bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD)
Authors: Haberichter Sandra L. , Castaman Giancarlo , Budde Ulrich , Peake Ian , Goodeve Anne , Rodeghiero Francesco , Federici Augusto B. , Batlle Javier , Meyer Dominique , Mazurier Claudine , Goudemand Jenny , Eikenboom Jeroen , Schneppenheim Reinhard , Ingerslev Jorgen , Vorlova Zdena , Habart David , Holmberg Lars , Lethagen Stefan , Pasi John , Hill Frank G. H. , Montgomery Robert R. 
Published: March 2008

AbstractThe decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth
Authors: Qiang Ya-Wei , Shaughnessy John D. , Yaccoby Shmuel 
Published: March 2008

AbstractCanonical Wnt signaling is central to normal bone homeostasis, and secretion of Wnt signaling inhibitors by multiple myeloma (MM) cells contributes to MM-related bone resorption and disease progression. The aim of this study was to test the effect of Wnt3a on bone disease and growth of MM cells in vitro and in vivo. Although Wnt3a activated canonical signaling in the majority of MM cell lines and primary cells tested, Wnt3a had no effect on MM cell growth in vitro. Moreover, forced expression of Wnt3a in H929 MM cells conferred no growth advantage over empty vector-transfected cells in vitro or importantly when grown subcutaneously in severe combined immunodeficient (SCID) mice. Importantly, although H929 cells stably expressing an empty vector injected into human bone grew rapidly and induced a marked reduction in bone mineral density, bones engrafted with Wnt3a-expressing H929 cells were preserved, exhibited increased osteoblast-to-osteoclast ratios, and reduced tumor burden. Likewise, treatment of myelomatous SCID-hu mice, carrying primary disease, with recombinant Wnt3a stimulated bone formation and attenuated MM growth. These results provide further support of the potential anabolic and anti-MM effects of enhancing Wnt signaling in the bone.
Protein Z–dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency
Authors: Zhang Jing , Tu Yizheng , Lu Lan , Lasky Nina , Broze George J. 
Published: March 2008

Abstract
Protein Z (PZ) is a plasma vitamin K–dependent protein that functions as a cofactor to dramatically enhance the inhibition of coagulation factor Xa by the serpin, protein Z–dependent protease inhibitor (ZPI). In vitro, ZPI not only inhibits factor Xa in a calcium ion–, phospholipid-, and PZ-dependent fashion, but also directly inhibits coagulation factor XIa. In murine gene-deletion models, PZ and ZPI deficiency enhances thrombosis following arterial injury and increases mortality from pulmonary thromboembolism following collagen/epinephrine infusion. On a factor VLeiden genetic background, ZPI deficiency produces a significantly more severe phenotype than PZ deficiency, implying that factor XIa inhibition by ZPI is physiologically relevant. The studies in mice suggest that human PZ and ZPI deficiency would be associated with a modest thrombotic risk with ZPI deficiency producing a more severe phenotype.
Basal secretion of von Willebrand factor from human endothelial cells
Authors: Giblin Jonathan P. , Hewlett Lindsay J. , Hannah Matthew J. 
Published: March 2008

AbstractEndothelial cells store the adhesive glycoprotein von Willebrand factor (VWF) in Weibel-Palade bodies (WPBs), distinctively shaped regulated secretory organelles that undergo exocytosis in response to secretagogue. A significant proportion of newly synthesized VWF is also secreted spontaneously from nonstimulated cells, through what is thought to be the constitutive secretory pathway. To learn more about VWF trafficking, we performed kinetic analyses of the storage and nonstimulated secretion of VWF in cultured human endothelial cells. We found that most VWF was secreted through a route that was significantly delayed compared with constitutive secretion, although this pathway was responsible for secretion of a small amount of uncleaved VWF precursor. Disruption of pH-dependent sorting processes with ammonium chloride converted the secretion kinetics of mature VWF to that of its precursor. Conversely, preventing constitutive secretion of nascent protein with brefeldin A had only a modest effect on the spontaneous release of VWF, showing that most VWF secreted by nonstimulated cells was not constitutive secretion but basal release of a post-Golgi storage organelle, presumably the WPB. These data suggest that VWF is sorted to the regulated secretory pathway in endothelial cells much more efficiently than previously reported.
Multi locus sequence typing of Chlamydiales: clonal groupings within the obligate intracellular bacteria Chlamydia trachomatis
Authors: Pannekoek Yvonne , Morelli Giovanna , Kusecek Barica , Morré Servaas A , Ossewaarde Jacobus M , Langerak Ankie A , van der Ende Arie 
Published: March 2008

Abstract

Background
The obligate intracellular growing bacterium Chlamydia trachomatis causes diseases like trachoma, urogenital infection and lymphogranuloma venereum with severe morbidity. Several serovars and genotypes have been identified, but these could not be linked to clinical disease or outcome. The related Chlamydophila pneumoniae, of which no subtypes are recognized, causes respiratory infections worldwide. We developed a multi locus sequence typing (MLST) scheme to understand the population genetic structure and diversity of these species and to evaluate the association between genotype and disease.

