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Skeletonema is a cosmopolitan diatom observed in coastal waters that forms extensive blooms, largely underpinning coastal ecosystems and fisheries. Recent revisions to the phylogeny of Skeletonema have shown multiple pseudocryptic species within the type species S. costatum. We developed a novel species-specific quantitative PCR (qPCR) method to track the annual dynamics of 7 Skeletonema species, including the pseudocryptic species, in the coastal waters of Ariake Sound, Japan. Fortnightly monitoring revealed that each Skeletonema species had different seasonality and occurrence patterns. The significant findings related to: (1) the species-specific ecological strategies and (2) the ecophysiology of the 5 pseudocryptic species assigned as S. costatum (sensu lato). Three Skeletonema species (S. costatum [sensu stricto], S. menzelii, and S. tropicum) formed blooms in summer, while the copy number of other species increased in winter (S. ardens, S. dohrnii/marinoi, S. grevillei, and S. japonicum). Bloom dynamics also differed among species, with either single intense bloom events or sustained moderate blooms. Summer species bloomed successively under the highly dynamic summer conditions (high freshwater input and anticyclonic tropical typhoons). By contrast, in winter, multi-species blooms were observed under conditions of low sea surface temperature and solar insolation. The single-peak species intensely bloomed during an ephemeral optimal time whereas others sustained their biomass in the pax between the intense blooms. Our in situ species-specific monitoring study connects ex situ physiology and in situ distributions, highlighting the diverse ecophysiology within this cosmopolitan diatom genus.

Changes in mRNA levels for the seven gene homologues to endoxyloglucan transferase-related protein, expansin, extensin, β-1,3 glucanase, glycine-rich protein, pectinacetylesterase and pectinesterase, which were obtained by random sequencing studies, were investigated in relation to rind development in citrus (Citrus unshiu Marc.) fruit. Expression patterns in the albedo and flavedo were classified into four types: Type-I, transcript levels low in early fruit development but increased at the ripening stage; Type-II, transcript levels high until mid-development and then decreased towards ripening; Type-III, detectable transcript limited to fruitlets at 26 days after flowering (DAF); Type-IV, ubiquitous during the development. Based on the expression patterns, we discuss the possible roles of these genes in rind development.

Recently, Japanese wine law has changed dramatically. In October 2015, the definition of “Japan wine” and the labelling rules were introduced, and the registration guidelines for the geographical indication (GI) were formulated. Up to now, the Commissioner of the National Tax Agency has designated two wine GIs: “Yamanashi” and “Hokkaido”. However, it is not easy for Japanese consumers to understand the value and the role of GI. The National Tax Agency, prefectures, municipal authorities and winery associations organise from time to time promotional events of GI wines to spread the notion of GI. Even though the majority of “Japan wine”, including GI wine, is consumed in the internal market, it is necessary to protect the Japanese GIs in foreign countries. Due to the EU-Japan EPA that ensures the mutual protection of GIs, it is quite probable that the GI will play an important role in the export of Japanese wine, liquor and agricultural products.

