bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptides in the crayfish stomatogastric nervous system
Authors: Skiebe Petra
Published: January 2003

Neuropeptides are peptides with profound effects on the nervous system. The function of neuropeptides can be studied in detail in the stomatogastric nervous system (STNS). Neuropeptides are ubiquitously distributed in the STNS and it contains well‐studied neural circuits that are strongly modulated by neuropeptides. The STNS controls the movements of the foregut in crustaceans and has been studied intensively in a variety of decapod crustaceans including crayfish. This article reviews our knowledge of neuropeptides in the crayfish STNS. Within crayfish, peptides reach the circuits of the STNS as neurohormones released by neurohaemal organs or by putative neurohemal zones located within the STNS. As transmitters, neuropeptides are present in identified motoneurons, interneurons, and sensory neurons (mainly shown by immunocytochemistry), indicating a multiple role of peptides in the plasticity of neural networks. Neuropeptides are not only present in varicosities within the neuropil of ganglia, but also in varicosities on muscles and within small neuropil patches along nerves. This suggests that the muscles of the stomach are under a more direct modulatory control than previously thought, and that information processing can also occur within nerves. In addition to anatomical studies, biochemical and electrophysiological methods were used. For example, MALDI‐TOF MS (matrix‐assisted laser desorption ionization time of flight mass spectrometry) revealed the presence of four different peptides of the orcokinin family within a single neuron, and electrophysiological experiments demonstrated that the networks of the STNS are not only under excitatory but also inhibitory peptidergic influence. Comparing the similarities and differences between the STNS of crayfish and that of other decapod crustaceans has already contributed to our knowledge about peptides and will further help to unravel peptide function in the plasticity of neural circuits. For example, the identified neurons in the STNS can be used to study co‐transmission because neuropeptides are co‐localized with classical transmitters, biogenic amines, or other peptides in these neurons. Microsc. Res. Tech. 60:302–312, 2003. © 2003 Wiley‐Liss, Inc.
Physiological functions of FMRFamide‐like peptides (FLPs) in crustaceans
Authors: Mercier A. Joffre , Friedrich Rainer , Boldt Maria
Published: January 2003

Neuropeptides play important roles in chemical signalling in the central and peripheral nervous systems. One of the largest families of neuropeptides is that of the FMRFamide‐like peptides (FLPs). This paper reviews what is known about the physiological functions of FLPs in crustaceans, focussing on the cardiovascular, digestive and neuromuscular systems. Microsc. Res. Tech. 60:313–324, 2003. © 2003 Wiley‐Liss, Inc.
Dopamine in crayfish and other crustaceans: Distribution in the central nervous system and physiological functions
Authors: Tierney Ann Jane , Kim Taylor , Abrams Reilly
Published: January 2003

Dopamine is widely distributed in the crustacean nervous system and has a diverse array of physiological effects. Immunocytochemical studies of several species have shown that dopamine‐ and/or tyrosine hydroxylase–containing cells occur in all ganglia of the central nervous system and that processes from some of these cells link ganglia of the ventral nerve cord. This study describes the distribution of tyrosine hydroxylase–containing cells in the central nervous system of a crayfish (Orconectes rusticus) and compares this information to available data from other species. The distribution of tyrosine hydroxylase (an enzyme in the synthetic pathway between tyrosine and dopamine) in O. rusticus is similar to that reported for marine species. However, differences were observed in the number of neurons in some ganglia and in the axonal projections of the L cell, which were more extensive in O. rusticus than in other species studied thus far. We also review the physiological effects of dopamine in crayfish and other crustaceans, focusing on the amine's actions in the endocrine, cardiovascular, and nervous systems, and on behavior when injected into freely‐moving animals. Microsc. Res. Tech. 60:325–335, 2003. © 2003 Wiley‐Liss, Inc.
Neural basis of a simple behavior: Abdominal positioning in crayfish
Authors: Larimer James L. , Moore Darrell
Published: January 2003

Crustaceans have been used extensively as models for studying the nervous system. Members of the Order Decapoda, particularly the larger species such as lobsters and crayfish, have large segmented abdomens that are positioned by tonic flexor and extensor muscles. Importantly, the innervation of these tonic muscles is known in some detail. Each abdominal segment in crayfish is innervated bilaterally by three sets of nerves. The anterior pair of nerves in each ganglion controls the swimmeret appendages and sensory supply. The middle pair of nerves innervates the tonic extensor muscles and the regional sensory supply. The superficial branch of the most posterior pair of nerves in each ganglion is exclusively motor and supplies the tonic flexor muscles of that segment. The extension and flexion motor nerves contain six motor neurons, each of which is different in axonal diameter and thus produces impulses of different amplitude. Motor programs controlling each muscle can be characterized by the identifiable motor neurons that are activated. Early work in this field discovered that specific central interneurons control the abdominal positioning motor neurons. These interneurons were first referred to as “command neurons” and later as “command elements.” Stimulation of an appropriate command element causes a complex, widespread output involving dozens of motor neurons. The output can be patterned even though the stimulus to the command element is of constant interval. The command elements are identifiable cells. When a stimulus is repeated in a command element, from either the same individual or from different individuals, the output is substantially the same. This outcome depends upon several factors. First, the command elements are not only identifiable, but they make many synapses with other neurons, and the synapses are substantially invariant. There are separate flexion‐producing and extension‐producing command elements. Abdominal flexion‐producing command elements excite other flexion elements and inhibit extensor command elements. The extension producing elements do the opposite. These interactions insure that interneurons of a particular class (flexion‐ or extension‐producing) synaptically recruit perhaps twenty others of similar output, and that command elements promoting the opposing movements are inhibited. This strong reciprocity and the recruitment of similar command elements give a powerful motor program that appears to mimic behavior. Microsc. Res. Tech. 60:346–359, 2003. © 2003 Wiley‐Liss, Inc.
Efficacy of interleukin‐10 gene electrotransfer into skeletal muscle in mice with collagen‐induced arthritis
Authors: Saidenberg‐Kermanac'h Nathalie , Bessis Natacha , Deleuze Virginie , Bloquel Carole , Bureau Michel , Scherman Daniel , Boissier Marie‐Christophe
Published: January 2003

Background

Gene therapy is very promising in the treatment of rheumatoid arthritis (RA). Electrotransfer is a recent method reported to enhance in vivo intramuscular DNA transfection. Interleukin‐10 (IL‐10) has antiinflammatory effects in RA and in collagen‐induced arthritis (CIA), a murine model of RA. In order to improve our strategy of gene therapy, we used electrotransfer to enhance penetration into skeletal muscle with CIA of plasmids encoding IL‐10.

Methods

CIA was induced in DBA/1 mice by immunization with bovine type II collagen. Injection into the tibial cranial muscle of low‐dose (200 ng) pCOR plasmid encoding murine IL‐10 (pCOR‐CMV‐mIL‐10) was immediately followed by application of square‐wave electric pulses (8 pulses of 200V/cm, 20 ms duration at 2 Hz). Control groups received empty plasmid or saline before electrotransfer.

Results

When electrotransfer was performed twice on days 10 and 25 postimmunization, CIA was significantly delayed (P < 0.05) and attenuated (P < 0.001) in groups treated by electrotransfer or pCOR‐CMV‐mIL‐10 plasmid vs. control groups. When electrotransfer of pCOR‐CMV‐mIL‐10 plasmid was performed on days 25 and 40 postimmunization, at disease onset, the clinical severity of CIA was reduced (P < 0.05). All groups which had been electrotransferred early or late by pCOR‐CMV‐mIL‐10 plasmid showed suppression of histological signs of arthritis.

Conclusions

Taken together, these data indicate that administration of an antiinflammatory plasmid‐born gene by electrotransfer of naked DNA is effective in vivo in an arthritis model. Copyright © 2002 John Wiley & Sons, Ltd.
Adenovirus‐mediated gene transfer to the transplanted piglet heart after intracoronary injection
Authors: Griscelli Frank , Belli Emre , Opolon Paule , Musset Karine , Connault Elisabeth , Perricaudet Michel , Serraf Alain , Mazmanian Guy‐Michel , Ragot Thierry
Published: January 2003

Background

The advent of cardiac gene therapy in clinical practice requires a more efficient and safer myocardial gene delivery in large animals. A new approach to adenovirus‐mediated intracoronary gene transfer in the piglet, using a heterotopic heart transplantation model, was designed to maximize the duration of contact between the vector and the heart in noncoronary flow conditions.

Methods

Recombinant adenoviruses harboring a nucleus‐localized β‐galactosidase gene under the control of a viral promoter were injected into the coronary vessels of the harvested hearts at a dose ranging from 1010 to 2 × 1011 pfu. The graft was maintained for 75 min in saline solution and then implanted in the abdomen of recipients. Gene transfer to allografts was evaluated 4 days after grafting by immunohistochemical and enzymatic analysis of β‐galactosidase expression.

Results

Transgene expression was detected in all cardiac areas and up to 64, 44, 32, and 15% of positive nuclei were estimated in the left ventricle wall in four animals out of eleven. In the remaining animals, transgene expression was focally distributed, mainly in the left ventricle wall. PCR analysis revealed the presence of adenoviral sequences, albeit minimal, in exposed organs such as the liver and lung.

Conclusions

This procedure demonstrated that direct intracoronary gene transfer can be achieved using an ex vivo gene transfer strategy. Copyright © 2002 John Wiley & Sons, Ltd.
Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo
Authors: Köping‐Höggård M. , Mel'nikova Y. S. , Vårum K. M. , Lindman B. , Artursson P.
Published: January 2003

Background

Chitosans of high molecular weights have emerged as efficient nonviral gene delivery systems, but the properties and efficiency of well‐defined low molecular weight chitosans (<5 kDa) have not been studied. We therefore characterized DNA complexes of such low molecular weight chitosans and related their physical shape and stability to their efficiency as gene delivery systems in vitro and in vivo.

Methods

Individual complexes between six different chitosan oligomers (6‐, 8‐, 10‐, 12‐, 14‐ and 24‐mers) and fluorescence‐labeled T4 DNA were visualized and classified into six physical shapes using video‐enhanced fluorescence microscopy. The effects of chitosan chain length, charge ratio (+/−) and solvent properties (pH and ionic strength) on the stability and structure of the complexes were studied. Gene expression in vitro and in vivo were studied using a luciferase reporter gene.

