bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-Threshold L-type Calcium Channels in Rat Dopamine Neurons
Authors: Durante P. , Cardenas C. G. , Whittaker J. A. , Kitai S. T. , Scroggs R. S.
Published: February 2004

Ca2+channel subtypes expressed by dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) were studied using whole cell patch-clamp recordings and blockers selective for different channel types (L, N, and P/Q). Nimodipine (Nim, 2 μM), ω-conotoxin GVIA (Ctx, 1 μM), or ω-agatoxin IVA (Atx, 50 nM) blocked 27, 36, and 37% of peak whole cell Ca2+channel current, respectively, indicating the presence of L-, N-, and P-type channels. Nim blocked approximately twice as much Ca2+channel current near activation threshold compared with Ctx or Atx, suggesting that small depolarizations preferentially opened L-type versus N- or P-type Ca2+channels. N- and L-channels in DA neurons opened over a significantly more negative voltage range than those in rat dorsal root ganglion cells, recorded from using identical conditions. These data provide an explanation as to why Ca2+-dependent spontaneous oscillatory potentials and rhythmic firing in DA neurons are blocked by L-channel but not N-channel antagonists and suggest that pharmacologically similar Ca2+channels may exhibit different thresholds for activation in different types of neurons.
Responses of Cerebellar Interpositus Neurons to Predictable Perturbations Applied to an Object Held in a Precision Grip
Authors: Monzée Joël , Smith Allan M.
Published: February 2004

Two monkeys were trained to lift and hold an instrumented object at a fixed height for 2.5 s using a precision grip. The device was equipped with load cells to measure both the grip and lifting or load forces. On selected blocks of 20-30 trials, a downward force-pulse perturbation was applied to the object after 1.5 s of stationary holding. The animals were required to resist the perturbation to obtain a fruit juice reward. The perturbations invariably elicited a reflex-like, time-locked increase in grip force at latencies between 50 and 100 ms. In this study, we searched for single cells in the interpositus and dentate nuclei with activity related to grasping and lifting, and we tested 127/150 task-related cells for their responses to the perturbation. Of the 127 cells, reflex-like increases or decreases in discharge frequency occurred in 75 cells (59%) at a mean latency of 36 ms. Preparatory increases in grip force preceding the perturbation appeared gradually and increased in strength with repetition in 39/127 (31%) cells. These preparatory increases did not immediately disappear when the perturbations were withdrawn but decreased progressively over repeated trials. Although a few cells showed anticipatory activity without a reflex-like response (15/127 or 12%), the majority of these cells (24/39) displayed both anticipatory and reflex-like responses. From an examination of the histological sections, cells with both anticipatory and reflex-like responses appeared to be confined to the dorsal anterior interpositus, adjacent to, but not within, the dentate nucleus. These results confirm and extend the suggestion by Dugas and Smith that the cerebellum plays a major role in organizing anticipatory responses to predictable perturbations in a manner that medial and lateral premotor areas of the cerebral cortex do not.
Tonotopic Organization in Human Auditory Cortex Revealed by Progressions of Frequency Sensitivity
Authors: Talavage Thomas M. , Sereno Martin I. , Melcher Jennifer R. , Ledden Patrick J. , Rosen Bruce R. , Dale Anders M.
Published: February 2004

Functional neuroimaging experiments have revealed an organization of frequency-dependent responses in human auditory cortex suggestive of multiple tonotopically organized areas. Numerous studies have sampled cortical responses to isolated narrow-band stimuli, revealing multiple locations in auditory cortex at which the position of response varies systematically with frequency content. Because appropriate anatomical or functional grouping of these distinct frequency-dependent responses is uncertain, the number and location of tonotopic mappings within human auditory cortex remains unclear. Further, sampling does not address whether the observed mappings exhibit continuity as a function of position. This functional magnetic resonance imaging study used frequency-swept stimuli to identify progressions of frequency sensitivity across the cortical surface. The center-frequency of narrow-band, amplitude-modulated noise was slowly swept between 125 and 8,000 Hz. The latency of response relative to sweep onset was determined for each cortical surface location. Because frequency varied systematically with time, response latency indicated the frequency to which a location was maximally sensitive. Areas of cortex exhibiting a progressive change in response latency with position were considered tonotopically organized. There exist two main findings. First, six progressions of frequency sensitivity (i.e., tonotopic mappings) were repeatably observed in the superior temporal plane. Second, the locations of the higher- and lower-frequency endpoints of these progressions were approximately congruent with regions reported to be most responsive to discrete higher- and lower-frequency stimuli. Based on these findings and previous anatomical work, we propose a correspondence between these progressions and anatomically defined cortical areas, suggesting that five areas in human auditory cortex exhibit at least six tonotopic organizations.
A Bayesian model for binary Markov chains
Authors: Assoudou Souad , Essebbar Belkheir
Published: February 2004

This note is concerned with Bayesian estimation of the transition probabilities of a binary Markov chain observed from heterogeneous individuals. The model is founded on the Jeffreys′ prior which allows for transition probabilities to be correlated. The Bayesian estimator is approximated by means of Monte Carlo Markov chain (MCMC) techniques. The performance of the Bayesian estimates is illustrated by analyzing a small simulated data set.
The pseudodifferential operator A(x, D)
Authors: Pathak R. S. , Pathak S.
Published: February 2004

The pseudodifferential operator (p.d.o.) A(x, D), associated with the Bessel operator d2/dx2 + (1 − 4μ2)/4x2, is defined. Symbol class is introduced. It is shown that the p.d.o. associated with a symbol belonging to this class is a continuous linear mapping of the Zemanian space Hμ into itself. An integral representation of p.d.o. is obtained. Using Hankel convolution ‐norm continuity of the p.d.o. is proved.
Asymptotics for critical nonconvective type equations
Authors: Hayashi Nakao , Kaikina Elena I. , Naumkin Pavel I.
Published: February 2004

We study large‐time asymptotic behavior of solutions to the Cauchy
problem for a model of nonlinear dissipative evolution equation. The linear part is a pseudodifferential operator and the nonlinearity is a cubic pseudodifferential operator defined by means of the inverse Fourier transformation and represented by
bilinear and trilinear forms with respect to the direct Fourier transform of the dependent variable. We consider nonconvective type nonlinearity, that is, we suppose that the total mass of the nonlinear term does not vanish. We consider the initial data,
which have a nonzero total mass and belong to the weighted Sobolev space with a sufficiently small norm. Then we give the main term of the large‐time asymptotics of solutions in the critical case. The time decay rate have an additional logarithmic
correction in comparison with the corresponding linear case.
Sequence analysis of myostatin promoter in cattle
Authors: Crisà A. , Marchitelli C. , Savarese M.C. , Valentini A.
Published: February 2004

Myostatin (GDF8) acts as a negative regulator of muscle growth. Mutations in the gene are responsible for the double muscling phenotype in several European cattle breeds. Here we describe the sequence of the upstream 5′ region of the myostatin gene. The sequence analysis was carried out on three animals of nine European cattle breeds, with the aim to search for polymorphisms. A T/A polymorphism at –371 and a G/C polymorphism at –805 (relative to ATG) were found. PCR- RFLP was used to further screen 353 animals of the nine breeds studied and to assess the frequencies of the SNPs. The promoter region of the gene contains several binding sites for transcription factors found also in other myogenic genes. This may play an important role in the regulation of the protein and consequently on muscular development.
The river buffalo (Bubalus bubalis, 2n = 50) cytogenetic map: assignment of 64 loci by fluorescence in situ hybridization and R-banding
Authors: Iannuzzi L. , Di Meo G.P. , Perucatti A. , Schibler L. , Incarnato D. , Gallagher D. , Eggen A. , Ferretti L. , Cribiu E.P. , Womack J.
Published: February 2004

Sixty-four genomic BAC-clones mapping five type I (ADCYAP1, HRH1, IL3, RBP3B and SRY) and 59 type II loci, previously FISH-mapped to goat (63 loci) and cattle (SRY) chromosomes, were fluorescence in situ mapped to river buffalo R-banded chromosomes, noticeably extending the physical map of this species. All mapped loci from 26 bovine syntenic groups were located on homeologous chromosomes and chromosome regions of river buffalo and goat (cattle) chromosomes, confirming the high degree of chromosome homeologies among bovids. Furthermore, an improved cytogenetic map of the river buffalo with 293 loci from all 31 bovine syntenic groups is reported.
From a sow’s ear to a silk purse: real progress in porcine genomics
Authors: Rothschild M.F.
Published: February 2004

An incredible amount of progress has occurred in the past decade since the pig genome map began to develop. The porcine genetic linkage map now has nearly 5,000 loci including several hundred genes, microsatellites and amplified fragment length polymorphism (AFLP) markers being added to the map. Thanks to somatic cell hybrid panels and then radiation hybrid panels the physical genetic map is also growing rapidly and now has over 4,000 genes and markers. Many quantitative trait loci (QTL) scans have been completed and together with candidate gene analyses have identified important chromosomal regions and individual genes associated with traits of economic interests. Using marker assisted selection (MAS) the commercial pig industry is actively using this information and traditional performance information to improve pig production. Large scale pig arrays are just now beginning to be used and co-expression of thousands of genes is now advancing our understanding of gene function. The pig’s role in xenotransplantation and biomedical research makes the study of its genome important for the study of human disease. Sequencing of the pig genome appears on the near horizon. This commentary will discuss recent advances in pig genomics, directions for future research and the implications to both the pig industry and human health.
Comparative mapping of genes flanking the human chromosome 12 evolutionary breakpoint in the pig
Authors: Farber C.R. , Raney N.E. , Rilington V.D. , Venta P.J. , Ernst C.W.
Published: February 2004

Genes located on human chromosome 12 (HSA12) are conserved on pig chromosomes 5 and 14 (SSC5 and SSC14), with HSA12q23.3→q24.11 harboring the evolutionary breakpoint between these chromosomes. For this study, pig sequence-tagged sites (STS) were developed for nine HSA12 genes flanking this breakpoint. Radiation hybrid (RH) mapping using the IMpRH panel revealed that COL2A1, DUSP6, KITLG, PAH and STAB2 map to SSC5, while PXN, PLA2G1B, SART3 and TCF1 map to SSC14. Polymorphisms identified in COL2A1, DUSP6, PAH, PLA2G1B and TCF1 were used for genetic linkage mapping and confirmed the map locations for these genes. Our results indicate that the HSA12 evolutionary breakpoint occurs between STAB2 and SART3 in a region spanning less than five million basepairs. These results refine the comparative map of the HSA12 evolutionary breakpoint region and help to further elucidate the extensive gene order rearrangements between HSA12 and SSC5 and 14.
Molecular characterization and mutational screening of the PRKAG3 gene in the horse
Authors: Park H.B. , Marklund S. , Jeon J.T. , Mickelson J.R. , Valberg S.J. , Sandberg K. , Andersson L.
Published: February 2004

