bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence rate of presumed thoracolumbar intervertebral disc disease in ambulatory dogs with spinal hyperpathia treated with anti‐inflammatory drugs: 78 cases (1997–2000)
Authors: Mann F. A. , Wagner‐Mann Colette C. , Dunphy Elizabeth D. , Ruben Dawn S. , Rochat Mark C. , Bartels Kenneth E. 
Published: October 2006

AbstractObjective:To determine the recurrence rate of clinical signs in dogs with spinal hyperpathia and mild neurological deficits due to presumed Hansen Type 1 thoracolumbar intervertebral disc disease (IVDD) that were managed medically with anti‐inflammatory agents, and to compare the recurrence rates between dogs treated with corticosteroids and those treated with nonsteroidal anti‐inflammatory drugs (NSAIDs).Design:Retrospective study.Setting:Private veterinary emergency clinic in a large metropolitan area.Animals, interventions, and measurements:Medical records were used to ascertain study eligibility, record patient signalment and condition severity, and document medical treatment regimen. Each dog was assigned a severity score: (1) spinal hyperpathia with no neurological deficits, (2) spinal hyperpathia with conscious proprioceptive deficits only, or (3) spinal hyperpathia with ataxia but still retaining ambulatory motor function. Owners of 78 dogs weighing less than 16 kg presented from 1997 through 2000 were sent a questionnaire to determine recurrence rate.Main results:All dogs recovered from the initial episode; 39 experienced recurrence and 39 did not. There was no statistically significant relationship between gender, age, or severity score and recurrence rate. Dogs treated with NSAIDs or methylprednisolone sodium succinate (MPSS) were less likely to experience recurrence than dogs treated with corticosteroids other than MPSS.Conclusion:A 50% recurrence of presumed IVDD occurred in this population of dogs after treatment with NSAIDs or corticosteroids. Those treated with NSAIDs or MPSS were less likely to experience a recurrence.
Abnormalities of the HPA axis in affective disorders: clinical subtypes and potential treatments
Authors: Porter Richard J. , Gallagher Peter 
Published: October 2006

Background:New evidence is emerging regarding abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function in subtypes of affective disorders. Adverse effects of HPA axis dysregulation may include dysfunction of monoaminergic transmitter systems, cognitive impairment and peripheral effects. Newer treatments specifically targeting the HPA axis are being developed.Objective:To review these developments focusing particularly on the glucocorticoid receptor (GR) antagonist mifepristone.Method:A selective review of the literature.Results:The function of GRs is increasingly being defined. The role of corticotrophin-releasing hormone (CRH) and dehydroepiandrosterone (DHEA) in the brain is also increasingly understood. HPA axis function is particularly likely to be abnormal in psychotic depression and bipolar disorder, and it is in these conditions that trials of the GR antagonist mifepristone are being focused. CRH antagonists and DHEA are also being investigated as potential treatments.Conclusion:Initial studies of mifepristone and other HPA-axis-targeting agents in psychotic depression and bipolar disorder are encouraging and confirmatory studies are awaited.
Efficacy and safety of pimecrolimus cream 1% in adult patients with vitiligo: Results of a randomized, double‐blind, vehicle‐controlled study
Authors: Dawid Markus , Veensalu Marge , Grassberger Maximilian , Wolff Klaus 
Published: October 2006

