bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo metabolism of pyronaridine characterized by low‐energy collision‐induced dissociation mass spectrometry with electrospray ionization
Authors: Lee Jaeick , Son Junghyun , Chung Suk‐Jae , Lee Eung‐Seok , Kim Dong‐Hyun
Published: September 2004

The in vitro and in vivo metabolism of pyronaridine, an antimalarial agent, was investigated in rats and humans. In vitro incubation of pyronaridine with rat and human liver microsomes resulted in the formation of 11 metabolites, with pyronaridine quinoneimine (M3) as the major metabolite. The structures of pyronaridine metabolites were characterized on the basis of the product ion mass spectra obtained under low‐energy collision‐induced dissociation (CID) ion trap mass spectrometry. Both pyronaridine (m/z 518) and M3 (m/z 516) produced the same product ion (m/z 447). These results could be explained by the characteristic neutral loss of a 69 Da fragment from M3 via γ‐H rearrangement and 1,7 sigmatropic shift, whereas the neutral loss of a 71 Da fragment from the pyronaridine occurred by charge site‐initiated heterolytic cleavage. These fragmentations were further supported by the tandem mass spectrum of D3‐pyronaridine. Other metabolites generated in the microsomal incubations were carbonylated, hydroxylated and O‐demethylated derivatives. Pyronaridine and its metabolites were detected in both feces and urine after intraperitoneal administration to rats. The in vivo metabolic profile in rats was different from the in vitro profile. M3, a chemically reactive quinonimine, was not detected whereas O‐demethylated derivatives (M14, M15, M16, and M19) were identified in fecal and urinary extracts. The role of quinoneimine metabolites in pyronaridine‐caused toxicity should be further evaluated, although these metabolites or their conjugates were not detected in urine and feces. Copyright © 2004 John Wiley & Sons, Ltd.
Genetic immunization and comprehensive screening approaches in HLA‐A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen
Authors: Martin P. , Parroche P. , Chatel L. , Barretto C. , Beck A. , Trépo C. , Bain C. , Lone Y.C. , Inchauspé G. , Fournillier Anne
Published: September 2004

Interferon‐γ (IFNγ)‐producing CD8+ T cells have been shown to play a key role in the control or eradication of hepatitis C virus (HCV) infections. In particular, T cells specific of the non‐structural protein 3 (NS3) are often associated with control of viremia. The aim of the study was to identify novel HLA‐A2 restricted CD8+ T cell epitopes specific of NS3 using a combination of comprehensive approaches. HLA‐A2.1 transgenic mice were immunized with a DNA vaccine optimized for NS3 specific epitope presentation and induced CD8+ T cell reactivity was screened using 42 algorithm‐predicted peptides as well as a library of 78 overlapping 15‐mer peptides spanning the whole protein. Three epitopes mapping within the NS3 protease (GLL: aa 1038–1047) or helicase (ATL: aa 1260–1268 and TLH: aa 1617–1625) were identified. These epitopes, which display similar and high in vitro binding capacities to soluble HLA‐A2 molecules, are able to induce either cytotoxic T lymphocytes (CTL) and/or IFNγ‐producing T cells. Comparative in vitro target cell sensitization studies revealed a higher immunogenicity of the GLL peptide as compared with both ATL and TLH peptides. This peptide was capable to recall in vitro HCV‐specific IFNγ and IL‐10‐producing T cells from peripheral blood mononuclear cells (PBMC) of chronically infected patients. These data increase the pool of NS3‐specific CD8+ T cell epitopes available to analyze HCV associated immunity and could contribute to the design and evaluation of candidate vaccines. J. Med. Virol. 74:397–405, 2004. © 2004 Wiley‐Liss, Inc.
Detection of human respiratory syncytial virus genotype specific antibody responses in infants
Authors: McGill A. , Greensill J. , Marsh R. , Craft A.W. , Toms G.L.
Published: September 2004

Infection and reinfection of infants with human respiratory syncytial virus (HRSV) occur despite the presence of serum anti‐viral glycoprotein antibodies similar to those, which afford protection in animal models of infection. Antigenic variation of the viral glycoproteins between different genotypes of the virus which co‐circulate in the population may contribute to the ability of the virus to escape from antibody‐mediated protection. In this study, we have investigated whether human infants infected with HRSV produced antibody responses recognising the antigenic differences between different contemporary genotypes of virus. Acute and convalescent sera from 26 infants were analysed for antibody responses to the glycoproteins of the virus isolated from their respiratory tract and to representative viruses of homologous and heterologous genotypes. All infants developed antibodies with similar reactivity for viruses of all contemporary isolates and genotypes when measured in an immunofluorescence assay against unfixed virus infected cells. However, when antibody responses to the individual glycoproteins were measured in a surace plasmon resonance (SPR) assay, although all infants developed genotype cross‐reactive antibodies to the F glycoprotein, anti‐G antibodies were detectable in only half of the infants and in all cases these were genotype specific. Possession of no or only genotype specific antibodies to the G glycoprotein may contribute to the susceptibility of infants to reinfection. In both assays, reactivity of anti‐glycoprotein antibodies with the sub‐group A archetypal strain, A2, was markedly lower than with any contemporary virus tested indicating that this strain alone is unsuitable for accurate assessment of infant antibody responses. J. Med. Virol. 74:492–498, 2004. © 2004 Wiley‐Liss, Inc.
Lysolecithin induces demyelination in vitro in a cerebellar slice culture system
Authors: Birgbauer Eric , Rao Tadimeti S. , Webb Michael
Published: September 2004