The PRKAG3 gene encodes a muscle-specific isoform of the regulatory γ subunit of AMP-activated protein kinase (AMPK). A major part of the coding PRKAG3 sequence was isolated from horse muscle cDNA using reverse-transcriptase (RT)-PCR analysis. Horse-specific primers were used to amplify genomic fragments containing 12 exons. Comparative sequence analysis of horse, pig, mouse, human, Fugu, and zebrafish was performed to establish the exon/intron organization of horse PRKAG3 and to study the homology among different isoforms of AMPK γ genes in vertebrates. The results showed conclusively that the three different isoforms (γ1, γ2, and γ3) were established already in bony fishes. Seven single nucleotide polymorphisms (SNPs), five causing amino acid substitutions, were identified in a screening across horse breeds with widely different phenotypes as regards muscle development and intended performance. The screening of a major part of the PRKAG3 coding sequence in a small case/control material of horses affected with polysaccharide storage myopathy did not reveal any mutation that was exclusively associated with this muscle storage disease. The breed comparison revealed several potentially interesting SNPs. One of these (Pro258Leu) occurs at a residue that is highly conserved among AMPK γ genes. In an SNP screening, the variant allele was only found in horse breeds that can be classified as heavy (Belgian) or moderately heavy (North Swedish Trotter, Fjord, and Swedish Warmblood) but not in light horse breeds selected for speed or racing performance (Standardbred, Thoroughbred, and Quarter horse) or in ponies (Icelandic horses and Shetland pony). The results will facilitate future studies of the possible functional significance of PRKAG3 polymorphisms in horses.
Homologous fission event(s) implicated for chromosomal polymorphisms among five species in the genus Equus
Authors: Myka J.L. , Lear T.L. , Houck M.L. , Ryder O.A. , Bailey E.
Published: February 2004

The genus Equus is unusual in that five of the ten extant species have documented centric fission (Robertsonian translocation) polymorphisms within their populations, namely E. hemionus onager, E. hemionus kulan, E. kiang, E. africanus somaliensis, and E. quagga burchelli. Here we report evidence that the polymorphism involves the same homologous chromosome segments in each species, and that these chromosome segments have homology to human chromosome 4 (HSA4). Bacterial artificial chromosome clones containing equine genes SMARCA5 (ECA2q21 homologue to HSA4q31. 21) and UCHL1 (ECA3q22 homologue to HSA4p13) were mapped to a single metacentric chromosome and two unpaired acrocentrics by FISH mapping for individuals possessing odd numbers of chromosomes. These data suggest that the polymorphism is either ancient and conserved within the genus or has occurred recently and independently within each species. Since these species are separated by 1–3 million years of evolution, this polymorphism is remarkable and worthy of further investigations.
Digging up the canine genome – a tale to wag about
Authors: Greer K.A. , Cargill E.J. , Cox M.L. , Clark L.A. , Tsai K.L. , Credille K.M. , Dunstan R.W. , Venta P.J. , Murphy K.E.
Published: February 2004

There is incredible morphological and behavioral diversity among the hundreds of breeds of the domestic dog, Canis familiaris. Many of these breeds have come into existence within the last few hundred years. While there are obvious phenotypic differences among breeds, there is marked interbreed genetic homogeneity. Thus, study of canine genetics and genomics is of importance to comparative genomics, evolutionary biology and study of human hereditary diseases. The most recent version of the map of the canine genome is comprised of 3,270 markers mapped to 3,021 unique positions with an average intermarker distance of ∼1 Mb. The markers include approximately 1,600 microsatellite markers, about 1,000 gene-based markers, and almost 700 bacterial artificial chromosome-end markers. Importantly, integration of radiation hybrid and linkage maps has greatly enhanced the utility of the map. Additionally, mapping the genome has led directly to characterization of microsatellite markers ideal for whole genome linkage scans. Thus, workers are now able to exploit the canine genome for a wide variety of genetic studies. Finally, the decision to sequence the canine genome highlights the dog’s evolutionary and physiologic position between the mouse and human and its importance as a model for study of mammalian genetics and human hereditary diseases.
Chicken genome sequence: a centennial gift to poultry genetics
Authors: Dodgson J.B.
Published: February 2004

A draft sequence of the chicken genome will be available by early 2004. This event conveniently marks the start of the second century of poultry genetics, coming 100 years after the use of the chicken to demonstrate Mendelian inheritance in animals by William Bateson. How will the second, post-genomic century of poultry genetics differ from the first? A whole genome shotgun (WGS) approach is being used to obtain the chicken sequence, with the goal of generating approximately six-fold coverage of the genome. Bacterial artificial chromosome (BAC) and fosmid clone end sequences, along with a BAC contig map integrated with genetic linkage and radiation hybrid maps, will form the platform for assembly of the WGS data. Rapid progress in global analysis of chicken gene expression patterns is also being made. Comparative genomics will link these new discoveries to the knowledge base for all other animal species. It’s hoped that the genome sequence will also provide common ground on which to unite studies of the chicken as a model species with those aimed at agriculturally-relevant applications. The current status of chicken genomics will be assessed with projections for its near and long term future.
Chromosome homology between chicken (Gallus gallus domesticus) and the red-legged partridge (Alectoris rufa); evidence of the occurrence of a neocentromere during evolution
Authors: Kasai F. , Garcia C. , Arruga M.V. , Ferguson-Smith M.A.
Published: February 2004