Summary Background: Vitiligo is an acquired, pigmentary skin disorder which is disfiguring and difficult to treat. In an earlier open label study in adult patients with vitiligo, pimecrolimus cream 1% was reported to have similar efficacy as clobetasol propionate 0.05%. We performed a double‐blind, intrapatient comparison of pimecrolimus cream 1% with placebo cream. Patients and methods: Twenty adult Caucasians with symmetrical vitiligo (predominantly on extremities, none in the face) were treated b.i.d. for 6 months left/right with pimecrolimus/vehicle (N = 10) or vehicle/pimecrolimus (N = 10), respectively. Primary efficacy endpoint was the size of the target lesion at month 6 and secondary efficacy endpoint was re‐pigmentation. Results: Treatment with pimecrolimus cream 1% or vehicle resulted in no significant change in mean target lesion size. Modest repigmentation (1–25%) was noted with pimecrolimus at month 2 in 12 of 17 patients (vehicle: 9 of 17 patients). Afterwards, the number of patients who experienced an improvement of pigmentation steadily decreased (3 of 14 patients with pimecrolimus and 2 of 14 with placebo at month 6).Treatment was well tolerated.There were no treatment‐related adverse events, no induction of skin atrophy nor any other application site side effects. Conclusion: In this group of adult patients with symmetrical vitiligo, treatment of body lesions (except face) with pimecrolimus cream 1% could not be shown to be effective.
Successful thalidomide therapy for actinic prurigo in a European woman
Authors: Holzer Anna , Wolf Peter , Legat Franz J. , Kerl Helmut , Hofer Angelika 
Published: October 2006

SummaryActinic prurigo is a rare, often difficult‐to‐treat, idiopathic photodermatosis. Actinic prurigo is divided into a hereditary form appearing in the Native American population and a sporadic form occurring in non‐Native Americans. We present a 28‐year‐old Caucasian woman who developed typical clinical signs and symptoms of actinic prurigo, just as had her mother and grandmother. The patient and her mother were HLA‐A24 and HLA‐DR 4 with the subtype HLA‐DRB1*0408. Based on clinical symptoms and the HLA pattern, the diagnosis of actinic prurigo was made. Treatment with thalidomide led to resolution of the disease. This case report of a Caucasian woman suffering from a hereditary form of actinic prurigo questions the established classification of actinic prurigo into a hereditary Native American form and a sporadic form occurring in the non‐Native American population.
Star Dust
Authors: Ney Edward P. 
Published: October 2006

Infrared astronomy has shown that certain classes of stars are abundant producers of refractory grains, which condense in their atmospheres and are blown into interstellar space by the radiation pressure of these stars. Metallic silicates of the kind that produce terrestrial planets are injected by the oxygen-rich stars and carbon and its refractories by carbon stars. Much of the interstellar dust may be produced by this mechanism. A number of "infrared stars" are completely surrounded by their own dust, and a few of these exhibit a unique morphology that suggests the formation of a planetary system or a stage in the evolution of a planetary nebula. Certain novae also condense grains, which are blown out in their shells.
In our own solar system, comets are found to contain the same silicates that are present elsewhere in the galaxy, suggesting that these constituents were present in the primeval solar nebula.
Large-Scale Integration: What Is Yet to Come?
Authors: Noyce Robert N. 
Published: October 2006

The rapid development of large-scale integrated circuits in the last two decades has revolutionized information handling. Higher levels of integration have been achieved principally by making the individual circuit elements smaller, but reduction of random defects and innovations in circuit design have also been important factors. Practical limits to the size of integrated circuits, such as those imposed by the use of photolithography to define the circuits, can be avoided by using other methods, such as solid-state diffusion or electron beams.
The prospects are that dimensions and defect densities will continue to be reduced while speed increases. Redundancy in circuits will lead to lower costs and higher levels of integration. As logic becomes more complex and applications narrower, the increased number of unique circuit designs needed tends to increase costs. The microprocessor was developed to answer this problem and will have a radical influence on future computing systems.
Phyllotaxis and the Fibonacci Series
Authors: Mitchison G. J. 
Published: October 2006

