アテナイとイアソス : 前412-394年IG II^23の再構成(奥田俊介先生、高木道信先生、高橋正先生退職記念号)

本論文では,イアソス出土のヘレニズム時代の碑文(lasos 3926)によって新たにもたらされたIG II^2 3+IG II^2 165に関する知見をもとに,碑文の新テキストを紹介するとともに,この碑文の決議年代が前394年ごろであること,およびその歴史的背景を考察した。顕彰された3名のイアソス人亡命者は,おそらく前412年以来,アテナイに身を寄せていたが,小アジア解放戦線にアテナイの将軍とともに加わって力を尽くしたものと思われる。彼らは,前394年に小アジアが開放され,イアソスが解放されると,アテナイから顕彰され,アテナイの保護のもと祖国にもどることに成功した。The author examines a new text of IG II^2 3+IG II^2 165, recently published by Fabiani, Habicht and Culasso Gastaldi, and considers its historical background and circumstance. This is an honorary decree for three lasians, Anaxagoras son of Apollonides, and Artemon and Kydias, sons of presumably Eumachos. The date of the decree is thought ca. 394 BCE through the analysis of lasian situation at that time. The three lasians were presumably expelled from lasos in 412 BCE and fled to Athens. They acted with Athenian generals who fought against the Spartans, and after the success of the liberation of the Greeks in Asia Minor in 394 BCE, they succeeded to return to their homeland lasos and were honored as proxenoi of the Athenians

ミレトス決議(IGI^321) : 125年の学説史

「ミレトス決議(IGI^321)」は,アテナイとミレトスとの関係を規定した前5世紀のアテナイの決議碑文である。決議年代を示唆する前426/5年のアルコン名が読めるにもかかわらず,前450/49年の決議として議論が重ねられてきた。1961年にマッティンリが前426/5年説を提唱したあとも,こうした議論の流れは今日までほとんど変わっていない。本稿は,奇妙な研究史の蓄積がなされてきた「ミレトス決議」の125年にわたる学説史を整理したものである

A Unique Carrier for Delivery of Therapeutic Compounds beyond the Blood-Brain Barrier

BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases

Molecular changes in the postmortem parkinsonian brain

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's-linked genes; Transition metals, calcium and calcium-binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways