bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of CCNU and DTIC Chemotherapy for Treatment of Resistant Lymphoma in Dogs
Authors: Flory A.B. , Rassnick K.M. , Al‐Sarraf R. , Bailey D.B. , Balkman C.E. , Kiselow M.A. , Autio K. 
Published: December 2008

Background:Pleotropic‐glycoprotein (P‐gp)–mediated resistance is the usual cause of relapse in dogs with lymphoma. 1‐(2‐chloroethyl)3‐cyclohexyl‐1‐nitrosurea (CCNU) and 5‐(3,3‐dimethyl‐1‐triazeno)‐imidazole‐4‐carboxamide (DTIC) are alkylating agents that are not affected by P‐gp and lack cross‐resistance to each other. A combination protocol offers the advantage of improved summation dose and synergistic activity.Hypothesis:A combination of CCNU and DTIC that is well tolerated can be used to treat dogs with lymphoma that developed resistance or failed to respond to previously administered chemotherapy.Animals:Fifty‐seven dogs with lymphoma that were resistant to treatment with standard chemotherapy (l‐CHOP;l‐asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone).Methods:Prospective phase I and II trials were performed. CCNU was given PO immediately before a 5‐h IV infusion of DTIC. Concurrent antiemetics and prophylactic antibiotics were used. Treatments were administered every 4 weeks.Results:Based on the results of 8 dogs in the phase I study, CCNU at 40 mg/m2PO combined with DTIC at 600 mg/m2IV was used to treat 57 dogs with resistant lymphoma. Thirteen (23%) dogs had a complete response (CR) for a median of 83 days and 7 (12%) had a partial response for a median of 25 days. The medianl‐CHOP CR duration of the dogs that did not respond to CCNU‐DTIC was significantly longer than that of the dogs that did achieve remission with CCNU‐DTIC (225 days versus 92 days,P= .02). The principal toxic event was neutropenia; the median neutrophil count 7 days after treatment was 1,275 cells/μL. Increases in alanine transaminase activity, possibly associated with hepatotoxicity, were detected in 7 dogs.Conclusions and Clinical Importance:A combination of CCNU and DTIC can be an effective option to rescue dogs with resistant lymphoma.
Polyneuropathy Associated with Forage Sources in Norwegian Horses
Authors: Hanche‐Olsen S. , Teige J. , Skaar I. , Ihler C.F. 
Published: December 2008

Background: Cases of hindlimb digital extensor weakness of unknown etiology have been observed in Norway since 1995.Hypothesis: We hypothesized that the observed bilateral extensor weakness was attributable to neuropathy of the distal nerves and that this was related to environmental factors, possibly dietary.Animals: Seventy‐five horses with digital extensor weakness occurring from 1995 to 2004 are described.Methods: Eleven horses were examined at The Norwegian School of Veterinary Science, and the medical records of 64 horses seen in ambulatory practice were reviewed.Results: There was no apparent sex, age, or breed predilection, but the majority were horses kept for pleasure or breeding purposes. Clinical signs varied from intermittent knuckling of the hindlimbs to paraplegia. Some horses showed no or only slow progression of signs, whereas others developed severe signs within hours. No other neurologic deficits were detected in any of the horses. Epidemiologic data and laboratory results were not supportive of an infectious etiology. The only common factor for all affected horses seemed to be feeding big bale silage or, occasionally, hay of poor microbiologic quality. Forty of the 75 horses were euthanized. Histopathologic examination of peripheral nervous tissue was performed in 22 horses, all of which had neuronal fiber degeneration. The majority of horses with mild signs recovered after 5–6 months of rest.Conclusions and Clinical Importance: Clinical signs correlated with polyneuropathy involving sciatic nerves.
Experimentally Induced Systemic Hyperchloremic Acidosis in Calves
Authors: Gentile A. , Lorenz I. , Sconza S. , Klee W. 
Published: December 2008