The principal conclusion is that Fibonacci phyllotaxis follows as a mathematical necessity from the combination of an expanding apex and a suitable spacing mechanism for positioning new leaves. I have considered an inhibitory spacing mechanism at some length, as it is a plausible candidate. However, the same treatment would apply equally well to depletion of, or competition for, a compound by developing leaves, and could no doubt accommodate other ingredients.
The mathematical principles involved are clear when it is assumed that only two leaves (the contacts) position a new leaf. There is some experimental evidence for this assumption. Nonetheless, it is not a precondition for Fibonacci phyllotaxis, since a computer model shows that this pattern is generated even when many leaves contribute to inhibition at a given point. Indeed, the Fibonacci pattern seems to be a robust and stable mathematical phenomenon, a finding which goes some way to explaining its widespread occurrence throughout the plant kingdom.
Selection of Retapamulin, a Novel Pleuromutilin for Topical Use
Authors: Rittenhouse Stephen , Biswas Sanjoy , Broskey John , McCloskey Lynn , Moore Terrance , Vasey Sandra , West Joshua , Zalacain Magdalena , Zonis Rimma , Payne David 
Published: October 2006

ABSTRACT

The in vitro activity of retapamulin was determined and compared to that of topical and community antibiotics. The MIC
90
s of retapamulin against
Staphylococcus aureus
and
Streptococcus pyogenes
were 0.12 μg/ml and 0.016 μg/ml, respectively. Retapamulin has a low propensity to select resistance and produces an in vitro postantibiotic effect.
Use of the Surgical Wound Infection Model To Determine the Efficacious Dosing Regimen of Retapamulin, a Novel Topical Antibiotic
Authors: Rittenhouse Stephen , Singley Christine , Hoover Jennifer , Page Roni , Payne David 
Published: October 2006

ABSTRACT

The effect of topically applied retapamulin ointment was evaluated using various dosing regimens in the
Staphylococcus aureus
and
Streptococcus pyogenes
wound infection model. Retapamulin (1%, wt/wt) was efficacious using twice-daily (b.i.d.) applications for 4 or 5 days. These data underpinned the decision to evaluate 1% retapamulin b.i.d. in clinical trials.
Biochemical Characterization of the Interactions of the Novel Pleuromutilin Derivative Retapamulin with Bacterial Ribosomes
Authors: Yan Kang , Madden Lenore , Choudhry Anthony E. , Voigt Christine S. , Copeland Robert A. , Gontarek Richard R. 
Published: October 2006

ABSTRACTRetapamulin is a semisynthetic pleuromutilin derivative being developed as a topical antibiotic for treating bacterial infections of the skin. It is potent in vitro against susceptible and multidrug-resistant organisms commonly associated with bacterial skin infections. We report detailed mode of action studies demonstrating that retapamulin binds to the bacterial ribosome with high affinity, inhibits ribosomal peptidyl transferase activity, and partially inhibits the binding of the initiator tRNA substrate to the ribosomal P-site. Taken together, these data distinguish the mode of action of retapamulin from that of other classes of antibiotics. This unique mode of action may explain the lack of clinically relevant, target-specific cross-resistance of retapamulin with antibacterials in current use.
Emergence of a Novel Lamivudine-Resistant Hepatitis B Virus Variant with a Substitution Outside the YMDD Motif
Authors: Yatsuji Hiromi , Noguchi Chiemi , Hiraga Nobuhiko , Mori Nami , Tsuge Masataka , Imamura Michio , Takahashi Shoichi , Iwao Eiji , Fujimoto Yoshifumi , Ochi Hidenori , Abe Hiromi , Maekawa Toshiro , Tateno Chise , Yoshizato Katsutoshi , Suzuki Fumitaka , Kumada Hiromitsu , Chayama Kazuaki 
Published: October 2006

