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Background Atrial fibrillation (AF) is known to increase the risks of cerebral and systemic embolism. Apart from vitamin K antagonists, edoxaban, a direct oral anticoagulant (DOAC), has been approved for oral anticoagulation in patients with non-valvular AF. On the other hand, DOACs are sometimes prescribed at off-label under-doses for patients who have undergone ablation for AF. Prothrombin fragment F1+2 is an activation peptide released from prothrombin during thrombin formation. The purpose of this study is to compare the effects of DOAC doses on coagulation and fibrinolytic markers. Methods and results A total of 88 patients with AF (age: 68±11 years, male:45%, paroxysmal AF n=49, persistent AF n=39) were recruited. All patients were received edoxaban (60mg or 30mg) once a day. For the purpose of the study, patients were divided into three groups according to whether they had been treated before the ablation procedure under an appropriate standard dose group (n=30 [34.1%]), appropriate low-dose group (n=35 [39.8%]), or off-label under-dose group (n=23 [26.1%]). We examined the coagulation and fibrinolytic markers, and echocardiographic parameters before ablation. All patients were followed up for 12 months after AF ablation. Creatinine clearance was significantly higher in appropriate standard-dose group than in appropriate low-dose or off-label under-dose group (101.1±38.4, 57.1±15.9 and 73.2±14.6 mL/min, respectively; P Conclusion Our results suggest that an appropriate standard dose of edoxaban is needed to suppress hypercoagulability in patients with AF. Funding Acknowledgement Type of funding sources: None. Prothrombin fragment F1+2 level

Background E/e' and the ratio of diastolic elastance (Ed)/arterial elastance (Ea) = (E/e')/(0.9 × systolic blood pressure), indices of left atrial (LA) pressure overload, are elevated in elderly women with heart failure with preserved ejection fraction (HFpEF). The severity of diastolic dysfunction is assessed by a combination of several indices of LA volume and pressure overload. However, which overload is more important as a single factor for the prognosis of these patients remains undefined. Methods We enrolled patients with HFpEF showing sinus rhythm (n=145; left ventricular ejection fraction >50%; men/women, 56/89; mean age, 80.5 years). Blood examination and transthoracic echocardiography were performed before discharge. All-cause mortality and admission for cardiac events were evaluated after more than 1 year (mean, 370 days). Results The all-cause mortality rate was 11% (16/145). There were significant differences in age (p=0.005), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level (p85 years (p888 pg/mL (p=0.003), E/e' >14.4 (p=0.020), and Ed/Ea >0.153 (p Conclusions LA pressure overload compared to volume overload was a useful marker for prognosis in elderly patients with HFpEF. As a single index for LA pressure overload in noninvasive echocardiographic findings, Ed/Ea may be more suitable than E/e'.

Background In patients with critical limb ischemia, it is desirable to obtain enough skin perfusion pressure (SPP) levels through revascularization. 2D-perfusion angiography is an emerging technology for the quantification of tissue perfusion consisted of 6 parameters calculated by time-density curve of digital subtraction angiography (DSA). Purpose We evaluated the feasibility of 2D-perfusion angiography for below the knee (BTK) endovascular therapy (EVT). We aimed to clarify which angiographical parameters of lower limb are related to SPP after EVT. Methods Consecutive 33 limbs (mean age 74.5 years, men 55%), which successfully underwent EVT for isolated BTK lesions, were enrolled in this study. We excluded Rutherford 6 limbs with severe gangrene or tissue loss, consequently 26 limbs were Rutherford 4 or 5 critical limb ischemia. We treated total 47 lesions, including 26 chronic total occlusive lesions. 5Fr guiding sheath was advanced to popliteal artery. DSA images were obtained by mechanical contrast infusion. We quantified indexed blood flow on below the ankle area by using 2D-perfusion angiography, and examined 6 parameters [arrival time (AT), time to peak (TTP), wash-in rate, width, area under the curve and mean transit time (MTT)] from acquired DSA. Hyperemia was induced by 20mg papaverine intra-arterial infusion through the guiding sheath. Results The parameters except wash-in rate were significantly shortened after hyperemia induced by intra-arterial papaverine infusion below the ankle region. Dorsal and plantar SPP were significantly correlated with hyperemic AT, hyperemic wash-in rate and AT ratio (hyperemic/rest) of lower ankle regions after EVT. However, only AT ratio was independently associated with dorsal SPP in multivariate analysis (P=0.032). A receiver operating characteristic curve showed hyperemic AT 50 mmHg after EVT with the area under the curve of 0.71 (95% confidence interval, 0.52–0.90) and 0.73 (95% confidence interval, 0.55–0.90), respectively. Representative Case of 2D-perfusion Conclusion Hyperemic AT

