Search

Collimated outflows (jets) are ubiquitous in the universe, appearing around sources as diverse as protostars and extragalactic supermassive black holes. Jets are thought to be magnetically collimated, and launched from a magnetized accretion disk surrounding a compact gravitating object. We have developed the first laboratory experiment to address time‐dependent, episodic phenomena relevant to the poorly understood jet acceleration and collimation region [1]. The experiments were performed on the MAGPIE pulsed power facility (1.5 MA, 250 ns) at Imperial College. The experimental results show the periodic ejections of magnetic bubbles naturally evolving into a heterogeneous jet propagating inside a channel made of self‐collimated magnetic cavities. The results provide a unique view of the possible transition from a relatively steady‐state jet launching to the observed highly structured outflows.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T19:05:04Z No. of bitstreams: 1 S1415-47572010000200023.pdf: 577990 bytes, checksum: 2d4ddab7107df037c33aa69f8fc613db (MD5) Made available in DSpace on 2013-08-22T19:05:04Z (GMT). No. of bitstreams: 1 S1415-47572010000200023.pdf: 577990 bytes, checksum: 2d4ddab7107df037c33aa69f8fc613db (MD5) Previous issue date: 2010-01-01 Made available in DSpace on 2013-09-30T20:08:45Z (GMT). No. of bitstreams: 2 S1415-47572010000200023.pdf: 577990 bytes, checksum: 2d4ddab7107df037c33aa69f8fc613db (MD5) S1415-47572010000200023.pdf.txt: 29479 bytes, checksum: 2b8e4f0ee53e29423415d28ce53b63b9 (MD5) Previous issue date: 2010-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:17:32Z No. of bitstreams: 2 S1415-47572010000200023.pdf: 577990 bytes, checksum: 2d4ddab7107df037c33aa69f8fc613db (MD5) S1415-47572010000200023.pdf.txt: 29479 bytes, checksum: 2b8e4f0ee53e29423415d28ce53b63b9 (MD5) Made available in DSpace on 2014-05-20T15:17:32Z (GMT). No. of bitstreams: 2 S1415-47572010000200023.pdf: 577990 bytes, checksum: 2d4ddab7107df037c33aa69f8fc613db (MD5) S1415-47572010000200023.pdf.txt: 29479 bytes, checksum: 2b8e4f0ee53e29423415d28ce53b63b9 (MD5) Previous issue date: 2010-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) In this study we investigated the prevalence of the oppA gene, encoding the oligopeptide binding protein (OppA) of the major bacterial oligopeptide uptake system (Opp), in different species of the genus Xanthomonas. The oppA gene was detected in two Xanthomonas axonopodis strains among eight tested Xanthomonas species. The generation of an isogenic oppA-knockout derivative of the Xac 306 strain, showed that the OppA protein neither plays a relevant role in oligopeptide uptake nor contributes to the infectivity and multiplication of the bacterial strain in leaves of sweet orange (Citrus sinensis) and Rangpur lime (Citrus limonia). Taken together these results suggest that the oppA gene has a recent evolutionary history in the genus and does not contribute in the physiology or pathogenesis of X. axonopodis. Universidade de São Paulo Departamento de Microbiologia Instituto Butantan Laboratório de Biofísica e Bioquímica Universidade de São Paulo Departamento de Parasitologia Universidade Federal de São Paulo (UNIFESP) Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Veterinária e Ciências Agrárias Universidade Estadual Paulista Júlio de Mesquita Filho Faculdade de Veterinária e Ciências Agrárias

A modified method of retropubic radical prostatectomy was devised. The root of the penis was compressed and the bilateral internal iliac arteries were clamped before the dissection of the prostate. The urethra was divided at the junction of the prostate and bladder so that the bladder stump thus created has the size of the tip of the middle finger. Vesicourethral anastomosis was done by Vest procedure. By this method 24 patients were operated. All patients except one were alive without recurrence after the mean follow-up of 32 months. This method seems to be good enough to recommend.

A 20 T class superconducting magnet has been constructed at the National Research Institute for Metals in Japan. The two outermost of the four coils have been operated at 4.2 K. Before operating all coils at 1.8 K, in saturated superfluid helium, breakdown voltages within the coils were measured. With an inner coil of preliminary design, the system should generate 20.4 T in a 44 mm free bore. >

Highly collimated outflows or jets are produced by a number of astrophysical objects including protostars. The morphology and collimation of these jets is thought to be strongly influenced by the effects of radiative cooling, angular momentum and the interstellar medium surrounding the jet. Astrophysically relevant experiments are performed with conical wire array z‐pinches investigating each of these effects. It is possible in each case to enter the appropriate parameter regime, leading the way towards future experiments where these different techniques can be more fully combined.