ABSTRACT
Lamivudine is a major drug approved for treatment of chronic hepatitis B virus (HBV) infection. Emergence of drug-resistant mutants with amino acid substitutions in the YMDD motif is a well-documented problem during long-term lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV with an intact YMDD motif, which included an amino acid substitution, rtA181T, in the reverse transcriptase (RT) domain of HBV polymerase. The substitution also induced a unique amino acid substitution (W172L) in the overlapping hepatitis B surface (HBs) protein. The YMDD mutant strains were not detected even by using the sensitive peptide nucleic acid-mediated PCR clamping method. The detected nucleotide substitution was accompanied by the emergence of an additional nucleotide substitution that induced amino acid change (S331C) in the spacer domain. The rtA181T mutant strain displayed a threefold decrease in susceptibility to lamivudine in in vitro experiments in comparison with the wild type. In vivo analysis using human hepatocyte-chimeric mice confirmed the resistance of this mutant strain to lamivudine. We developed a method to detect this novel rtA181T mutation and a previously reported rtA181T mutation with the HBs stop codon using restriction fragment length polymorphism PCR and identified one patient with the latter pattern among 40 patients with lamivudine resistance. In conclusion, although the incidence is not high, we have to be careful regarding the emergence of lamivudine-resistant mutant strains with intact YMDD motif.
Impact of Sample Size on the Performance of Multiple-Model Pharmacokinetic Simulations
Authors: Tam Vincent H. , Kabbara Samer , Yeh Rosa F. , Leary Robert H. 
Published: October 2006

ABSTRACT
Monte Carlo simulations are increasingly used to predict pharmacokinetic variability of antimicrobials in a population. We investigated the sample size necessary to provide robust pharmacokinetic predictions. To obtain reasonably robust predictions, a nonparametric model derived from a sample population size of ≥50 appears to be necessary as the input information.
Calcineurin Promotes Infection of the Cornea by
Candida albicans
and Can Be Targeted To Enhance Fluconazole Therapy
Authors: Onyewu Chiatogu , Afshari Natalie A. , Heitman Joseph 
Published: October 2006

ABSTRACT

In an established
Candida albicans
murine keratitis model, combination therapy with ophthalmic preparations of fluconazole and cyclosporine A (CsA) demonstrated in vivo drug synergy and effectively resolved wild-type
C. albicans
infection more rapidly than monotherapy with either drug. Calcineurin, the target of CsA, was also found to contribute to pathogenicity.
Evaluation of the Activities of Pyrimethamine Analogs against
Plasmodium vivax
and
Plasmodium falciparum
Dihydrofolate Reductase-Thymidylate Synthase Using In Vitro Enzyme Inhibition and Bacterial Complementation Assays
Authors: Bunyarataphan Sasinee , Leartsakulpanich Ubolsree , Taweechai Supannee , Tarnchompoo Bongkoch , Kamchonwongpaisan Sumalee , Yuthavong Yongyuth 
Published: October 2006

ABSTRACT

Pyrimethamine analogs were examined as potential agents against vivax malaria using a bacterial surrogate system carrying
Plasmodium vivax
dihydrofolate reductase-thymidylate synthase (PvDHFR-TS), in which the PvDHFR complemented chemically knocked out host dihydrofolate reductase. The system was initially tested with
P. falciparum
dihydrofolate reductase-thymidylate synthase and was found to have good correlation with the parasite-based system. The 50% inhibitory concentrations derived from PvDHFR-TS-dependent bacteria were correlated with their corresponding inhibition constants (

K
i

) from an enzyme inhibition assay, pointing to the likelihood that the potent enzyme inhibitors will also have potent antimalarial activities. Active compounds against both wild-type and S58R S117N (SP21) double-mutant
P. vivax
include analogs with structures which can avert a steric clash with the asparagine (S117N) side chain of the mutant, similar to those found for homologous
Plasmodium falciparum
mutants, raising the possibility that the same compounds can be developed against both types of antifolate-resistant malaria. This rapid and convenient drug screening system should be useful for development of new antifolates against
P. vivax
, for which a continuous culture system is not yet available.
Analysis of the Topology of
Vibrio cholerae
NorM and Identification of Amino Acid Residues Involved in Norfloxacin Resistance
Authors: Singh Anil Kumar , Haldar Rajen , Mandal Debabrata , Kundu Manikuntala 
Published: October 2006