Background:Among the various metabolic disturbances occurring in calves affected by neonatal diarrhea or ruminal acidosis, acidemia constitutes an important condition requiring specific therapy. Although various attempts have been made to estimate the degree of metabolic acidosis on the basis of clinical signs alone, some doubts have been raised regarding the accuracy and predictive value of the clinical variables suggested.Hypothesis:The induction of metabolic acidosis in healthy calves via the infusion of hydrochloric acid (HCl) will lead to a clinical picture similar to that seen in neonatal calves with diarrhea or ruminal acidosis.Animals:The study was carried out on 15 Holstein male calves between 5 and 19 days of age.Methods:Hyperchloremic metabolic acidosis was induced over a period of 80 minutes by an IV infusion of 4,000 mL of 0.9% NaCl solution containing 400 mM HCl.Results:Acidemia occurred rapidly and increased constantly up to a maximum value, which was reached in all calves by the end of the administration and amounted to a 22.4 mM/L mean base deficit (range from 17.0 to 33.1 mM/L). Despite the relatively severe acute acid‐base imbalance during the entire observation period, no calves showed any clinical signs or depressed appetite.Conclusions and Clinical Importance:Factors other than a disturbance of the acid‐base balance should be considered to be primarily responsible for the clinical picture in calves affected by diarrhea or ruminal acidosis.
The Bone Biologic Effects of Zoledronate in Healthy Dogs and Dogs with Malignant Osteolysis
Authors: Fan T.M. , De Lorimier L.P. , Garrett L.D. , Lacoste H.I. 
Published: December 2008

Background: Malignant osteolysis is a process whereby cancer cells in concert with osteoclasts erode bone matrix. Aminobisphosphonates (NBPs) such as zoledronate induce osteoclast apoptosis and thereby decrease malignant skeletal destruction, severity of bone pain, and frequency of pathologic fracture.Hypothesis: IV‐administered zoledronate will reduce homeostatic bone turnover in healthy dogs and pathologic bone resorption in dogs diagnosed with primary and secondary bone tumors.Animals: Six healthy dogs and 20 dogs with naturally occurring primary or metastatic bone tumors were administered zoledronate IV.Methods: Prospective study: In all dogs, healthy (n = 6) and with malignant osteolysis (n = 20), the bone biologic effects of zoledronate were evaluated by quantifying changes in serum C‐telopeptide (CTx) or urine N‐telopeptide (NTx) concentrations or both. In dogs with osteosarcoma (OSA) (n = 10), serial changes in tumor relative bone mineral density (rBMD) assessed by dual‐energy x‐ray absorptiometry were used to characterize zoledronate's antiresorptive effects within the immediate tumor microenvironment. Additionally, the biochemical tolerability of zoledronate was assessed in 9 dogs receiving multiple (≥2) consecutive treatments.Results: All dogs had significant reductions in serum CTx or urine NTx concentrations or both after zoledronate administration. In a subset of dogs with appendicular OSA, reduced urine NTx concentrations and increased primary tumor rBMD coincided with improved limb usage as reported by pet owners in dogs treated with zoledronate and concurrent oral analgesics. Multiple zoledronate infusions were not associated with biochemical evidence of toxicosis.Conclusions and Clinical Importance: In dogs with skeletal neoplasms, IV‐administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.
Secondary Metabolites Produced by the Marine Bacterium
Halobacillus salinus
That Inhibit Quorum Sensing-Controlled Phenotypes in Gram-Negative Bacteria
Authors: Teasdale Margaret E. , Liu Jiayuan , Wallace Joselynn , Akhlaghi Fatemeh , Rowley David C. 
Published: December 2008

ABSTRACT

Certain bacteria use cell-to-cell chemical communication to coordinate community-wide phenotypic expression, including swarming motility, antibiotic biosynthesis, and biofilm production. Here we present a marine gram-positive bacterium that secretes secondary metabolites capable of quenching quorum sensing-controlled behaviors in several gram-negative reporter strains. Isolate C42, a
Halobacillus salinus
strain obtained from a sea grass sample, inhibits bioluminescence production by
Vibrio harveyi
in cocultivation experiments. With the use of bioassay-guided fractionation, two phenethylamide metabolites were identified as the active agents. The compounds additionally inhibit quorum sensing-regulated violacein biosynthesis by
Chromobacterium violaceum
CV026 and green fluorescent protein production by
Escherichia coli
JB525. Bacterial growth was unaffected at concentrations below 200 μg/ml. Evidence is presented that these nontoxic metabolites may act as antagonists of bacterial quorum sensing by competing with
N
-acyl homoserine lactones for receptor binding.
Production of Glucaric Acid from a Synthetic Pathway in Recombinant
Escherichia coli
Authors: Moon Tae Seok , Yoon Sang-Hwal , Lanza Amanda M. , Roy-Mayhew Joseph D. , Prather Kristala L. Jones 
Published: December 2008