The alpha(1L)-adrenoceptor has pharmacological properties that distinguish it from three classical alpha(1)-adrenoceptors (alpha(1A), alpha(1B) and alpha(1D)). The purpose of this was to identify alpha(1L)-adrenoceptors in mice and to examine their relationship to classical alpha(1)-adrenoceptors.Radioligand binding and functional bioassay experiments were performed on the cerebral cortex, vas deferens and prostate of wild-type (WT) and alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptor gene knockout (AKO, BKO and DKO) mice.The radioligand [(3)H]-silodosin bound to intact segments of the cerebral cortex, vas deferens and prostate of WT, BKO and DKO but not of AKO mice. The binding sites were composed of two components with high and low affinities for prazosin or RS-17053, indicating the pharmacological profiles of alpha(1A)-adrenoceptors and alpha(1L)-adrenoceptors. In membrane preparations of WT mouse cortex, however, [(3)H]-silodosin bound to a single population of prazosin high-affinity sites, suggesting the presence of alpha(1A)-adrenoceptors alone. In contrast, [(3)H]-prazosin bound to two components having alpha(1A)-adrenoceptor and alpha(1B)-adrenoceptor profiles in intact segments of WT and DKO mouse cortices, but AKO mice lacked alpha(1A)-adrenoceptor profiles and BKO mice lacked alpha(1B)-adrenoceptor profiles. Noradrenaline produced contractions through alpha(1L)-adrenoceptors with low affinity for prazosin in the vas deferens and prostate of WT, BKO and DKO mice. However, the contractions were abolished or markedly attenuated in AKO mice.alpha(1L)-Adrenoceptors were identified as binding and functional entities in WT, BKO and DKO mice but not in AKO mice, suggesting that the alpha(1L)-adrenoceptor is one phenotype derived from the alpha(1A)-adrenoceptor gene.

alpha(1)-Adrenoceptors in the rabbit prostate have been studied because of their controversial pharmacological profiles in functional and radioligand binding studies. The purpose of the present study is to determine the native profiles of alpha(1)-adrenoceptor phenotypes and to clarify their relationship.Binding experiments with [3H]-silodosin and [3H]-prazosin were performed using intact tissue segments and crude membrane preparations of rabbit prostate and the results were compared with alpha(1)-adrenoceptor-mediated prostate contraction.[3H]-Silodosin at subnanomolar concentrations bound specifically to intact tissue segments of rabbit prostate. However, [3H]-prazosin at the same range of concentrations failed to bind to alpha(1)-adrenoceptors of intact segments. Binding sites of [3H]-silodosin in intact segments were composed of alpha(1L) phenotype with low affinities for prazosin (pKi=7.1), 5-methyurapidil and N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dimethyl-1H-indole-3-ethamine hydrochloride (RS-17053), and alpha(1A)-like phenotype with moderate affinity for prazosin (pKi=8.8) but high affinity for 5-methyurapidil and RS-17053. In contrast, both radioligands bound to a single population of alpha(1)-adrenoceptors in the membrane preparations at the same density with a subnanomolar affinity, showing a typical profile of 'classical' alpha(1A)-adrenoceptors (pKi for prazosin=9.8). The pharmacological profile of alpha(1)-adrenoceptor-mediated prostate contraction was in accord with the alpha(1L) phenotype observed by intact segment binding approach.Three distinct phenotypes (alpha(1L) and alpha(1A)-like phenotypes in the intact segments and a classical alpha(1A) phenotype in the membranes) with different affinities for prazosin were detected in rabbit prostate. It appears that the three phenotypes are phenotypic subtypes of alpha(1A)-adrenoceptors, but are not genetically different subtypes.

In addition to alpha1A, alpha1B and alpha1D-adrenoceptors (ARs), putative alpha1L-ARs with a low affinity for prazosin have been proposed. The purpose of the present study was to identify the alpha1A-AR and clarify its pharmacological profile using a radioligand binding assay.Binding experiments with [3H]-silodosin and [3H]-prazosin were performed in intact tissue segments and crude membrane preparations of rat cerebral cortex. Intact tissue binding assays were also conducted in rat tail artery.[3H]-silodosin at subnanomolar concentrations specifically bound to intact tissue segments and membrane preparations of rat cerebral cortex at the same density (approximately 150 fmol mg(-1) total tissue protein). The binding sites in intact segments consisted of alpha1A and alpha1L-ARs that had different affinities for prazosin, while the binding sites in membranes showed an alpha1A-AR-like profile having single high affinity for prazosin. [3H]-prazosin also bound at subnanomolar concentrations to alpha1A and alpha1B-ARs but not alpha1L-ARs in cerebral cortex; the binding densities being approximately 200 and 290 fmol mg(-1) protein in the segments and the membranes, respectively. In the segments of tail artery, [3H]-silodosin only recognized alpha1A-ARs, whereas [3H]-prazosin bound to alpha1A and alpha1B-ARs.The present study clearly reveals the presence of alpha1L-ARs as a pharmacologically distinct entity from alpha1A and alpha1B-ARs in intact tissue segments of rat cerebral cortex but not tail artery. However, the alpha1L-ARs disappeared after tissue homogenization, suggesting their decomposition and/or their pharmacological profile changes to that of alpha1A-ARs.