Results

Free DNA appeared as extended coils. Chitosan complexes had a variety of physical shapes depending on the experimental conditions. In general, the fraction of complexes that had nonaggregated, globular structures increased with increasing chain length of the chitosan oligomer, increasing charge ratio and reduction of pH (from 6.5 to 3.5). A further increase in charge ratio for globular complexes or a further reduction in pH (to 2.5) increased the fraction of aggregates, indicating a window where pharmaceutically desirable globules are obtained. Gene transfection efficiencies in vitro and in vivo were related to the physical shape and stability of the complexes. Only the 24‐mer formed stable complexes that gave a high level of gene expression comparable to that of high molecular weight ultrapure chitosan (UPC) in vitro and in vivo.

Conclusions

Chitosan oligomers form complexes with DNA in a structure‐dependent manner. We conclude that the 24‐mer, which has more desirable physical properties than UPC, is more attractive as a gene delivery system than the conventional high molecular weight chitosans. Copyright © 2002 John Wiley & Sons, Ltd.
A study on the intra‐annual variation and the spatial distribution of precipitation amount and duration over Greece on a 10 day basis
Authors: Bartzokas A. , Lolis C. J. , Metaxas D. A.
Published: January 2003

The intra‐annual variation of precipitation amount and duration and their spatial distribution during the year are studied on a 10 day basis for the Greek region, using S‐mode and T‐mode factor analysis. (i) For the intra‐annual variation of precipitation amount, two modes were revealed: the first shows one broad maximum during the conventional winter in stations affected by the sea; the second presents two maxima, the first during late autumn–early winter and the second during late spring, corresponding to the northern mainland stations. (ii) For the spatial distribution of precipitation, three main patterns were revealed: the first one is the ‘winter’ pattern, with the maximum over the west windward area; the second is the ‘summer’ pattern, with a maximum over the north inland region; and the third is the ‘autumn’ pattern, with the maximum over northwestern Greece. (iii) For precipitation duration, two types of intra‐annual variation were revealed. The first one is similar to the first of the analysis for precipitation amount; the second presents two maxima, the first during the beginning of December and the second during the middle of February, corresponding to the areas of northwestern and northeastern Greece. (iv) For the spatial distribution of precipitation duration, three main patterns were revealed: the first is the ‘summer’ pattern, which is similar to the second of the analysis for precipitation amount; the second is the ‘winter’ pattern, with the spatial maximum located over the eastern mainland and western Crete; finally, the third one is the ‘autumn’ pattern, with the maximum in northwestern Greece. During the third 10 day period of October and the second 10 day period of February, precipitation seems to present singularities, possibly due to fluctuations in atmospheric circulation. The above intra‐annual variations and spatial distribution patterns are connected to the seasonal variations of the depression trajectories, the atmospheric instability, the influence of sea‐surface temperature as a cyclogenesis factor, and the windward or leeward character of the various areas (orographic effect). Copyright © 2003 Royal Meteorological Society.
Leg muscle strength is reduced in Parkinson's disease and relates to the ability to rise from a chair
Authors: Inkster Lisa M. , Eng Janice J. , MacIntyre Donna L. , Stoessl A. Jon
Published: January 2003

Individuals with Parkinson's disease (PD) have difficulties rising from a chair; however, factors contributing to this inability have never been investigated. We compared lower extremity strength between individuals with PD and healthy controls and quantified the relationships between strength and the ability to rise from a chair. Ten men with mild PD and 10 sex‐ and age‐matched controls performed maximal concentric, isokinetic knee and hip extensor torque on an isokinetic dynamometer to quantify muscle strength. Subjects also rose from a chair at their comfortable pace without the use of their arms and the duration of this task provided a measure of sit‐to‐stand (STS) ability. Subjects with PD were tested in an on‐ and off‐medication state on different days. Mean hip and knee extensor torques were lower in subjects with PD, with greater deficits found at the hip. Greater hip strength was related to better STS ability in subjects with PD while greater knee strength was related to better STS ability in controls. These results show that individuals with mild PD generate smaller extremity forces compared to controls. Reduced strength, particularly at the hip, may be one factor that contributes to the difficulty of persons with PD to rise from a chair.
Restless legs syndrome in Parkinson's disease: A case‐controlled study
Authors: Krishnan Pudukode R. , Bhatia Manvir , Behari Madhuri
Published: January 2003

Restless legs syndrome (RLS) is a disorder of motor activity with a circadian pattern, occurring frequently in patients with Parkinson's disease (PD). We sought to estimate the prevalence of RLS in Indian PD patients. One hundred twenty‐six consecutive PD patients and 128 healthy age‐ and sex‐matched controls were evaluated using a predesigned questionnaire. RLS was present in 10 of 126 cases of PD (7.9%) and 1 of 128 controls (0.8%, P = 0.01). PD patients with RLS were older than those without RLS (63.70 ± 7.80 years vs. 57.37 ± 10.04 years; P = 0.05) and had higher prevalence of depression (40% vs. 10.3%; P = 0.023). No demographic factors or factors related to PD correlated with the presence or severity of RLS. RLS is more common among patients with PD than controls. A greater medical recognition of this disorder is needed in view of available effective treatment. © 2002 Movement Disorder Society
Familial blepharospasm is inherited as an autosomal dominant trait and relates to a novel unassigned gene
Authors: Defazio Giovanni , Brancati Francesco , Valente Enza Maria , Caputo Viviana , Pizzuti Antonio , Martino Davide , Abbruzzese Giovanni , Livrea Paolo , Berardelli Alfredo , Dallapiccola Bruno
Published: January 2003