AimsWe report the clinical results of glenoid osteotomy in patients with atraumatic posteroinferior instability associated with glenoid dysplasia.Patients and MethodsThe study reports results in 211 patients (249 shoulders) with atraumatic posteroinferior instability. The patients comprised 63 men and 148 women with a mean age of 20 years. The posteroinferior glenoid surface was elevated by osteotomy at the scapular neck. A body spica was applied to maintain the arm perpendicular to the glenoid for two weeks postoperatively. Clinical results were evaluated using the Rowe score and Japan Shoulder Society Shoulder Instability Score (JSS-SIS); bone union, osteoarthrosis, and articular congruity were examined on plain radiographs.ResultsThe Rowe score improved from 36 to 88 points, and the JSS-SIS improved from 47 to 81 points. All shoulders exhibited union without progression of osteoarthritis except one shoulder, which showed osteoarthritic change due to a previous surgery before the glenoid osteotomy. All but three shoulders showed improvement in joint congruency. Eight patients developed disordered scapulohumeral rhythm during arm elevation, and 12 patients required additional open stabilization for anterior instability.ConclusionGood results can be expected from glenoid osteotomy in patients with atraumatic posteroinferior instability associated with glenoid dysplasia. Cite this article: Bone Joint J 2018;100-B:331–7.

X-ray absorption spectra (XAS) of the lowest excited singlet, triplet, and ground states (S 1 , T 1 , S 0 -XAS) of benzoic acid and methyl benzoate in the O 1s region were calculated. Resonant core transition to a hole at the highest occupied molecular orbital (HOMO) created by valence excitation was predicted about 3 eV below the lowest peak of S 0 -XAS but with very weak intensity. A strong peak of the T 1 -XAS well separated from S 0 -XAS peaks is found for both molecules so that identification of the core-excitations from the T 1 and selective excitation of the T 1 become possible. Bond dynamics of oxygen-containing bonds in the potential energy surface of valence and core doubly excited states are estimated by using molecular dynamics simulation. Enhancement in known state-selective dissociation and new type of state selectiteve dissociation are predicted for the core excitations from valence excited state.

Vitrification is widely used for assisted reproductive technology (ART). Most vitrification devices require the skillful placement of embryos into the carrier and aspiration of excessive vitrification solution.To evaluate the efficacy and safety of the Cryoroom as a vitrification device.Mouse and human embryos were vitrified with Cryoroom or Cryotop, and the developmental potency was assessed in vitro. Mouse monozygotic twin blastocysts were vitrified with Cryoroom or Cryotop for microarray analysis.In mouse and human embryos, there were no differences between the survival and developmental progress in each device. In silico, the Cryoroom device showed no changes, particularly in DNA methylation after vitrification compared with the Cryotop. These results showed that the form and function of the device may affect the gene expression levels in vitrified embryos.The Cryoroom represents a safe and potentially revolutionary vitrification device for ART.

PDGF has been shown to contribute to hypertrophy in vascular smooth muscle cells (VSMC). PDGF-AA differentially promotes protein synthesis in VSMC from spontaneously hypertensive rats (SHR) but not in those from Wistar-Kyoto rats (WKY). This observation has led us to postulate a role for PDGF alpha receptor (PDGFR-alpha) in the hypertensive hypertrophy of blood vessels. Western and Northern blot analyses demonstrated a high and specific expression of the PDGFR-alpha protein and mRNA in SHR cells but not in WKY cells. To clarify the mechanism of the differential expression of the PDGFR-alpha gene, we isolated the promoter region of the gene. Studies on the promoter functions indicated that this promoter is active in SHR cells but not in WKY cells. The regulatory domain responsible for this difference was narrowed to the sequence between -246 and -139, which enhanced the promoter activity of SHR fivefold over the basal activity. DNase I footprinting and gel-shift assay indicated that this sequence specifically interact with nuclear proteins from VSMC through the binding site for CCAAT/enhancer-binding proteins, and members of the C/enhancer-binding protein family play a significant role in the strain-specific transcription of the PDGFR-alpha gene.