The single cell gel eletrophoresis or the comet assay was established in the freshwater snail Biomphalaria glabrata . For detecting DNA damage in circulating hemocytes, adult snails were irradiated with single doses of 2.5, 5, 10 and 20 Gy of 60 Co gamma radiation. Genotoxic effect of ionizing radiation was detected at all doses as a dose-related increase in DNA migration. Comet assay in B. glabrata demonstrated to be a simple, fast and reliable tool in the evaluation of genotoxic effects of environmental mutagens.

This paper, at first, discuss the availability of a cavity resonance method using the resonance frequencies of some TM0m0 modes in a circular cavity to measure the frequency dependence of a dielectric rod sample. The influence of sample insertion holes to the measurement are estimated accurately on the basis of the rigorous analysis by the Ritz-Galerkin method. Some dielectric rod samples were measured by using two modes TM010 and TM020 hi each of two cavities with different heights. The measurement precision for the relative permittivity was improved within 0.3 %, compared with 3 to 7 % in the perturbation method. Then one of the cavities was set in an environmental test equipment and the temperature dependences of dielectric rod samples were measured. As a result, the present method is useful to measure the frequency and temperature dependences of dielectric rod samples.

Miniaturized environmental sensor chips for data gathering are useful for various applications, such as anthropometric or body-motion measurement. In this study, we propose a microelectromechanical system (MEMS) multi-sensor for environmental sensing. The system includes a sensor and peripheral interface circuitry chips. The sensor chip has a 3-axis accelerometer, with a pressure sensor and a humidity sensor. All sensors are built on a 10 times 5 mm2 silicon-on-insulator SOI) wafer by the bulk MEMS process using deep reactive-ion etching RIE). The interface circuitry for each sensor is produced on a semi-custom Bi-CMOS application specific integrated circuit ASIC) chip by a Japanese IC foundry service of MICS.

This study describes a human activity monitoring system that uses microelectromechanical systems (MEMS) sensors. The prototype system contains four sensors for ambient monitoring: 3-axis acceleration, barometric pressure, temperature, and relative humidity. The peripheral circuitry for each sensor is connected to a one-chip microprocessor. The measured data is stored in memory and transferred via a wireless transmitter. We measured a human subject's daily life activities, and using data mining, we were able to obtain a representation of that subject's life circumstances.

In this work, mice genetically modified [HIII line] were immunized against different Bothrops snake venoms to produce anti-Bothrops serum (antivenom). The Neutron Activation Analysis (NAA) and Energy Dispersive X-Ray Fluorescence (EDXRF) techniques were used to evaluate Ca and Fe concentrations in blood of these immunized mice in order to establish a potential correlation between both phenotypes: antibody response and blood constituents after Bothrops venom administration. The results were compared with the control group (mice not immunized) and with human being estimative. These data are important for clinical screening of patients submitted to immunological therapy as well as the understanding of the envenoming mechanisms.

Two cases of progressive interstitial lung disease associated with polymyositis/dermatomyositis are presented. Both patients were refractory to conventional therapy with high-dose corticosteroids, cyclosporine, and intermittent pulse cyclophosphamide, and thus a therapeutic trial of tacrolimus was instituted. Tacrolimus was markedly effective in achieving subjective, laboratory and radiographic improvement in both patients.

A new delay compensation method is derived for servo systems using state prediction control and disturbance observer. The delay in the closed loop deteriorates the stability margin because of the phase delay in high frequency region. The proposed method consists of three steps, (1) state estimation with state observer, (2) state prediction, and (3) state feedback of predicted state. For SISO(single input, single output) systems, the proposed method can be rewritten in the scheme of conventional disturbance observer design by using Youla parameterization. This result can be drawn by the analysis of the closed loop system poles and by applying the separation theorem. Improvement of the stability margin is confirmed by simulation in the track following mode of a hard disk drive with the synchronous servo scheme.

Mutations in the precore region and core promoter were compared between patients with acute and chronic hepatitis B.There were 69 patients with acute self-limited hepatitis B and 210 with chronic hepatitis B who had been followed for15 years. The hepatitis B virus (HBV) of genotypes A, B and C was detected in 14 (23%), 8 (13%) and 28 (45%) of the patients with acute self-limited hepatitis, respectively, in contrast to 11 (5%), 25 (12%) and 167 (80%) of those with chronic hepatitis.At presentation, hepatitis B e antigen (HBeAg) in serum was the more common (82% versus 65%, P0.05), and the wild-type sequences of the precore region (100% versus 74%, P0.001) and core promoter (88% versus 36%, P0.00001) were more frequent in the 50 patients with acute self-limited hepatitis than the 203 patients with chronic hepatitis B who were infected with HBV of genotype A, B or C. Wild-types of both the precore region and core promoter persisted in acute self-limited hepatitis, while they decreased from 28% to 10% in chronic hepatitis over the course of15 years.HBV with the wild-type sequences of the precore region and core promoter prevails in patients with acute self-limited hepatitis, unlike in patients with chronic hepatitis.

