Deposition of insoluble amyloid fibrils in tissues is a common hallmark of a wide range of human diseases referred to as amyloidoses, including Alzheimer's disease, type II diabetes mellitus. The amyloid deposits cause cell dysfunction, death, and subsequently severe impairment in tissues. Elucidation of amyloid formation mechanisms is essential for prevention of the onset and development of amyloidoses. Accumulated experimental evidence demonstrates that membrane lipids enhance the fibril formation of amyloidogenic proteins. Our group demonstrated that amyloid formation by amyloid β-protein (Aβ) was facilitated by gangliosides in lipid raft-like model membranes. Phosphatidylserine and phosphatidylglycerol were also reported to trigger fibril formation by human islet amyloid polypeptide (hIAPP). However, it is not verified whether the proposed lipid-protein interactions can occur on plasma membranes of live cells. The author developed a method for visualizing amyloid fibrils on live cell membranes and investigated the roles of gangliosides and cholesterol in lipid rafts for amyloid formation. Congo red, an amyloid-specific dye, was found to be a promising compound for staining amyloids in live cells. Aβ was accumulated on cholesterol-dependent ganglioside-rich domains in PC12 neuronal cells in a time- and concentration-dependent manner, leading to cell death. Nerve growth factor-induced differentiation of PC12 cells increased both gangliosides and cholesterol and thereby greatly potentiated the accumulation and cytotoxic effect of Aβ. Amyloid formation by hIAPP was also facilitated by gangliosides in lipid rafts. Membrane lipid compositions, in this case, gangliosides in lipid rafts, actually caused striking change in amyloid formation on cell membranes.

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  The present study was undertaken to investigate the beneficial effects of Atorvastatin and Simvastatin in cognitive dysfunctions of rats. Alprazolam, Scopolamine and high fat diet (HFD) induced amnesia served as interoceptive memory models where as, Water-maze and Elevated plus-maze served as exteroceptive models. A total of 38 groups of rats were used in this investigation. Escape latency time (ELT) recorded during acquisition trials conducted from day 1 to day 4, in water maze was taken as an index of acquisition, where as mean time spent in target quadrant during retrieval trial on day 5, was taken as the index of retrieval (memory). On elevated plus-maze, transfer latency (TL) measured on 1st d served as the index of acquisition and TL recorded on 2nd d was taken as the index of retrieval (memory). Alprazolam (0.5 mg kg^-1 intraperitoneally), Scopolamine (0.4 mg kg^-1 intraperitoneally) and HFD treated (for 90 days) rats exhibited amnesia as reflected by impairment in learning ability as well as memory, when tested on both, water maze and elevated plus maze. Atorvastatin (5 mg kg^-1 orally) as well as Simvastatin (5 mg kg^-1 orally) significantly attenuated Alprazolam, Scopolamine and HFD induced amnesia. These results highlight the ameliorative role of statins in experimental amnesia with possible involvement of their cholesterol dependent as well as cholesterol independent actions.

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The biosynthetic pathway of α, γ-diaminobutyric acid, 6moles of which are involved in the colistin molecule as a main component, was investigated. On the basis of the isotopic results using aspartic acid-U-¹⁴C as a precursor and also the finding of transaminase activity between α-ketoglutaric acid and α, γ-diaminobutyric acid, though in reverse reaction, α, γ-diaminobutyric acid was proved to be synthesized from aspartic acid via aspartyl-phosphate and aspartic β-semialdehyde. α, γ-Diaminobutyric acid did not inhibit aspartokinase activity of this bacterium, the first enzyme involved in the process of α, γ-diaminobutyric acid synthesis from aspartic acid, while the end product amino acids such as lysine, threonine and methionine showed inhibition for aspartokinase activity.
On the other hand, α, γ-diaminobutyric acid might be rate-limiting factor in colistin formation, because of stimulatory effect of this diamino acid when added to the medium on colistin production. Furthermore, colistin production appeared to be related with the defect of TCA-cycle and further the resultant increase in activities of the key enzymes such as isopropylmalate synthetase, α-acetolactate synthetase and aspartokinase involved in the biosynthetic pathways of valine, leucine and isoleucine, respectively.