To cite this article: Seike M, Furuya K, Omura M, Hamada-Watanabe K, Matsushita A, Ohtsu H. Histamine H4 receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge. Allergy 2010; 65: 319–326. Abstract Background: The present study observed effects of the histamine H4 receptor on chronic allergic contact dermatitis induced by repeated challenge in mice. Methods: Acute contact dermatitis was induced by single epicutaneous challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the ear. Chronic allergic contact dermatitis was developed by repeated epicutaneous challenge using TNCB on the dorsal back skin. H4 receptor antagonist JNJ7777120 was administered to wild-type mice, while H4 receptor agonist 4-methylhistamine was administered to histidine decarboxylase (HDC) (−/−) mice that synthesized no histamine. Results: HDC (−/−) mice did not differ phenotypically from HDC (+/+) mice, and H4 receptor antagonist/agonist did not have clinical effects in terms of acute contact dermatitis reactions. H4 receptor antagonist ameliorated skin eczematous lesions induced by repeated TNCB challenge in HDC (+/+) mice. On the contrary, H4 receptor agonist exacerbated skin lesions exclusively in HDC (−/−) mice. Application of H4 receptor agonist induced migration of mast cells and eosinophils in skin lesions, and H4 receptor antagonist suppressed these changes. H4 receptor was immunohistochemically detected on mast cells in eczematous lesions. Levels of interleukin (IL)-4, -5, and -6 in lesions were decreased, whereas levels of interferon-γ and IL-12 were increased by H4 receptor antagonistic activity. Serum Immunoglobulin E levels rapidly increased with repeated challenge, but decreased with H4 receptor antagonist. Conclusion: Because chronic allergic contact dermatitis is developed by H4 receptor stimulation, H4 receptor antagonists might represent new candidate drugs for treating chronic allergic contact dermatitis.

We report on the growth of very thick (>260 μm) high-crystalline-quality single-crystal CdTe epitaxial films on (211) Si substrates in a metalorganic vapor-phase epitaxy reactor, and the development of gamma ray detectors and their radiation detection properties. Films were grown with a high growth rate varying from 40 μm/h to 70 μm/h. A heterojunction diode was fabricated by growing a 90-μm-thick CdTe layer on an n +-Si substrate, which exhibited good rectifying behavior and had a low reverse bias leakage current of 0.18 μA/cm2 at 100 V bias. The diode clearly demonstrated its gamma radiation detection capability by resolving energy peaks from the 241Am radioisotope during room-temperature measurements. By cooling the diode detector to −30°C, the leakage current could be reduced by three orders of magnitude from the room-temperature value. At this operating condition dramatic improvements in the pulse height spectrum were observed.

CdTe/n+-Si heterojunction diodes were fabricated and characterized for the development of gamma ray detectors. With the careful control of the growth parameters thick single crystal CdTe epilayers of high-crystalline quality were grown directly on the (211) Si substrates in a metalorganic vapor phase epitaxy. The heterojunction diode was fabricated by growing a 5 mum thick n-type CdTe buffer layer on the n+-Si substrate, followed by the 100 mum thick undoped p-CdTe layer growth. The diode fabricated showed very good rectification property with a low value of the reverse bias leakage current, typically 1.2 times 10-7 A/cm2 for an applied reverse bias of 50V. The diode clearly demonstrated its gamma radiation detection capability by resolving energy peaks from the 241Am radioisotope during the radiation detection test performed at room temperature.

A capillary tube is widely used as an expansion device for small refrigeration cycles. This series of papers discusses the influence of mixing refrigeration oil with the refrigerant on the flow through the capillary tube. In the first report, the mass flow rate and temperature and pressure distributions are examined experimentally when miscible or immiscible oil is mixed with refrigerant. In this study, a theoretical model is developed to estimate the influence of oil on the properties of refrigerant/oil mixture and on the mass flow rate. The theoretical model for the miscible combination is also applicable to the immiscible one, since the immiscible oil mixes homogeneously in the liquid phase in the capillary tube. The mass flow rates in both cases of miscible and immiscible combinations are calculated within an error of ±5% in comparison to measured data. In the immiscible combination, however, the model tends to underestimate the mass flow rate slightly as the oil concentration becomes larger than 0.1.

Tailor welded blanks (TWBs) – pressing blanks arranged to combine, by welding, multiple steel sheets of different thicknesses and properties, and which may or may not have been surface-treated – are now extensively used in the automotive industry for fabrication of car body panels. TWBs were initially used at mass production level in Germany in the early 1980s and have since seen rapidly increasing engineering applications worldwide.1, 2 TWBs were originally viewed as a way of boosting material yields through reuse of pressed-off edge material as well as of cutting manufacturing costs by reducing the number of component spot welds, number of welding operations, and number of pressing dies through integral forming of multiple pressings after pre-welding of blanks from conventional spot welding production.