ABSTRACT

A synthetic pathway has been constructed for the production of glucuronic and glucaric acids from glucose in
Escherichia coli
. Coexpression of the genes encoding
myo
-inositol-1-phosphate synthase (Ino1) from
Saccharomyces cerevisiae
and
myo
-inositol oxygenase (MIOX) from mice led to production of glucuronic acid through the intermediate
myo
-inositol. Glucuronic acid concentrations up to 0.3 g/liter were measured in the culture broth. The activity of MIOX was rate limiting, resulting in the accumulation of both
myo
-inositol and glucuronic acid as final products, in approximately equal concentrations. Inclusion of a third enzyme, uronate dehydrogenase (Udh) from
Pseudomonas syringae
, facilitated the conversion of glucuronic acid to glucaric acid. The activity of this recombinant enzyme was more than 2 orders of magnitude higher than that of Ino1 and MIOX and increased overall flux through the pathway such that glucaric acid concentrations in excess of 1 g/liter were observed. This represents a novel microbial system for the biological production of glucaric acid, a “top value-added chemical” from biomass.
Shiga Toxins, and the Genes Encoding Them, in Fecal Samples from Native Idaho Ungulates
Authors: Gilbreath Jeremy J. , Shields Malcolm S. , Smith Rebekah L. , Farrell Larry D. , Sheridan Peter P. , Spiegel Kathleen M. 
Published: December 2008

ABSTRACTCattle are a known reservoir of Shiga toxin-producingEscherichia coli. The prevalence and stability of Shiga toxin and/or Shiga toxin genes among native wild ungulates in Idaho were investigated. The frequency of both Shiga genes and toxin was similar to that reported for Idaho cattle (∼19%).
Overexpression of Wild-Type Aspartokinase Increases
l
-Lysine Production in the Thermotolerant Methylotrophic Bacterium
Bacillus methanolicus
Authors: Jakobsen Øyvind M. , Brautaset Trygve , Degnes Kristin F. , Heggeset Tonje M. B. , Balzer Simone , Flickinger Michael C. , Valla Svein , Ellingsen Trond E. 
Published: December 2008

ABSTRACT

Aspartokinase (AK) controls the carbon flow into the aspartate pathway for the biosynthesis of the amino acids
l
-methionine,
l
-threonine,
l
-isoleucine, and
l
-lysine. We report here the cloning of four genes (
asd
, encoding aspartate semialdehyde dehydrogenase;
dapA
, encoding dihydrodipicolinate synthase;
dapG
, encoding AKI; and
yclM
, encoding AKIII) of the aspartate pathway in
Bacillus methanolicus
MGA3. Together with the known AKII gene
lysC
,
dapG
and
yclM
form a set of three AK genes in this organism. Overexpression of
dapG
,
lysC
, and
yclM
increased
l
-lysine production in wild-type
B. methanolicus
strain MGA3 2-, 10-, and 60-fold (corresponding to 11 g/liter), respectively, without negatively affecting the specific growth rate. The production levels of
l
-methionine (less than 0.5 g/liter) and
l
-threonine (less than 0.1 g/liter) were low in all recombinant strains. The AK proteins were purified, and biochemical analyses demonstrated that they have similar
V
max
values (between 47 and 58 μmol/min/mg protein) and

K
m

values for
l
-aspartate (between 1.9 and 5.0 mM). AKI and AKII were allosterically inhibited by
meso
-diaminopimelate (50% inhibitory concentration [IC
50
], 0.1 mM) and by
l
-lysine (IC
50
, 0.3 mM), respectively. AKIII was inhibited by
l
-threonine (IC
50
, 4 mM) and by
l
-lysine (IC
50
, 5 mM), and this enzyme was synergistically inhibited in the presence of both of these amino acids at low concentrations. The correlation between the impact on
l
-lysine production in vivo and the biochemical properties in vitro of the individual AK proteins is discussed. This is the first example of improving
l
-lysine production by metabolic engineering of
B. methanolicus
and also the first documentation of considerably increasing
l
-lysine production by overexpression of a wild-type AK.
Inactivation of
Ascaris
Eggs in Source-Separated Urine and Feces by Ammonia at Ambient Temperatures
Authors: Nordin Annika , Nyberg Karin , Vinnerås Björn 
Published: December 2008

