Plasma unconjugated bile acids as novel biomarker for schizophrenia.

In this study, we measured conjugated and unconjugated free bile acids (BAs) in plasma from patients with schizophrenia and healthy subjects to examine the possibility of BA as a biomarker for schizophrenia. Although the levels of each BA conjugate showed no significant differences, significant differences for three unconjugated bile acids were observed in the plasma between patients with schizophrenia and healthy subjects. Additionally, a more than three times difference between patients and healthy subjects was observed in the mean value of the total concentrations of primary BAs. These results indicate that cholic acid and chenodeoxycholic acid levels in plasma may be novel diagnostic markers for a sub-population of patients with schizophrenia. Thus, future studies should elucidate the relationship between this increase in BA levels and the pathology of schizophrenia and verify the potential of unconjugated BA in plasma as biomarkers for schizophrenia.

Extremely Photostable Electron-Deficient Phthalocyanines that Generate High Levels of Singlet Oxygen.

A robust lead-mediated synthetic procedure for the generation of phthalocyanines substituted with electron-withdrawing groups has been developed. The free-base phthalocyanine and various metal complexes were prepared without discernible degradation of the peripheral electron-withdrawing substituents. Upon irradiation with red light, some of the thus-obtained metal complexes generated high levels of singlet oxygen. In particular, a palladium complex exhibited attractive photostability upon exposure to singlet oxygen as a bleaching agent. The photostability of such complexes that may manifest concomitantly to the generation of high levels of singlet oxygen was attributed to the presence of the electron-withdrawing groups, which results in energetically low-lying highest occupied molecular orbitals.

Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan.

Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014-2016 (8%) was significantly lower than the frequency in 2005-2007 (41%), 2008-2010 (35%), and 2011-2013 (25%). This reduction was closely associated with changes in genotypes.

A Novel IgM-capture enzyme-linked immunosorbent assay using recombinant Vag8 fusion protein for the accurate and early diagnosis of Bordetella pertussis infection.

An ELISA that measures anti-PT IgG antibody has been used widely for the serodiagnosis of pertussis; however, the IgG-based ELISA is inadequate for patients during the acute phase of the disease because of the slow response of anti-PT IgG antibodies. To solve this problem, we developed a novel IgM-capture ELISA that measures serum anti-Bordetella pertussis Vag8 IgM levels for the accurate and early diagnosis of pertussis. First, we confirmed that Vag8 was highly expressed in all B. pertussis isolates tested (n = 30), but little or none in other Bordetella species, and that DTaP vaccines did not induce anti-Vag8 IgG antibodies in mice (i.e. the antibody level could be unaffected by the vaccination). To determine the immune response to Vag8 in B. pertussis infection, anti-Vag8 IgM levels were compared between 38 patients (acute phase of pertussis) and 29 healthy individuals using the anti-Vag8 IgM-capture ELISA. The results revealed that the anti-Vag8 IgM levels were significantly higher in the patients compared with the healthy individuals (P < 0.001). ROC analysis also showed that the anti-Vag8 IgM-capture ELISA has higher diagnostic accuracy (AUC, 0.92) than a commercial anti-PT IgG ELISA kit. Moreover, it was shown that anti-Vag8 IgM antibodies were induced earlier than anti-PT IgG antibodies on sequential patients' sera. These data indicate that our novel anti-Vag8 IgM-capture ELISA is a potentially useful tool for making the accurate and early diagnosis of B. pertussis infection.

Bronchitis caused by Bordetella holmesii in a child with asthma misdiagnosed as mycoplasmal infection.

We report a case of a bronchitis caused by Bordetella holmesii in a 2-year-old girl with asthma. The patient had a moderate fever and productive cough, and her condition was initially diagnosed as mycoplasmal bronchitis on the basis of her clinical symptoms and rapid serodiagnosis of mycoplasmal infection. She was treated with a bronchodilator and clarithromycin, which resulted in complete recovery. However, after the initial diagnosis, nucleic acid amplification tests of her sputum showed the absence of both Mycoplasma pneumoniae and Bordetella pertussis infections. Sputum culture showed the presence of a slow-growing, gram-negative bacillus in pure culture on Bordetella agar plates; the bacillus was later identified as B. holmesii. B. holmesii infection is rare in immunocompetent children; however, the organism is a true pathogen that can cause bronchitis in young children with asthma.