Blepharospasm (BSP) is a common form of primary torsion dystonia (PTD). Although most cases are sporadic, an increased familial incidence of BSP has been reported. Precisely how blepharospasm is inherited remains unclear. We report on two Italian families with adult‐onset focal BSP inherited as an autosomal dominant trait with reduced penetrance. None of the affected family members had the 3‐bp (GAG) or the 18‐bp deletion in the DYT1 gene. In one family, linkage analysis allowed us to exclude segregation of the disease with the known PTD loci (DYT1, DYT6, DYT7, and DYT13). These findings suggest that primary familial adult‐onset BSP is a distinct entity among inherited PTD and is caused by a novel, unmapped gene. ©
Movement Disorder Society
Cerebrospinal fluid Aβ42 is reduced in multiple system atrophy but normal in Parkinson's disease and progressive supranuclear palsy
Authors: Holmberg Björn , Johnels Bo , Blennow Kaj , Rosengren Lars
Published: January 2003

The 42‐amino–acid isoform of β‐amyloid Aβ42 in the cerebrospinal fluid (CSF) has recently been proposed as a biochemical marker for Alzheimer's disease (AD) and subcortical white‐matter dementia (SWD). In both of these conditions, concentration of CSF‐Aβ42 is reduced. We quantified CSF‐Aβ42 from patients fulfilling strict clinical criteria for multiple system atrophy (MSA; n = 36), Parkinson's disease (PD; n = 48) and progressive supranuclear palsy (PSP; n = 15). The study groups were consecutively recruited among patients referred to a movement disorder unit, and 32 healthy, age‐matched volunteers were used as controls. The CSF concentration of Aβ42 was significantly reduced in the MSA group (P < 0.001), whereas the PD and PSP groups did not differ from controls. On an individual basis, low content of Aβ42 was seen in 9 MSA patients regardless of age and disease duration. Three PD patients with long disease duration also had low concentrations but all PSP patients were normal. We conclude that the reduced CSF‐Aβ42 concentration may be a clue to the pathogenesis of MSA. There is a decreased production, or more possible, an increased consumption of CSF‐Aβ42. The analysis of this protein may also become a supplement to the clinical differentiation of parkinsonian syndromes in a movement disorder unit.
Dopaminergic response in Parkinsonian phenotype of Machado‐Joseph disease
Authors: Buhmann Carsten , Bussopulos Alexandra , Oechsner Matthias
Published: January 2003

We report on a patient with genetically proven Machado‐Joseph Disease (MJD) presenting with signs indistinguishable from Parkinson's disease (PD), including levodopa response and typical levodopa‐induced motor fluctuations. Only after 10 years of prolonged benefit from levodopa and different dopamine agonists (DA), the patient developed cerebellar ataxia and pyramidal signs. Preferential D3‐receptor–stimulating dopamine agonists especially showed a benefit at the time, when D2 receptor binding was reduced in IBZM SPECT. This is the first report of a meaningful response to DA in MJD. © 2002 Movement Disorder Society
Secondary progressive chronic manganism associated with markedly decreased striatal D2 receptor density
Authors: Kessler Kirn R. , Wunderlich Gilbert , Hefter Harald , Seitz Rüdiger J.
Published: January 2003

We describe a patient with chronic manganism due to intoxication 40 years ago. Whereas previous reports on acute or subacute intoxication have shown no or only small reductions in striatal D2 receptor density, we found markedly decreased D2 receptor density using 18F‐methylspiperone PET in this very late stage of chronic manganism, supporting the hypothesis that manganese intoxication may trigger a neurodegenerative disease process. © 2002 Movement Disorder Society
Pathogenic role of glial cells in Parkinson's disease
Authors: Teismann Peter , Tieu Kim , Cohen Oren , Choi Dong‐Kug , Wu Du Chu , Marks Daniel , Vila Miquel , Jackson‐Lewis Vernice , Przedborski Serge
Published: January 2003

An erratum for this article appears in the January, 2004 issue of Movement Disorders (Mov Disord 2004;19:119).

