bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic-Pharmacodynamic Comparison of Amphotericin B (AMB) and Two Lipid-Associated AMB Preparations, Liposomal AMB and AMB Lipid Complex, in Murine Candidiasis Models
Authors: Andes D. , Safdar N. , Marchillo K. , Conklin R. 
Published: January 2006

ABSTRACT

It is generally accepted that the lipid formulations of amphotericin B (AMB) are not as potent as conventional AMB on a milligram-per-kilogram basis. We used a neutropenic murine disseminated candidiasis model to compare the in vivo potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC) pharmacodynamically. The pharmacokinetics of the antifungals were examined in serum and in three organs commonly seeded in disseminated candidiasis (kidneys, liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen studies were used with each of the compounds. Determinations of the numbers of CFU in the kidneys were performed following the administration of three escalating single doses of the polyenes at various times over 48 h. The areas under the time-kill curves (AUTKs) for each dose level of the drugs were compared by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five
Candida
isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The organism burdens in the mouse kidneys were similarly used as the treatment end point. Additional multiple regimen-dosing-studies were performed with a single
Candida albicans
isolate, and the microbiologic outcomes in four internal organs (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h). The relationship between the dose and the drug exposure expressed by the pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed by using a maximum-effect model. ANOVA was used to compare the drug exposures necessary to achieve the 25% effective dose (ED
25
), ED
50
, ED
75
, and 1 log
10
killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent than either ABLC or L-AMB. The time-kill curves for both lipid formulations were very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold more potent than each of the lipid formulations against five
Candida
isolates in the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in the other end organs. The difference in pharmacokinetics in serum accounted for much of the difference in potency between AMB and ABLC (ratio of serum ABLC area under the curve of effective doses to serum AMB area under the curve of effective doses, 1.2). The differences in the kinetics in the various end organs between AMB and L-AMB were better at explaining the disparate potencies at these infection sites (ratio of organ L-AMB area under the curve of effective doses to organ AMB area under the curve of effective doses, 1.1).
Distribution of Tetracycline Resistance Genes in
Actinobacillus pleuropneumoniae
Isolates from Spain
Authors: Blanco Mónica , Gutiérrez-Martin César B. , Rodríguez-Ferri Elías F. , Roberts Marilyn C. , Navas Jesús 
Published: January 2006

ABSTRACT

Actinobacillus pleuropneumoniae
is the etiological agent of porcine pleuropneumonia. Tetracycline is used for therapy of this disease, and
A. pleuropneumoniae
carrying the
tet
(B) gene, coding for an efflux protein that reduces the intercellular tetracycline level, has been described previously. Of the 46 tetracycline-resistant (Tc
r
) Spanish
A. pleuropneumoniae
isolates used in this study, 32 (70%) carried the
tet
(B) gene, and 30 of these genes were associated with plasmids. Eight (17%) isolates carried the
tet
(O) gene, two (4%) isolates carried either the
tet
(H) or the
tet
(L) gene, and all these genes were associated with plasmids. This is the first description of these
tet
genes in
A. pleuropneumoniae
. The last two Tc
r
isolates carried none of the
tet
genes examined. Except for
tet
(O)-containing plasmids, the other 34 Tc
r
plasmids were transformable into an
Escherichia coli
recipient. Two plasmids were completely sequenced. Plasmid p11745, carrying the
tet
(B) gene, was 5,486 bp and included a
rep
gene, encoding a replication-related protein, and two open reading frames (ORFs) with homology to mobilization genes of
Neisseria gonorrhoeae
plasmid pSJ7.4. Plasmid p9555, carrying the
tet
(L) gene, was 5,672 bp and, based on its G+C content, consisted of two regions, one of putative gram-positive origin containing the
tet
(L) gene and the other comprising four ORF
s
organized in an operon-like structure with homology to mobilization genes in other plasmids of gram-negative bacteria.
Inhibition of
Candida parapsilosis
Mitochondrial Respiratory Pathways Enhances Susceptibility to Caspofungin
Authors: Chamilos Georgios , Lewis Russell E. , Kontoyiannis Dimitrios P. 
Published: January 2006