The title compound, KW-3902 {1,3-dipropyl-8-(3-tricyclo[3.3.1.0 3,7 ]nonyl)-3,7-dihydro-1H-purine-2,6-dione, C 20 H 28 N 4 O 2 }, is a selective adenosine Al-receptor antagonist. In the crystal of KW-3902, the mirror plane of the 3-noradamantyl group is nearly in the plane of the xanthine moiety. The two propyl side chains have fully extended conformations and are on the same side of the xanthine plane.

Among various types of ionizing radiation, the beta emitter radionuclides are involved in many sectors of human activity, such as nuclear medicine, nuclear industries and biomedicine, with a consequently increased risk of accidental, occupational or therapeutic exposure. Despite their recognized importance, there is little information about the effect of beta particles at the cellular level when compared to other types of ionizing radiation. Thus, the objective of the present study was to evaluate the genotoxic and cytotoxic effects of (90)Sr/(90)Y-a pure, highly energetic beta source-on Chinese hamster ovary (CHO) cells and to compare them with data obtained with (60)Co. CHO cells irradiated with different doses of (60)Co (0.34 Gy min(-1)) and (90)Sr/(90)Y (0.23 Gy min(-1)) were processed for analysis of clonogenic death, induction of micronuclei (MN) and interphase death. The survival curves obtained for both types of radiation were fitted by the exponential quadratic model and were found to be similar. Also, the cytogenetic results showed similar frequencies of radio-induced MN between gamma and beta radiations and the MN distribution pattern among cells did not follow the expected Poisson probability pattern. The relative variance values were significantly higher in cells irradiated with (90)Sr/(90)Y than with (60)Co in all exposure doses. The irradiated cells showed more necrotic cells 72 h and 96 h after exposure to beta than to gamma radiation. In general, the (90)Sr/(90)Y beta-radiation was more damaging than (60)Co gamma-rays. The data obtained also demonstrated the need to use several parameters for a better estimate of cellular sensitivity to the action of genotoxic agents, which would be important in terms of radiobiology, oncology and therapeutics.

This paper reports, for the first time, the development of 500 V, 3 A single chip inverter ICs. The chip size of the IC is 7.1/spl times/5.2 mm/sup 2/, which is only 30% larger than that of 500 A, 1 A inverter ICs. The chip size reduction has been realized by 35% improvement in lateral IGBT on-resistance and an optimized layout of LIGBT unit cells and bonding pads.

We have developed a new surface mount LD module. This module is suitable for mass production while making cost reductions and providing simple and stable handling. The module simplifies the assembly procedure, and it is possible to mount this module directly onto the printed circuit board. The module was produced using hybrid integrated mounting technology including passive alignment technique of optical devices, plastic molded package technique, and a receptacle interface. The module showed a sufficient reliability in application of the trunk line. We describe the structure of the module and key technologies, and propose a method for assuring the reliability of the module with the plastic molded package by sampling tests.

We consider the windup phenomena which is usually observed in servo systems. Due to the integral term of servo controllers, windup phenomena arise when the control input to the plant is saturated. It is not only with PI or PID servo controllers, but also with high order servo controllers which contain nearly zero poles, for example, designed by the H/sub /spl infin// optimum control theory. To avoid this problem, anti-windup (AW) control algorithms have been proposed. In this paper, we investigate some effective methods for the high order servo controllers, and propose a new AW strategy based on a saturated state observer.

A highly efficient RF suppression circuit for fluorescent lamp inverters based on charge pump and partial smoothing capacitors is proposed. The circuit consists of a pumping capacitor, a partial smoothing capacitor and a control switch. The pumping capacitor is of comparatively small capacitance and the control switch operates to ensure that the pumping capacitor charging current is proportional to the AC power supply voltage even across the interval where the AC voltage is near zero. Effective use of current charging reduces the RF harmonic components in the supply current and improves the power factor. The charging voltage of the pumping capacitor (Vcp) and the charging voltage of the partial smoothing capacitor (Vch) together effect inverter driving of the lamp circuit. When the lamp starts, the control switch provides the high voltage, Vcp+Vch. After the lamp has started, Vcp and Vch are switched in alternation. During the period in which the partial smoothing capacitor is charging, the time constants of the choke coil at the rectifier circuit input and the partial smoothing circuit are optimized, while use of the charging voltage of the pump capacitor prevents the sudden appearance of a charging current at the input. Test circuits exhibited a power factor of 97.4% (well above the 85% rating), and the third to eleventh harmonics were at about half of the rated values, demonstrating the feasibility of a high-power-factor low-RF inverter.

