor V activity of <3%, and factor V inhibitor of 2 BU. Having experienced a persistent bleeding tendency for one month, the patient was started on prednisolone (0.8 mg/kg/day). Within a few days, the inhibitor became undetectable and clinical bleeding disappeared. Although clinical improvement was achieved, she died 6 months after the initial bleeding episode from the progression of a lung cancer. An autopsy revealed squamous cell carcinoma of the lung and hepatocellular carcinoma.