Frictional problems in superconducting magnets are related to the stability and reliability of the magnets, because frictional heating causes quench of the magnet and the frictional resistance determines the limit of the shear force at the contacting surfaces. To find those materials possessing low friction, the frictional properties of ceramics of ZrO2 and Si3N4, three different kinds of MoS2 coated films and polyethylene fibre reinforced plastics (DFRPs) were examined at 4 K in liquid helium under reciprocating sliding conditions. The two ceramics showed similar tendencies in terms of friction. The organically bonded MoS2 film exhibited the lowest coefficient of friction of 0.06, while the coefficient of friction of DFRP was lower than that of glass fibre reinforced epoxy (GFRP).

Cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats express both alpha and beta isoforms of the platelet-derived growth factor (PDGF) receptors at high levels (100,000 and 240,000 sites/cell, respectively). In this cell type, PDGF-BB elicited a mitogenic response; however, PDGF-AA increased only protein synthesis without activating DNA synthesis. Protein kinase C (PKC) was activated by PDGF-AA as well as PDGF-BB with concomitant translocation from cytosol to membrane fractions. However, the hypertrophic effect of PDGF-AA was not affected by depletion of cellular PKC, whereas the mitogenic action of PDGF-BB was partially attenuated by the depletion. Following incubation with PDGF-AA or -BB, phospholipase C-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3-kinase were tyrosine phosphorylated; however, the phosphorylation of Ras-GTPase-activating protein was induced only by PDGF-BB. Both PDGF isoforms resulted in a prompt and transient increase in the level of 1,2-diacylglycerol (DAG), presumably through the action of PLC-gamma 1. After returning to basal levels, the rate of DAG synthesis steadily increased for at least 15 min due to activation of phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC). Incubation with PDGF-BB-activated phospholipase D (PLD) in a PKC-dependent manner resulting in the formation of phosphatidic acid (PA). PA was also formed by the sequential reactions of PC-PLC and DAG kinase in the PDGF-BB-stimulated VSMC, and these sequential reactions were not affected by PKC depletion. In contrast, PDGF-AA stimulation did not result in increased PA synthesis as neither PLD nor DAG kinase activities were affected. PA may be a significant second messenger in the activation of DNA synthesis by PDGF-BB. These results indicate that signaling mechanisms of the PDGF-alpha and -beta receptors in VSMC are distinctly different in signal transduction in VSMC and that the alpha receptor promotes cellular hypertrophy (but not hyperplasia), whereas a mitogenic response is mediated only through the beta receptor.

When cultured in the presence of fetal calf serum, aortic vascular smooth muscle cells (VSMC) derived from spontaneously hypertensive rats (SHR) grow faster than those from normotensive control Wistar-Kyoto (WKY) rats. In order to investigate the mechanism underlying this growth abnormality, we measured phospholipase D (PLD) activity in VSMC taken from both SHR and WKY rats. Upon stimulation with serum, platelet-derived growth factor (PDGF) and porbol 12-myristate 13-acetate (TPA), phosphatidylethanol (PEt) was produced in the presence of ethanol. The responses of the VSMC from SHR (SHR-cells) to all stimuli were significantly greater than those of the VSMC from WKY rats (WKY-cells), which suggests an enhanced PLD activity in the SHR-cells. Since PLD is regarded as an enzyme involved in signal transduction leading to cell proliferation, this PLD hyper-reactivity in the SHR-cells may account at least partially for the growth abnormality in the SHR-cells.

There are two major isoforms of the angiotensin II receptor, type 1 (AT1) and type 2 (AT2). AT2 is distinguished from AT1 with respect to its ligand selectivity, its insensitivity to non-hydrolyzable GTP analogues, and its as yet unidentified biological functions. In the present study we have expression-cloned AT2 cDNA from a cDNA library of a rat pheochromocytoma cell line (PC12w). Rat AT2 cDNA encodes a 363-amino acid protein that has seven transmembrane domains. AT1 is the closest in homology to AT2 but with only a 32% identity of amino acid sequence. Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan. Northern blot analysis revealed that the mRNA of rat AT2 was expressed not only in PC12w cells but also in the adrenal glands and in the inferior olive of the brain, both of which are known to contain AT2 type binding sites. The expressed AT2 receptor mediated angiotensin II-induced inhibition of protein tyrosine phosphatase, an action that was dependent on a pertussis toxin-sensitive G-protein-coupled mechanism in COS-7 cells. The AT2-specific ligand CGP42112A was an agonist rather than antagonist in the inhibition of phosphotyrosine phosphatase. AT2 did not cause a decrease in cGMP in PC12w or COS-7 cells expressing AT2 stably. These results indicate that the AT2 receptor is structurally and functionally different from AT1 and suggest novel functional roles of the renin-angiotensin system in cross-talk with phosphotyrosine signaling by modulating protein phosphotyrosine levels.