We propose a top-down hardware/software co-simulation method for embedded systems and introduce a component logical bus architecture as an interface between software components and hardware components. Co-simulation using a component logical bus architecture is possible in the same environment from the stage at which the processor is not yet determined to the stage at which the processor is modeled in register transfer language. A model whose design is based on a component logical bus architecture is replaceable and reusable. By combining such replaceable models, it is possible to quickly realize seamless co-simulation. We further describe experimental results of our approach.

Presents an overview of a knowledge representation and control mechanisms of the concurrent production system CONPUS and distributed CONPUS (D-CONPUS). CONPUS is an object-oriented knowledge representation system for describing distributed production systems, whose rules are working concurrently. D-CONPUS is made up a group of sites working CONPUSs, which are interconnected by a network. The knowledge-base of CONPUS consists of a set of rulesets and a shared database. A ruleset is a unit for specifying a group of rules and its own database, as an autonomous object. The rulesets are described for cooperative problem solving, which can work simultaneously and independently to each other. A collection of rulesets are organized as a network data structure, and a ruleset has some slots for controlling its behaviors. The ruleset is activated by message passing, or by taking opportunity when suitable conditions are satisfied. A shared database is a database which is shared by rulesets in CONPUS, and, D-CONPUS has a global database which is shared by sites working CONPUS. Since the shared and the global database are shared by the rulesets and the sites, and rules are fired in parallel, CONPUS and D-CONPUS provide facilities to maintain consistency of the databases.

The stimulus of audio signals are conveyed to human via a three stages process; perception/spl rarr/recognition/spl rarr/susceptibility. It shows we need a methodology to optimize human perceptual factors, not just easily measured criteria like power and timing. In this paper, we propose a method for reconfigurable multimedia equipment development using inverse problem. The method consists of two means. One is an inverse problem method for stimulus on three levels for the identification of an unknown circuit and the optimization of human sensibilities with a reconfigurable architecture. The other is four steps environment for the systematic design and development from the conceptual stage through to the production. Two expedients are interconnected and efficiently linked, so that the development cycle can be shortened and the desired characteristics for human sensibilities are satisfied effectively. This proposal was applied to the development of a television receiver set and audio circuitry, and its effectiveness was confirmed.

This paper proposes two methods for a rapid prototyping of top-down system-on-chip (SOC) design using laser programmable gate arrays (LPGAs). The first one is a design flow of SOC consisting of four steps: concept-making, virtual-world prototyping, synthesis, and real-world prototyping. The steps can be undertaken individually or in tandem and provisional product models are transformed from upper stream (concept-making) to lower stream (synthesis) either automatically or semi-automatically. This method differs from ordinary rapid prototyping methods in that design evaluation is shifted more upper stream. The SOC device is manufactured early; the steps follow concept-making, virtual-world prototyping, synthesis and real-world prototyping (in the ordinary case, from real-world prototyping to synthesis). This method allows the device to be evaluated in the actual operating environment. The second method we propose is based on LPGAs and use of a real-time production fabrication system (RPFS). With these design methods and environment, we can get a shortest time to market which offers exciting audio and video capabilities while giving designers the flexibility they need to rapidly produce innovative and creative products. This paper describes the application of these methods to develop video signal processors for LCD projectors, demonstrating their efficiency for design tuning and performance optimization.

To clarify the mechanism of origin of duodenal wall cysts in patients with chronic pancreatitis, developing into duodenal stenosis.Specimens from 12 pancreatoduodenectomized patients with chronic pancreatitis and 51 controls were studied histopathologically and immunohistochemically. Variously shaped cystic lesions, averaging about 15 mm in diameter, were found in the duodenum in six of the 12 patients with chronic pancreatitis, but were not observed in the controls. Each case had an average of two cysts, which were located mainly in the muscularis propria of the duodenum with or without submucosal or extraduodenal-peripancreatic extensions. The inner part of the cyst wall consisted of a moderate rim of granulation tissue, with both myofibroblasts and smooth muscle proliferation in the tissue surrounding the cyst and the submucosal layer of the duodenum, occasionally accompanied by an epithelial lining. A ductal structure in the muscularis propria of the duodenum, possibly a ductal component of ectopic pancreatic tissue, was found in five of the six cases. Some of these structures showed cystic changes. Three of the six patients had accompanying duodenal stenosis.Duodenal wall cysts occur mainly in the muscularis propria of the duodenum associated with both myofibroblasts and smooth muscle proliferation, and may result in duodenal stenosis. These cysts may be derived from a ductal component of ectopic pancreatic tissue.