Objective To compare the effectiveness and efficiency of transperitoneal anterior laparoscopic adrenalectomy with that of retroperitoneal posterior laparoscopic adrenalectomy. Patients and methods A retrospective comparison was undertaken of 28 patients who underwent transperitoneal anterior laparoscopy with 22 patients who underwent retroperitoneal posterior laparoscopy between April 1994 and November 2000. There were 18 men and 32 women (mean age 51.0 years, range 23–68) with varying diagnoses. Of the 50 patients, 31 had primary aldosteronism, eight had Cushing's syndrome, three had phaeochromocytoma, one had an 18-hydroxydeoxycorticosterone-induced adenoma and seven had non-functioning adrenal adenoma. Adrenal tumours were confirmed by hormonal assays, biochemical tests and computed tomography. To determine the site of the functioning adenoma, hormones were assayed from adrenal vein sampling. Thirty adrenal tumours were located on the right and 20 on the left. Results There were no significant differences in general demographic variables between the transperitoneal and retroperitoneal groups. The mean duration of surgery for transperitoneal and retroperitoneal laparoscopy was 202 and 221 min, respectively, and the mean blood loss 113 and 192 mL, respectively. The time to first oral intake, days to full diet, time until ambulatory and duration of hospitalization did not differ significantly between the two approaches. As the body mass index increased, the duration of surgery increased for both approaches. As more procedures were performed the duration of surgery decreased for both approaches. Conclusions There were no significant differences between the transperitoneal and retroperitoneal approaches for laparoscopic adrenalectomy.

Room temperature nuclear radiation detectors with energy discrimination capability developed by growing thick cadmium telluride (CdTe) epitaxial layers directly on n+-Si substrates in a metal-organic vapor phase epitaxy system is reported for the first time. The CdTe/n+-Si heterojunction diode detector exhibited good rectification and charge collection properties. The reverse leakage currents were typically 1times10-7 to 5times10-7 A/cm2 at 50-V bias. The detector clearly demonstrated its energy discrimination capability by resolving gamma peak from the 241Am radioisotope during radiation detection test at room temperature

Mitotic cells from Rough lemon (Citrus jambhiri Lush.), Ohta ponkan (C. reticulata Blanco) and two somatic hybrid plants obtained from protoplast fusion were analysed by double staining with chromomycin A3 (CMA) and 4′-6-diamidino-2-phenylindole. Only CMA-positive bands were observed in metaphasic chromosomes. The two parental karyotypes (2n=2x=18) were heteromorphic, yielding some marker chromosomes that could be identified in the somatic hybrids. One of the somatic hybrids had 2n=37 chromosomes, and the possible extra chromosome was distinguishable. The second somatic hybrid was tetraploid (2n=4x=36), with one of the chromosomes bearing a putative structural alteration. Furthermore, aneusomaty and some mitotic abnormalities were also observed in this latter plant. Such irregularities are reported for the first time for citrus somatic hybrids, and their possible causes and implications are discussed.

Somatic hybrids were obtained by the symmetric fusion of embryogenic callus cells from tetraploid 'Mame' kumquat [Fortunella hindsii (Champ.) Swing.] and mesophyll cells from diploid trifoliate orange [Poncirus trifoliata (L.) Raf.]. Southern blot analysis of three regenerants revealed that they carried specific rDNA fragments from both fusion partners, thereby confirming their hybridity. In contrast, mitochondrial DNA (mtDNA) and chloroblast DNA (cpDNA) were unidirectionally transmitted from the callus parent without any evidence of recombination. No differences in the restriction fragment patterns of rDNA, mtDNA or cpDNA could be detected among the regenerants. Flow cytometry showed that two regenerants were hexaploids, as expected, but that one was pentaploid, probably due to elimination of chromosomes prior to the regeneration of this plant.