In cultured rat vascular smooth muscle cells, platelet-derived growth factor (PDGF) beta receptor was expressed at a high level, whereas PDGF-alpha receptor was not detected. PDGF-BB showed a high binding activity at 4 degrees C in the cells and was not displaced by PDGF-AA or -AB. This result indicates that PDGF-AB as well as PDGF-AA does not bind to the cells lacking PDGF-alpha receptor at 4 degrees C. However, at 37 degrees C, PDGF-AB bound to the cells and induced the internalization of PDGF-beta receptor. DNA synthesis was also stimulated potentially by PDGF-AB as well as PDGF-BB in the cells, although PDGF-AA was completely inactive. At 37 degrees C, PDGF-AB caused tyrosine phosphorylation of a group of proteins including PDGF-beta receptor and phospholipase C-gamma 1, but at a slower rate than PDGF-BB. At 4 degrees C, PDGF-AB did not stimulate protein tyrosine phosphorylation, whereas PDGF-BB did. A chemical cross-linking experiment showed that PDGF-beta receptor was dimerized by PDGF-AB as well as PDGF-BB. These results indicate that PDGF-beta receptor binds PDGF-AB without participation of PDGF-alpha receptor at 37 degrees C (but not at 4 degrees C), and PDGF-AB as well as PDGF-BB acts as a potent mitogen in the vascular smooth muscle cells.

To investigate the regulatory mechanism of the vascular renin-angiotensin system, we perfused isolated rat hind legs with plasma-free buffer and quantified angiotensin peptides in the perfusate. Angiotensin release from hind legs was increased in rats pretreated with losartan (DuP 753) and rats fed a low sodium diet with subsequent furosemide and was decreased in nephrectomized rats and rats given dexamethasone, ethynylestradiol, and triiodothyronine. Using these models, we have attempted to identify which step or component of angiotensin metabolism determines angiotensin release level. Changes caused by these manipulations in plasma renin concentration and basal angiotensin release from hind legs were almost parallel, whereas plasma angiotensinogen concentration and the angiotensin release changed in opposite directions. Infusion of renin in hind legs caused a marked increase in angiotensin release and continued even 1 hour after cessation of renin infusion. Infusion of angiotensinogen did not alter the angiotensin release. Angiotensin clearance and angiotensin I conversion were not affected by either nephrectomy or losartan pretreatment. Aortic renin messenger RNA level was extremely low and not increased by nephrectomy or losartan pretreatment, although kidney renin messenger RNA level was increased by losartan pretreatment. These results provide evidence that plasma renin of kidney origin is the major source of vascular functional renin and plays the determining role in the regulation of vascular angiotensin release. Plasma-derived or locally produced angiotensinogen, locally produced renin, converting enzyme, and angiotensin clearance are not considered to be the primary determinant in the regulation of vascular angiotensin release in these acute and subacute experimental models.

The differing signal transductions elicited by three isoforms of platelet-derived growth factor (PDGF) were studied in cultured rat vascular smooth muscle cells (VSMC), which show different mitogenic responses to the three PDGF isoforms. PDGF-BB elicited a variety of cellular signals, including the phosphorylation on tyrosine of phospholipase C-gamma 1 (PLC-gamma 1) and the PDGF receptor, formation of inositol 1,4,5-trisphosphate and diacylglycerol, degradation of phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) and elevation of intracellular calcium ([Ca2+]i). However, PDGF-AB failed to show some of these signals, although it stimulated [3H]thymidine incorporation to almost the same extent as PDGF-BB. Importantly, phosphorylation on tyrosine of the PLC-gamma 1 was far less (< 6.25%) in the case of PDGF-AB than that of PDGF-BB when assessed by immunoblotting. On the other hand, calcium ion entry from the extracellular medium was comparable in PDGF-AB- and PDGF-BB- stimulated VSMC. PDGF-AA, which did not stimulate [3H]thymidine incorporation, failed to show any of these effects with the exception of diacylglycerol formation. These observations suggest that the three PDGF isoforms stimulate different signal transduction pathways and that calcium ion entry, but not tyrosine phosphorylation of PLC-gamma 1, is essential for PDGF-induced mitogenesis in VSMC.