ABSTRACT

NorM, a putative efflux pump of
Vibrio cholerae
, is a member of the multidrug and toxic compound extrusion family of transporters. We demonstrate that NorM confers resistance to norfloxacin, ciprofloxacin, and ethidium bromide. Inactivation of
norM
rendered
V. cholerae
hypersensitive towards these fluoroquinolones. Multiple sequence alignment of members of its family identified several regions of high sequence conservation. The topology of NorM was determined using β-lactamase and chloramphenicol acetyltransferase fusions. The amino acid residues G
184
, K
185
, G
187
, P
189
, E
190
, G
192
, and G
195
in the periplasmic loops and L
381
, R
382
, G
383
, Y
384
, K
385
, and D
386
in the cytoplasmic loops, as well as all the acidic and cysteine residues of NorM, were mutated. Mutants G184V, G184W, K185I, P189S, E190K, and E190A lost the norfloxacin resistance-imparting phenotype characteristic of NorM. Mutants E124V, D155V, G187V, G187R, C196S, Y384H, Y384S, and Y384F exhibited partial resistance to norfloxacin. Mutants with replacements of G
184
or G
187
by A, K
185
by R, and E
190
by D retained the norfloxacin resistance phenotype of NorM. Analysis of the accumulation of norfloxacin in intact cells of
Escherichia coli
expressing NorM or its mutants in the presence or absence of carbonyl cyanide
m
-chlorophenylhydrazone supported the results obtained through susceptibility testing and argued in favor of NorM-mediated efflux as the determining factor in norfloxacin susceptibility in the genetically manipulated strains. Taken together, these results suggested that E
124
, D
155
, G
184
, K
185
, G
187
, P
189
, E
190
, C
196
, and Y
384
are likely involved in NorM-dependent norfloxacin efflux. Except for D
155
, C
196
, and Y
384
, all of these residues are located in periplasmic loops.
Duration of Outpatient Fecal Colonization Due to
Escherichia coli
Isolates with Decreased Susceptibility to Fluoroquinolones: Longitudinal Study of Patients Recently Discharged from the Hospital
Authors: Lautenbach Ebbing , Tolomeo Pam , Mao Xiangqun , Fishman Neil O. , Metlay Joshua P. , Bilker Warren B. , Nachamkin Irving 
Published: October 2006

ABSTRACT

Among 10 subjects colonized with
Escherichia coli
isolates with reduced susceptibility to fluoroquinolones, the median duration of colonization following hospital discharge was 80 days (range, 8 to 172 days). Colonization was longer for isolates demonstrating organic-solvent tolerance than for isolates that were not organic-solvent tolerant (151 versus 29 days, respectively;
P
= 0.07) but was not associated with other resistance mechanisms, demographics, or antibiotic use.
Chain-Terminating Dinucleoside Tetraphosphates Are Substrates for DNA Polymerization by Human Immunodeficiency Virus Type 1 Reverse Transcriptase with Increased Activity against Thymidine Analogue-Resistant Mutants
Authors: Meyer Peter R. , Smith Anthony J. , Matsuura Suzanne E. , Scott Walter A. 
Published: October 2006