ABSTRACT

Among the
Candida
species,
Candida parapsilosis
has a unique mitochondrial respiratory network. The addition of inhibitors of the respiratory pathways in three clinical isolates of
C. parapsilosis
with high (≥2- μg/ml) MICs of caspofungin significantly (fivefold) decreased caspofungin MICs but did not change fluconazole MICs.
Dehydrative Glycosylation in Water Using a Brønsted Acid–Surfactant-Combined Catalyst
Authors: Aoyama Naohiro , Kobayashi Shu 
Published: January 2006

Abstract
Brønsted acid–surfactant-combined catalyst, dodecylbenzenesulfonic acid (DBSA), was used in catalytic dehydrative glycosylation reactions in water. 1-Hydroxy sugars, such as O-benzyl-protected furanose and pyranose, reacted with alcohols and a nitrogen nucleophile in the presence of a catalytic amount of DBSA to afford the desired adducts in good yields. Detailed study of the glycosylation of 2-deoxy-d-ribofuranose showed that hydrophobicity of the substrates was important to attain higher yields. Regarding the α/β selectivities, d-ribose and d-mannose derivatives gave the products in high β- and α-selectivities, respectively.
Lrrk2 and Lewy body disease
Authors: Ross Owen A. , Toft Mathias , Whittle Andrew J. , Johnson Joseph L. , Papapetropoulos Spiridon , Mash Deborah C. , Litvan Irene , Gordon Mark F. , Wszolek Zbigniew K. , Farrer Matthew J. , Dickson Dennis W. 
Published: January 2006

AbstractObjectiveThe Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease.MethodsHerein, we report that the most common neuropathology of G2019S‐associated Parkinson's disease is Lewy body disease.ResultsLrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance.InterpretationTherapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease. Ann Neurol 2006;59:388–393
Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine monkeys
Authors: Samadi Pershia , Grégoire Laurent , Rouillard Claude , Bédard Paul J. , Di Paolo Thérèse , Lévesque Daniel 
Published: January 2006

AbstractObjectiveThe objective of the present study was to investigate the effect of docosahexaenoic acid (DHA), a polyunsaturated fatty acid (omega‐3), on levodopa‐induced dyskinesias (LIDs) in parkinsonian 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–treated monkeys.MethodsWe explored the effect of DHA in two paradigms. First, a group of MPTP monkeys was primed with levodopa for several months before introducing DHA. A second group of MPTP monkeys (de novo) was exposed to DHA before levodopa therapy.ResultsDHA administration reduced LIDs in both paradigms without alteration of the anti‐parkinsonian effect of levodopa indicating that DHA can reduce the severity or delay the development of LIDs in a nonhuman primate model of Parkinson's disease.InterpretationThese results suggest that DHA can reduce the severity or delay the develoment of LIDs in a nonhuman primate model of Parkinson's disease. DHA may represent a new approach to improve the quality of life of Parkinson's disease patients. Ann Neurol 2006;59:282–288
Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy
Authors: Reed Patrick , Porter Neil C. , Strong John , Pumplin David W. , Corse Andrea M. , Luther Paul W. , Flanigan Kevin M. , Bloch Robert J. 
Published: January 2006

AbstractObjectiveWe examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered.MethodsUnfixed biopsies of control and FSHD deltoid and biceps muscles, snap‐frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde‐fixed samples were stained with heavy metals, embedded, thin‐sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils.ResultsConfocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100nm in controls to values as high as 550nm in FSHD.InterpretationOur results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD. Ann Neurol 2006;59:289–297
Severe episodic neurological deficits and permanent mental retardation in a child with a novel FHM2 ATP1A2 mutation
Authors: Vanmolkot K. R. J. , Stroink H. , Koenderink J. B. , Kors E. E. , van den Heuvel J. J. M. W. , van den Boogerd E. H. , Stam A. H. , Haan J. , De Vries B. B. A. , Terwindt G. M. , Frants R. R. , Ferrari M. D. , van den Maagdenberg A. M. J. M. 
Published: January 2006