Chromosome-specific paints from macrochromosomes 1–9 and Z of the chicken were hybridised to metaphases of the red-legged partridge and revealed no inter-chromosomal rearrangements. The results from chromosome painting are similar to previous studies on the Japanese quail but different from findings in guinea fowl and several species of pheasant. The difference in centromere position in chicken and partridge chromosome 4, previously assumed to be the result of an inversion, was confirmed. However, FISH mapping of BAC clones from chicken chromosome 4 revealed that the order of loci was the same in both species, indicating the occurrence of a neocentromere during divergence.
Hearing Loss in Athyroid Pax8 Knockout Mice and Effects of Thyroxine Substitution
Authors: Christ Stephanie , Biebel Ulrich W. , Hoidis Silvi , Friedrichsen Sönke , Bauer Karl , Smolders Jean W.Th.
Published: February 2004

Pax8–/– mice do not develop thyroid follicular structures and thus provide an ideal animal model to study the consequences of congenital hypothyroidism. Despite their athyroidism, Pax8–/– mice survive up to postnatal day 21 (P21). No auditory brain stem responses (ABR) to sound could be recorded in these animals at 130 dB SPL, even at P21, when hearing reaches adult sensitivity in control mice. Abnormalities in the outer and middle ear structures were found in a considerable percentage of Pax8–/– animals. Maturation of the inner ear appeared delayed by about 1 week with respect to euthyroid controls. Hearing of adult Pax8–/– mice could be nearly normalized by early postnatal substitution with thyroxine (T4), but structural and functional restoration of hearing was incomplete. Even when T4 substitution was initiated at P1, ABR thresholds, measured at 6 weeks of age or more, were increased by about 20 dB, and each day of delay in the start of T4 substitution resulted in an additional threshold loss of about 4 dB. The most prominent structural deficit in Pax8–/– animals in which T4 substitution was started at P8 or later was an abnormally thick tectorial membrane. In these late-substituted animals, disarray of stereovilli from inner and outer hair cells was observed and also outer hair cell loss was found, predominantly in the basal part of the cochlea. The degree of structural disorder increased the later T4 substitution was initiated. The structural and functional consequences of postnatal athyroidism observed in Pax8–/– mice are largely in agreement with and extend those data obtained from hypothyroid animal models in which hypothyroidism was induced by goitrogenic agents (methimazole, propylthiouracil) or animal models with disrupted genes for the TSH receptor or the thyroid hormone receptors. The hearing loss and also the recovery effect by T4 substitution in Pax8–/– mice is larger than that in the other models. Although Pax8–/– mice are born by euthyroid Pax8+/– dams, the Pax8–/– phenotype could not be completely restored by immediate postnatal T4 substitution, indicating that some deficits are the consequence of prenatal T4 deficiency of the offspring.
Purification and Characterization of a Major Cross-Reactive Allergen from Epicoccum purpurascens
Authors: Bisht Vandana , Arora Naveen , Singh B.P. , Gaur S.N. , Sridhara Susheela
Published: February 2004

Background:Epicoccum purpurascens (formerly nigrum) (EP), is a ubiquitous saprophytic mould found both indoors and outdoors. Several studies have reported sensitization to EP in 5–7 % of different populations worldwide. The diagnosis of mould allergy requires a standardized fungal extract that contains all its important allergenic proteins. The crude allergen extract from EP was standardized earlier, however none of its allergens have been purified. Methods: A major allergen from spore-mycelia extract of EP was purified using concanavalin A (Con A) Sepharose chromatography, gel filtration and electro-elution. The allergen isolated was characterized for its IgE-binding ability and cross-reactivity with five well-known allergenic fungi by ELISA and immunoblot. Results: A 33.5-kD glycoprotein allergen of EP, Epi p 1, was purified to homogeneity. All the EP allergic patients’ sera tested recognized this protein. Periodate modification of Epi p 1 showed partial loss in IgE binding while proteinase K treatment caused complete loss in binding to IgE. Dose-dependent inhibition in binding of rabbit anti Epi p 1 antibodies was obtained with Epi p 1, Aspergillus fumigatus, Alternaria alternata, Curvularia lunata, Cladosporium herbarum and Fusarium solani in ELISA. Rabbit antibodies to all the above five fungi recognized Epi p 1 in immunoblot, confirming that Epi p 1 shares common epitopes with the fungi tested. Conclusion: A major glycoprotein allergen of 33.5 kD was purified from EP which cross-reacts with other fungi. Hence this glycoprotein can be exploited to reduce the panel of allergen extracts used for therapy of mould allergy.
The FcγRIIa Polymorphism in Children with Atopic Diseases
Authors: Pawlik A. , Carlsson L. , Meisel P. , Czaja-Bulsa G. , Mokrzycka M. , Gawrońska-Szklarz B.
Published: February 2004

Background: Fcγ receptor II (FcγRIIa) is the most widely distributed of the classes of FcR and is expressed in polymorphic forms on most types of hematopoietic cells. Recent data suggest that this polymorphism may be relevant to FcγRIIa function. This might be linked to variability in immune response and therefore related to the pathogenesis of atopic diseases. The aim of the study was to evaluate the FcγRIIa polymorphism in children with atopic diseases. Methods: In the study were included 140 atopic children, 77 with food allergy and 126 healthy subjects as the control group. The FcγRIIa polymorphism was determined using the polymerase chain reaction method. Results: The distribution of FcγRIIa genotypes in atopic children did not differ from that of healthy controls. Moreover, there was no association between the FcγRIIa genotypes and atopic diseases. Conclusion: It seems that the FcγRIIa polymorphism does not represent an important genetic risk factor for atopic diseases susceptibility.
Expression of Functional Activating and Inhibitory Fcγ Receptors on Human B Cells
Authors: Rabinovitch Nathan , Gelfand Erwin W.
Published: February 2004