The purpose of this study was to evaluate the degree of cytological radiation damage to peripheral blood lymphocytes induced by 153Sm-EDTMP applied for palliation of metastatic bone pain. Blood samples from 16 patients (46-82 years old), 10 without previous radiotherapy and 6 with previous radiotherapy, were collected before and one hour after the administration of a mean activity of 41.7+/-5.8 MBq/kg of 153Sm-EDTMP. Then the lymphocytes were cultured for cytokinesis block micronucleus (MN) assay. The number of MNper binucleated cells (BC) in patients without previous radiotherapy before the treatment was of 0.030 (+/- 0.016) and after one hour 0.035 (+/- 0.013), although we could find inter individual differences. The basal MN/BC of the patients with no previous radiotherapy was similar to the controls. The increment in the percentage of BC with MN was similar in patients with and without previous radiotherapy. The observed mean of MN/BC is equivalent to a dose range of 0.05 to 0.10 Gy of 153Sm-EDTMP in vitro. The relatively low frequency of lymphocyte with micronuclei after the exposure to 153Sm-EDTMP supported the contention that radiation damage in lymphocytes of patients with painful bone metastases is minimal.

DNA integrity is threatened by the damaging effects of physical and chemical agents that can affect its function. Nucleotide excision repair (NER) is one of the most known and flexible mechanisms of DNA repair. This mechanism can recognize and remove damages causing DNA double-helix distortion, including the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine-pyrimidone (6-4) photoproducts, promoted by ultraviolet light (UV). The human syndrome xeroderma pigmentosum (XP) is clinically characterized chiefly by the early onset of severe photosensitivity of the exposed regions of the skin, a very high incidence of skin cancers and frequent neurological abnormalities. The xpa gene seems to be involved during UV damage recognition, in both global genome repair (GGR) and transcription-coupled repair (TCR). The modulation of xpa expression may modify the DNA repair rate in the cell genome, providing a valuable contribution to an understanding of the NER process. The controlled expression of the cDNA xpa in XP12RO deficient cells was achieved through the transfection of a muristerone-A inducible vector, pINXA. The INXA15 clone shows good induction of the XPA protein and total complementation of XP12RO cell deficiency. Overexpression of this protein resulted in UV cell survival comparable to normal control human cells. Moreover, low expression of the XPA protein in these cells is sufficient for total complementation in cellular UV sensitivity and DNA repair activity. These data demonstrate that XPA protein concentration is not a limiting factor for DNA repair.

To investigate the host genetic factors affecting the clinical course of falciparum malaria, polymorphism of the tumor necrosis factor-alpha (TNF-alpha) promoter region was analyzed in patients with cerebral malaria. Two hundred and forty-three Myanmar patients with falciparum malaria at Mae Sot Malaria clinic and Mae Sot General Hospital located at the border between Thailand and Myanmar, were included in this study. Among the patients (128 from Karen, 115 from Burma), 200 were uncomplicated and 43 had cerebral malaria. The TNF-alpha 5'- flanking region showed biallelic polymorphic sites at -238, -308, -857, -863, -1031, and there were 7 alleles (TNFP-A, B, C, D, M1, M4, M7) found in the patients from Myanmar. We found that the TNFP-D allele was significantly associated with cerebral malaria in the populations from Karen (Pc0.0001, OR=124.86) and Burma (Pc0.0001, OR=34.50). TNFP-D showed no significant linkage disequilibrium with any alleles of HLA-B or HLA-DRB1, suggesting that TNFP-D was primarily associated with cerebral malaria in Myanmar.

Cellular and extracellular volume changes caused by ATP were investigated in the liver as well as the possible formation of diffusion barriers, which could be responsible for some of its metabolic effects.The experimental system was the bivascularly perfused rat liver. [(14)C]Sucrose and [(3)H]water were simultaneously injected into either the portal vein or the hepatic artery. Mean transit times, distribution spaces, variances and linear superimpositions were calculated.In the portal system, ATP reduced the transit time in the great vessels, had little or no effect on sinusoidal and cellular spaces, but impaired the flow-limited distribution of both [(14)C]sucrose and [(3)H]water. In the arterial bed ATP infused into either the portal vein or the hepatic artery produced vasodilation and increased the aqueous extra-sucrose space. These effects were inhibited by Nomega-nitro-L-arginine methyl ester infused into the hepatic artery.Sucrose and extra-sucrose space changes caused in the arterial bed by portally infused ATP are most probably analogous to the transhepatic vasodilation effect already described for the rabbit liver. Impairment of flow-limited distribution of tracers in the sinusoidal bed indicates that ATP induces the formation of permeability barriers, which could be responsible for some of its metabolic effects.

Dissemination of benign ependymoma is relatively rare, especially when a local tumor is under control. The majority of the failures take place within a few years after surgery. However, we experienced a case in which multiple spinal cord dissemination was found 13 years after resection of the fourth ventricle ependymoma without a local failure. A 38-year-old man had undergone a subtotal resection of the fourth ventricle ependymoma and radiation therapy to the posterior fossa when he was 25 years old. Follow-up MR imaging repeated once every one or two years detected no recurrence until he began to complain of lumbago and numbness of the right foot 13 years after the surgery. MR imaging revealed multiple nodules along the whole spinal cord. Examination of the cerebrospinal fluid detected tumor cells with ependymal cell features. He underwent radiation therapy to the whole spine, and remained stable at 18 months after the therapy. This case alerts us to the necessity for long-term radiological follow-up including the spinal cord even in benign ependymomas, although it is still not certain for how long and how often we should do it.