ABSTRACT

Nucleoside reverse transcriptase inhibitors are an important class of drugs for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Resistance to these drugs is often the result of mutations that increase the transfer of chain-terminating nucleotides from blocked DNA termini to a nucleoside triphosphate acceptor, resulting in the generation of an unblocked DNA chain and synthesis of a dinucleoside polyphosphate containing the chain-terminating deoxynucleoside triphosphate analogue. We have synthesized and purified several dinucleoside tetraphosphates (ddAp
4
ddA, ddCp
4
ddC, ddGp
4
ddG, ddTp
4
ddT, Ap
4
ddG, 2′(3′)-
O
-(
N
-methylanthraniloyl)-Ap
4
ddG, and AppNHppddG) and show that these compounds can serve as substrates for DNA chain elongation and termination resulting in inhibition of DNA synthesis. Thymidine analogue-resistant mutants of reverse transcriptase are up to 120-fold more sensitive to inhibition by these compounds than is wild-type enzyme. Drugs based on the dinucleoside tetraphosphate structure could delay or prevent the emergence of mutants with enhanced primer unblocking activity. In addition, such drugs could suppress the resistance phenotype of mutant HIV-1 that is present in individuals infected with resistant virus.
Peptide Deformylase Inhibitors as Potent Antimycobacterial Agents
Authors: Teo Jeanette W. P. , Thayalan Pamela , Beer David , Yap Amelia S. L. , Nanjundappa Mahesh , Ngew Xinyi , Duraiswamy Jeyaraj , Liung Sarah , Dartois Veronique , Schreiber Mark , Hasan Samiul , Cynamon Michael , Ryder Neil S. , Yang Xia , Weidmann Beat , Bracken Kathryn , Dick Thomas , Mukherjee Kakoli 
Published: October 2006

ABSTRACT

Peptide deformylase (PDF) catalyzes the hydrolytic removal of the N-terminal formyl group from nascent proteins. This is an essential step in bacterial protein synthesis, making PDF an attractive target for antibacterial drug development. Essentiality of the
def
gene, encoding PDF from
Mycobacterium tuberculosis
, was demonstrated through genetic knockout experiments with
Mycobacterium bovis
BCG. PDF from
M. tuberculosis
strain H37Rv was cloned, expressed, and purified as an N-terminal histidine-tagged recombinant protein in
Escherichia coli
. A novel class of PDF inhibitors (PDF-I), the
N
-alkyl urea hydroxamic acids, were synthesized and evaluated for their activities against the
M. tuberculosis
PDF enzyme as well as their antimycobacterial effects. Several compounds from the new class had 50% inhibitory concentration (IC
50
) values of <100 nM. Some of the PDF-I displayed antibacterial activity against
M. tuberculosis
, including MDR strains with MIC
90
values of <1 μM. Pharmacokinetic studies of potential leads showed that the compounds were orally bioavailable. Spontaneous resistance towards these inhibitors arose at a frequency of ≤5 × 10
−7
in
M. bovis
BCG. DNA sequence analysis of several spontaneous PDF-I-resistant mutants revealed that half of the mutants had acquired point mutations in their formyl methyltransferase gene (
fmt
), which formylated Met-tRNA. The results from this study validate
M. tuberculosis
PDF as a drug target and suggest that this class of compounds have the potential to be developed as novel antimycobacterial agents.
Complete DNA Sequence, Comparative Genomics, and Prevalence of an IncHI2 Plasmid Occurring among Extraintestinal Pathogenic
Escherichia coli
Isolates
Authors: Johnson Timothy J. , Wannemeuhler Yvonne M. , Scaccianoce Jennifer A. , Johnson Sara J. , Nolan Lisa K. 
Published: October 2006

ABSTRACT

We have sequenced a large plasmid that occurs among avian pathogenic
Escherichia coli
isolates. This plasmid, pAPEC-O1-R, is a 241,387-bp IncHI2 plasmid which is cotransmissible via bacterial conjugation with a ColBM virulence plasmid, encodes resistance to eight antimicrobial agents, and appears to occur at low rates among extraintestinal
E. coli
isolates.
Effects of Various Media on the Activity of NXL103 (Formerly XRP 2868), a New Oral Streptogramin, against
Haemophilus influenzae
Authors: Pankuch Glenn A. , Hoellman Dianne , Bryskier André , Lowther John , Appelbaum Peter C. 
Published: October 2006

ABSTRACT

The activity of NXL103 against 108 strains of
Haemophilus influenzae
was tested using
Haemophilus
test media (HTM) obtained from various sources. With the exception of those obtained with stored HTM, MICs did not differ significantly, with MIC
50
and MIC
90
values of 0.5 and 0.5 to 1 μg/ml, respectively, in each medium.