Demyelination is a hallmark of several human diseases, including multiple sclerosis. To understand better the process of demyelination and remyelination, we explored the use of an in vitro organotypic cerebellar slice culture system. Parasagittal slices of postnatal Day 10 (P10) rat cerebella cultured in vitro demonstrated significant myelination after 1 week in culture. Treatment of the cultures at 7 days in vitro (DIV) with the bioactive lipid lysolecithin (lysophosphatidylcholine) for 15–17 hr in vitro produced marked demyelination. This demyelination was observed by immunostaining for the myelin components myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase). After a transient demyelinating insult with lysolecithin in vitro, the cultures recovered with oligodendrocyte differentiation recapitulating a normal time course; there was initially re‐expression of CNPase and MBP during this recovery, and this was followed by MOG. In addition, there seemed to be some limited remyelination during the recovery phase. Lysolecithin thus induces demyelination in an in vitro organotypic cerebellar slice culture system, providing a model system for studying myelination, demyelination, and remyelination in vitro. © 2004 Wiley‐Liss, Inc.
Hypothyroidism impairs long‐term potentiation in sympathetic ganglia: Electrophysiologic and molecular studies
Authors: Alzoubi K.H. , Bedawi A.S. , Aleisa A.M. , Alkadhi K.A.
Published: September 2004

Electrophysiologic and molecular techniques were used to study the effect of adult‐onset hypothyroidism on synaptic plasticity in the superior cervical sympathetic ganglion. Ganglia excised from adult thyroidectomized and sham‐operated rats were subjected to a brief high‐frequency stimulation of the preganglionic nerve to express long‐term potentiation (gLTP). Western blotting was carried out to determine the protein levels of key signaling molecules that may be involved in the expression of gLTP. Input/output relationship in ganglia from hypothyroid rats indicated a normal basal synaptic transmission, whereas activity‐dependent types of synaptic plasticity, posttetanic potentiation (PTP) and gLTP, were impaired. Immunoblot analysis showed that both calcium/calmodulin kinase II (CaMKII) and phosphorylated CaMKII (P‐CaMKII) levels were reduced markedly in hypothyroid rat ganglia compared to those from euthyroid controls. Additionally, protein levels of nitric oxide synthase‐1, heme oxygenase‐2, calmodulin, protein kinase C (PKC), and calcineurin were also reduced in hypothyroid rat ganglia. The results indicate that abnormally low basal levels of signaling molecules may be responsible for hypothyroidism‐induced impairment of gLTP in superior cervical ganglia. In addition, the results indicate that synaptic plasticity in sympathetic ganglia may involve a molecular sequence of events similar to that proposed for LTP in the hippocampus. © 2004 Wiley‐Liss, Inc.
Determination of perfluorooctane sulfonate and perfluorooctanoic acid in human plasma by large volume injection capillary column switching liquid chromatography coupled to electrospray ionization mass spectrometry
Authors: Holm Anders , Wilson Steven R. , Molander Paal , Lundanes Elsa , Greibrokk Tyge
Published: September 2004

Rapid, selective, and sensitive methodology for the quantification of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in human plasma using packed capillary liquid chromatography coupled to electrospray ionization ion‐trap mass spectrometry has been developed. Plasma proteins were precipitated using acetonitrile and the resulting supernatant was diluted 1 + 1 with water containing 10 mM ammonium acetate (NH4Ac) prior to injection. Sample volumes of 250 μL were loaded onto a 30 mm×0.32 mm ID 10 μm Kromasil C18 precolumn by a carrier solution consisting of 10 mM NH4Ac in ACN/H2O (5/95, v/v) at a flow rate of 100 μL/min, providing on‐line analyte enrichment and sample clean‐up. Backflushed elution onto a 100 mm×0.32 mm ID 3.5 μm Kromasil C18 analytical column was conducted using an ACN/H2O solvent gradient containing 10 mM NH4Ac. In order to improve the robustness and performance of the method, perfluoroheptanoic acid (PFHA) was used as internal standard. Separation and detection of PFOA, PFHA, and PFOS were achieved within 10 minutes. Ionization was performed in the negative mode in the m/z range 250–550. The method was validated over the concentration range 1–200 ng/mL for PFOA and over the range 5–200 ng/mL untreated plasma for PFOS, yielding correlation coefficients of 0.997 (PFOA) and 0.996 (PFOS), respectively. The within‐assay (n = 6) and between‐assay (n = 6) precisions were in the range 2.1–9.2 and 5.6–12%, respectively. The concentration limits of detection (cLOD) of PFOA was 0.5 ng/mL while the cLOD of PFOS was estimated to be 0.2 ng/mL in untreated plasma.
Enantiomer separations on a vancomycin stationary phase and retention mechanism of pressurized capillary electrochromatography
Authors: Yao Chuanyi , Tang Shaokun , Gao Ruyu , Jiang Chun , Yan Chao
Published: September 2004