Summary Offering the advantages of high welding speed and low heat distortion, laser welding is an attractive process for joining thin steel sheet. This paper describes an investigation of the static and fatigue strength of laser-welded lap joints in thin steel sheet with different sheet thicknesses and tensile strengths and compares the results with those obtained for spot-welded joints. To evaluate the static strength of the joints, a method for estimation of the joint strength and fracture mode is established. To evaluate the fatigue strength of the joints, the mixed-mode fracture-mechanics criterion of Erdogan and Sih is used, giving good characterisation of the fatigue strength, including that of the spot-welded joints.

Double fluorochrome staining with chromomycin A3 (CMA) and 4′-6-diamidino-2-phenylindole (DAPI) was used to characterize and compare the distribution of constitutive heterochromatin along chromosomes of Citrus, Poncirus and Fortunella species. Only CMA-positive bands were distinguishable in metaphase chromosomes. Preferential distribution of heterochromatin in terminal regions, mainly of the long arm, and centromeric regions of a few long chromosomes was a common feature of these genera. Heteromorphism between possible homologous chromosomes was present in the majority of species. Citrus and Poncirus revealed some remarkably uniform chromosomes without any intensively fluorescing region, whereas Fortunella cultivars were differentiated by the presence of CMA bands in all chromosomes. Through measurements assisted by a computer, amounts of CMA-positive regions were shown to be highest in Fortunella. Similarities between Citrus and Poncirus suggest little heterochromatin diversification among karyotypes of these genera, whereas Fortunella, with higher amounts and more homogenous distribution of heterochromatin, is more divergent.

The aim of the present study was to determine the precision of the PiCCO(®) system for post-cardiac arrest patients who underwent therapeutic hypothermia. The precision of the measurements for cardiac output, global end-diastolic volume, extravascular lung water and the pulmonary vascular permeability index was assessed using the least significant change; this was regarded as precise when less than 15%. A total of 462 measurement sets were prospectively performed on 88 patients following successful resuscitation after cardiac arrest. Using the mean value of three injections for a measurement, the least significant change for the cardiac output, global end-diastolic volume, extravascular lung water and pulmonary vascular permeability index measurements were found to be 7.8%, 8.5%, 7.8% and 12.1%, respectively. No significant differences between hypothermia (n=150) and non-hypothermia (n=312) were found. The PiCCO-derived variables were found to be precise for post-cardiac arrest patients even under conditions of varying body temperature.

Background. To the authors' knowledge, there have been no reports describing a case of malignant paraganglioma that produces both adrenocorticotropic hormone (ACTH) and interleukin-6 (IL-6). Methods. The clinical course and pathophysiology of a patient with Cushing's syndrome induced by ectopic ACTH syndrome caused by a cervical malignant paraganglioma with elevated plasma levels of IL-6 was investigated. Results. Ultrasonography, computed tomography, and magnetic resonance imaging of the neck revealed the presence of a tumor around the area from which the blood sample that showed the highest levels of ACTH and IL-6 was obtained by selective catheterization. Immunohistochemical staining of the removed tissue demonstrated the presence of ACTH and IL-6 proteins in the tumor cells. Reverse transcriptase-polymerase chain reaction also revealed the existence of IL-6 mRNA in those cells. Conclusion. The malignant paraganglioma of ectopic ACTH syndrome may produce IL-6. The present investigation provides new observations concerning ectopic ACTH syndrome.

[1-14C]Arachidonic acid was incubated with isolated bovine adrenal fasciculata cells for 15 min at 37gC. The metabolites were separated and purified by reverse- and straight-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry or radioimmunoassay. Identified metabolites were 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), leukotriene B4 and 11,14,15-trihydroxy-5,8,12-eicosatrienoic acid (11,14,15-THET). Addition of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE), an intermediate metabolite of 15-lipoxygenase pathway to microsomes of bovine adrenal fasciculata cells resulted in the formation of 11,14,15-THET. The formation of 11,14,15-THET by microsomes was not dependent on the presence of NADPH, while it was dose-dependently suppressed by ketoconazole, a potent inhibitor of cytochrome P-450 dependent enzymes. These results indicate that 5- and 15-lipoxygenase pathways of arachidonic acid may exist in bovine adrenal fasciculata cells and that 15-HPETE is further metabolized to 11,14,15-THET by adrenal microsomal cytochrome P-450.