Recent studies have suggested the importance of phosphatidylcholine (PC) metabolism in growth factor-stimulated cells. In these cells, PC is hydrolyzed not only by PC-specific phospholipase C but also by phospholipase D (PLD). In the present investigation, we show that the simple addition of PC-hydrolyzing PLD from Streptomyces chromofuscus to the culture medium of vascular smooth muscle cells elicits choline release into the medium accompanied by the formation of phosphatidic acid. In the presence of ethanol, this treatment elicits a formation of phosphatidylethanol (PEt) at the expense of phosphatidic acid. Furthermore, we show here that exogenous addition of S. chromofuscus PLD induces a marked DNA synthesis in quiescent vascular smooth muscle cells. This DNA synthesis induced by S. chromofuscus PLD is, like platelet-derived growth factor (PDGF)-elicited DNA synthesis, largely dependent on the presence of insulin. In addition, S. chromofuscus PLD-induced PEt formation and DNA synthesis were not affected by protein kinase C down-regulation, whereas PDGF-induced PEt formation and DNA synthesis were significantly inhibited. These observations strongly suggest that protein kinase-dependent activation of PLD is involved in mitogenic signal in PDGF-stimulated cells and that exogenously added PLD acts as a competence factor in the same way as PDGF.

‘‘Nongold’’ NiGe Ohmic contacts were developed by a lift‐off and annealing technique that was extensively used to fabricate the conventional AuGeNi contacts. The optimum conditions to prepare thermally stable, low resistance NiGe Ohmic contacts were determined by changing the Ge concentrations of the NiGe contacts from 13 to 43 at. %, and the deposition sequences of the Ni and Ge layers. Contact resistances of ∼0.8 Ω mm were obtained for both two‐layered Ni/Ge and three‐layered Ni/Ge/Ni contacts, with Ge concentrations of ∼38 at. % after annealing at 600 °C. The thermal stability of the electrical properties during subsequent annealing at 400 °C after contact formation was found to be influenced by the microstructure at the GaAs/metal interface. The excellent stability was obtained only when the NiGe contacts formed high melting point NiGe compounds. The present result indicated that removal of Au from the AuGeNi contacts was not satisfactory enough to improve the thermal stability of the AuGeNi contacts after contact formation. A model for the current transport mechanism through the GaAs/NiGe interface was also proposed by correlating the electrical properties and the microstructure. This model explained well the dependences of the contact resistances on the Ge concentrations and the deposition sequence of the Ni and Ge layers.

1. 1. Euglena gracilis SM-ZK (a non-photosynthetic mutant), cultured in Koren-Hutner medium, containing glucose, malate and glutamate as the main nutrients, were incubated anaerobiosis for 24 hr, and then returned to aerobic conditions. Wax esters, which were synthesized from paramylon (the reserved polysaccharide) for ATP generation under anaerobiosis (wax ester fermentation) were promptly degraded immediately after the cells were replenished with sufficient O 2 . A large part (about 70%) of the decomposed wax esters were converted back to paramylon. 2. 2. When cells were fed with [1–14C]acetate or [U- 14 C]acetate immediately after transfer from anaerobic to aerobic conditions, radioactivity incorporated into paramylon in the cells fed with [U- 14 C]acetate was about 1.5-times as high as that with [1- 14 C]acetate, proposing that glyoxylate cycle participates in the conversion from wax esters to paramylon. 3. 3. Paramylon synthesis from [1- 14 C]acetate was considerably activated by anaerobic preincubation of cells for several hours. 4. 4. Isocitrate lyase and malate synthase occurred in cells cultured in Koren-Hutner medium, but the activities were obviously lower than those in cells grown on ethanol. These enzymes were not induced by the anaerobic preincubation.

Pigmented mammary Paget's disease is a rare variant of mammary Paget's disease. The clinical appearance mimics malignant melanoma. This paper describes a case of asymptomatic, slightly pigmented spots on the right mammary nipple. The pigmented nipple was histopathologically diagnosed as mammary Paget's disease with an underlying intraductal carcinoma. This case suggests the importance of conducting skin biopsies of developing pigmented spots on the nipples in elderly people.