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of these neurons is associated with a glial response composed mainly of activated microglial cells and, to a lesser extent, of reactive astrocytes. This glial response may be the source of trophic factors and can protect against reactive oxygen species and glutamate. Alternatively, this glial response can also mediate a variety of deleterious events related to the production of pro‐oxidant reactive species, and pro‐inflammatory prostaglandin and cytokines. We discuss the potential protective and deleterious effects of glial cells in the SNpc of PD and examine how those factors may contribute to the pathogenesis of this disease. © 2002 Movement Disorder Society
Substantia nigra lesions in viral encephalitis
Authors: Savant Charulata Sankhla , Singhal B.S. , Jankovic Joseph , Khan Mak , Virani Amin
Published: January 2003

Post‐encephalitic parkinsonism is a well‐known entity, but involvement of the basal ganglia is rarely documented. We describe a 21‐year‐old man who developed parkinsonism following encephalitic illness presumed to be of viral origin with substantia nigra lesions evident on magnetic resonance imaging scan.
Genetic association of Huntington's disease and restless legs syndrome? A family report
Authors: Evers Stefan , Stögbauer Florian
Published: January 2003

We report on a family with comorbidity of Huntington's disease (HD) and idiopathic restless legs syndrome (RLS). All family members investigated and affected by RLS are also affected by HD, but not vice versa. The association of HD and RLS is discussed with respect to dopaminergic dysfunction. © 2002 Movement Disorder Society
Intensity distribution inside scatterers with negative‐real permittivity and permeability
Authors: Ruppin R.
Published: January 2003

The electric field distribution inside a cylindrical or spherical scatterer with negative‐real permittivity and permeability is investigated. For large‐size parameters, intensity tends to focus on the main axis at a location shifted from the center towards the front surface. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 150–154, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10705
Multi‐wavelength Yb‐doped fiber‐ring laser
Authors: Chi Ronghua , Lu Kecheng , Chen Shengping
Published: January 2003

A multi‐wavelength ytterbium‐doped fiber‐ring laser is obtained using a spatial‐mode beating filter, placing a section of a G.652 fiber sample into the single Yb‐doped fiber ring cavity. Up to six stable laser wavelengths can be obtained in the region of 1030 nm at room temperature. By changing the states of the polarization controller, the amount of lasing wavelength and the space can be controlled. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 170–172, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10711
Multiwavelength fiber laser using a Sagnac loop filter
Authors: Das Gautam , Lit John W. Y.
Published: January 2003

A Sagnac interferometer has been used in the ring cavity to produce a multiwavelength fiber laser. The results show that an elliptical‐core erbium‐doped fiber can produce more stable lasing lines compared to a normal erbium‐doped fiber. The principle of operation is based on polarization‐dependent gain phenomena in erbium‐doped fiber. The number of lasing lines and stability may be adjusted by using a polarization controller to control the polarization of the wave inside the cavity. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 200–202, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10719
Multi‐channel long‐distance optical fiber transmission using dispersion‐induced microwave transmission windows
Authors: Gutiérrez‐Martínez C. , Mollier P. , Porte H. , Zaldívar‐Huerta I. , Carcaño‐Rivera L. , Goedgebuer J. P.
Published: January 2003

In this paper, the model and implementation of an optical transmission system using a multi‐longitudinal mode optical source and a dispersive optical channel are described. Such a system exhibits multi‐bandpass transmission windows, as a result of a combination of the wideband optical spectrum and chromatic dispersion on the optical channel. As shown in this paper, the band‐pass windows are centered at frequencies that depend on the spectral free range of the optical source and optical channel length. In the telecommunications domain, band‐pass transmission windows can be used for multiplexing analog and/or digital signals, as an alternative way for transmitting baseband and modulated subcarriers, through optical‐fiber links. To show such a potential application, the multiplexed transmission of two microwave signals, using two adjacent band‐pass windows, is also described in this paper. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 202–206, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10720
A low‐phase‐noise local oscillator for a Ka‐band satellite transponder
Authors: Ryu Keun‐Kwan , Lee Moon‐Que , Yom In‐Bok , Lee Seong‐Pal
Published: January 2003

A low‐phase‐noise local oscillator (LO) is developed for a Ka‐band satellite transponder. A novel dielectric resonator‐voltage controlled oscillator (DR‐VCO) is also designed by using a high‐impedance inverter coupled with a dielectric resonator to improve the phase‐noise performance out of the loop bandwidth. This LO performs the harmonic suppression characteristics above 43.83 dBc and requires 2.6‐watt power consumption. The phase‐noise characteristics are exhibited as −102.5 dBc/Hz at 10‐KHz offset frequency and −104.0 dBc/Hz at 100‐KHz offset frequency, respectively, with output power of 13.50 dBm ± 0.33 dB over a temperature range of −20 ∼ +70°C. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 216–218, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10724
A simple and accurate expression for the bandwidth of electrically thick rectangular microstrip antennas
Authors: Guney K.
Published: January 2003

A new, very simple closed‐form expression for computing the bandwidth of rectangular microstrip antennas with thick substrates is presented. It is obtained by means of a curve‐fitting technique, and is useful for the computer‐aided design of microstrip antennas. The theoretical bandwidth results obtained by using this new bandwidth expression are in very good agreement with the experimental results reported elsewhere. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 36: 225–228, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10727
Stress intensity factor analysis of interface cracks using X‐FEM
Authors: Nagashima Toshio , Omoto Youhei , Tani Shuichi
Published: January 2003