Several chiral drugs, promethazine, carteolol, celiprolol, and albuterol, were resolved with vancomycin as the chiral stationary phase by pressurized capillary electrochromatography (pressurized CEC) and capillary HPLC. The effects of pressure and electrical field strength on efficiency, resolution, and capacity factor in pressurized CEC were investigated. A mathematical model describing the relationship of capacity factor in pressurized CEC with voltage, pressurized flow velocity, electroosmotic mobility, and electrophoretic mobility was established, which was in good agreement with the experimental data.
Inverse problem of theory of the laser irradiation scattering in
two-dimensional irregular integrated optical waveguide in the
presence of statistic noise
Authors: Egorov A A
Published: September 2004

The linear inverse problem of the theory of the light
scattering in two-dimensional integrated optical waveguide with
statistical irregularities in presence of noise (non exact data)
is investigated. The approximated correct solution of the inverse
problem of the theory of waveguide scattering in hand is obtained
for the natural physic and mathematics restrictions of imposed on
a ``measured'' scattering pattern. The algorithm of restoring an
autocovariance function of waveguide irregularities is based on a
combination of classic regularization and quasi-optimal
filtration.
Function series with multifractal variations
Authors: Barral Julien , Seuret Stephane
Published: September 2004

In this paper, we study three classes of multifractal function series using a work achieved for a new class of measures defined in [3].

The originality of these function series consists in the fact that the sizes of the jumps (or of the amplitudes of the pulses) depend on the location of the jump points and on a measure μ. In particular, there may be a strong heterogeneity in the distribution of the size of the jumps. These function series f are defined by

where ψj,k is a contracted and dilated version of a single function ψ. This function ψ will either be a wavelet, a pulse, or a piecewise linear function.

We show that under suitable conditions on the measure μ, the multifractal spectrum of f can be computed. For large classes of measures, the spectrum is linear between 0 and a critical value hc, and if h ≥ hc, f and μ share the same spectrum. This untypical shape is the result of the combination of the multifractal measure μ with the rapid variations or discontinuities of the functions ψj,k. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Technology and Stress Relaxation of Biaxially Oriented Polyolefin Shrink Films
Authors: Bobovitch Arthur , Unigovski Yakov , Jarashneli Albert , Gutman Emmanuel M.
Published: September 2004

In the present study the influence of the heating rate on the stability of the double bubble technological process was investigated. It was shown that increasing the heating rate decreases the stability of the process and causes the lower elongation of the films produced. The morphological transformations of linear low density polyethylene (LLDPE) film were explained using X‐ray and transmission electrom microscopy (TEM) methods. The stress relaxation behavior of co‐extruded LLDPE/ethylene‐vinyl‐acetate (EVA) film was studied using the relaxation time spectrum approach. The influence of vinyl‐acetate (VA) content in EVA copolymers on the relaxation time spectrum was observed.
New Approaches for the Development of Highly Stable Polypropylene
Authors: Terano Minoru , Liu Boping , Nakatani Hisayuki
Published: September 2004

Effects of primary structure on the degradation of polypropylene (PP) were studied using PPs having a variety of tacticities or a random ethylene sequence with the aim of improving the stability of PP. Thermal stabilities of isotactic, atactic and syndiotactic PPs (iPP, aPP and sPP) having similar molecular weights were investigated in terms of stereoregularity under the same conditions. The sPP showed the highest stability, suggesting that the racemic structure of the main chain interferes with the chain reaction of radical species. Moreover, iPP was prepared to evaluate the thermal stability with a random ethylene sequence (ethylene‐propylene random copolymer: rPP). The rPP was more stable than iPP. The existence of the ethylene sequence in the main chain was found to be effective in achieving high stability.
From Mumford–Shah to Perona–Malik in image processing
Authors: Kawohl B.
Published: September 2004

In mathematical image processing we are often presented with amazing examples of image enhancement algorithms. Yet, when applied to different noisy images, they can produce unwanted effects. The analysis of such algorithms lags behind their intuitive development. Two essentially different models have found wide recognition: a variational approach due to Mumford and Shah, and an anisotropic diffusion approach leading to an evolution type equation by Perona and Malik. In this survey we shall explain a surprising connection between these two approaches. Copyright © 2004 John Wiley & Sons, Ltd.
Broadband high‐efficiency microstrip antenna array with corporate‐series‐feed
Authors: Lee Byungje , Kang Gi‐Cho , Yang Sung‐Hyun
Published: September 2004

A linearly polarized microstrip antenna array in the Ku‐band achieves high efficiency by having the proper impedance matching throughout the array and by properly using the corporate and series feeds with microstrip transmission lines. The efficiency of the antenna array is 83.3%. The cavity‐backed microstrip patch is used as the element of the antenna array to obtain relatively wide bandwidth. The auto‐tracking antenna in the azimuth direction is developed with a very low profile as well as a low manufacturing cost for the vehicle's rooftop mounting. The main beam of array is tilted 15° away from the broadside direction to provide optimum coverage for Korea satellite III. The measured gain of an antenna array is 23.8 dBi at the center frequency of 12.5 GHz. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 43: 181–183, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20413
Wideband circularly polarized radial stub fed slot antenna
Authors: Rao Patnam H.
Published: September 2004