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Extracellular vesicles (EVs) are particles released not only from blood cells but also from various organs. EVs, which are lipid bilayer vesicles, contain proteins, DNAs, and RNAs. The RNA and proteins within EVs display cell-specific characteristics. EVs derived from tumor cells are identified as biomarkers with diagnostic accuracy exceeding 90% for early cancer detection. Furthermore, EV RNA in serum has serves as a biomarker for toxicity. EVs have been found in various body fluids, including saliva, tears, urine, and amniotic fluid. In this study, we aimed to investigate the potential use of EV RNA in amniotic fluid as an indicator of developmental toxicity. Pregnant mice were exposed to valproic acid (VPA), a developmental toxicant, at concentrations of 0, 300, or 600 mg/kg/day on gestational days (GDs) 9–11. The study involved measuring VPA concentration in maternal plasma and fetuses on GD11, fetal weight on GD15 and 18, and assessing external morphological abnormalities on GDs11, 15 and 18. Additionally, EVs were collected from fetal amniotic fluid, and a comprehensive gene expression analysis of EV RNA was conducted on GD15. As a result, the concentration of VPA in the fetuses was not associated with the implantation location. Additionally, the VPA-treated group exhibited intrauterine growth retardation and teratogenic effects, including neural tube defects and digit malformations. EV RNA analysis identified differentially expressed EV small RNAs, both suppressed and induced, in the VPA-treated group compared with the control (vehicle, 0.5% Methylcellulose) group. These findings suggest that EV RNA in amniotic fluid serve as an indicator of developmental toxicity.

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A perforator-pedicled propeller (PPP) flap is often employed for reconstruction of the distal lower extremity. However, flap congestion that often causes flap necrosis occurs in the propeller flap. Although several procedures have been reported previously, a preferable method for preventing congestion and rescuing massive flap necrosis in PPP flap cases is undetermined.
A healthy 41-year-old man who sustained a pilon fracture in his right leg required soft tissue reconstruction because of strong edema that did resolve even after a staged protocol. A PPP flap pedicled with a perforator from the posterior tibial artery was harvested and rotated 180° to cover the defect. After reconstructive surgery, the flap developed severe congestion indicating the possibility of near-total flap loss. The flap was rescued by rotating it back to where its perfusion was stable. It was then rotated again in stages into the targeted position every 2 to 3 days over a period of 7 days. The flap was rescued and the wound was healed.
Delayed in-stage rotation of the flap was one of the options for salvaging a PPP flap from congestion especially in cases with severe soft tissue edema such as pilon fracture.

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Prostatic Adenocarcinoma (PA) and Benign Prostatic Hyperplasia (BPH) have their etiology not fully understood mainly in glycidic aspects. Glycan changes are associated with cell alterations where glycosylation is carried out by glycosyltransferases, such as fucosyltransferases (FUTs). These enzymes catalyze the insertion of L-fucose residues in a variety of glycan structures often in the final stage of glycosylation. The present study aimed to investigate the expression of FUT3 and FUT6 in PA and BPH as well as to correlate immunostaining of these transferases with PA clinic-histopathologic data. The FUT3 and FUT6 expressions were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded biopsies of PA (n=40) and BPH (n=40). FUT3 and FUT6 showed a high expression in both prostatic diseases, especially FUT6. FUT6 was more immunoexpressed in PA cases than the FUT3 (p<0.0001) as well as in BPH cases but in a not significant way (p=0.0661). Besides, FUT3 was more expressed in BHP lesion than in PA cases (p<0.0001). Our study presented a new data about FUT3 and FUT6 expression in PA and BPH, revealing high FUT6 expression in both lesions and FUT3 overexpression in BHP in relation to PA, proposing that this enzyme could be a promising biomarker for benign prostate alterations.

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Niemann–Pick disease type C (NPC) is an autosomal recessive disorder that is characterized by progressive neuronal degeneration. Patients with NPC have a wide age of onset and various clinical symptoms. Therefore, the discovery and diagnosis of NPC are very difficult. Conventional laboratory tests are complicated and time consuming. In this context, biomarker searches have recently been performed. Our research group has previously also investigated NPC biomarkers based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) and related techniques. To identify biomarker candidates, nontargeted analysis with high-resolution MS and MS/MS scanning is commonly used. Structural speculation has been performed using LC/MS/MS fragmentation and chemical derivatization, while identification is performed by matching authentic standards and sample specimens. Diagnostic performance evaluation was performed using the validated LC/MS/MS method and analysis of samples from patients and control subjects. NPC biomarkers, which have been identified and evaluated in terms of performance, are various classes of lipid molecules. Oxysterols, cholenoic acids, and conjugates are cholesterol-derived molecules detected in the blood or urine. Plasma lyso-sphingolipids are biomarkers for both NPC and other lysosomal diseases. N-palmitoyl-O-phosphocholine-serine is a novel class of lipid biomarkers for NPC. This article reviews biomarkers for NPC and the analysis methods employed to that end.

