A chemical neurotoxin, MPTP induces Parkinson's disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish

Parkinson's disease (PD) is the second most common neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. To create a new model of PD, we used medaka (Oryzias latipes), a small teleost that has been used in genetics and environmental biology. We identified tyrosine hydroxylase (TH) immunopositive dopaminergic and noradrenergic fibers and neurons in the medaka brain. Following establishment of a method for counting the number of dopaminergic neurons and an assay for the evaluation of the medaka behavior, we exposed medaka to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP). The treatment of medaka at the larval stage, but not at adult stage, decreased the number of dopaminergic cells in the diencephalon and reduced spontaneous movement, which is reminiscent of human PD patients and other MPTP-induced animal PD models. Among TH⁺ neurons in the medaka brain, only a specific cluster in the paraventricular area of the middle diencephalon was vulnerable to MPTP toxicity. Detailed examinations of medaka transiently exposed to MPTP at the larval stage revealed that the number of dopaminergic cells was not fully recovered at their adult stage. Moreover, the amounts of dopamine persistently decreased in the brain of these MPTP-treated fish. MPTP-treated medaka is valuable for modeling human PD.     

Circulating cell-free mRNA in plasma as a tumor marker for patients with primary and recurrent gastric cancer

BACKGROUND: The diagnostic value of circulating mRNA for the early detection of primary and recurrent gastric cancer was evaluated. PATIENTS AND METHODS: Circulating hTERT and MUC1 mRNA were amplified in the plasma from 52 gastric cancer patients (40 preoperative and 12 postoperative patients) and 20 healthy controls. The results were compared with those of a circulating cancer cell assay and methylation-specific polymerase chain reaction assay. RESULTS: Cell-free mRNA of the analyzed genes was detected in 6 (15%) preoperative gastric cancer patients (hTERT: 3 and MUC1: 4 patients) and 2 follow-up patients. These mRNAs were not detected in the plasma from healthy volunteers. There was no correlation between the results of the cell-free mRNA and the other assays. CONCLUSION: Detection of circulating cell-free mRNA might serve as a new complementary tumor marker for gastric cancer.     

Prognostic significance for stroke of a morning pressor surge and a nocturnal blood pressure decline: the Ohasama study

There is continuing controversy over whether the pattern of circadian blood pressure (BP) variation that includes a nocturnal decline in BP and a morning pressor surge has prognostic significance for stroke risk. In this study, we followed the incidence of stroke in 1430 subjects aged > or =40 years in Ohasama, Japan, for an average of 10.4 years. The association between stroke risk and the pattern of circadian BP variation was analyzed with a Cox proportional hazards model after adjustment for possible confounding factors. There was no significant association between total stroke risk and the nocturnal decline in BP (percentage decline from diurnal level) or between total stroke risk and the morning pressor surge. The cerebral infarction risk was significantly higher in subjects with a <10% nocturnal decline in BP as compared with subjects who had a > or =10% nocturnal decline in BP (P=0.04). The morning pressor surge was not associated with a risk of cerebral infarction. On the other hand, an increased risk of cerebral hemorrhage was observed in subjects with a large morning pressor surge (> or =25 mm Hg; P=0.04). Intracerebral hemorrhage was also observed more frequently in extreme dippers (those with a > or =20% nocturnal decline in BP) than dippers (those with a 10% to 19% decline; P=0.02). A disturbed nocturnal decline in BP is associated with cerebral infarction, whereas a large morning pressor surge and a large nocturnal decline in BP, which are analogous to a large diurnal increase in BP, are both associated with cerebral hemorrhage.