Immunogenetic mechanism of Beh?et's disease

In order to investigate the immunogenetic mechanism of Beh?et's disease, frequencies of HLA antigens were studied in patients. The subjects consisted of 66 patients and 99 normal controls. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR, -DQ antigens. HLA-DP antigens were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant increase of HLA-B15 was observed in the patients. In contrast, no significant difference was observed in HLA-Bw52 which possesses only two different amino acids from HLA-B15. On the contrary, frequencies of HLA-A11, HLA-Aw33, HLA-B35, HLA-B44 and HLA-DQw1 were significantly lower in the patients than in the controls. No significant difference was observed in HLA-DP antigens. These results suggest that Beh?et's disease involves both disease susceptibility factors and disease resistance factors and that such genetic factors are mapped within or very close to the HLA-B gene in the class I gene region. Additionally class II HLA-DQ antigen is associated with disease resistance factors.     

AUTOPSY FINDINGS IN TWO PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA Special References to Apolipoprotein B Localization and Internalization Defect of Low Density Lipoprotein

We have experienced two autopsy cases of familial hypercholesterolemia of type I la homozygote, one was a 21-year-old female with a defect in the internalization of low density lipoprotein which is thought to be the first autopsy report in the world, and the other was a 31-year-old male with a receptor negative for low density lipoprotein. Autopsy findings, in addition to marked skin xanthomatosis, disclosed reversed distribution of the aortic atherosclerosis, diffuse atherosclerotic narrowing of coronary arteries which led to myocardial necrosis, xanthomatous aortic and mitral valve, and much less severity of cerebral arteries rather than that of aorto-coronary atherosclerosis. We have examined the apolipoprotein B accumulation on these aortas, coronary arteries, and cardiac valves, which showed better correlation between apolipoprotein B deposit areas and preferential accumulation of Alcian blue positive areas suggested to contain sulfate glycosaminoglycan, and documented very rare localization of renal and osseous xanthomas in a patient with internalization defect of low density lipoprotein.     

Uric Acid Levels in Tissues and Plasma of Mice during Aging

Here we quantified the uric acid (UA) levels in 11 tissues and plasma of C57BL/6 male mice to track its turnover during 3 to 30 months of aging. UA levels in the adrenal glands, heart, and spleen increased with aging until 30 months of age. Similarly, UA levels in the liver, kidneys, pancreas, and testes increased until the mice were 24 months old. UA levels also rose in the lungs and skeletal muscles from 3 to 6 months and 6 to 12 months, respectively, and then remained at almost the same levels until 30 months of age. In the skin, UA decreased from 3 to 6 months and then stayed nearly constant until 30 months of age. Moreover, the small intestines and plasma had quite stable UA levels during aging. Thus, our assessment of 11 tissue types from mice showed that the UA levels increased in most tissues during aging.     

Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells

Dendritic cells (DCs) play important roles in tumor immunology. Leukemic cells in patients with myeloid neoplasms can differentiate into DCs in vivo (referred to as in vivo leukemic DCs), which are postulated to affect anti-leukemia immune responses. We established a reproducible culture system of in vitro FLT3 ligand-mediated DC (FL-DC) differentiation from murine lineage(-) Sca-1(+) c-Kit(high) cells (LSKs), which made it possible to analyse the effects of target genes on steady-state DC differentiation from hematopoietic stem/progenitor cells. Using this system, we analysed the effects of various myeloid neoplasm-related gene abnormalities, termed class I and class II mutations, on FL-DC differentiation from LSKs. All class II mutations uniformly impaired FL-DC differentiation maintaining a plasmacytoid DC (pDC)/conventional DC (cDC) ratio comparable to the control cells. In contrast, class I mutations differentially affected FL-DC differentiation from LSKs. FLT3-ITD and a constitutively active form of Ras (CA-N-Ras) yielded more FL-DCs than the control, whereas the other class I mutations tested yielded less FL-DCs. Both FLT3-ITD and FLT3-tyrosine kinase domain (TKD) mutation showed a comparable pDC/cDC ratio as the control. CA-N-Ras, c-Kit-TKD, TEL/PDGFRβ, and FIP1L1/PDGFRα showed a severe decrease in the pDC/cDC ratio. CA-STAT5 and CA-MEK1 severely inhibited pDC differentiation. FLT3-ITD, CA-N-Ras, and TEL/PDGFRβ aberrantly induced programmed death ligand-1 (PD-L1)-expressing DCs. In conclusion, we have established a simple, efficient, and reproducible in vitro FL-DC differentiation system from LSKs. This system could uncover novel findings on how myeloid neoplasm-related gene abnormalities differentially affect FL-DC differentiation from murine hematopoietic stem/progenitor cells in a gene-specific manner.     

The effect of placebo administration on the first-night effect in healthy young volunteers

The first-night effect is a well-known phenomenon that is considered to result from a subject's lack of adaptation to the unfamiliar environment of a sleep laboratory and to the technical equipment used for polysomnography. The effect has been explored as a laboratory model for transient insomnia. The main characteristics of this effect are short total sleep time (TST) and rapid eye movement (REM) sleep, a lower sleep efficiency index, and longer REM sleep latency. Previous studies have reported that personality traits (such as trait anxiety) are a potential cause of the first-night effect and that the placebo effect is closely related to the anxiety levels of the subjects. To the best of our knowledge, there are no reports regarding the effects of a placebo on first-night sleep. This omission can be explained by the fact that the polysomnographic recordings obtained during the first night of a study are generally excluded from the analysis in order to avoid the inclusion of the first-night effect. In the present study, 8 male university students were subjected to polysomnographic examinations during drug-free, placebo-administration, and benzodiazepine-administration conditions in order to clarify the placebo effect on sleep during consecutive nights, particularly on the first night. The recordings for each condition were conducted for 4 consecutive nights. A placebo or 5 mg nitrazepam was administered at 2230 h using a double-blind crossover design, while no drug was administered during the drug-free condition. There was a 10-day interval between the examination of each condition. Polysomnographic recording was started at 2300 h and continued until the natural awakening of the subjects on the next morning. Subsequently, the subjects were requested to fill in a rating scale that is used to evaluate the subjective perception of sleep. An increase in stage-2 sleep associated with the first-night effect was observed on the first night during the drug-free and placebo-administration conditions. However, REM sleep reduction associated with the first-night effect was detected on the first night during the drug-free condition; this decrease in REM sleep was counteracted by the placebo during the placebo-administration condition. The nitrazepam, but not the placebo, decreased both slow-wave sleep (SWS) and REM sleep. The values for the tendency to fall asleep, feeling refreshed upon awakening in the morning, and the tension upon awakening in the morning were improved to a greater extent by the placebo and nitrazepam administrations than when no drug was administered. These results demonstrate the possibility that placebo administration may have a hypnotic/anxiolytic effect and may improve transient insomnia without causing SWS and REM sleep reductions.