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九州4施設における昭和56, 57年度の白癬菌培養成績を報告するとともに九州大学における昭和47年から昭和57年までの白癬菌培養成績と白癬患者数の統計を加え, 最近の九州地方における白癬菌相の動態についてのべた。九州大学の最近11年間の総分離株数は1,692株である。内訳はTrichophyton rubrumが1,303株(77%), T. mentagrophytes 271株(16%), Microsporum canis 48株(3%), Epidermophyton floccosum 40株(2%), M. gypseum 15株, T. verrucosum 6株, T. violaceum 4株, T. glabrum 4株, T. tonsurans 1株であつた。九州本土3施設の最近2年間の総分離株数は960株で, T. rubrum 716株(75%), T. mentagrophytes 183株(19%), M. canis 41株(4%), E. floccosum 12株, M. gypseum, T. glabrumがそれぞれ3株ずつ, T. tonsurans, T. violaceumがそれぞれ1株ずつであつた。琉球大学の最近2年間の総分離株数は148株で, T. rubrum 69株(47%), M. canis 49株(33%), T. mentagrophytes 25株(17%), M. gypseum 2株, T. glabrum 2株, E. floccosum 1株であつた。最近の九州地方の白癬菌相の特徴として, M. canisの浸淫がさらに著しくなつたこと, T. violaceum, T. glabrumは減少しつつあることがあげられる。

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It is still a problem concerned that the radioactive Cs is concentrated in MSW incineration residues such as fly ash. Therefore, further developments in incineration technology and management for the MSW containing radioactive materials are needed. In this study, the radioactive Cs and other elements were measured at two types of MSW incineration plants that were a stoker furnace with ash melting furnace, and a gasification and melting furnace. The measurements mainly covered the influence of the change in the composition of the waste incinerated and the ratio of the bottom ash and the fly ash to be melted in the ash melting furnace. The results obtained are;1) Si affects the fate of radioactive Cs in the bottom ash and slag, and Cl affects that in the fly ashes both from incineration and melting process, 2) Radioactive concentration of the slag increases with the decrease of the slag basicity defined as the ratio of CaO/SiO_2, which may suggest that the basicity is a practical index for the radioactive concentration in the produced slag.

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Purpose: We investigated the significance of CD24 and CD44 expression for predicting responses to chemotherapy and prognosis in primary breast cancer patients. Patients and Methods: Diagnosis of breast cancer was confirmed by core needle biopsy, and immunohistochemical studies were performed. Preoperatively, patients received anthracyclinecontaining chemotherapy. Expression of CD44 and CD24 was assessed immunohistochemically and the relationship with chemotherapy response and with prognosis was analyzed. Results : Between 2001 and 2004, 139 women were enrolled in this study. In the correlation analysis, CD24 expression was negatively associated with pathological response to chemotherapy (p=0.0003). A machine learning technique with an alternating decision tree (ADTree) showed that four logical rules are involved in predicting the response depending on the combination of CD24, HER2, tumor stage, CD44, progesterone receptor, and patient age. In the survival analysis, patients having CD44 (++) showed a significantly favorable prognosis as compared with others (p=0.0002). A multivariate analysis showed that CD44 expression had an independent prognostic value (p<0.001). Conclusion : We found a significant correlation between CD44 expression and prognosis and between CD24 expression and response to chemotherapy. CD24 and CD44 expressions would be useful predictive markers, although further studies are needed.

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The macroscopical and microscopical structures of the medulla oblongata and the pons of the mouse, and the retrograde degenerative changes appearing in the dorsal vagal nucleus after division of the vagus in the cervical region are presented. To study these subjects, Nissl staining, a modification of Cajal's silver impregnation and myelin technique were used. The results obtained are summarized as follows:
1. The dorsal vagal nucleus is composed of cells of three types: the large, the medium-sized and the small. The large and the medium-sized cells have a well-defined nucleus with a clear nucleolus, and a moderate amount of Nissl granules. The small cells are spindly or oval in shape, with a comparatively large nucleus and scanty Nissl granules.
2. About 70 % of the cells in the dorsal vagal nucleus undergo chromatolytic changes following section of the cervical vagus. This proves that it is one of the main sources of vagal preganglionic fibers. The chromatolytic cells are most numerous in the rostral second one-fifth part, and decrease gradually toward the rostral and the caudal parts.
3. About 30% of the cells in the nucleus, however, show- no changes after the same operation. It seems that these unchanged cells are composed of afferent vagal cells and some efferent elements other than the efferent nerve cells concerning the cervical vagus.
4. The present results do not agree with the conclus i o n of some earlier workers who mentioned that the medial part of this nucleus is motor and the lateral is sensory.
5. It is difficult to confirm strictly the localization of cardiac innervation within the dorsal vagal nucleus, though the present results seem to support roughly the view that the caudal portion of the nucleus concerns with cardiac innervation.
6. A small proportion of vagal f ibers decussate within the medulla, since a few chromatolytic cells are found in the heterolateral nucleus after cutting the cervical vagus. However, the appearance and localization of changed cells in the heterolateral side are irregular.
7. No chromatolytic change occurs in the hypoglossal nucleus and the nucleus of the solitary bundle following division of the vagus in the cervical region.
8. Macroscopically aspects of the medulla oblongata and the pons of the mouse are described.