The site of action of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) in ACTH-induced stimulation of steroidogenesis was examined in rat adrenocortical fasciculata cells. Prior addition of AA861, a specific inhibitor of 5-lipoxygenase, had no significant effect on cyclic AMP-dependent protein kinase activity and cholesterol esterase activities, when stimulated by ACTH in adrenocortical cells, compared with that stimulated by ACTH alone. Cholesterol accumulation in the mitochondria of cells treated with ACTH and cycloheximide was also not altered by pretreatment with AA861. We found, however, that pregnenolone formation, stimulated by ACTH, decreased in a dose-dependent manner when cells were pretreated with AA861. The inhibition of ACTH-stimulated pregnenolone formation by treatment with AA861 was restored only by prior addition of 5-HPETE. Furthermore, addition of AA861 also did not affect the conversion of pregnenolone into corticosterone. In conclusion, 5-HPETE may act at the level of the mitochondria in ACTH-induced steroidogenesis in rat adrenal fasciculata cells. Journal of Endocrinology (1990) 125, 89–96

High-performance CMOS-FinFET with dopant-segregated Schottky source/drain (DS-Schottky S/D) technology has been demonstrated. Thanks to the low parasitic resistance in DS-Schottky S/D, high drive current of 960 muA/mum was achieved for nFET with Lg = 15 nm and Wfin =15 nm at Vd= 1.0 V and Ioff= 100 nA/mum. Furthermore, the propagation delay time has been successfully improved down to less than 5 ps in the ring oscillator with DS-Schottky S/D CMOS-FinFET with 15 nm gate length

A3MCNP (Automatic Adjoint Accelerated MCNP) is a revised version of the MCNP Monte Carlo code, which automatically prepares variance reduction parameters for the CADIS (Consistent Adjoint Driven Importance Sampling) methodology. Using a deterministic 'importance' (or adjoint) function, CADIS performs source and transport biasing within the weight-window technique. The current version of A3MCNP uses the three-dimensional (3-D) Sn transport TORT code to determine a 3-D importance function distribution. Based on simulation of several real-life problems, it is demonstrated that A3MCNP provides precise calculation results with a remarkably short computation time by using the proper and objective variance reduction parameters. However, since the first version of A3MCNP provided only a point source configuration option for large-scale shielding problems, such as spent-fuel transport casks, a large amount of memory may be necessary to store enough points to properly represent the source. Hence, we have developed an improved version of A3MCNP (referred to as A3MCNPV) which has a volumetric source configuration option. This paper describes the successful use of A3MCNPV for a concrete cask neutron and gamma-ray shielding problem, and a PWR dosimetry problem.

The recent individualization in customer demand and fluctuation in business environment require manufacturing systems to follow the changing small trends promptly. This paper proposes Flow Oriented Approach, a method to design manufacturing system information, to accelerate diversified autonomous improvement activities performed by personnel from many departments. Based on this approach, raw data generated and used in manufacturing system are categorized according to work objectives, combined to messages, and made to flow through the system on autonomous decentralized system architecture. A tool on this architecture is also proposed for personnel to use manufacturing information selectively and promptly. This approach makes it possible to process data variously and extract useful information for improvement activities without disturbing on-line operation, in comparison with information sharing by shared files. The proposed approach has been applied to actual manufacturing systems and evaluated in several improvement activities.