We investigated the influence of unilateral vertebral artery (VA) occlusion on bilateral inner ear blood flow in rats using laser Doppler flowmetry for the measurement of bilateral cochlear blood flow (CBF) and photochemically initiated thrombosis for VA occlusion. BP and CBF showed little change by unilateral VA occlusion alone. However, subsequent hypotension induced by venesection not only reduced CBF but also caused imbalance between bilateral CBF reduction rates. CBF changed independently of BP, indicating the existence of a local CBF regulatory system.

We discuss a method for computing an accurate optical kernel for large area optical proximity correction (OPC). The kernel can be calculated quickly in the Fourier domain, where the higher Fourier terms are cut by a finite pupil. We apply this method to the image simulation of the fine pattern exposed by the optical system with various coherence factors and various defocuses. It is in good agreement with the rigorous result within 5% error. Also, we present a photoresist profile computation method using the kernel for a chemically amplified resist.

MRE11 plays a role in DNA double-strand break repair. Hypomorphic mutations of MRE11 have been demonstrated in ataxia-telangiectasia (AT)-like disorder. ATM mutations play a causal role in AT and have been demonstrated in lymphoid malignancies in patients without AT histories. By analogy with the relationship of ATM to lymphoid malignancies, it is probable that alterations of MRE11 are associated with tumor formation. We performed a mutation analysis of MRE11 in 159 unselected primary tumors. Three missense mutations at conserved positions were found in breast and lymphoid tumors. Additionally, an aberrant transcript without genomic mutation was found in a breast tumor. These findings suggest an occasional role for MRE11 alterations in the development of primary tumors.

Vitamin B1 (thiamin), taken-up into cells, is converted to thiamin diphosphate (TDP), and TDP acts as a cofactor for several enzymes involving in carbohydrate metabolism. CoA-dependent oxidative decarboxylation of pyruvate is catalyzed by pyruvate dehydrogenase multienzyme complex (PDC) with NAD+ as an electron acceptor in most organisms involving mammals and higher plants. PDC consists of three component enzymes, one of which is pyruvate dehydrogenase (lipoamide) which contains TDP as a prosthetic group. Similar multienzyme complex for 2-oxoglutarate or branched chain 2-oxoacids is also found in mammals. In anaerobic bacteria, archaebacteria and anaerobic protozoa, pyruvate:ferredoxin oxidoreductase (PFOR) functions for the oxidative decarboxylation of pyruvate with ferredoxin in place of NAD+. PFOR contains TDP as a cofactor; however its structure is quite different from PDC and 1-3[4Fe-4S] clusters are involved as redox centers. Pyruvate:NADP+ oxidoreductase (PNOR), which catalyzes the oxidative decarboxylation of pyruvate with NADP+ as an electron acceptor, occurs in mitochondria of Euglena gracilis, a protist containing chloroplasts. PNOR consists of two functional domains, one of which contains TDP and 3[4Fe-4S] clusters and resembles PFOR. Another domain involves FMN and FAD as redox centers and its structure is similar to NADPH-cytochrom P450 reductase.

Two phase {gamma}-based TiAl alloys are attractive for structural applications at high temperatures because they possess good elevated-temperature mechanical properties, low density, and good creep and oxidation resistance. The microstructures of these alloys consist of plates of the near equiatomic {gamma} phase (L1{sub 0}-ordered structure) and the Ti{sub 3}Al {alpha}{sub 2} phase (D0{sub 19}-ordered structure). It is of great interest to study the details of the lamellar {alpha}{sub 2} + {gamma} microstructure because the interface stability is the key to providing a usable high temperature material. Polysynthetically twinned (PST) TiAl crystals have been developed in order to systematically study the lamellar microstructure. These PST materials contain no high angle grain boundaries and have an single set of aligned lamellar of {alpha}{sub 2} and {gamma} phases. Therefore, PST samples facilitate the study of the dependence of mechanical properties on lamellar structure by providing a known, consistent set of aligned lamellar. Previous transmission electron microscopy studies of PST TiAl have shown that Cr and Mo segregation occurs at certain non-coherent {gamma}/{gamma} twin boundaries. These studies also found a depletion of aluminum at certain {gamma}/{gamma} interfaces, showing ``{alpha}{sub 2}-like`` compositions. However, no evidence was found of even a few unit cells of the D0{sub 19}-ordered structure at the interface by microdiffraction. This paper investigates the feasibility of applying atom probe field ion microscopy to PST TiAl samples and presents some preliminary characterization results from {gamma}/{gamma} interfaces in PST TiAl.