Wideband circular polarization with a boresight axial ratio of ≤ 2.2 dB is achieved over 35% of bandwidth by sequential rotation of linearly polarized radial stub‐fed slot elements (2 × 2 array). The effect of the feed interactions upon the antenna radiation pattern is also analysed. The impedance bandwidth of the antenna is 40%, centered at 2.1 GHz for VSWR ≤ 1.5. The average measured gain of the antenna is 3 dB. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 43: 211–213, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20421
High‐efficiency generation of cladding pumped Erbium‐ytterbium co‐doped double clad fiber ring laser operating in L‐band
Authors: Shu‐Min Zhang , Fu‐Yun Lu , Jian Wang , Fa‐Jie Dong , Hongjie Wang , Xiaoyi Dong
Published: September 2004

A novel Er3+/Yb3+ co‐doped double‐clad fiber‐ring laser, which utilizes amplified spontaneous emission as a secondary pump source in order to operate in L‐band, is demonstrated. Six laser diodes are used to cladding‐pump Er3+/Yb3+ co‐doped double‐clad fiber. When the pumping power of entering fiber is 2731.8 mW, the maximum output power is 518.4 mW, and the slope efficiency is 19%. The relationship between the output power and the splitting ratio of the output coupler is also studied in this paper. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 43: 213–215, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20422
Comparison between two stable hybridized 2D generalized FDTD algorithms for multiscale analysis
Authors: Marrone M. , Mittra R.
Published: September 2004

In this paper, we carry out a numerical comparison between two hybrid 2D generalized finite‐difference time‐domain (FDTD) algorithms, designed to analyze objects with fine details, without using the very small time steps dictated by the Courant condition. We evaluate the accuracy and the computational complexity of the above algorithms, employing either subgridding or triangular gridding to model the fine details. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 43: 221–225, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20424
Guide wavelength estimation of sandwich‐type double‐layer slotline
Authors: Han Ki Jin , Kim Jeong Phill
Published: September 2004

A novel approximate method for estimating the guide wavelength of a double‐layer slotline is presented. The guide wavelength curve of a physically symmetric double‐layer slotline is estimated from the data of two special types of slotline. A linear combination of two curves in the former approximation is used for a general double‐layer slotline. The results of the proposed method are compared with numerical computation and its high level of accuracy is confirmed. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 43: 261–264, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20437
Complete assignment of 1H and 13C NMR data for three aryltetralin lignan lactones
Authors: da Silva Rosangela , Heleno Vladimir Constantino Gomes , de Albuquerque Sérgio , Bastos Jairo Kenupp , e Silva Márcio Luis Andrade , Donate Paulo Marcos , da Silva Gil Valdo José
Published: September 2004

We describe the complete 1H and 13C NMR analysis of three aryltetralin lignan lactones (polygamain, morelensin and 4,5‐dimethoxymorelensin) using modern NMR techniques such as COSY, HMQC, HMBC, 2D‐J‐resolved and NOE experiments. The relative stereochemistry of these compounds, which is very important with regard to their biological activity, was completely determined. Copyright © 2004 John Wiley & Sons, Ltd.
Sleep disorders, epilepsy, and autism
Authors: Malow Beth A.
Published: September 2004

The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum disorders. Epilepsy and sleep have reciprocal relationships, with sleep facilitating seizures and seizures adversely affecting sleep architecture. The hypothesis put forth is that identifying and treating sleep disorders, which are potentially caused by or contributed to by autism, may impact favorably on seizure control and on daytime behavior. The article concludes with some practical suggestions for the evaluation and treatment of sleep disorders in this population of children with autism. MRDD Research Reviews 2004;10:122–125. © 2004 Wiley‐Liss, Inc.
Epileptic encephalopathies and their relationship to developmental disorders: Do spikes cause autism?
Authors: Tharp Barry R.
Published: September 2004

Epileptic encephalopathies are progressive clinical and electroencephalographic syndromes where deterioration is thought to be caused by frequent seizures and abundant EEG epileptiform activity. Seizures occur in approximately 10–15% of children with pervasive developmental disorders (PDD) and 8–10% have epileptiform EEG abnormalities without seizures. Thirty percent of children with PDD have regression of social behavior and language at 2–3 years of age. Some authors speculate that the regression is caused by epileptiform activity even in the absence of overt clinical seizures (“autism with epileptic regression”) and suggest that elimination of the epileptiform activity, either medically or surgically, should lead to improvement in behavior. This review examines the data showing that interictal epileptiform discharges are associated with transient clinical dysfunction and discusses the implications of these observations for autistic behavioral abnormalities. The results of resective surgery, vagal nerve stimulation, and multiple subpial transaction on children with autism and epileptiform EEG abnormalities are also discussed. I conclude that there is no evidence that interictal dischargesper secause (or contribute to) the complex behavioral phenotype of autism. There is no justification to support the use of anticonvulsant medication or surgery in children with PDDwithout seizures; that is,there is no evidence that treatmentto eliminate EEG spikes will have a therapeutic effect on the behavioral abnormalities of PDD and autism. MRDD Research Reviews 2004;10:132–134. © 2004 Wiley‐Liss, Inc.
Lennox–Gastaut syndrome: Potential mechanisms of cognitive regression
Authors: Blume Warren T.
Published: September 2004