To investigate the effects of Z-100, an arabinomannan extracted from Mycobacterium tuberculosis, on the LP-BM5 murine leukemia virus (LP-BM5 MuLV) infection in mice.C57BL/6 mice infected intraperitoneally with 4.5 x 10(2) PFU/mouse of LP-BM5 MuLV (MAIDS mice) were treated intraperitoneally with a 10-mg/kg dose of Z-100 every other day beginning 1 day after the viral infection. MAIDS mice treated with Z-100 were compared with control mice (MAIDS mice treated with saline) for their survival and splenomegaly after LP-BM5 infection. Cytokine-producing profiles of splenic T cells from these two groups of mice were also compared.When MAIDS mice treated with Z-100 were compared with those of control mice, a decrease in splenomegaly and lymphadenopathy was observed. Splenomegaly was markedly enhanced in MAIDS mice treated intraperitoneally with IL-4 or IL-10. When MAIDS mice were treated with Z-100, their survival rates were significantly increased compared to those of controls. Splenic T cells from control mice produced type-2 cytokines (IL-4 and IL-10). However, a decreased production of type-2 cytokines by splenic T cells from MAIDS mice treated with Z-100 was demonstrated.Z-100 could decrease the severity of the LP-BM5 MuLV infection through the regulation of MAIDS-associated type-2 T-cell responses.

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P

Results of past space experiments suggest that the biological effect of space radiation could be enhanced under microgravity. To assess the radiation risk for humans during long-term spaceflight, it is very important to clarify whether human cells exhibit a synergistic effect of radiation and microgravity.If significant synergism occurs in human cells, genetic changes induced during spaceflight may be detected by using human tumor HCT-116 cells which are hypermutable due to a defect in the DNA mismatch repair system.Cultured HCT-116 cells were loaded on the Space Shuttle Discovery (STS-95) and grown during the 9-d mission. After landing, many single-cell clones were isolated, microsatellite repetitive sequences in each clone were amplified by PCR, and mutations in the microsatellite loci were detected as changes in the length of PCR fragments. Mutation frequencies of ouabain-resistant phenotype were also analyzed.The frequencies of microsatellite mutations as well as ouabain-resistant mutations in the flight sample were similar to those of the ground control samples. Some cells were treated in space with bleomycin which mimics the action of radiation, but the frequencies of microsatellite mutations were not significantly different between the flight and the ground control samples.Under the present flight conditions, neither space radiation (about 20 mSv during this mission) nor microgravity caused excess mutations in human cells.

Since it is a disease mainly caused by plaque--an aggregate of various bacteria--periodontal disease can be considered a local infection. Thus, it has seemed reasonable to utilize antibiotics to suppress the intrapocket bacteria, specifically or nonspecifically. When antibiotics are administered orally, however, massive doses over a prolonged period of time are needed to attain a therapeutic effect. This increases the risk of adverse reactions as well as developing resistant strains of bacteria. To overcome these problems, local drug delivery systems (LDDS) were devised to combat the local infection. However, the intrapocket antibiotic delivery systems have yet to be fully evaluated for clinical effectiveness; to prove the therapeutic effectiveness of locally administered antibiotics, the drug must reach the base of the periodontal pocket and the effective concentration of the antibiotic against the pathogenic bacteria must be maintained for a long time. This concise review presents with figures, tables, and a comprehensive list of references the many studies which have used the various tetracyclines as LDDS to treat periodontal disease.

Among various environmental genotoxins, ionizing radiation has received special attention because of its mutagenic, carcinogenic and teratogenic potential. In this context and considering the scarcity of literature data, the objective of the present study was to evaluate the effect of 90Sr beta-radiation on human cells. Blood cells from five healthy donors were irradiated in vitro with doses of 0.2-5.0Gy from a 90Sr source (0.2Gy/min) and processed for chromosome aberration analysis and for comet assay. The cytogenetic results showed that the most frequently found aberration types were acentric fragments, double minutes and dicentrics. The alpha and beta coefficients of the linear-quadratic model, that best fitted the data obtained, showed that 90Sr beta-radiation was less efficient in inducing chromosome aberrations than other types of low linear energy transfer (LET) radiation such as 3H beta-particles, 60Co gamma-rays, 137Cs and 192Ir and X-rays. Apparently, 90Sr beta-radiation in the dose range investigated had no effect on the modal chromosome number of irradiated cells or on cell cycle kinetics. Concerning the comet assay, there was an increase in DNA migration as a function of radiation dose as evaluated by an image analysis system (tail moment) or by visual classification (DNA damage). The dose-response relation adequately fitted the non-linear regression model. In contrast to the cytogenetic data, 90Sr beta-radiation induced more DNA damage than 60Co gamma-radiation when the material was analyzed immediately after exposures. A possible influence of selective death of cells damaged by radiation was suggested.