Background: The CD32 (FcγII) receptor is involved in the regulation of the B cell response to antigen. The sole Fc receptor demonstrated in mice is the inhibitory FcγIIB receptor. Crosslinking this receptor does not lead to downstream signaling or cell activation. Instead, when immune complexes bind to Fcy on murine B cells, cell activation through the B cell antigen receptor is attenuated. The objective of this study was to evaluate the expression of the FcγII receptor and the response to immune complex stimulation in human B cells. Methods: Human lymphoblastoid, peripheral and tonsillar B cells were stained with anti-CD32 antibodies IV.3 and 8.26 to determine the relative expression of the activating (FcγIIA) and inhibitory (FcγIIB) isoforms of CD32. Tetanus immune complexes were added to B cells and the activation of c-Jun amino-terminal kinase was assayed. Results: Unlike murine cells, human B cells express high levels of the activating form of the Fcγ receptor IIA. Addition of immune complexes to peripheral B cells resulted in signaling of Jun kinase, an important downstream kinase involved in the regulation of B cell function. The level of expression of FcγIIA on human B cells was not uniform, but depended on activation status. Peripheral blood B cells expressed high levels of FcγIIA, while tonsillar B cells predominantly expressed FcγIIB. Furthermore, when peripheral B cells were activated, the expression of FcγIIA relative to FcγIIB decreased. Conclusion: The response of human B cells to binding of immune complexes depends on the relative expression of activating (FcγIIA) versus inhibitory (FcγIIB) receptors.
The Legal Hermeneutics of Al-shāfi'ī and Ibn Qutayba: A Reconsideration*
Authors: Lowry Joseph
Published: February 2004

In a 1993 monograph Norman Calder argued that Shāfi ī's (d. 204/820) Risāla must be a product of the early fourth/tenth centuries. Calder's argument, which has not been seriously challenged, rested mostly on a comparison of the Risāla's hermeneutic techniques with those of Ibn Qutayba's (d. 276/889) Ta wīl mukhtalif al-hadīth. A comparison of these two works shows that the evidence is much more equivocal than Calder allowed. Moreover, the overriding purposes of the two works differ to an extent which robs Calder's argument of much of its force. A close examination of the two authors' hermeneutics shows, however, that Ibn Qutayba's relatively unsystematic Ta wīl stands closer to classical usūl al-fiqh in several important respects than does Shāfi'ī's Risāla. The relationship between the two works is thus broadly consistent with their traditional datings and ascriptions.
The Common Link and its Relation to the Madār
Authors: Ozkan Halit
Published: February 2004

I examine here the use of the term madār in the Muslim hadīth literature in an effort to reassess G.H.A. Juynboll's claim that this term is equivalent to his common link. I argue that there are significant differences between the understanding and use of madār by both classical and contemporary Muslim scholars, on the one hand, and Juynboll's notion of the common link, on the other. After summarizing Juynboll's conclusions, I present and discuss some examples of the use of madār chosen from authoritative hadīth commentaries and rijāl books; discuss how Muslim scholars understood the term madār; and reevaluate Juynboll's ideas about the related terms, mutābi'āt and shawāhid.
Fatwā and War: On the Allegiance of the American Muslim Soldiers in the Aftermath of September 11
Authors: Nafi Basheer
Published: February 2004

The domination of the world system by the nation-state poses a formidable challenge to modern Islamic political and juristic discourse, especially when the state is secular and non-Islamic. In this article, I examine a collective fatwā, issued a few weeks after the September 11 attacks on Washington D. C. and New York City. The fatwā gave permission to American Muslim soldiers to participate in the American military efforts against the perpetrators of the attacks, even if that involved the declaration of war against a Muslim country. By giving such permission, the fatwā implies that the principle allegiance of the American Muslim soldier is to his own country, especially in a situation of war. Issued by a group of Muslim 'ulama' and intellectuals with a Salafī-reformist background, this fatwā represents an Islamic attempt by Muslims to address some of the major changes in the world system. I also examine Muslim opposition to the fatwā, mostly from other Islamic Salafī circles, which points to a profound division within Salafism.
A Murābaha Transaction in An English Court - The London High Court of 13th February 2002 in Islamic Investment Company of the Gulf (Bahamas) Ltd. V. Symphony Gems N.V. & Ors.
Authors: Bälz Kilian
Published: February 2004

Islamic finance is based on the application of Sharī'a rules to modern financing transactions. The Islamic finance industry has grown considerably over the last two decades and Islamic financing transactions today often have a global reach. As a consequence, traditional Islamic contractual structures are reformulated in the language of international commercial agreements and Sharī'a a based transactions are adjudicated in non-Islamic jurisdictions. In examining a recent case of the London High Court dealing with an Islamic murābaha agreement this essay investigates the complex interaction between and among Islamic contractual structures, English style contractual drafting and principles of international commercial law.
Using Grounded Theory to Examine People's Attitudes Toward How Animals are Used
Authors: Vrij Aldert , Nunkoosing Karl , Knight Sarah , Cherryman Julie
Published: February 2004