AbstractObjectiveAttacks of familial hemiplegic migraine (FHM) are usually associated with transient, completely reversible symptoms. Here, we studied the ATP1A2 FHM2 gene in a young girl with episodes of both very severe and transient neurological symptoms that were triggered by mild head trauma as well as permanent mental retardation. Her family members suffered from hemiplegic and confusional migraine attacks.MethodsMutation analysis of the ATP1A2 gene was performed by direct sequencing of all exons and flanking intronic regions, using genomic DNA of the proband. Functional consequences of the mutation were analyzed by cellular survival assays.ResultsWe identified a novel G615R ATP1A2 mutation in the proband and several of her family members. Functional analysis of mutant Na,K‐ATPase in cellular survival assays showed a complete loss‐of‐function effect.InterpretationPermanent mental retardation in children may be caused by ATP1A2 mutations. Ann Neurol 2006;59:310–314
The human immunodeficiency virus reduces network capacity: Acoustic noise effect
Authors: Tomasi Dardo , Chang Linda , de Castro Caparelli Elisabeth , Telang Frank , Ernst Thomas 
Published: January 2006

AbstractObjectiveIncreased acoustic noise (AN) during working memory leads to increased brain activation in healthy individuals and may have greater impact in human immunodeficiency virus (HIV) patients.ResultsCompared with control subjects, HIV patients showed reduced AN activation and lower neuronal marker N‐acetylaspartate in prefrontal and parietal cortices. Competing use of the working memory network between AN and cognitive load showed lower dynamic range of the hemodynamic responses in prefrontal and parietal cortices in HIV patients.InterpretationThese findings suggest that reduced reserve capacity of the working memory network in HIV patients and additional stress (eg, AN) might exhaust the impaired network for more demanding tasks. Ann Neurol 2006;59:419–423
Mild‐onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene
Authors: Janson Christopher G. , Kolodny Edwin H. , Zeng Bai‐Jin , Raghavan Srinivasa , Pastores Gregory , Torres Paola , Assadi Mitra , McPhee Scott , Goldfarb Olga , Saslow Beth , Freese Andrew , Wang D. J. , Bilaniuk Larissa , Shera David , Leone Paola 
Published: January 2006

AbstractWe describe two sisters with a mild‐onset variant of Canavan's disease who presented at age 50 and 19 months with developmental delay but without macrocephaly, hypotonia, spasticity, or seizures. Remarkably, both patients had age‐appropriate head control, gross motor development, and muscle tone. There were very mild deficits in fine motor skills, coordination, and gait. Both sisters had a history of strabismus, but otherwise vision was normal. The older child showed evidence of mild cognitive and social impairment, whereas language and behavior were normal for age in the infant. Both patients were found to be compound heterozygotes for C914A (A305E) and G212A (R71H) mutations in ASPA. Like all other known ASPA mutations, this previously unknown G212A mutation appears to have low absolute enzyme activity. Nevertheless, it is associated in these patients with an extremely benign phenotype that is highly atypical of Canavan's disease. Biochemical and clinical data were evaluated using a generalized linear mixed model generated from 25 other subjects with Canavan's disease. There were statistically significant differences in brain chemistry and clinical evaluations, supporting a distinct variant of Canavan's disease. Future studies of ASPA enzyme structure and gene regulation in these subjects could lead to a better understanding of Canavan's pathophysiology and improvements in ASPA gene therapy Ann Neurol 2006;59:428–431
Biochemical and pathological characterization of Lrrk2
Authors: Giasson Benoit I. , Covy Jason P. , Bonini Nancy M. , Hurtig Howard I. , Farrer Matthew J. , Trojanowski John Q. , Van Deerlin Vivianna M. 
Published: January 2006