Lennox–Gastaut (L‐G) syndrome is an intractable generalized epilepsy of childhood onset, associated with spike waves at a slow rate and paroxysmal fast activity. These epileptiform discharge patterns are thought to reflect excessive neocortical excitability and arise from neuronal and synaptic features peculiar to the immature central nervous system. The epileptic processes associated with L‐G syndrome may lead to enduring patterns of abnormal activity and connectivity. These abnormal patterns compete with normal developmental mechanisms and may result in subsequent impairment and/or regression of cognition. Recurring or prolonged seizures themselves may also damage the brain. We hypothesize that the presence of slow spike waves diverts the brain from normal developmental processes toward seizure‐preventing mechanisms. Adding to this burden, antiepileptic medications, sleep disruption, and social isolation all retard cognitive development and the learning process at a crucial time of brain maturation. MRDD Research Reviews 2004;10:150–153. © 2004 Wiley‐Liss, Inc.
Rett syndrome: Of girls and mice—Lessons for regression in autism
Authors: Glaze Daniel G.
Published: September 2004

Rett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females. Regression is a defining feature of RTT. During the regression stage, RTT girls display many autistic features, such as loss of communication and social skills, poor eye contact, and lack of interest, and initially may be given the diagnosis of autism. The discovery of the genetic cause of RTT, mutations in the MECP2 gene, a transcriptional repressor, has promoted the early diagnosis of RTT and development of mouse models. The phenotype of one mouse model includes features such as regression and abnormal behavioral and social interactions. The timing of the period of regression in RTT—during ages 1 to 2 years—parallels the period of intense synaptic development. The effects of the MECP2 mutation also increases concomitantly with peak synaptogenesis. Neuropathological findings in Rett include the selective reduction of dendritric spines in the pyramidal cells of RTT brains; this feature has also been reported in autism. Studies have observed that MECP influences the expression of brain‐derived neurotrophic factor and thus may influence synaptic plasticity. Abnormalities in synapse maintenance and modulation may contribute to regression in RTT and autism. Studies of the clinical aspects of the regression period and of the mouse model may be useful in understanding the pathophysiology of RTT and other neurodevelopmental disorders such as autism. A recent study observed abnormal expression of MeCP2 in RTT and other neurodevelopmental disorders such as autism. Although the genetic background and certain clinical features differ in RTT and autism, a similar mechanism involving MeCP2 regulation and expression may contribute to regression. MRDD Research Reviews 2004;10:154–158. © 2004 Wiley‐Liss, Inc.
Assessment of recovery following a novel partial nerve lesion in a rat model
Authors: Malushte Tejashree S. , Kerns James M. , Huang Chris C. , Shott Susan , Safanda John , Gonzalez Mark
Published: September 2004

Partial nerve lesions with a varying degree of retained function and often a painful neuroma pose a dilemma for the clinician. Surgical treatment of partial nerve lesion is perilous because of possible damage to intact axons and subsequent loss of retained function. We present a new rat model of a partial nerve lesion, allowing further study to improve treatment for this condition. A partial (50%) lesion of the tibial portion of the rat sciatic nerve was created and compared to standard crush and neurectomy control lesions. The extent of lost function and the progress of postoperative recovery following the three lesions were compared using serial walking track analyses and end‐point muscle weight ratios for atrophy as outcome measures. All groups had tibial functional indices (TFI) significantly different from one another after 1 week. TFIs for the crush group returned to normal by 4 weeks, whereas the neurectomy group showed no recovery. The partial lesion group gradually improved, reaching a plateau of 44% by 7 weeks. Gastrocnemius muscle weight ratios for the partial, crush, and neurectomy lesions at 9 weeks were 0.63, 0.87, and 0.32, respectively. There was a strong correlation between the TFI and muscle weight ratios (r2 = 0.89; P < 0.001) suggesting that these outcome measures are highly predictive of function. In conclusion, the partial lesion showed a gradual but incomplete functional recovery with a complementary degree of muscle atrophy. The model may prove useful in the evaluation of proposed treatments for partial nerve lesions and the associated painful state. Muscle Nerve 2004
Fatigue of rat hindlimb motor units: Biochemical– physiological associations
Authors: Callister Robert J. , Sesodia Sanjay , Enoka Roger M. , Nemeth Patti M. , Reinking Robert M. , Stuart Douglas G.
Published: September 2004

Associations between fatigability and biochemical properties within motor unit (MU) types were explored in two hindlimb muscles of the adult rat. Type FF MUs in extensor digitorum longus and type S units in soleus were subjected either to a moderate (type FF) or severe (type S) 6‐min, fatigue‐inducing stimulation protocol. For both MU types, the range of values for their fatigability was considerably greater than the ranges in the activity levels of three enzymes in the units' constituent muscle fibers (MFs). These enzymes represented major energy‐yielding pathways: adenylokinase, for high‐energy phosphate metabolism; lactate dehydrogenase, for anaerobic glycolysis; and malate dehydrogenase, for oxidative metabolism. There were also relatively weak associations between the fatigue indices of the MUs and the activity levels of the three enzymes. Thus, this work supports previous conclusions that the force decline exhibited by MUs during electrically evoked contractions depends on both MF biochemistry and other intracellular mechanisms. Electromyographic measurements suggested that these other mechanisms are distal to the intramuscular branches of the axon in type FF units, and distal to excitation–contraction coupling in type S units. Muscle Nerve, 2004
Physiotherapy for female stress urinary incontinence: Individual therapy at the outpatient clinic versus home‐based pelvic floor training: A 5‐year follow‐up study
Authors: Parkkinen A. , Karjalainen E. , Vartiainen M. , Penttinen J.
Published: September 2004

Aims

To compare the long‐term effects of individual physiotherapy at an outpatient clinic, including electrical stimulation (ES), active pelvic floor muscle exercises (PFMEs), and training with a vaginal ball (VB), with home‐based active PFMEs and training with a VB, in cases of female stress urinary incontinence (SUI).