The extended finite element method (X‐FEM) proposed by Belytschko et al. (International Journal for Numerical Methods in Engineering 1999; 45: 602; 1999; 46: 131; 2001; 50: 993) uses interpolation functions based on the concept of partition of unity, and considers the asymptotic solution and the discontinuity of displacement fields near a crack independently of the finite element mesh. This paper describes the application of X‐FEM to stress analyses of structures containing interface cracks between dissimilar materials. In X‐FEM, an interface crack can be modelled by locally changing an interpolation function in the element near a crack. The energy release rate should be separated into individual stress intensity factors, K1 and K2, because the stress field around the interface crack has mixed modes coupled with mode‐I and mode‐II. For this purpose, various evaluation methods used in conjunction with numerical methods such as FEM and BEM are reviewed. These methods are examined in numerical examples of elastostatic analyses of structures containing interface cracks using X‐FEM. The numerical results show that X‐FEM is an effective method for performing stress analyses and evaluating stress intensity factors in problems related to bi‐material fractures. Copyright © 2003 John Wiley & Sons, Ltd.
Optimization of thermo‐elasto‐plastic processes using Eulerian sensitivity analysis
Authors: Paul S. , Michaleris P. , Shanghvi J. Y.
Published: January 2003

A computational scheme for the analysis and optimization of quasi‐static thermo‐mechanical processes is presented in this paper. In order to obtain desirable mechanical transformations in a workpiece using a thermal treatment process, the optimal control parameters need to be determined. The problem is addressed by posing the process as a decoupled thermo‐mechanical finite element problem and performing an optimization using gradient methods. The forward problem is solved using the Eulerian formulation since it is computationally more efficient compared to an equivalent Lagrangian formulation. The design sensitivities required for the optimization are developed analytically using direct differentiation. This systematic design approach is applied to optimize a laser forming process. The objective is to maximize the angular distortion of a specimen subject to the constraint that the phase transition temperature is not exceeded at any point in the model. Copyright © 2003 John Wiley & Sons, Ltd.
Healing of adsorbed polymer layers in a narrow gap following removal by shear
Authors: Raviv Uri , Klein Jacob
Published: January 2003

The shear and normal forces between layers of poly(ethylene oxide) (PEO), of molecular weights Mw = 37 kg/mol adsorbed onto smooth, curved solid (mica) surfaces across the good solvent toluene have been determined using a surface force balance (SFB). The equilibrium Fn(D) profiles are closely similar to those measured in earlier studies between adsorbed PEO layers. The shearing motion causes the removal of polymer from within the intersurface gap during sliding. The recovery of the adsorbing layer has been measured and the amount of adsorption with time was calculated. Our findings showed that there is no migration of polymers on the surfaces and that the recovery of the layer is controlled by the rate of diffusion of polymer chains into the gap. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of the structure of the polymer matrix on the terthiophene chromophore dispersion in dichroic polyethelene films
Authors: Pucci Andrea , Ruggeri Giacomo , Moretto Letizia , Bronco Simona
Published: January 2003

In the frame of an ongoing research project dealing with linear optical polarizers produced by dispersing terthiophene derivatives in ultra‐high‐molecular‐weight polyethylene (UHMWPE) and successive orientation by uniaxial stretching of the derived films, the present paper describes the use of linear‐low‐density polyethylene (LLDPE) or high‐density polyethylene (HDPE) as an alternative polymer matrix in relation also to the possibility of taking different preparation routes. The study was performed with the easily prepared 5,5″‐bis‐thiooctadecyl‐2,2′:5′,2″‐terthiophene as the chromophore which was blended in a Brabender mixer at 180 °C and concentration 0.2–2% w/w with LLDPE or HDPE in the bulk. The morphology and optical properties of the films obtained by compression moulding were compared with those of a similar film in UHMWPE prepared by solution casting. Differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis of the unoriented films of the former type were also performed. These data suggest the improved dispersion of the chromophore in case of the films obtained by melt processing. After uniaxial stretching up to 14–30 times the original length, molecular orientation was evaluated in different cases by measuring the dichroic ratio [R = A∥/A⟂] and the order parameter [S = (R − 1)/(R + 2)]. Also the polarizer performance was detected by comparing the dependence of polarizing efficiency on single‐piece transmittance of the different samples. Copyright © 2003 John Wiley & Sons, Ltd.
A model for the future conduct of pharmacovigilance
Authors: Waller Patrick C. , Evans Stephen J. W.
Published: January 2003

A scientific model to support excellence in pharmacovigilance has been developed from first principles by brainstorming sessions and discussions with experts in the field. The model represents a long‐term vision of how pharmacovigilance could be conducted in the future. So far it has been developed without any consideration of constraints such as resources or the need for legislative change. Although the vision is holistic, it would be possible to test and implement parts of the model in a piecemeal fashion. Copyright © 2002 John Wiley & Sons, Ltd.
Prolongation of the QT interval and cardiac arrhythmias associated with cisapride: limitations of the pharmacoepidemiological studies conducted and proposals for the future
Authors: Layton Deborah , Key Cheryl , Shakir Saad A. W.
Published: January 2003

