Several studies indicate that the mu-opioid receptor plays a role in addiction not only to opiate drugs but also to alcohol and non-opiate addictive drugs. Our studies aim to reveal the associations between gene polymorphisms and methamphetamine (MAP) dependence/psychosis. We newly identified several polymorphisms and four substantial linkage disequilibrium (LD) blocks in the mu-opioid receptor (OPRM1) gene. We found significant differences in both genotype and allele frequencies of the single-nucleotide polymorphism (SNP) IVS2+G691C between control (n=232) and MAP-dependent/psychotic patients (n=128). There was also a significant association between IVS2+G691C and patients with transient psychosis. These results suggest that the OPRM1 gene variations may be a factor in development and prognosis of MAP psychosis.

Adult↗

PubMedDate not supplied

Activation mechanism of brain microglia in patients with diffuse neurofibrillary tangles with calcification: a comparison with Alzheimer disease.

Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles (NFTs) without senile plaques (SPs). In this study, we investigated the distribution of human leukocyte antigen (HLA)-DR-positive activated microglia in postmortem brain tissue of six patients with DNTC and six patients with Alzheimer disease (AD). HLA-DR-positive activated microglia were observed to associate with SPs in AD. In the DNTC brain, which lacks SPs, HLA-DR-positive microglia were mainly accumulated around weakly tau-positive NFTs, which were also positive for anti-amyloid-P and anti-C3d antibodies. The results of this study suggest that the complement pathway is also activated in the DNTC brain and that immune and inflammatory responses, including microglia activation, may occur around extracellular NFTs in DNTC patients.

Aged↗

PubMedDate not supplied

Inhibition by interleukin 18 of osteolytic bone metastasis by human breast cancer cells.

Effects of interleukin (IL)-18 on experimental bone metastasis of human breast cancer cells, MDA-231 cells, in nude mice were investigated. In addition, effects of IL-18 on subcutaneous growth of MDA-231 cells were examined. Bone metastasis was produced by an intracardiac injection of MDA-231 cells. Twenty eight days after the cell injection, severe osteolytic bone metastasis was examined by X-ray radiography, and both non-osteolytic and osteolytic bone metastases were examined microscopically. IL-18 (1 microgram/mouse) was injected intraperitoneally according to protocols A and B. In protocol A, IL-18 was injected daily from day 7 after an intracardiac or subcutaneous injection of cells, and in protocol B, it was injected daily for 7 days each before and after the cell injection. In protocol A, IL-18 injections significantly suppressed both the incidence of osteolytic bone metastasis detected by X-ray radiography (about 80% vs. about 20% for the control group vs. the treatment group) and the number of its foci/mouse (1.6 vs. 1 for the control group vs. the treatment group). However, they did not cause significant effects on either the incidence of bone metastasis detected microscopically or the number of its foci/mouse. In protocol B, IL-18 injections caused no significant effects on either the incidence of osteolytic bone metastasis detected by X-ray radiography or the number of its foci/mouse. They caused no significant effects on the incidence of bone metastasis detected microscopically, but significantly decreased the number of its foci/mouse (about 2.0 vs. about 1 for the control group vs. the treatment group). In both protocols A and B, IL-18 injections produced no significant effect on the tumor take and subsequent growth of tumors after a subcutaneous injection of the cancer cells. Since in protocol A, IL-18 appears to have exerted its action after establishment of metastasis by cancer cells to the bone marrow, the effects of IL-18 found in Protocol A indicate that IL-18 inhibited osteolytic growth at bone metastatic sites of breast cancers. On the other hand, since in protocol B IL-18 is likely to have functioned around the time when lodging of cancer cells and early development of metastasis occur in the bone marrow, the effects of IL-18 found in Protocol B indicate that the cytokine also suppresses an early stage of bone metastasis of breast cancers, although, this effect was less apparent than the effect on osteolytic growth. Therefore, IL-18 may be useful for suppression of osteolytic bone metastasis which is a serious problem in patients of advanced breast cancers.

Animals↗