Two hundred and forty consecutive Japanese patients with 280 primary total hip arthroplasties (THA) were analyzed to clarify the incidence of ectopic bone formation and its predisposing factors and to examine its effect on the clinical results. Ectopic bone formation after THA was found in 61 joints (22%). The predisposing factors were male patients and a hypertrophic type of osteoarthritis. It was revealed that extensive ectopic bone formation, class 3 according to Brooker's classification, restricted flexion and abduction motion of the hip joint.

In rats with ischemia induced by occlusion of the anterior inferior cerebellar artery (AICA) or vertebral artery (VA), we investigated the auditory brainstem response (ABR), electrocochleogram and caloric test result. Upon occlusion of the VA, there was no change of the ABR, whereas in the caloric test the duration of nystagmus upon stimulation of both ears shortened. Upon occlusion of the AICA, the cochlear blood flow (CoBF) showed one of three patterns of change no change: n = 5; decrease: n = 10; and transient decrease with recovery: n = 5. The cochlear potentials were dependent on the residual CoBF. In the caloric test, when the left AICA was occluded, the duration of nystagmus induced by stimulation of the left (ipsilateral) ear was shorter than that induced by the right (contralateral) ear. Based on the functional test results, we conclude that in this model of ischemia the function of the vestibular structures including the semicircular canals is more severely affected than is the hearing function.

We studied the efficacy of intrapleural administration of bleomycin for the management of malignant pleural effusions of non-small cell lung cancer in 24 cases. Bleomycin 60 mg was administered into the pleural space after tube drainage. If the effusion continued, one additional dose was given. The efficacy was seen in 18 cases (75%). The main adverse drug reaction was transient fever among others. There was little toxicity and no cases of pulmonary fibrosis. Intrapleural administration of bleomycin is useful in management of malignant pleural effusions.

Forty-two patients with stage IIIA (bronchoscopically T3 and/or bulky N2) and stage IIIB NSCLC were treated with concurrent chemoradiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m2 and etoposide, 40 mg/m2 by continuous infusion (day 1-5) of weeks 1 and 5 simultaneously with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between 10/90 and 12/92, 43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 37/5; mean age, 61 yrs (range, 31-74 yrs); stage IIIA/IIIB = 10/32; 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassified; PS 0/1/2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR, 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia, 15%; Grade 2-3 esophagitis, 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective randomized studies should be conducted for further evaluation of this treatment modality.

In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF) stimulated phosphatidic acid synthesis by activating both of the two alternative pathways, diacylglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was partially inhibited by genistein or R 59022, but these inhibitors had no effect on phorbol ester-induced DNA synthesis. Further, the specific effects of these inhibitors on PDGF-induced DNA synthesis were additive.

There are two major isoforms of the angiotensin II receptor, type 1 (AT1) and type 2 (AT2). AT2 is distinguished from AT1 with respect to its ligand selectivity, its insensitivity to non-hydrolyzable GTP analogues, and its as yet unidentified biological functions. In the present study we have expression-cloned AT2 cDNA from a cDNA library of a rat pheochromocytoma cell line (PC12w). Rat AT2 cDNA encodes a 363-amino acid protein that has seven transmembrane domains. AT1 is the closest in homology to AT2 but with only a 32% identity of amino acid sequence. Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan. Northern blot analysis revealed that the mRNA of rat AT2 was expressed not only in PC12w cells but also in the adrenal glands and in the inferior olive of the brain, both of which are known to contain AT2 type binding sites. The expressed AT2 receptor mediated angiotensin II-induced inhibition of protein tyrosine phosphatase, an action that was dependent on a pertussis toxin-sensitive G-protein-coupled mechanism in COS-7 cells. The AT2-specific ligand CGP42112A was an agonist rather than antagonist in the inhibition of phosphotyrosine phosphatase. AT2 did not cause a decrease in cGMP in PC12w or COS-7 cells expressing AT2 stably. These results indicate that the AT2 receptor is structurally and functionally different from AT1 and suggest novel functional roles of the renin-angiotensin system in cross-talk with phosphotyrosine signaling by modulating protein phosphotyrosine levels.