A programming methodology and supporting system for the SFC language HI-FLOW are proposed. Through field studies of applications in tire manufacturing plants, various problems in the HI-FLOW system were recognized and classified. A method for design was incorporated into HI-FLOW which addresses and corrects previous problems. Final testing of the enhanced HI-FLOW in various time manufacturing machines was successful and the problems were eliminated. >

An automation system architecture for implementing autonomous decentralized systems (ADSs) called Hi-Cell is described. A project model of human organization featuring activities such as teaming is proposed as an analog for Hi-Cell behavior. Familiar team behaviors such as task allocation, learning, and cooperation are explored in the automation domain. >

Under severe economic situations, the computer systems of companies have to produce new products or supply new services flexibly in order to meet changing customers' demands. To realize a flexible computer system, the system should be able to expand and modify its software as well as its hardware rapidly. Moreover, companies have recently been tackling business process re-engineering (BPR) to share various kinds of information among different departments, for quick response to consumers' needs and cost reduction. An open ADS (autonomous decentralized system) architecture, which is a new control and information system architecture, is proposed to fulfil the flexibility of such a system. This paper introduces a practical manufacturing system realized on this platform. This system is developed based on the Hi-Cell concept that is defined as an assembly of autonomies called HIC (Homogeneous max Intelligent Cells). In this system, techniques for resumption have been applied and evidence for their effectiveness has been presented.

In factory automation systems, conventional hierarchal systems are no longer able to meet changing demands of customers today. Flexible systems, which are realized by making flat and autonomous judgment of workers in each section, to meet these demands rapidly are required. The paper proposes the expanded Hi-Cell system architecture which coordinates the whole system under the autonomous judgment of local workers. A system realized by this architecture prevents unnecessary information for each worker working locally and protects bad effects from others. The effectiveness of this system is proved by being adapted to the actual application of a tyre production system. >

To compare the effectiveness and efficiency of transperitoneal anterior laparoscopic adrenalectomy with that of retroperitoneal posterior laparoscopic adrenalectomy.A retrospective comparison was undertaken of 28 patients who underwent transperitoneal anterior laparoscopy with 22 patients who underwent retroperitoneal posterior laparoscopy between April 1994 and November 2000. There were 18 men and 32 women (mean age 51.0 years, range 23-68) with varying diagnoses. Of the 50 patients, 31 had primary aldosteronism, eight had Cushing's syndrome, three had phaeochromocytoma, one had an 18-hydroxydeoxycorticosterone-induced adenoma and seven had non-functioning adrenal adenoma. Adrenal tumours were confirmed by hormonal assays, biochemical tests and computed tomography. To determine the site of the functioning adenoma, hormones were assayed from adrenal vein sampling. Thirty adrenal tumours were located on the right and 20 on the left.There were no significant differences in general demographic variables between the transperitoneal and retroperitoneal groups. The mean duration of surgery for transperitoneal and retroperitoneal laparoscopy was 202 and 221 min, respectively, and the mean blood loss 113 and 192 mL, respectively. The time to first oral intake, days to full diet, time until ambulatory and duration of hospitalization did not differ significantly between the two approaches. As the body mass index increased, the duration of surgery increased for both approaches. As more procedures were performed the duration of surgery decreased for both approaches.There were no significant differences between the transperitoneal and retroperitoneal approaches for laparoscopic adrenalectomy.