We have studied the antagonist action of prazosin and KMD-3213 in a constitutively active mutant of the human alpha-1a adrenoceptor in which Ala(271) was substituted to Thr and was expressed in CHO cells. Inverse agonism was characterized by up-regulation of receptor density, a decrease in basal GTPgammaS binding, and a reduction in basal inositol-1,4,5-trisphosphate (IP(3)) level. According to the above criteria, prazosin acted as an inverse agonist, whilst KMD-3213 behaved as a neutral antagonist. Compared with the wild-type receptor, mutant receptor exhibited single affinity sites for [(3)H]-prazosin, [(3)H]-KMD and the non-radioactive ligands tested, and displayed significantly higher affinities for several agonists but not for the two antagonists. Administration of KMD-3213 to prazosin-treated CHO cells expressing the mutant receptor reversed the inverse agonism of prazosin resulting in rapid increases in cellular IP(3), in intracellular [Ca(2+)] and in the rate of extracellular acidification. These results indicated that a neutral antagonist can reverse the action of an inverse agonist at the receptor site. The distinct properties of inverse agonist and neutral antagonist in affecting receptor function may be important for the clinical use of such antagonists.

Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

We have isolated a cDNA clone of the rabbit alpha(1b)-adrenoceptor which has an open reading frame of 1557 nucleotides encoding a protein of 518 amino acids. The sequence shows higher identity to those of hamster, human, and rat alpha(1b)-adrenoceptors than to those of rabbit alpha(1a)- and alpha(1d)-adrenoceptors. The pharmacological binding properties of this clone expressed in Cos-7 cells showed a characteristic profile as alpha(1b)-adrenoceptor; high affinity for prazosin (pK(i)=10.3), relatively high affinity for tamsulosin (9.5) and low affinity for (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2, 2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]indoline-7-carboxamid e (KMD3213) (8.5), 2-(2,6-dimethoxy-phenoxyethyl)-aminomethyl-1, 4-benzodioxane hydrochloride (WB4101) (8.7), and 8-[2-[4-(2-methoxy-phenyl)-L-piperazinyl]-8-azaspiro[4,5]decane-7, 9-dione dihydrochloride (BMY7378) (7.3). We have compared the levels of mRNA expression of three alpha(1)-adrenoceptor subtypes in rabbit tissues using the competitive reverse transcription/polymerase chain reaction (RT/PCR) assay. In most rabbit tissues except heart, alpha(1a)-adrenoceptor mRNA was expressed 10 folds more than the other two subtypes. However, binding experiments with [3H]prazosin and [3H]KMD3213 in rabbit tissues revealed a poor relationship between binding density and mRNA level. Especially, alpha(1b) binding sites were exclusively predominant in spleen, whereas the alpha(1b) subtype was minor at the mRNA level. These results indicate a high identity of structural and pharmacological profiles of three distinct alpha(1)-adrenoceptor subtypes between rabbit and other species, but there are species differences in their distribution.

To develop PET ligands for mapping central nervous system (CNS) adenosine A2a receptors that are localized in the striatum and are coupled with dopamine receptors, 3 11C-labeled xanthine-type adenosine A2a antagonists, [11C]KF18446 ([7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthin e), [11C]KF19631 ([7-methyl-11C]-(E)-1,3-diallyl-7-methyl-8-(3,4,5-trimethoxystyryl)xanth ine), and [11C]CSC ([7-methyl-11C]-8-chlorostyrylcaffeine), were compared with [11C]KF17837 ([7-methyl-11C]-(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylx anthine).The regional brain uptake of the tracers, the effect of the coinjected adenosine antagonists on the uptake, and the metabolism were studied in mice. In rats, the regional brain uptake of the tracers was visualized by ex vivo autoradiography (ARG). The A2a receptor binding of antagonist 1 was also measured by in vitro ARG. Imaging of the monkey brain was performed with PET with antagonist 1.In mice, the highest striatal uptake was found for antagonist 1 followed by antagonists 2 and 4. The uptake was inhibited by each of 3 KF compounds and by CSC, but not by an A1 antagonist KF15372. Another selective nonxanthine-type A2a antagonist SCH 58261 significantly decreased the striatal uptake of only antagonist 1, the labeled metabolites of which were less than 20% in the plasma 30 min postinjection, but were negligible in the brain tissue. In ex vivo ARG, antagonist 1 showed the highest striatal uptake and the highest uptake ratio of the striatum to the other brain regions. A high and selective binding of antagonist 1 to the striatum was also confirmed by in vitro ARG. PET with antagonist 1 visualized adenosine A2a receptors in the monkey striatum.These results indicate that antagonist 1 ([11C]KF18446) is the most suitable PET ligand for mapping adenosine A2a receptors in the CNS.