Materials and Method

Thirty‐three women with SUI (outpatient clinic group [Group I, n = 16] and home group [Group II, n = 17]) participated in the 5‐year follow‐up study. Both groups had an active PFME program and they used a VB during daily activities for intensive pelvic floor muscle (PFM) training. Group I was also treated at the outpatient clinic with maximal interferential ES, using frequencies varying from 10 to 50 Hz, and individually instructed exercises with biofeedback were carried out at the same time, once a week, an average of nine times in the first year. After baseline examinations, both groups visited the outpatient clinic at 4 months, 12 months, and at 5 years.

Results

At 12 months, there were no statistically significant differences between the study groups in any of the outcome variables, but within the groups both the subjective and objective results were significantly better in comparison with the initial values. After 12 months, two (3%) patients in Group I continued physiotherapy and seven (41%) patients in Group II needed physiotherapy because of an unsatisfactory outcome. At 5 years, according to the urinary incontinence severity score (UISS) questionnaire, subjective discomfort had decreased in both groups (P < 0.01) and 21 of the 33 women (64%) perceived a subjective cure or improvement in their condition. The mean objective urine leakage verified by the pad test decreased from 23.0 to 1.0 g in Group I and from 13.0 to 1.0 g in Group II (P < 0.001 for both groups). The strength of PFMs tested in a standing position increased by 26% in Group I and by 19% in Group II (P values 0.001 and 0.084, respectively), and in a lying position by 28% in Group I and by 32% in Group II (P values 0.001 and 0.008, respectively).

Conclusions

Home‐based PFMEs and training with a VB proved to be equally effective as once‐a‐week supervised therapy, and the 5‐year follow‐up results demonstrated a successful response in the treatment of female SUI. © 2004 Wiley‐Liss, Inc.
Sojourn times in a two‐stage queueing network with blocking
Authors: Gómez‐Corral A.
Published: September 2004

The model considered in this paper involves a tandem queue consisting of a sequence of two waiting lines. The main feature of our model is blocking, i.e., as soon as the second waiting line reaches a certain upper limit, the first line is blocked. The input of units to the tandem queue is the MAP (Markovian arrival process), and service requirements are of phase type. Our objective is to study the sojourn time distribution under the first‐come‐first‐serve discipline by analyzing the sojourn time through times until absorption in appropriately defined quasi‐birth‐and‐death processes and continuous‐time Markov chains. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004
Mechanosensation and pain
Authors: Lewin Gary R. , Moshourab Rabih
Published: September 2004

The ability of cells to detect and transduce mechanical stimuli impinging on them is a fundamental process that underlies normal cell growth, hearing, balance, touch, and pain. Surprisingly, little research has focused on mechanotransduction as it relates to the sensations of somatic touch and pain. In this article we will review data on the wealth of different mechanosensitive sensory neurons that innervate our main somatic sense organ the skin. The role of different types of mechanosensitive sensory neurons in pain under physiological and pathophysiological conditions (allodynia and hyperalgesia) will also be reviewed. Finally, recent work on the cellular and molecular mechanisms by which mechanoreceptive sensory neurons signal both innocuous and noxious sensation is evaluated in the context of pain. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 30–44, 2004
Temperature perception and nociception
Authors: Green Barry G.
Published: September 2004

The specificity theory of somesthesis holds that perceptions of warmth, cold, and pain are served by separate senses. Although no longer accepted in all its details, the theory's basic assumptions of anatomical and functional specificity have remained guiding principles in research on temperature perception and its relationship to pain. This article reviews the response characteristics of thermoreceptors, temperature‐sensitive nociceptors, and their associated pathways in the context of old and new perceptual phenomena, most of which cannot be satisfactorily explained by the specificity theory. The evidence indicates that throughout most of the perceptual range, temperature sensitivity depends upon coactivation of, and interactions among, thermal and nociceptive pathways that are composed of both specific “labeled lines” and nonspecific, multimodal fibers. Adding to this complexity is evidence that tactile stimulation can influence the way in which thermal stimulation is perceived. It is argued that thermoreception is best defined as a functional subsystem of somesthesis that serves the very different and sometimes conflicting demands of thermoregulation, protection from thermal injury, and haptic perception. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 13–29, 2004
Invertebrate nociception: Behaviors, neurons and molecules
Authors: Tobin David M. , Bargmann Cornelia I.
Published: September 2004

Genetic analysis of nociceptive behaviors in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster has led to the discovery of conserved sensory transduction channels and signaling molecules. These are embedded in neurons and circuits that generate responses to noxious signals. This article reviews the neurons and molecular mechanisms that underlie invertebrate nociception. We begin with the neurobiology of invertebrate nociception, and then focus on molecules with conserved functions in vertebrate nociception and sensory biology. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 161–174, 2004
Responsibilities and roles of boards in nonprofit organizations: The Israeli case
Authors: Iecovich Esther
Published: September 2004