Simultaneous Determination of Five Bile Acids as Potential Biomarkers for Alzheimer's Disease in Mouse Brain and Plasma.

In this study, we developed an analytical method using LC-MS/MS for the simultaneous determination of five bile acids (BAs) that have been recently reported as candidate diagnostic biomarkers for Alzheimer's disease (AD) or AD related factors in the brain. The measurement of BAs in the brains of healthy mice led to the determination of candidate diagnostic markers for AD, such as cholic acid and deoxycholic acid, and other bile acids, such as chenodeoxycholic acid noted for the ameliorating effect on the symptoms of AD. Significant positive correlations were observed between the brain and plasma concentrations of four BAs in healthy young mice. These results indicate that the BA level in the brain may be estimated by the corresponding BA level in the plasma. Thus, our study suggested that the proposed method for the analysis of the five bile acids would aid in the diagnosis of AD or in studies that use AD model mice.

Treatment With Quadrivalent Human Papillomavirus Vaccine for Juvenile-Onset Recurrent Respiratory Papillomatosis: Case Report and Review of the Literature.

Although juvenile-onset recurrent respiratory papillomatosis (JoRRP) generally involves a benign tumor on the larynx and other respiratory tract areas, almost all patients with this disease require repeated surgical intervention (to prevent airway obstruction during the course of illness) and various adjuvant therapies such as interferon, cidofovir, acyclovir, ribavirin, indole-3-carbinol, HspE7, mumps vaccine, photodynamic therapy, propranolol, cimetidine, and bevacizumab. Some case reports recently described the effectiveness of the quadrivalent human papillomavirus vaccine (HPV4) as an adjuvant therapy. On the basis of these reports, we administered HPV4 to a 2-year-old boy with JoRRP. However, no therapeutic effect was found. A review of the available literature revealed that current evidence for the effectiveness of therapeutic HPV4 and other adjuvant therapies for JoRRP is inconsistent. Therefore, the prophylactic use of currently available HPV vaccine for adolescents is the most effective strategy for preventing not only anogenital cancers but also genital warts, which might be a risk factor for JoRRP among their children in the future.

Genetic analysis of Bordetella pertussis isolates from the 2008-2010 pertussis epidemic in Japan.

A large pertussis epidemic occurred between 2008 and 2010 in Japan. To investigate epidemic strains, we analyzed 33 Bordetella pertussis isolates from the epidemic period by sequencing virulence-associated genes (fim3, ptxP, ptxA, and prn) and performing multilocus variable-number tandem repeat analysis (MLVA), and compared these results with those of 101 isolates from non-epidemic, earlier and later time periods. DNA sequencing of the fim3 allele revealed that the frequency of fim3B was 4.3%, 12.8%, 30.3%, and 5.1% within isolates in 2002-2004, 2005-2007, 2008-2010, and 2011-2012, respectively. The isolation rate of the fim3B strain therefore temporarily increased during the epidemic period 2008-2010. In contrast, the frequencies of the virulence-associated allelic variants, ptxP3, ptxA1, and prn2, increased with time during overall study period, indicating that these variants were not directly involved in the occurrence of the 2008-2010 epidemic. MLVA genotyping in combination with analysis of allele types showed that the prevalence of an MT27d strain temporarily increased in the epidemic period, and that this strain carried virulence-associated allelic variants (fim3B, ptxP3, ptxA1, and prn2) also identified in recent epidemic strains of Australia, Europe, and the US. Phenotypic analyses revealed that the serotype Fim3 strain was predominant (≥ 87%) during all the periods studied, and that the frequency of adhesion pertactin (Prn) non-expressing B. pertussis decreased by half in the epidemic period. All MT27d strains expressed Prn and Fim3 proteins, suggesting that B. pertussis MT27d strains expressing Prn and Fim3B have the potential to cause large epidemics worldwide.