ABSTRACT

Sustainable management of toilet waste must prevent disease transmission but allow reuse of plant nutrients. Inactivation of uterus-derived
Ascaris suum
eggs was studied in relation to ammonia in source-separated urine without additives and in human feces to which urea had been added, in order to evaluate ammonia-based sanitation for production of safe fertilizers from human excreta. Urine was used concentrated or diluted 1:1 and 1:3 with tap water at 4, 14, 24, and 34°C. Fecal material, with and without ash, was treated with 1% or 2% (wt/wt) urea at 24 and 34°C. At 34°C eggs were inactivated in less than 10 days in urine and in amended feces. At 24°C only feces with 2% (wt/wt) urea or 1% (wt/wt) urea at high pH (10) inactivated all eggs within 1 month, and no inactivation was observed after 75 days in urine diluted 1:3 (18 ± 11 mM NH
3
). At temperatures of ≥24°C, NH
3
proved to be an efficient sanitizing agent in urine and feces at concentrations of ≥60 mM. Treating fecal material at 34°C can give a 6-log
10
egg inactivation within 1 month, whereas at 24°C 6 months of treatment is necessary for the same level of egg inactivation. At temperatures of 14°C and below, inactivation rates were low, with viable eggs after 6 months even in concentrated urine.
A 1.1-Kilobase Region Downstream of the
bin
Operon in
Bacillus sphaericus
Strain 2362 Decreases Bin Yield and Crystal Size in Strain 2297
Authors: Park Hyun-Woo , Tang Mujin , Sakano Yuko , Federici Brian A. 
Published: December 2008

ABSTRACT

The 2297 strain of
Bacillus sphaericus
produces a crystal of the Bin (binary) toxin that is approximately fourfold larger than that of strain 2362, the strain currently used in VectoLex, a commercial mosquito larvicide. Comparison of the regions downstream from the
bin
operon in these two strains showed that strain 2362 contained a 1.6-kb region with four
orf
genes not found in strain 2297. Insertion of a 1.1-kb portion of this region from strain 2362 by homologous recombination downstream from the
bin
operon in strain 2297 reduced Bin toxin production by 50 to 70% and toxicity to fourth-instar larvae of
Culex quinquefasciatus
by 68%. These results suggest that the 1.6-kb region downstream from the
bin
operon in
B. sphaericus
2362 is responsible for the lower Bin yield and smaller crystal size characteristic of this strain.
Isolation and Characterization of Intestinal
Escherichia coli
Clones from Wild Boars in Germany
Authors: Schierack Peter , Römer Antje , Jores Jörg , Kaspar Heike , Guenther Sebastian , Filter Matthias , Eichberg Jürgen , Wieler Lothar H. 
Published: December 2008

ABSTRACT

Our understanding of the composition of
Escherichia coli
populations in wild boars is very limited. In order to obtain insight into the
E. coli
microflora of wild boars, we studied
E. coli
isolates from the jejunums, ileums, and colons of 21 wild boars hunted in five geographic locations in Germany. Ten isolates per section were subjected to clonal determination using pulsed-field gel electrophoresis. One representative isolate per clone was further investigated for virulence traits, phylogenetic affiliation, and antimicrobial susceptibility. Macrorestriction analysis of 620 isolates revealed a range of clone diversity among the sections and animals, with up to 9 and 16 different clones per section and animal, respectively. Most of the clones for a given animal were shared between two adjacent intestinal sections. The overall highest clonal diversity was observed within the colon. While the
astA
gene was present in a large number of clones, other virulence genes and hemolytic ability were detected only sporadically. Clones of all four ECOR groups dominated the intestinal sections. Phylogenetic analysis and the occurrence of virulence genes correlated with the isolation frequencies for clones. All
E. coli
clones from wild boars were susceptible to all antimicrobial agents tested. In conclusion, though several parameters (including an animal-specific and highly diverse
E. coli
clone composition, the simultaneous occurrence of single clones in two adjacent intestinal sections of a given animal, and a higher
E. coli
diversity in the large intestine than in the small intestine) of
E. coli
populations of wild boars were similar to those of previously described
E. coli
populations of conventionally reared domestic pigs, our data also indicate possible differences, as seen for the
E. coli
diversity in the large intestine, the occurrence of certain virulence genes and phylogenetic groups, and antimicrobial susceptibilities.
Differential Role of Passerine Birds in Distribution of
Borrelia
Spirochetes, Based on Data from Ticks Collected from Birds during the Postbreeding Migration Period in Central Europe
Authors: Dubska Lenka , Literak Ivan , Kocianova Elena , Taragelova Veronika , Sychra Oldrich 
Published: December 2008