Not all hazards can be identified from clinical studies prior to marketing of medicinal products. Pre‐marketing large‐scale trials for cisapride did not report any serious cardiac arrhythmias. After a long period of availability in several countries it was withdrawn in 2000 because of reports of serious, and in many cases fatal, cardiac events. Whilst spontaneous reporting systems for adverse drug reactions (ADRs) have limitations such as under‐reporting, they are an effective system for signal generation, particularly of rare ADRs. Pharmacoepidemiological studies aim to identify and calculate the incidence of adverse reactions, with increased sensitivity to less common ADRs compared to randomised controlled trials, yet cohort sizes may be insufficient to detect very rare ADRs such as drug‐induced Torsade de Pointes, with an estimated incidence of the order of 1 per 12 000 to 1 per 120 000 patients. Several pharmacoepidemiological studies investigated adverse events associated with cisapride, one of which specifically examined the association between serious cardiac arrhythmias and cisapride. These observational studies were conducted using large population databases, but each failed to identify sufficient cases to establish a causal relationship. Explanations include that the cohort sample sizes were too small, and either under‐, or mis‐reporting of events of interest may have occurred. To estimate the risk of very rare adverse events, pharmacoepidemiological studies require very large numbers. Furthermore, the events in question need to be clinically recognisable by doctors and adequately documented in patients' notes, computer records, or on study questionnaires. The establishment of a national registry for drug‐induced QT prolongation to identify cases and correlate clinical information may help to better identify these rare ADRs earlier. Such proactive surveillance could avoid unnecessary delays for other drugs where QT prolongation and serious cardiac arrhythmias may be an issue. Copyright © 2002 John Wiley & Sons, Ltd.
Comparing patterns of long‐term benzodiazepine use between a Dutch and a Swedish community
Authors: van Hulten Rolf , Isacson Dag , Bakker Albert , Leufkens Hubert G.
Published: January 2003

Background

There is much concern about the widespread long‐term use of benzodiazepines. Utilisation data can give a foundation for interventions for appropriate use.

Objective

To compare long‐term usage patterns of benzodiazepines in a Dutch and a Swedish community in different periods.

Methods

Eight‐year follow‐up patterns of use were investigated with respect to the characteristics of those who continued use over the whole follow‐up period. In the Dutch community of 13 500, the data of a cohort of 1358 benzodiazepine users were analysed during the years 1984–1991; in the Swedish community of 20 000 people, a cohort of 2038 benzodiazepine users was followed from 1976.

Results

At the end of the follow‐up period, 32.9% of the Dutch cohort and 33% of the Swedish cohort had continued use of benzodiazepines. The two overall survival curves showed similar patterns. Stratification for age, gender, previous versus initial use and heavy versus non‐heavy use showed comparable proportions of patients continuing benzodiazepine use over time.

Conclusion

The parallels in the results of two cohorts in different countries and different periods are striking and give support to the idea to stimulate interventions to reduce long‐term benzodiazepine use. Copyright © 2002 John Wiley & Sons, Ltd.
Molecular cloning and expression of a variant form of hippostasin/KLK11 in prostate
Authors: Nakamura Terukazu , Mitsui Shinichi , Okui Akira , Miki Tsuneharu , Yamaguchi Nozomi
Published: January 2003

Background

Hippostasin is a kallikrein‐like serine protease, which has two alternatively spliced isoforms, brain‐type and prostate‐type. We previously reported alternative expression of hippostasin in prostate cancer cell lines.

Methods

We studied the expression of a variant‐form hippostasin (isoform 3) mRNA by RT‐PCR. Localization of the isoform 3 protein was examined by immunohistochemistry. The enzymatic activity of the recombinant protein was measured with synthetic substrates.

Results

A novel isoform of hippostasin contains 25 additional amino acids in the catalytic triad of brain‐type hippostasin. Its mRNA was expressed in normal prostate tissue, BPH, and prostate cancer cell lines. The protein was localized in the prostate secretory epithelium. The enzyme activity was similar to that of brain‐type hippostasin, which has kallikrein‐like activity.

Conclusions

In this study, we have identified a third isoform of hippostasin, which was designated variant‐form (isoform 3). Hippostasin isoform 3 may play a role in the prostate, including reproductive and/or tumorigenic functions. Prostate 54: 299–305, 2003. © 2003 Wiley‐Liss, Inc.
Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism
Authors: Ji Qing , Chang Lilly , VanDenBerg David , Stanczyk Frank Z. , Stolz Andrew
Published: January 2003

BACKGROUND

As androgens play an essential role in prostate cancer, we sought to develop a real‐time PCR to characterize mRNA expression profiles of human members of the Aldo‐Keto Reductase (AKR) 1C gene family, as well as of 5α‐steroid reductase Type II (SRD5A2) in prostate cancer samples. Functional activity and regulation of AKR1C2, a 3α‐hydroxysteroid dehydrogenase (HSD) type III, was also assessed in prostate cancer cell lines.

METHODS

Gene specific PCR primers were established and relative gene expression of human AKR1C family members was determined in paired samples of cancerous and surrounding unaffected prostate tissue.