In this study, nine roles and responsibilities of boards of directors in nonprofit organizations in Israel are examined and perceptions of these roles and responsibilities by chairpersons of the boards and the executive directors are compared. Four groupings of board roles were found: senior human resource management, maintenance of relationships with the task environment, policymaking, and fiscal management and fundraising. The findings show that in most organizations boards fulfill all these roles and play a significant role in decision making. A significant consensus exists between chairpersons and executive directors in respect to most of the boards' roles, whereas significant differences in perceptions were found in respect to financial matters and maintenance of relationships with the task environment.
The devil is in the details: Implementing secular outcome measurement methods in faith‐based organizations
Authors: Fischer Robert L.
Published: September 2004

Faith‐based organizations (FBOs) are now being encouraged to seek federal funding for the purpose of supporting faith‐based delivery of social services in local communities (that is, the Compassionate Capital Fund). This shift in the federal perspective has resulted in increased attention to the effectiveness of the services provided by FBOs. Though rigorous demonstrations are needed to determine the relative effectiveness of FBO services, other available alternatives offer a viable avenue to aid FBOs in improving their programs and monitoring their success. One such alternative is the use of outcome measurement techniques, such as those that have been infusing the nonprofit sector in the United States since the mid‐1990s, particularly among United Way–funded programs. This chapter discusses how to adapt secular outcomes measurement approaches to faith‐based organizations and their programs and the likely pitfalls that FBOs will face.
Spouses of persons with dementia: Their healthcare problems, utilization, and costs
Authors: Kolanowski Ann M. , Fick Donna , Waller Jennifer L. , Shea Dennis
Published: September 2004

Spouses of persons with dementia (PWD) often experience poor health outcomes related to the experience of living with the afflicted spouse. Using the Anderson and Aday Healthcare Utilization Model, we conducted a retrospective review of an administrative database from a private healthcare insurer to compare health problems that precipitate utilization, patterns of utilization, and costs of care of spouses of PWD (n = 979) to those of spouses of persons without dementia (n = 979). Spouses of PWD were treated for more anxiety disorders (OR = 2.97; 95% CI = 1.63–5.44), falls (OR = 7.72; 95% CI = 2.73‐21.84), rheumatologic diseases (OR = 2.5; 95% CI = 1.24–5.06), and diabetes with no complications (OR = 1.53; 95% CI = 1.06‐2.22), but less pneumonia (OR = .55; 95%; CI = .35–.88) than comparison spouses. Spouses of PWD had a higher number of emergency room (ER) visits (p = .01). There were no differences in costs between the groups. The findings can be used to develop interventions for spouses of PWD. © 2004 Wiley Periodicals, Inc. Res Nurs Health 27:296–306, 2004
First identification of an ancient Egyptian mummified human placenta
Authors: Mekota A.‐M. , Grupe G. , Zimmerman M. R. , Vermehren M.
Published: September 2004

In the course of excavations at Thebes‐West, Upper Egypt, a human organ was recovered from the poorly preserved torso of a female mummy, which was archaeologically dated to the New Kingdom. In the field, the organ was tentatively identified as a liver, but without much certainty. After rehydration and fixation, histological observations led to a rejection of this diagnosis and resulted in the hypothesis that this organ could be a placenta. Comparative histology, performed on an experimentally mummified modern human placenta, revealed a close similarity of microstructural features, which strongly supports the diagnosis of the organ as a placenta. In this paper, we can therefore present the first report of an ancient Egyptian mummified human placenta and provide new insight into Egyptian funeral practices in general, and the fate of the excavated female in particular. Copyright © 2004 John Wiley & Sons, Ltd.
PGD analysis for aneuploidy in a patient heterozygous for a polymorphism of chromosome 16 (16qh−)
Authors: Colls Pere , Sandalinas Mireia , Pagidas Kelly , Munné Santiago
Published: September 2004

Objectives

Detection and study of a polymorphism of chromosome 16qh in preimplantational embryos as well as in peripheral blood from the carrier.

Methods

A polymorphism of chromosome 16 (16qh−) was detected in PGD analysis for aneuploidy using a probe for the centromeric region of chromosome 16. The lack of pericentromeric heterochromatin in one of the chromosomes 16 could lead to misdiagnosis in PGD. PGD analysis using telomeric probes for this chromosome was performed to confirm the polymorphism as well as to avoid misdiagnosis in embryo blastomeres. FISH in lymphocyte metaphases was used to detect the carrier.

Results

Telomeric probes allowed detection of a polymorphism for the centromeric region of chromosome 16. FISH with centromeric and telomeric probes in lymphocyte metaphases of the parents showed that the patient was the carrier of the polymorphism.

