BackgroundAggregatable amyloid β-peptide (Aβ) and non-aggregatable p3-Alcα are metabolic products of the γ-secretase cleavage of amyloid β-protein precursor (APP) and Alcadeinα (Alcα), respectively. Familial AD (FAD) -linked mutations in the presenilin 1 or 2 (PS1 or PS2) component of γ-secretase can cause alternative intramembranous processing of APP and Alcα, leading to a coordinated generation of variants of both Aβ and p3-Alcα. Variant Alcα peptides have been observed in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and sporadic Alzheimer's disease (AD). Since, like APP, Alcα is largely expressed in brain, one might predict that alternative processing of Alcα would be reflected in body fluids of some AD patients. These patients with misprocessing of multiple γ-secretase substrates might define an endophenotype of p3-Alcα, in whom AD is due either to dysfunction of γ-secretase or to a disorder of the clearance of hydrophobic peptides such as those derived from transmembrane domains.ResultsWe developed a simple procedure for extraction of p3-Alcα from plasma and for analyzing this extract in a sensitive, p3-Alcα-specific sandwich enzyme-linked immunosorbent assay (ELISA) system. Plasma p3-Alcα levels and Aβ40 levels were examined in sporadic AD subjects from two independent Japanese cohorts. In some of these patients, levels of plasma p3-Alcα were significantly higher, and were accompanied by parallel changes in Aβ40 levels. This AD-related difference was more marked in female subjects, but this phenomenon was not observed in subjects with frontotemporal lobar degeneration (FTLD).ConclusionReagents and procedures have been established that enable extraction of p3-Alcα from plasma and for quantification of plasma p3-Alcα levels by ELISA. Some populations of AD subjects apparently show increased levels of both p3-Alcα and Aβ40. Quantification of p3-Alcα level may be useful as a readily accessible biomarker for a population of sporadic AD patients in which disease pathogenesis is associated with either dysfunction of γ-secretase or with a disorder of the clearance of transmembrane domain-derived peptides.

From the brown alga, Sargassum tortile, seven new benzoquinones and hydroquinones bearing diterpenoid side chains were isolated. 2-Geranylgeranyl-6-methylbenzoquinone, which is likely to be a basic substance of the diterpenoid-substituted benzoquinones distributed in many Sargassum species, was also obtained.

Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins (α, β, γ) that share identical localization and function to the amyloid-β protein precursor (AβPP) in the brain. Alcs are proteolyzed in neurons through successive cleavages via secretases, resulting in non-aggregative p3-Alc, where p3 corresponds to the AβPP-fragment. We found p3-Alcα detected in human plasma reflected the pathological process of amyloid-β accumulation in Alzheimer's disease (AD) patients and therefore investigated the utility of p3-Alcα as a plasma biomarker in AD. We measured p3-Alcα plasma levels in 83 sporadic-AD, 18 mild cognitive impaired (MCI), and 24 control subjects using the sandwich-ELISA system. Pooled samples with previously published data (171 AD and 45 controls) were also analyzed. The plasma p3-Alcα concentrations in patients with AD and MCI were significantly higher compared with control subjects (224.7 ± 40.4, 223.3 ± 53.9, and 189.1 ± 32.9 pg/ml, respectively; p = 0.0012). In AD patients, the plasma p3-Alcα concentration significantly correlated with age (r = 0.23, p = 0.037) and serum creatinine levels (r = 0.23, p = 0.0012). Even after adjusting for confounding factors of age, gender, renal function, and ApoE-ε4, high plasma p3-Alcα levels were correlated with significant AD risk, with an odds ratio 1.47 (95% confidence interval: 1.18-1.93, p = 0.0019) for every 10 pg/ml increase. Pooled analysis further confirmed these findings. Increased plasma p3-Alcα, evident in the early stages of cognitive impairment, suggests that Alc metabolites are useful plasma biomarkers of AD.

An autopsy case of yolk sac tumor of the liver in a 29‐year‐old female was reported. The tumor was found originally in the right anterior segment of the liver on the first operation. The autopsy disclosed that the liver was almost entirely replaced by multiple, round tumor nodules. The tumor masses continuously extended to the peritoneum and to the subcutaneous tissue. There were no tumors in other organs including the ovaries, gut, stomach, lung, uterus, and kidneys, indicating that the tumor originated in the liver. Microscopically, the tumor showed typical characteristics of the yolk sac tumor. An immunohistochemical study showed that AFP was distributed fine granularly in the cytoplasm of tumor cells. Electron microscopic observation disclosed large amounts of electron‐dense material being closely related to basement membrane.

The possible benefit of oxygenation during initial cold flushing was investigated as means of improving the quality of live preservation in rats. In five group of animals (total 61 experiments), the lives were flushed with different perfusates. Non-oxygenated groups included controls, Collins' solution alone and Collins' solution containing perfluorotributylamine (FC-43). In the oxygenated groups, Collins' solution alone and collins' solution containing FC-43 were oxygenated by bubbling. The hepatic ATP level and histopathological changes were used to assess the quality of liver preservation. Oxygenation during the initial cooling process proved to be effective in maintaining energy metabolism and preventing the characteristic microscopic changes of ischemic damage. Oxygenated Collins' solution containing FC-43 showed a much longer lasting effect compared with oxygenated Collins' solution alone. Without FC-43. Under light microscopy, in integrity of the liver appeared to be well preserved up to eight hours with the former solution. It is concluded that enhanced oxygenation with FC-43 in the initial cold flushing period can improve the quality of liver preservation.