The differing signal transductions elicited by three isoforms of platelet-derived growth factor (PDGF) were studied in cultured rat vascular smooth muscle cells (VSMC), which show different mitogenic responses to the three PDGF isoforms. PDGF-BB elicited a variety of cellular signals, including the phosphorylation on tyrosine of phospholipase C-gamma 1 (PLC-gamma 1) and the PDGF receptor, formation of inositol 1,4,5-trisphosphate and diacylglycerol, degradation of phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) and elevation of intracellular calcium ([Ca2+]i). However, PDGF-AB failed to show some of these signals, although it stimulated [3H]thymidine incorporation to almost the same extent as PDGF-BB. Importantly, phosphorylation on tyrosine of the PLC-gamma 1 was far less (6.25%) in the case of PDGF-AB than that of PDGF-BB when assessed by immunoblotting. On the other hand, calcium ion entry from the extracellular medium was comparable in PDGF-AB- and PDGF-BB- stimulated VSMC. PDGF-AA, which did not stimulate [3H]thymidine incorporation, failed to show any of these effects with the exception of diacylglycerol formation. These observations suggest that the three PDGF isoforms stimulate different signal transduction pathways and that calcium ion entry, but not tyrosine phosphorylation of PLC-gamma 1, is essential for PDGF-induced mitogenesis in VSMC.

Recent studies have suggested the importance of phosphatidylcholine (PC) metabolism in growth factor-stimulated cells. In these cells, PC is hydrolyzed not only by PC-specific phospholipase C but also by phospholipase D (PLD). In the present investigation, we show that the simple addition of PC-hydrolyzing PLD from Streptomyces chromofuscus to the culture medium of vascular smooth muscle cells elicits choline release into the medium accompanied by the formation of phosphatidic acid. In the presence of ethanol, this treatment elicits a formation of phosphatidylethanol (PEt) at the expense of phosphatidic acid. Furthermore, we show here that exogenous addition of S. chromofuscus PLD induces a marked DNA synthesis in quiescent vascular smooth muscle cells. This DNA synthesis induced by S. chromofuscus PLD is, like platelet-derived growth factor (PDGF)-elicited DNA synthesis, largely dependent on the presence of insulin. In addition, S. chromofuscus PLD-induced PEt formation and DNA synthesis were not affected by protein kinase C down-regulation, whereas PDGF-induced PEt formation and DNA synthesis were significantly inhibited. These observations strongly suggest that protein kinase-dependent activation of PLD is involved in mitogenic signal in PDGF-stimulated cells and that exogenously added PLD acts as a competence factor in the same way as PDGF.

In cultured vascular smooth muscle cells (VSMC), angiotensin II (Ang II) induces a biphasic diacylglycerol (DAG) formation peaking at 15 sec and 5 min. Although it has been well established that the first peak is produced by the hydrolysis of inositol 4,5-bisphosphate (PIP2), the origin of the second DAG peak has never been examined in detail. In the present paper, we provide evidence that the second peak of DAG formation in Ang II-stimulated VSMC originates mainly from PC.

In earlier articles it was suggested that there is a relation between vertigo and the posterior circulation. This study was designed to ascertain the course of the branches of the vertebral artery and the basilar artery, as well as the principal blood vessels of the vestibular nucleus by using radiographic three-dimensional observation. We studied 27 human brains (17 males, 10 females) fixed with the arterial embalming method at the Department of Anatomy of Kawasaki Medical School. The results were as follows: 1. Many variations in the course of the anterior inferior cerebellar artery and the posterior inferior cerebellar artery were observed, but the most frequent pattern, observed in 56% of our subjects, was the anterior inferior cerebellar arteries originating from the basilar artery and the posterior inferior cerebellar arteries from the vertebral artery. 2. Measurement of the inside diameter of both vertebral arteries showed the diameter of the left side to be thicker than that of the right side. 3. Perforating branches in the brain stem consisted of the pontine branches from the basilar artery and small branches from the anterior inferior cerebellar artery. Moreover, the transverse section showed a large number of them to originate from the ventral part of the brain stem.

In a glass industry a material sheet of glass continuously flows out of a glass production furnace. Point-like defects locations are detected by a defect sensor. Rectangular glass plates of various sizes are cut out from the semi-infinite material sheet. Even a slight improvement of the overall yield rate considerably reduces the cost because of a large volume production. This paper is concerned with an optimal production strategy which maximizes the yield rate while meeting plate demands. The strategy consists of two parts,: an optimal cutting algorithm cuts the material sheet, given a pair of plates,: the optimal combination algorithm selects the optimal pairs. A Dynamic Programming is used to derive the optimal cutting algorithm, while a Linear Programming or a 0-1 Programming are used for the optimal combination algorithm. Several tens of percent increase of the yield rate is attained by application of the optimal production strategy.