Previous studies indicate that the D(3) dopamine (DA) receptor is preferentially expressed in limbic forebrain DA terminal areas and may mediate functional effects opposite those of the D(1) and D(2) receptor types. However, the locations of the D(3) receptors that regulate behavior, and the range of behavioral functions regulated, are not clear.The objective of this study was to evaluate behavioral and cellular effects of the preferential D(3) dopamine receptor antagonist, U99194A.In experiment 1, the rewarding effect of U99194A (5.0, 10.0 and 20.0 mg/kg, SC) was measured in terms of its ability to lower the threshold for lateral hypothalamic self-stimulation (LHSS) in ad libitum fed rats. To amplify a possibly weak reward signal, testing was also conducted in food-restricted rats. The ability of U99194A to alter the threshold-lowering effect of d-amphetamine was also assessed. In experiment 2, effects of U99194A on horizontal and vertical motor activity were compared in ad libitum fed and food-restricted rats. In experiment 3, effects of a behaviorally active dose of U99194A (5.0 mg/kg) on brain c-fos expression were measured and compared to those produced by d-amphetamine (0.5 mg/kg, IP). In experiment 4, the motor and cellular activating effects of U99194A were challenged with the D(1) dopamine receptor antagonist, SCH-23390 (0.1 mg/kg).U99194A displayed no rewarding efficacy in the LHSS paradigm. U99194A did, however, augment the rewarding effect of d-amphetamine. U99194A also produced a motor activating effect, reversible by SCH-23390, which was greater in food-restricted than ad libitum fed rats. The pattern and intensity of fos-like immunoreactivity (FLI) induced by U99194A was similar to that produced by d-amphetamine and was blocked, in caudate-putamen and nucleus accumbens, by SCH-23390.These results indicate that U99194A has psychostimulant-like effects on motor activity and striatal c-fos expression that are dependent upon the D(1) DA receptor. However, doses of U99194A that are adequate to stimulate motor activity and c-fos expression in striatal and limbic structures do not possess direct rewarding effects in the LHSS paradigm. Overall, these results seem consistent with the hypothesis that D(3) antagonism enhances D(1)/D(2) mediated signaling with behavioral effects dependent on both the density of D(3) receptors and the prevailing level of DA transmission in particular brain regions.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes’ C cancers (failure-free survival. P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes’ B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. (C) 2001 Cancer Research Campaign.

We studied 1,020 patients with hypertension visiting our outpatient clinic during a five-year period, from 1995 until 1999. Those subjects were screened by determining plasma renin activity (PRA) and plasma aldosterone concentration (PAC) after testing routine laboratory examinations in order to differentiate secondary hypertension from essential hypertension. All patients with low-reninemic hypertension were examined by furosemide plus the upright test. This led to an increase in diagnoses of primary aldosteronism (PA) (confirmed by captopril-loading test). Our studies demonstrated that the incidence of PA is 5.4%, and also that the plasma potassium level is not always beneficial for suspecting the presence of PA, because 28% of the patients with PA show only hypokalemia. We would like to emphasize that adrenal venous sampling plays a critical role in establishing the optimal management for patients with PA, because CT imaging is limited to detection of adrenal masses.

We isolated a cDNA clone encoding limonoid UDP-glucosyltransferase (limonoid GTase) from the albedo of Satsuma mandarin (Citrus unshiu Marc.) and investigated the contribution to limonoid glucoside accumulation in fruit. The isolated cDNA clone (CitLGT) was 1732 bp in length encoding 511 deduced amino acids with a predicted molecular mass of 57.5 kDa. The products of in vitro translation from an expression vector had the limonoid GTase activity. Southern blot analysis of genomic DNA indicated that CitLGT was present as a single copy gene in the Citrus genome. The amount of transcript corresponding to CitLGT mRNA changed the same way as the fluctuation of limonin glucoside content during fruit development of navel orange (Citrus sinensis Osb.). This indicates that the transcription of CitLGT regulates the conversion of limonoid aglycones to glucosides in citrus fruit.

Toxic effects of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were studied in male Syrian golden hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) particles were instilled intratracheally twice a week a total of 16 times, while InAs (7.7 mg/kg) was instilled a total of 14 times. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the instillation period, the cumulative body weight gain of the InAs-, but not the GaAs- or As2O3-treated hamsters was suppressed significantly, when compared with the control group. Slight to severe inflammatory responses were observed in the lung for all treatment groups. The most severe inflammatory change, characterized by an accumulation of neutrophils and macrophages, exudation, thickness of the pleura and fibrotic proliferation was found in the InAs-treated hamsters. Extensive alveolar or bronchiolar cell hyperplasia with or without keratinizing squamous cell metaplasia was observed in almost all the InAs-treated hamsters. Furthermore, squamous cell metaplasia or squamous cell hyperplasia developed in some of the InAs-treated hamsters, but not in the GaAs- or As2O3-treated hamsters. Slight to mild lesions were found in the convoluted tubules of the kidney in both the GaAs and InAs groups. From the present study, the toxic potency of these particles was provisionally estimated to be in the following order: InAsGaAsAs2O3, at the dosage level used in this study. Furthermore, there was evidence that InAs particles could induce pulmonary, renal or systemic toxicity, and as such, InAs particles may produce pulmonary precancerous change when instilled intratracheally into hamsters.

