Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice.     

Next-Generation Sequencing-Based Molecular Diagnosis of Choroideremia

We screened patients with choroideremia using next-generation sequencing (NGS) and identified a novel mutation and a known mutation in the CHM gene. One patient presented an atypical fundus appearance for choroideremia. Another patient presented macular hole retinal detachment in the left eye. The present case series shows the utility of NGS-based screening in patients with choroideremia. In addition, the presence of macular hole in 1 of the 2 patients, together with a previous report, indicated the susceptibility of patients with choroideremia to macular hole.Key Words: Choroideremia, Next-generation sequencing, Diagnosis, Utility     

Role of Maternal Antibodies in Infants with Severe Diseases Related to Human Parechovirus Type 3

Human parechovirus type 3 (HPeV3) is an emerging pathogen that causes sepsis and meningoencephalitis in young infants. To test the hypothesis that maternal antibodies can protect this population, we measured neutralizing antibody titers (NATs) to HPeV3 and other genotypes (HPeV1 and HPeV6) in 175 cord blood samples in Japan. The seropositivity rate (>1:32) for HPeV3 was 61%, similar to that for the other genotypes, but decreased significantly as maternal age increased (p<0.001). Furthermore, during the 2014 HPeV3 epidemic, prospective measurement of NATs to HPeV3 in 45 patients with severe diseases caused by HPeV3 infection showed low NATs (<1:16) at onset and persistently high NATs (>1:512) until age 6 months. All intravenous immunoglobulin samples tested elicited high NATs to HPeV3. Our findings indicate that maternal antibodies to HPeV3 may help protect young infants from severe diseases related to HPeV3 and that antibody supplementation may benefit these patients.     

Acute myocardial infarction associated with myocardial bridging in a young adult

A 28-year-old man was admitted because of chest pain. Emergency coronary angiography showed a massive thrombus in the proximal segment and another occlusive thrombus in the distal segment of the left anterior descending artery. He was treated with thrombolytic therapy. Repeat coronary angiography showed disappearance of the thrombi in the proximal and distal segments and obvious myocardial bridging in the mid segment. Intravascular ultrasound revealed an atherosclerotic plaque in the segment immediately proximal to the myocardial bridging, but did not reveal any plaque within or distal to the site. He was discharged 12 days later.     

The alcohol-related problems survey: identifying hazardous and harmful drinking in older primary care patients

OBJECTIVES: Older adults can incur problems at low levels of alcohol consumption because of age-related physiological changes, declining health and functional status, and medication use. We have developed and tested a screening measure specifically for older people, the Alcohol-Related Problems Survey (ARPS), to identify older adults with these risks. DESIGN: Survey. SETTING: Academic and community primary care clinics. PARTICIPANTS: Five hundred forty-nine current drinkers aged 65 and older, mostly white with high school or more education. MEASURES: Alcohol use was classified as harmful, hazardous, or nonhazardous depending upon consumption alone or combined with selected comorbidities and medication use. Harmful drinking (including alcohol abuse or dependence) means the presence of problems (e.g., hypertension, adverse drug events, legal problems) due to drinking. Hazardous drinking means risks for problems are likely. Nonhazardous drinking poses no known risks for problems. RESULTS: Eleven percent of subjects were harmful drinkers and 35% were hazardous drinkers. Harmful drinking was more common in men than women and in persons younger than 75 than those aged 75 and older. Similar proportions of men and women and younger and older age groups were hazardous drinkers. Most harmful drinkers were identified by their use of alcohol with their comorbidity, whereas most hazardous drinkers were identified by their use of alcohol with medications. Test-retest reliability was substantial (kappa = 0.65). CONCLUSION: Physicians are urged to screen for alcohol-related problems in older persons. The ARPS reliably identifies harmful, hazardous, and nonhazardous drinking in older adults resulting most often from the interaction between alcohol and disease and medication use.     

Generation of a large number of functional dendritic cells from human monocytes expanded by forced expression of cMYC plus BMI1

Anticancer vaccination therapies with monocyte-derived dendritic cells (DC) are widely conducted. A large number of primary monocytes (approximately 10⁸ cells) are needed to generate the number of DC required to achieve an effect upon vaccination, and monocytes are usually purified from peripheral blood mononuclear cells obtained by apheresis procedure, which is somehow invasive for cancer patients. As a means to facilitate the generation of DC for therapeutic use, we herein report a method to amplify human monocytes. We found that lentivirus-mediated transduction of cMYC along with BMI1 induced proliferation of CD14⁺ monocytes derived from 9 out of 12 blood donors, and we named the monocyte-derived proliferating cells CD14-ML. Their proliferation continued for 3–5 weeks in the presence of M-CSF and GM-CSF, resulting in 20–1000-fold amplification. Importantly, the expanded CD14-ML differentiated into fully functional DC (CD14-ML-DC) upon the addition of IL-4 to the culture. We successfully stimulated autologous CD8⁺ T cells with CD14-ML-DC pulsed with cytomegalovirus peptide or MART-1 peptide to generate antigen-specific CTL lines. This is the first report describing the method for in vitro expansion of human peripheral blood monocytes.