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アンダーセンサンプラーのようなカスケードインパクターは, エアロゾルの粒度分布を決定する捕集装置として大変広く使用されてきた。しかしながら, 捕集表面が粒度分布に重要な影響を与える事が知られている。最も重要な捕集誤差は, 捕集表面からの粒子の “跳ね返り現象” に関係している。最適な捕集表面の選択を行う為に, 異なった捕表面を持つ3台のアンダーセンサンプラーを使用してエアロゾルサンプリソグの比較テストを行った。
最初のテストにおいては, ポリエチレンシート, ガラス板, 石英フィルターを捕集表面として使用した。重量および元素分析の結果, 石英フィルターが適した捕集表面である事が判った。
2回目のテストにおいては, パラフィンとワセリンでコーティングした2種類のガラス板とポリエチレンシートを捕集表面として使用した。パラフィンとワセリンでコーティングした捕集表面は高い捕集効率を示し, 特に “跳ね返り現象” による粗大粒子の損失を防いだ, それ故に, パラフィンおよびワセリンでコーティングした捕集表面は, 捕集したエアロゾル中の各元素の平均粒径値を増加させた。例えば, ワセリンおよびパラフィンをガラス板にコーティングした捕集表面とポリエチレンシートの捕集表面から得られたナトリウム平均粒径は, それぞれ4.2, 3.3, 21μmであった。これは, 平均粒径がそれぞれの捕集表面によって大きく異なる事を示した。
2回のテストの結果から, 正確な粒子の粒度分布を得るには, 粘着性又は柔かい捕集表面を用いたアンダーセンサンプラーを使用すべきである。

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The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. Statins inhibit cholesterol biosynthesis, leading to enhanced uptake of low-density lipoprotein (LDL) from the circulation via LDL receptors. This strong cholesterol-lowering action contributes to the beneficial effects of statins. For example, large clinical trials have demonstrated that statins significantly reduce cardiovascular risk. Recent research has shown that statins have other multiple actions involved in endothelial function, cell proliferation, inflammatory response, immunological reactions, platelet function, and lipid oxidation. These "pleiotropic actions" of statins probably provide a significant contribution to the reduction of cardiovascular events. This review summarizes the pleiotropic actions of statins in both basic and clinical studies. It also considers the potential for statin therapy in the treatment of stroke and dementia.

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本報では,イカリソウ属,アメリカイカリソウ属の主として花における維管束走向を調べた。花の各器官は,イカリソウ属では十字対生に,アメリカイカリソウ属では3数性の輪生配列をしているが,両属とも花被は3つのグループすなわち,外がく片,内がく片,花弁に分けることができる。内がく片と花弁は,その成長が遅れる。花床での維管束走向は両属でほぼ同じであった。外側の花被片では跡が1管束性で,内側の花被片,雄〓では跡が2管束性になる傾向がある。イカリソウ属では3管束性の跡も観察される。雌〓の維管束走向も両属でほとんど差はなく,2つのシステムからなっている。1つは背管束で,これは雌〓が果実となって裂けた時の一方の裂片に相当する部分を走る。もう一方は裂開した果実の種子をつける裂片に相当する部分を走る。これは主に腹管束,胚珠管束から成る。これらの結果をメギ属,ヒイラギナンテン属,トガクシソウ属の場合と比較してみると,トガクシソウ属では花床で維管束が2重構造になるということを除くと,同様の傾向を示していると言える。雌〓についても,メギ属,ヒイラギナンテン属,トガクシソウ属では漿果になり,イカリソウ属,アメリカイカリソウ属では袋果になるが,維管束走向,その他の形質からして,これらは基本的に同じ構造をしていると考えられる。

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Niemann–Pick disease type C (NPC) is an autosomal recessive disorder that features progressive neurodegeneration. Because NPC patients have mutations in NPC1 or NPC2 cholesterol transporting proteins, failures in cholesterol and other lipid trafficking occur. NPC patients represent a wide clinical spectrum in terms of age of onset and type of symptoms. Because conventional diagnostic methods are time-consuming and complicated, biomarker tests have attracted increased attention. In this review, recently reported biomarkers for NPC are discussed in detail. For example, oxysterols and some cholenoic acid conjugates, metabolized from excess cholesterol in NPC cells, can be detected in urine or plasma. In addition, two types of lysosphingolipids, sphingosylphosphorylcholine and glycosylsphingosine, are present at increased concentrations in NPC patients. A more recently discovered biomarker is N-palmitoyl-O-phosphorylcholine, previously called “lysosphingomyelin-509.” These biomarkers are helpful for the early diagnosis of NPC and may contribute to a good prognosis for NPC patients.

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