ABSTRACT

Borrelia
spirochetes in bird-feeding ticks were studied in the Czech Republic. During the postbreeding period (July to September 2005), 1,080 passerine birds infested by 2,240
Ixodes ricinus
subadult ticks were examined.
Borrelia garinii
was detected in 22.2% of the ticks,
Borrelia valaisiana
was detected in 12.8% of the ticks,
Borrelia afzelii
was detected in 1.6% of the ticks, and
Borrelia burgdorferi
sensu stricto was detected in 0.3% of the ticks. After analysis of infections in which the blood meal volume and the stage of the ticks were considered, we concluded that Eurasian blackbirds (
Turdus merula
), song thrushes (
Turdus philomelos
), and great tits (
Parus major
) are capable of transmitting
B. garinii
; that juvenile blackbirds and song thrushes are prominent reservoirs for
B. garinii
spirochetes; that some other passerine birds investigated play minor roles in transmitting
B. garinii
; and that the presence
B. afzelii
in ticks results from infection in a former stage. Thus, while
B. garinii
transmission is associated with only a few passerine bird species, these birds have the potential to distribute millions of Lyme disease spirochetes between urban areas.
Construction and Enhancement of a Minimal Genetic AND Logic Gate
Authors: Sayut Daniel J. , Niu Yan , Sun Lianhong 
Published: December 2008

ABSTRACT

The ability of genetic networks to integrate multiple inputs in the generation of cellular responses is critical for the adaptation of cellular phenotype to distinct environments and of great interest in the construction of complex artificial circuits. To develop artificial genetic circuits that can integrate intercellular signaling molecules and commonly used inducing agents, we have constructed an artificial genetic AND gate based on the P

luxI

quorum-sensing promoter and the
lac
repressor. The hybrid promoter exhibited reduced basal and induced expression levels but increased expression capacity, generating clear logical responses that could be described using a simple mathematical model. The model also predicted that the AND gate's logic could be improved by altering the properties of the LuxR transcriptional activator and, in particular, by increasing its rate of transcriptional activation. Following these predictions, we were able to improve the AND gate's logic by ∼1.5-fold using a LuxR mutant library generated by directed evolution, providing the first example of the use of mutant transcriptional activators to improve the logic of a complex regulatory circuit. In addition, detailed characterizations of the AND gate's responses shed light on how LuxR, LacI, and RNA polymerase interact to activate gene expression.
Enhanced Secretion of Biologically Active Murine Interleukin-12 by
Lactococcus lactis
Authors: Fernandez Antonio , Horn Nikki , Wegmann Udo , Nicoletti Claudio , Gasson Michael J. , Narbad Arjan 
Published: December 2008

ABSTRACT

The novel signal peptide SLPmod was used for the secretion of murine interleukin-12 (mIL-12) by
Lactococcus lactis
. A >4-fold increase in secretion was observed when SLPmod was used instead of the Usp45-derived secretion signal. Oral delivery of this cytokine using the autoinducible host
L. lactis
FI5876 utilizing SLPmod resulted in a significant increase in mIL-12 plasma levels in mice.
Molecular Detection, Penetrance, and Transmission of an Inherited Virus Responsible for Behavioral Manipulation of an Insect Parasitoid
Authors: Patot Sabine , Lepetit David , Charif Delphine , Varaldi Julien , Fleury Frédéric 
Published: December 2008

ABSTRACT

For insects, the prevalence of numerous vertically transmitted viruses can be high in their host populations. These viruses often have few, if any, pathological effects on their hosts, and consequently, many of them can remain unnoticed for long periods, despite their potential role in the evolution of the host phenotype. Some females of
Leptopilina boulardi
, a solitary parasitoid of
Drosophila
larvae, are infected by an inherited virus (LbFV) that manipulates the behavior of the wasp by increasing its tendency to lay eggs in a host that is already parasitized (superparasitism). This behavioral alteration allows horizontal transmission of the virus within superparasitized
Drosophila
larvae. Using suppressive subtractive hybridization with infected and uninfected lines, we identified one putative viral sequence. Based on this sequence, we developed a simple PCR test. We tested the correlation between the superparasitism phenotype and PCR amplification of the putative viral marker using several experimental conditions (including horizontal transfers) and several parasitoid genotypes. All of the results revealed that there was a perfect match between the superparasitism phenotype and the amplification profile, which validated use of the molecular marker as a tool to track the presence of the virus and provided the first genomic data for this fascinating virus. The results also show that there was very efficient horizontal and vertical transmission of LbFV, which probably explains its high prevalence in the French populations that we sampled (67 and 70% of infected females). This manipulative virus is likely to play a major role in the ecology and evolution of its parasitoid host.