This study uses qualitative methodology to examine why people have different attitudes toward different types of nonhuman animal use. Seventeen participants took part in a semi-structured interview. The study used Grounded Theory to analyze the interviews and developed a model that consists of 4 major themes: (a) "attitudes toward animals," (b) "knowledge of animal use procedures," (c) "perceptions of choice," and (d) "cost-benefit analysis. "The findings illustrate that cognitive processing, characteristics of the species of animal being used, and the type of animal use can all influence attitudes toward animal use. Because previous research has focused on participant variables such as age and gender to explain variance in attitudes toward animal use (Furnham & Pinder, 1990; Kellert & Berry, 1981) and measured attitudes toward animal use in general (rather than distinguishing between different types of use) (Armstrong & Hutchins, 1996), these findings can add to knowledge of people's views on animal use. This paper discusses how such views may be justified and maintained.
Controlling the Wilderness: The Work of Wilderness Officers
Authors: Lawson Helene
Published: February 2004

Ideologies having roots in the legal structure of the system of wildlife protection characterize the work culture of the Pennsylvania wilderness officer. This paper examines these ideologies and the characteristically strong social solidarity of the community of wilderness officers. Wilderness officers are both law enforcement agents and conservationists. They mediate between human and animal as well as between what is considered scientific management and what is considered unenlightened and even lawless behavior. In performing this boundary work, wilderness officers participate in the social construction of the science of land management, which views animals as renewable resources. The wilderness officer's job is to insure the continuation of this resource as a part of the natural heritage of Pennsylvania and the United States. The wilderness officer's concept of "animal" becomes a byproduct of this social construction and of the culture of hunting that supports it. The rural upbringing common to many officers suits them ideally to their task.
An Exploration of the Sculptures of Greyfriars Bobby, Edinburgh, Scotland, and the Brown Dog, Battersea, South London, England
Authors: Kean Hilda
Published: February 2004

This article analyzes the sculptural depiction of two nonhuman animals, Greyfriars Bobby in Edinburgh, Scotland and the Brown Dog in Battersea, South London, England. It explores the ways in which both these cultural depictions transgress the norm of nineteenth century dog sculpture. It also raises questions about the nature of these constructions and the way in which the memorials became incorporated within particular human political spaces. The article concludes by analyzing the modern "replacement" of the destroyed early twentieth century statue of the Brown Dog and suggests that the original meaning of the statue has been significantly altered.
As Charming as a Pig:The Discursive Construction of the Relationship Between Pigs and Humans
Authors: Stibbe Arran
Published: February 2004

In the past, pigs were kept near their guardians' (owners') homes, ate leftovers from their guardians' kitchens and enjoyed a generally close relationship with humans. The closeness of the relationship, combined with its ultimate end in the killing of the pig, led to a sense of shame (Leach, 1964). This shame manifested itself in negative expressions about pigs within the English language, which remain to this day. However, the relationship between humans and pigs is becoming increasingly distant, with decisions affecting pigs' lives made in the offices of agricultural industry executives far from the intensive farms on which the pigs live. The new relationship has led to the evolution of a new discourse about pigs, that of the modern pork industry. Because of its technical and scientific nature, this new discourse does not contain the explicit insults of mainstream discourse.Yet, embedded within it are a series of implicit ideological assumptions designed to justify the confinement and exploitation of pigs in high intensity farms. This paper investigates the discourses surrounding pigs in both mainstream (British) culture and the pork industry and discusses attempts to challenge these discourses.
A Bird in the House: An Anthropological Perspective on Companion Parrots
Authors: Anderson Patricia
Published: February 2004

Although companion birds are the third most-common animal companion—after dogs and cats—in U.S. households, few anthrozoological publications focus on them. This study examines the role of companion parrots in American households. The study combines a literature review with the results of a survey of bird owners and participant observation. The study uses the resulting qualitative and quantitative data in addressing the social dynamics of companion parrot ownership in the household. The data support the impression that companion parrots increasingly are being considered family members, or "Fids" ("Feathered Kids"), thus following current trends in American society that accord companion animals in general a greater investment in time, money, and emotion. However, the general public is not well informed about the complexities of captive parrot care, and psittacine wellness is an important concern.
Quinidine as a Probe for the Role of P‐Glycoprotein in the Intestinal Absorption and Clinical Effects of Fentanyl
Authors: Kharasch Evan D. , Hoffer Christine , Altuntas T. Gul , Whittington Dale
Published: February 2004