The effect of anti-regucalcin monoclonal antibody on neutral phoshatase activity in rat liver cytosol was investigated. Phosphotyrosine, phosphoserine, and phosphothreonine were used as the substrate toward phosphatase assay. Liver cytosolic phosphatase activity with three phosphoaminoacids was significantly increased in the presence of anti-regucalcin antibody (100 and 200 ng/ml) in the enzyme reaction mixture with calcium chloride (0.1 mM) or EGTA (1.0 mM). The effect of anti-regucalcin antibody was completely abolished in the presence of exogenous regucalcin (1.0 microM), indicating the involvement of endogenous regucalcin. The anti-regucalcin anti body- increased phosphatase activity was not significantly altered in the presence of trifluoperazine (20 microM), an antagonist of calmodulin, or akadaic acid ( 10 microM), an inhibitor of protein phosphatase, although these inhibitors caused a slight decrease in liver cytosolic phosphatase activity. The effect of endogenous regucalcin might be not related to calmodulin, and it was insensitive to okadaic acid. The present findings suggest that endogenous regucalcin is involved in the regulation of protein phasphatase in rat liver cytoplasm.

Alterations of the p16 gene in neuroblastoma are very rare. Pronounced expression of p16 at both the transcript and protein levels, however, was observed in 7 of 19 (39%) neuroblastoma cell lines and 2 of 6 (33%) primary neuroblastoma samples. As p16 expression is tightly controlled in a feedback loop with Rb, we investigated the possibility that changes in p16 expression were reflective of alterations of the downstream components in the G1 regulatory pathway. Two cell lines and one primary sample highly expressing p16 were shown to harbor CDK4 amplification. The cyclin D2 gene was infrequently expressed in neuroblastoma cell lines and did not correlate with p16 expression. Slight variations in the expression of CDK6, cyclins D1, D3 and E; and E2F1 and E2F2 among the cell lines were observed, without apparent correlation with p16 status. No mutations to the p16-binding site of CDK4 and CDK6 nor any mutations to the coding region of p16 itself were identified in neuroblastoma cell lines. Despite frequent N-myc amplification in these cell lines, no relationship with this gene was observed either. All cell lines contained Rb protein with varying degrees of phosphorylation, which bears no correlation with p16 expression. Overall, alterations of the G1 pathway in neuroblastoma included relatively frequent p16 expression and infrequent CDK4 amplification and cyclin D2 expression. Despite a reported feedback relationship between p16 expression and Rb/G1 deregulation, p16 expression in neuroblastoma cell lines is independent of Rb gene and phosphorylation status and, in contrast to other cell lines where expression of p16 leads to G1/S arrest, neuroblastoma cell lines proliferate in the presence of elevated levels of p16.

This paper proposes an efficient compensation method using a first-order approximation of time axis scaling for the variations of the room acoustic transfer function. The time axis scaling model is based on the fact that the change of the sound velocity due to the change of room temperature is a dominant factor for the variations of room impulse response affected by environmental conditions. In this paper, the effectiveness of the compensation method is evaluated using room impulse responses measured in the real environment. As the results, it is clarified that the variations of room impulse response can be modeled by the first-order approximated time axis scaling when the successive re-estimation is performed every small change of temperature. Furthermore, it is shown that the compensation method applied to an inverse filtering based dereverberation approach improves the intelligibility and speech recognition rates dramatically.