Conclusion

It is highly recommended that telomeric probes for chromosome 16 be used in preimplantation genetic diagnosis when a high frequency of monosomy for chromosome 16 is observed after regular aneuploidy analysis. Copyright © 2004 John Wiley & Sons, Ltd.
Double‐outlet right ventricle with absent left ventricle and mitral atresia in a fetus with a deletion 22q12
Authors: L'Herminé‐Coulomb Aurore , Houyel Lucille , Aboura Azzedine , Audibert François , Dal Soglio Dorothée , Tachdjian Gérard
Published: September 2004

Interstitial deletions of chromosomal region 22q12 are rare. We report the prenatal diagnosis of a de novo interstitial deletion 22q12. The fetus was karyotyped because of a complex cardiac anomaly. Conventional and molecular cytogenetics showed a female karyotype with a de novo pericentric inversion of one chromosome 22 associated with a deletion of the chromosomal region 22q12 leading to a partial monosomy 22q12. At autopsy, the fetus showed double‐outlet right ventricle (DORV) with absent left ventricle and mitral atresia. This observation suggests that one or several genes for the early looping step of heart development may reside in chromosomal region 22q12. Further studies are needed to identify these genes, and to search microdeletions of 22q12 region in patients with DORV. Copyright © 2004 John Wiley & Sons, Ltd.
Total cell‐free DNA (β‐globin gene) distribution in maternal plasma at the second trimester: a new prospective for preeclampsia screening
Authors: Farina Antonio , Sekizawa Akihiko , Iwasaki Mariko , Matsuoka Ryu , Ichizuka Kiyotake , Okai Takashi
Published: September 2004

Objectives

Levels of cell‐free foetal DNA (f‐DNA) in maternal plasma are higher in those asymptomatic subjects who will eventually develop preeclampsia. f‐DNA is, however, informative only for those women bearing a male foetus, by amplification of Y‐specific sequences and represents a small fraction of total circulating DNA that can be dosed by using ubiquitous genes as well as β‐globin. In this study, we examined the quantitative distribution of total DNA by amplification of β‐globin gene, in asymptomatic women matched with controls to evaluate its possible role in predicting preeclampsia.

Methods

Forty‐eight low‐risk women (8 asymptomatic cases matched for gestational age at the second trimester with 40 controls) were enrolled in the present study. β‐globin concentrations were converted into multiples of the median of the controls (MoM), in order to assess the possible different distribution of β‐globin MoM in cases and controls.

Results

MoM values were as follows: controls, 1.00 ± 0.59; asymptomatic cases, 1.99 ± 1.95. After Gaussian conversion of data, at a false‐positive rate (FPR) of 5%, the detection rate (DR) was 46%.

Conclusion

β‐globin (total DNA) levels are higher in those patients who subsequently developed preeclampsia and can potentially be used in screening for early detection of the disease. These findings represent a step forward in the study of cell‐free DNA in maternal blood as a screening variable, because it overcomes the gender limitations of foetal DNA screening. Copyright © 2004 John Wiley & Sons, Ltd.
Activation and expression of proteins during synchronous germination of aerial spores of Streptomyces granaticolor
Authors: Bobek Jan , Halada Petr , Angelis Jakub , Vohradský Jiři , Mikulík Karel
Published: September 2004

Synchronously germinating aerial spores of Streptomyces granaticolor were used to study protein activation and expression during the transition from dormant to metabolically active vegetative forms. The first phase of protein activation is associated with the solubility of proteins. Three major chaperones, DnaK, Trigger factor, and GroEL, were identified in spores. Enhancement in rate of protein synthesis during germination was accompanied by the association of TF and DnaK with ribosomes. During germination, the chaperones TF, GroEL, and DnaK undergo reversible phosphorylation. GroEL was phosphorylated on both Ser and Thr, whereas phosphorylation of DnaK and TF was detected on Thr only. A proteomic approach was used to gain more information on protein expression during germination on two types of media differing in the ability of cells to produce antibiotic granaticin. To obtain an overview of the metabolic activity of germinating spores, glycolytic enzymes, enzymes of citric acid cycle, metabolism of amino acids and nucleic acids, and components of the protein synthesis system were identified and analyzed using the proteomic database. The results were deposited on the SWICZ proteomic server and are accessible on http://proteom.biomed.cas.cz.
The influence of agr and σB in growth phase dependent regulation of virulence factors in Staphylococcus aureus
Authors: Ziebandt Anne‐Kathrin , Becher Dörte , Ohlsen Knut , Hacker Jörg , Hecker Michael , Engelmann Susanne
Published: September 2004

The expression of many virulence determinants in Staphylococcus aureus is tightly coordinated generally by global regulatory elements such as accessory gene regulator (agr), staphylococcal accessory regulator and the alternative sigma factor σB. We have compared the two‐dimensional (2‐D) protein pattern of extracellular protein extracts of wild‐type cells with the 2‐D patterns of the respective regulatory mutants in order to identify proteins whose amount is influenced by a mutation in agr or sigB. In order to quantify changes in the level of interesting proteins we used the Ettan‐fluorescence difference gel electrophoresis technique (Amersham Biosciences). As in most bacteria, the amount of extracellular proteins was strongly regulated and increased mainly in the stationary phase of growth at high cell densities. By comparing the extracellular protein pattern of the RN6390 rsbU strain with that of an isogenic agr mutant RN6911 we show that the level of about 70 protein spots changed in the mutant. To analyze the role of σB in virulence gene expression an RsbU+ (RN6390 RsbU+) derivative was included in this study. The protein pattern of the RsbU+ strain (RN6390 RsbU+) was very similar to that of the Δagr/ΔrsbU mutant strain (RN6911) indicating an opposing effect of agr and rsbU on the expression of the same genes.