RESULTS

AKR1C2 preferentially reduces DHT to the weak metabolite 5α‐androstane‐3α,17β‐diol (3α‐diol) without conversion of 3α‐diol to DHT in the PC‐3 cell line, and its expression was increased by DHT treatment in LNCaP cells. Selectively reduced expression of AKR1C2 mRNA, but not AKR1C1 (97% sequence identity), was found in approximately half of the pairs whereas AKR1C3 relative expression was not significantly altered. No aberrant expression of AKR1C4 expression or significant differences in SRD5A2 gene expression were found.

CONCLUSIONS

AKR1C2 functions as a DHT reductase in prostate‐derived cells lines and is regulated by DHT. Additional studies are needed to further define the significance of reduced AKR1C2 expression in prostate cancer and its potential role in modulating local availability of DHT. Prostate 54: 275–289, 2003. © 2003 Wiley‐Liss, Inc.
Leptomycin B stabilizes and activates p53 in primary prostatic epithelial cells and induces apoptosis in the LNCaP cell line
Authors: Lecane Philip S. , Kiviharju Taija M. , Sellers Robert G. , Peehl Donna M.
Published: January 2003

Background

Previous studies showed that primary cultures of normal and malignant human prostatic epithelial cells are defective in their ability to upregulate the tumor suppressor protein p53 in response to DNA damage. This dysfunctional regulation of p53 may be relevant to both the high incidence of prostate cancer and its resistance to chemotherapy. Leptomycin B (LMB) has recently been found to increase the protein level and transcriptional activity of p53 by interfering with nucleocytoplasmic export and subsequent degradation by the proteasome. We investigated the ability of LMB to activate p53 in prostatic epithelial cells.

Methods

Primary cultures and the cell lines LNCaP and DU 145 were treated with LMB. p53 protein was evaluated in Western blots and by immunocytochemistry. Induction of downstream targets of p53 was evaluated in Western and Northern blots. Growth inhibition, cell cycle arrest, and apoptosis in response to LMB were measured in clonal growth assays, by flow cytometry, and by Hoescht/propidium iodide staining, respectively.

Results

Treatment of prostatic epithelial cells with LMB led to post‐translational stabilization of p53, activation of downstream target genes, and induction of cell cycle arrest in primary cultures and apoptosis in LNCaP (with wild‐type p53) but not DU 145 (with mutant p53) cells.

Conclusions

p53 in primary cultures of normal and malignant prostate cells, although dysfunctional in that it is not responsive to DNA damage, is activated by LMB. The ability of LMB to stabilize p53 and induce expression of p53‐responsive growth inhibitory genes may be a useful lead in the development of chemopreventive or therapeutic small molecules that can modulate p53 function in prostatic epithelial cells. Prostate 54: 258–267, 2003. © 2003 Wiley‐Liss, Inc.
Repair of impurity‐poisoned protein crystal surfaces
Authors: Plomp M. , McPherson A. , Malkin A.J.
Published: January 2003

The surface morphology of Bence–Jones protein (BJP) crystals was investigated during growth and dissolution by using in situ atomic force microscopy (AFM). It was shown that over a wide supersaturation range, impurities adsorb on the crystalline surface and ultimately form an impurity adsorption layer that prevents further growth of the crystal. At low undersaturations, this impurity adsorption layer prevents dissolution. At greater undersaturation, dissolution takes place around large particles incorporated into the crystal, leading to etch pits with impurity‐free bottoms. On restoration of supersaturation conditions, two‐dimensional nucleation takes place on the impurity‐free bottoms of these etch pits. After new growth layers fill in the etch pits, they cover the impurity‐poisoned top layer of the crystal face. This leads to the resumption of its growth. Formation of an impurity‐adsorption layer can explain the termination of growth of macromolecular crystals that has been widely noted. Growth‐dissolution‐growth cycles could be used to produce larger crystals that otherwise would have stopped growing because of impurity poisoning. Proteins 2003;50:486–495. © 2003 Wiley‐Liss, Inc.
Alpha helix shortening in 1522 MSP‐1 conserved peptide analogs is associated with immunogenicity and protection against P. falciparum malaria
Authors: Cubillos Marcia , Espejo Fabiola , Purmova Jindra , Martinez Juan C. , Patarroyo M.E.
Published: January 2003

1522 is a nonimmunogenic conserved high‐activity binding peptide (HABP) belonging to Plasmodium falciparum MSP‐1 protein N‐terminal fragment. The key amino acids in binding to red blood cells (RBC) were identified and replaced by others having similar mass but different charge. Because conserved HABPs are not antigenic nor immunogenic, immunogenicity and protectivity studies were then conducted on them in the Aotus monkey. 1H‐NMR studies included the lead peptide 1522 as well as the analogs 9782, 13446, 13448, and 13442 to relate their structure to biological function. All the peptides presented α‐helical structure, with differences observed in helix location and extension. The nonprotective 1522 peptide was totally helical from the N‐ to the C‐terminus, very similar to nonprotective 13442 and 13448 peptides whose extension was almost totally helical. The 9782 and 13446 protective peptides, however, possessed a shorter helical region where modified critical binding residues were not included. A more flexible region was generated at the C‐terminus in those peptides with a shorter helical region, leading to a greater number of conformers. These data suggest that peptide flexibility results in increased interaction with immune system molecules, generating protective immunity. Proteins 2003;50:400–409. © 2003 Wiley‐Liss, Inc.