The mechanism of individual variability in the fentanyl dose‐effect relationship is unknown. The efflux pump P‐glycoprotein (P‐gp) regulates brain access and intestinal absorption of numerous drugs. Evidence exists that fentanyl is a P‐gp substrate in vitro, and P‐gp affects fentanyl analgesia in animals. However, the role of P‐gp in human fentanyl disposition and clinical effects is unknown. This investigation tested the hypothesis that plasma concentrations and clinical effects of oral and intravenous fentanyl are greater after inhibition of intestinal and brain P‐gp, using the P‐gp inhibitor quinidine as an in vivo probe. Two randomized, double‐blind, placebo‐controlled, balanced, two‐period crossover studies were conducted in normal healthy volunteers (6 males and 6 females) after obtaining informed consent. Pupil diameters and/or plasma concentrations of fentanyl and norfentanyl were evaluated after oral or intravenous fentanyl (2.5 μg/kg), dosed 1 hour after oral quinidine (600 mg) or placebo. Quinidine did not alter the magnitude or time to maximum miosis, time‐specific pupil diameter, or subjective self‐assessments after intravenous fentanyl but did increase the area under the curve (AUC) of miosis versus time (13.6 ± 5.3 vs. 8.7 ± 5.0 mm•h, p < 0.05) and decreased the effect of elimination (kel 0.35 ± 0.16 vs. 0.52 ± 0.24 h−1, p < 0.05). Quinidine increased oral fentanyl plasma Cmax (0.55 ± 0.19 vs. 0.21 ± 0.1 ng/mL) and AUC (1.9 ± 0.5 vs. 0.7 ± 0.3 ng•h•mL−1) (both p < 0.05) but had no effect on apparent elimination. Plasma norfentanyl/fentanyl AUC ratios were not diminished by quinidine. Quinidine significantly increased maximum miosis after oral fentanyl (3.4 ± 1.3 vs. 2.3 ± 1.3 mm, p < 0.05), commensurate with increases in plasma concentrations, but concentration‐effect relationships and the rate constant for the transfer between plasma and effect compartment (ke0) (1.9 ± 1.0 vs. 3.6 ± 2.6 h−1) were not significantly different. Quinidine increased oral fentanyl plasma concentrations, suggesting that intestinal P‐gp or some other quinidine‐sensitive transporter affects the absorption, bioavailability, and hence clinical effects of oral fentanyl. Quinidine had less effect on fentanyl pharmacodynamics, suggesting that if quinidine is an effective inhibitor of brain P‐gp, then P‐gp appears to have less effect on brain access of fentanyl.
Single Oral Dose Safety, Tolerability, and Pharmacokinetics of PNU‐96391 in Healthy Volunteers
Authors: Rodríguez Carlos A. , Azie Nkechi E. , Adams Gregory , Donaldson Kirsteen , Francom Steven F. , Staton Brian A. , Bombardt Paul A.
Published: February 2004

The safety, tolerability, and pharmacokinetics of PNU‐96391, an orally active weak dopamine D2 receptor antagonist with modulatory properties of central dopaminergic function, was characterized. Fifty‐three healthy normal volunteers were enrolled in this randomized, double‐blinded, placebo‐controlled, single‐dose study. Subjects were assigned to single oral doses of placebo and 1, 3, 10, 30, 100, 150, and 200 mg PNU‐96391. Safety and tolerability were assessed using telemetry, Holter monitoring, surface ECG, vital signs, safety laboratories, and adverse event reports. Pharmacokinetic parameters were determined by model‐independent techniques. Adverse events were infrequent, of mild to moderate intensity, and in the dose range of 1 to 150 mg. Dose escalation was stopped at 200 mg because of severe nausea, dizziness, lightheadedness, and tachycardia. Besides the increase in heart rate, no other drug‐related effects on vital signs were observed. Safety laboratory measurements were not significantly changed. Evidence of drug activity was demonstrated by a dose‐dependent elevation in serum prolactin. PNU‐96391 was rapidly absorbed, with maximum concentrations achieved between 0.5 and 4 hours in all subjects. The half‐life of the drug was short (2 to 6 h). The main metabolite, PNU‐100014, was rapidly formed, with a tmax ranging from 1 to 6 hours. Peak levels of the metabolite are approximately half of the parent drug, and the half‐life is slightly longer (4 to 10 h). Increases in dose resulted in linear increases in exposure for both PNU‐96391 and PNU‐100014. Hence, PNU‐96391 was well tolerated at doses ranging from 1 to 150 mg.
The Pharmacokinetics of Sodium Oxybate Oral Solution following Acute and Chronic Administration to Narcoleptic Patients
Authors: Borgen Lowell A. , Okerholm Richard A. , Lai Allen , Scharf Martin B.
Published: February 2004

This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma‐hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open‐label, two‐period, two‐treatment study design was used. Trial subjects included 13 patients with polysomnographically confirmed narcolepsy. The patients were administered a bedtime dose of 4.5 g of sodium oxybate while in a sleep research center. They were subsequently treated with sodium oxybate at the nightly dose of 4.5 g for 8 weeks. The patients then returned to the sleep center and were again treated with the 4.5‐g sodium oxybate dose at bedtime. Blood samples (5 mL) were collected at 18 time points before and up to 7 hours after both the first dose of sodium oxybate and following 8 weeks of dosing. Plasma samples were analyzed for oxybate content by a validated liquid chromatography/tandem mass spectrometry (LC/MS/ MS) method. Noncompartmental methods were applied in the determination of pharmacokinetic parameters from each patient's plasma oxybate concentration versus time curve. No serious adverse events were recorded, and all patients completed the study. Headache, enuresis, and leg cramps were reported as adverse experiences. With both acute and chronic dosing, sodium oxybate was rapidly absorbed and eliminated with an apparent half‐life of about 40 minutes. The only changes observed in the kinetics of oxybate after 8 weeks of treatment were a 13% and 16% increase in peak concentration (Cmax) and systemic exposure (AUC), respectively. The pharmacokinetics of sodium oxybate in narcoleptic patients were not changed in any clinically significant manner when the drug was chronically administered. The drug was well tolerated.
Pharmacokinetics and Safety of Fosfluconazole after Single Intravenous Bolus Injection in Healthy Male Japanese Volunteers
Authors: Sobue Satoshi , Sekiguchi Kaneo , Shimatani Katsuyoshi , Tan Keith
Published: February 2004