AbstractObjectiveMutations in leucine‐rich repeat kinase 2 (LRRK2) recently have been identified as the most common genetic cause of late‐onset sporadic and familial Parkinson's disease (PD). The studies herein explore the biological and pathological properties of Lrrk2.MethodsGenetic analysis was performed to identify autopsied patients with the most common Lrrk2 mutation (G2019S). Using an antibody specific to Lrrk2, the biochemical and immunocytochemical distribution of Lrrk2 was assessed.ResultsThree patients with the G2019S Lrrk2 mutation were identified. Two patients demonstrated classic PD with Lewy bodies, although concurrent pathological changes consistent with Alzheimer's disease were also present in one of these individuals. The third patient was characterized by parkinsonism without Lewy bodies but demonstrated dystrophic neurites in the substantia nigra intensely stained for Lrrk2. Lrrk2 accumulations were unique to this patient and Lrrk2 was not detected in other types of pathological inclusions. Biochemical analysis showed that Lrrk2 is predominantly a soluble approximately 250kDa cytoplasmic protein expressed throughout the brain but also in many other organs.InterpretationThe reasons for the selective predisposition of patients with mutations in LRRK2 to develop parkinsonism remains unclear, but Lrrk2 mutations may prime select neuronal populations to cellular insults that can lead to aberrant protein aggregation. Ann Neurol 2006;59:315–322
Broca's arrow: Evolution, prediction, and language in the brain
Authors: Cooper David L. 
Published: January 2006

AbstractBrodmann's areas 44 and 45 in the human brain, also known as Broca's area, have long been associated with language functions, especially in the left hemisphere. However, the precise role Broca's area plays in human language has not been established with certainty. Broca's area has homologs in the great apes and in area F5 in monkeys, which suggests that its original function was not linguistic at all. In fact, great ape and hominid brains show very similar left‐over‐right asymmetries in Broca's area homologs as well as in other areas, such as homologs to Wernicke's area, that are normally associated with language in modern humans. Moreover, the so‐called mirror neurons are located in Broca's area in great apes and area F5 in monkeys, which seem to provide a representation of cause and effect in a primate's environment, particularly its social environment. Humans appear to have these mirror neurons in Broca's area as well. Similarly, genetic evidence related to the FOXP2 gene implicates Broca's area in linguistic function and dysfunction, but the gene itself is a highly conserved developmental gene in vertebrates and is shared with only two or three differences between humans and great apes, five between humans and mice, and eight between humans and songbirds. Taking neurons and portions of the brain as discrete computational segments in the sense of constituting specific Turing machines, this evidence points to a predictive motor and conceptual function for Broca's area in primates, especially for social concepts. In human language, this is consistent with evidence from typological and cognitive linguistics. Anat Rec (Part B: New Anat) 289B:9–24, 2006. © 2006 Wiley‐Liss, Inc.
Subcellular, cellular, and circuit mechanisms underlying classical conditioning in Hermissenda crassicornis
Authors: Blackwell Kim T. 
Published: January 2006

AbstractA breakthrough for studying the neuronal basis of learning emerged when invertebrates with simple nervous systems, such as the sea slug Hermissenda crassicornis, were shown to exhibit classical conditioning. Hermissenda learns to associate light with turbulence: prior to learning, naive animals move toward light (phototaxis) and contract their foot in response to turbulence; after learning, conditioned animals delay phototaxis in response to light. The photoreceptors of the eye, which receive monosynaptic inputs from statocyst hair cells, are both sensory neurons and the first site of sensory convergence. The memory of light associated with turbulence is stored as changes in intrinsic and synaptic currents in these photoreceptors. The subcellular mechanisms producing these changes include activation of protein kinase C and MAP kinase, which act as coincidence detectors because they are activated by convergent signaling pathways. Pathways of interneurons and motorneurons, where additional changes in excitability and synaptic connections are found, contribute to delayed phototaxis. Bursting activity recorded at several points suggest the existence of small networks that produce complex spatiotemporal firing patterns. Thus, the change in behavior may be produced by a nonlinear transformation of spatiotemporal firing patterns caused by plasticity of synaptic and intrinsic channels. The change in currents and the activation of PKC and MAPK produced by associative learning are similar to those observed in hippocampal and cerebellar neurons after rabbit classical conditioning, suggesting that these represent general mechanisms of memory storage. Thus, the knowledge gained from further study of Hermissenda will continue to illuminate mechanisms of mammalian learning. Anat Rec (Part B: New Anat) 289B:25–37, 2006. © 2006 Wiley‐Liss, Inc.
The sensitivity of human event‐related potentials and reaction time to mobile phone emitted electromagnetic fields
Authors: Hamblin D.L. , Croft R.J. , Wood A.W. , Stough C. , Spong J. 
Published: January 2006

AbstractThere is some evidence to suggest that exposure to mobile phones (MPs) can affect neural activity, particularly in response to auditory stimuli. The current investigation (n = 120) aimed to test recent findings in this area, namely that N100 amplitude and latency would decrease, and that P300 latency and reaction time (RT) would increase under active relative to sham exposure during an auditory task. Visual measures were also explored. A double blind, counterbalanced, crossover design was employed where subjects attended two sessions 1 week apart. In both sessions participants (1) performed auditory and visual oddball tasks while electroencephalogram (EEG) was recorded with a MP set to sham exposure mounted over the temporal region, and (2) performed the same tasks while the handset was set to active/sham. When active, the MP transmitted for 30 min at 895 MHz (average power 250 mW, pulse modulated at 217 Hz, average SAR 0.11 W/kg). Paired t‐tests compared difference scores from the sham/sham session to those from the sham/active condition. The study was designed to detect differences of ${1\over4}$ of a standard deviation with a power of 0.80. There was no significant difference between exposure conditions for any auditory or visual event related potential (ERP) component or RT. As previous positive findings were not replicated, it was concluded that there is currently no evidence that acute MP exposure affects these indices of brain activity. Bioelectromagnetics 27:265–273, 2006. © 2006 Wiley‐Liss, Inc.
CNS viral infection diverts homing of antibody‐secreting cells from lymphoid organs to the CNS
Authors: Tschen Shuen‐Ing , Stohlman Stephen A. , Ramakrishna Chandran , Hinton David R. , Atkinson Roscoe D. , Bergmann Cornelia C. 
Published: January 2006

AbstractNeurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus‐specific Ab‐secreting cells (ASC). Although virus‐specific ASC declined in cervical lymph node and spleen after infectious virus clearance, virus‐specific serum Ab was sustained at steady levels, with a delay in neutralizing Ab. Virus‐specific ASC within the CNS peaked rapidly 1 wk after control of infectious virus and were retained throughout chronic infection, consistent with intrathecal Ab synthesis. Surprisingly, frequencies of ASC in the BM remained low and only increased gradually. Nevertheless, virus‐specific ASC induced by peripheral infection localized to both spleen and BM. The data suggest that CNS infection provides strong stimuli to recruit ASC into the inflamed tissue through sustained up‐regulation of the CXCR3 ligands CXCL9 and CXCL10. Irrespective of Ag deprivation, CNS retention of ASC coincided with elevated BAFF expression and ongoing differentiation of class II+ to class II–CD138+CD19+ plasmablasts. These results confirm the CNS as a major ASC‐supporting environment, even after resolution of viral infection and in the absence of chronic ongoing inflammation.
Structural and Dynamic Studies of Zinc, Gallium, and Cadmium Complexes of a Dicarboxylate Pendant‐Armed Cross‐Bridged Cyclen
Authors: Niu Weijun , Wong Edward H. , Weisman Gary R. , Peng Yijie , Anderson Carolyn J. , Zakharov Lev N. , Golen James A. , Rheingold Arnold L. 
Published: January 2006

AbstractInadvertently, the wrong X‐ray structure was reported1 for the Zn‐CB‐DO2A complex. Instead, the structural data for a related zinc complex was actually presented. The first paragraph of the section X‐ray Structural Data and Figure 5 on page 3312, Table 1 on page 3313, the last two sentences of the paragraph [Zn·1](NaClO4)1.5 and Table 3 on page 3314, and the paragraph X‐ray Crystallography on page 3315 should be replaced as follows (in addition, a corrected X‐ray CIF file was deposited with the CCDC):