This was a single blind, placebo‐controlled, escalating single‐dose, three‐period crossover study using two subject cohorts to investigate the safety, tolerability, and pharmacokinetics in healthy male Japanese subjects after intravenous bolus injection of fosfluconazole 50 to 2000 mg, a phosphate prodrug of fluconazole (FLCZ). Fosfluconazole was rapidly converted to FLCZ with only minor amounts excreted in the urine (less than 4% of the dose). Fosfluconazole had a volume of distribution at the higher doses, which was similar to the extracellular volume in man (0.2 L/kg) and was eliminated with a terminal half‐life of 1.5 to 2.5 hours. There was apparent dose proportionality in FLCZ pharmacokinetics. Cmax and AUC of FLCZ appeared to increase proportionally with increasing doses of fosfluconazole. There were no apparent dose‐dependent trends in tmax, t1/2, or mean residence time (MRT) of FLCZ. Bolus injection of fosfluconazole was well tolerated at doses of up to 2000 mg in healthy Japanese subjects.
Indinavir and Rifabutin Drug Interactions in Healthy Volunteers
Authors: Kraft Walter K. , McCrea Jacqueline B. , Winchell Gregory A. , Carides Alexandra , Lowry Richard , Woolf Eric J. , Kusma Sandra E. , Deutsch Paul J. , Greenberg Howard E. , Waldman Scott A.
Published: February 2004

Two studies examined the pharmacokinetics of indinavir and rifabutin when coadministered in healthy subjects. Rifabutin, which induces the expression of cytochrome P450 (CYP) 3A, and indinavir, which inhibits that enzyme system, are frequently coadministered in patients infected with HIV. The second study was undertaken to determine if altering the dose of rifabutin coadministered with indinavir would minimize the drug interaction observed in the first study. Two studies, each with a three‐period crossover design, were performed. In study 1, standard doses of rifabutin and indinavir (300 mg of rifabutin qd and 800 mg indinavir q8h) were administered as monotherapy (with placebo to the other drug) or in combination to 10 volunteers for 10 days. In study 2, 150 mg qd of rifabutin together with 800 mg q8h of indinavir, 300 mg qd of rifabutin alone, or 800 mg q8h of indinavir alone was administered to 14 volunteers for 10 days. In study 1, the geometric mean ratio (GMR) (90% confidence interval [CI]) of the AUC(0–8h) of indinavir, coadministered with rifabutin 300 mg qd compared to indinavir alone (with rifabutin placebo), was 0.66 (0.56, 0.77), while that of the AUC(0–24h) of rifabutin, coadministered with indinavir compared to rifabutin alone (with indinavir placebo), was 2.73 (1.99, 3.77). In study 2, the GMR (90% CI) of the AUC(0–8h) of indinavir, coadministered with rifabutin 150 mg qd compared to indinavir alone, was 0.68 (0.60, 0.76), while that of the AUC(0–24h) of rifabutin, when rifabutin 150 mg qd was coadministered with indinavir compared to rifabutin 300 mg qd alone, was 1.54 (1.33, 1.79). For both studies 1 and 2, indinavir and rifabutin administered alone or in combination were generally well tolerated. No clinical or laboratory adverse experience was serious. These data demonstrate the important pharmacokinetic interactions between indinavir and rifabutin when they are coadministered. Indeed, these observations formed the basis for the subsequent ACTG 365 study that explored dose adjustments for these agents in combination regimens to preserve the sustained antiviral activity of indinavir in the absence of adverse events as a result of elevated circulating levels of rifabutin.
Similarity of Insulin Detemir Pharmacokinetics, Safety, and Tolerability Profiles in Healthy Caucasian and Japanese American Subjects
Authors: Jhee Stan S. , Lyness William H. , Rojas Patrick B. , Leibowitz Mark T. , Zarotsky Victoria , Jacobsen Lisbeth V.
Published: February 2004

The objective of this study was to compare the pharmacokinetics of insulin detemir in three ascending doses in healthy Japanese and Caucasian subjects. This was an open‐label, single‐center, parallel‐group design evaluating 30 subjects (15 Japanese and 15 Caucasians). Subjects received a total of three subcutaneous injections (one injection per visit) of insulin detemir (0.19, 0.38, 0.75 U/kg [1 U = 24 nmol]) in ascending order. Following drug administration, subjects received intravenous glucose in 0.5‐mg/kg/min increments every 30 minutes, followed by a constant rate of 2.0 mg/kg/min for up to 12 hours. For pharmacokinetic evaluations, serial blood sampling was performed over a period of 30 hours after dosing. Of the subjects, 36 were enrolled, and 30 completed the study. There was a linear dose‐response relationship between the three ascending insulin detemir doses and serum insulin detemir AUC values for both the Japanese and Caucasian subjects. The two dose‐response regression lines had equivalent slopes but slightly different intercepts (although not statistically significant). This difference may be due to variation in AUC, body weight differences, or chance. Six subjects discontinued the study, 2 as a result of adverse events (blood draw–related ecchymosis and hypoglycemia). The most frequent treatment‐emergent adverse events (TEAE) were headache, dizziness, and reactions related to blood draws/infusion sites. All TEAEs were mild to moderate in severity. The results show that an increase in insulin detemir dose will result in a similar increase in insulin detemir concentration in the two ethnic groups. Therefore, therapeutic dosing of insulin detemir is expected to be similar in both ethnic groups, with no special dose adjustment or algorithm based on race. Insulin detemir at 0.19, 0.38, and 0.75 U/kg was generally well tolerated in both Japanese and Caucasian subjects.