Results
A collection of 26 strains of C. trachomatis of different serovars and clinical presentation and 18 strains of C. pneumoniae were included in the study. For comparison, sequences of C. abortus, C. psittaci, C. caviae, C. felis, C. pecorum (Chlamydophila), C. muridarum (Chlamydia) and of Candidatus protochlamydia and Simkania negevensis were also included. Sequences of fragments (400 – 500 base pairs) from seven housekeeping genes (enoA, fumC, gatA, gidA, hemN, hlfX, oppA) were analysed. Analysis of allelic profiles by eBurst revealed three non-overlapping clonal complexes among the C. trachomatis strains, while the C. pneumoniae strains formed a single group. An UPGMA tree produced from the allelic profiles resulted in three groups of sequence types. The LGV strains grouped in a single cluster, while the urogenital strains were distributed over two separated groups, one consisted solely of strains with frequent occurring serovars (E, D and F). The distribution of the different serovars over the three groups was not consistent, suggesting exchange of serovar encoding ompA sequences. In one instance, exchange of fumC sequences between strains of different groups was observed. Cluster analyses of concatenated sequences of the Chlamydophila and Chlamydia species together with those of Candidatus Protochlamydia amoebophila and Simkania negevensis resulted in a tree identical to that obtained with 23S RNA gene sequences.

Conclusion
These data show that C. trachomatis and C. pneumoniae are highly uniform. The difference in genetic diversity between C. trachomatis and C. pneumoniae is in concordance with a later assimilation to the human host of the latter. Our data supports the taxonomy of the order of Chlamydiales.
Drug 9AA reactivates p21/Waf1 and Inhibits HIV-1 progeny formation
Authors: Wu Weilin , Kehn-Hall Kylene , Pedati Caitlin , Zweier Lynnsey , Castro Iris , Klase Zachary , Dowd Cynthia S , Dubrovsky Larisa , Bukrinsky Michael , Kashanchi Fatah 
Published: March 2008

Abstract
It has been demonstrated that the p53 pathway plays an important role in HIV-1 infection. Previous work from our lab has established a model demonstrating how p53 could become inactivated in HIV-1 infected cells through binding to Tat. Subsequently, p53 was inactivated and lost its ability to transactivate its downstream target gene p21/waf1. P21/waf1 is a well-known cdk inhibitor (CKI) that can lead to cell cycle arrest upon DNA damage. Most recently, the p21/waf1 function was further investigated as a molecular barrier for HIV-1 infection of stem cells. Therefore, we reason that the restoration of the p53 and p21/waf1 pathways could be a possible theraputical arsenal for combating HIV-1 infection. In this current study, we show that a small chemical molecule, 9-aminoacridine (9AA) at low concentrations, could efficiently reactivate p53 pathway and thereby restoring the p21/waf1 function. Further, we show that the 9AA could significantly inhibit virus replication in activated PBMCs, likely through a mechanism of inhibiting the viral replication machinery. A mechanism study reveals that the phosphorylated p53ser15 may be dissociated from binding to HIV-1 Tat protein, thereby activating the p21/waf1 gene. Finally, we also show that the 9AA-activated p21/waf1 is recruited to HIV-1 preintegration complex, through a mechanism yet to be elucidated.
Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production
Authors: Osorio Yaneth , Bonilla Diana L , Peniche Alex G , Melby Peter C , Travi Bruno L 
Published: March 2008

AbstractThe maintenance of host defense during pregnancy may depend on heightened innate immunity. We evaluated the immune response of pregnant hamsters during early infection with Leishmania (Viannia) panamensis, a cause of American cutaneous leishmaniasis. At 7 days post-infection, pregnant animals showed a lower parasite burden compared with nonpregnant controls at the cutaneous infection site (P=0.0098) and draining lymph node (P=0.02). Resident peritoneal macrophages and neutrophils from pregnant animals had enhanced Leishmania killing capacity compared with nonpregnant controls (P=0.018 each). This enhanced resistance during pregnancy was associated with increased expression of inducible NO synthase (iNOS) mRNA in lymph node cells (P=0.02) and higher NO production by neutrophils (P=0.0001). Macrophages from nonpregnant hamsters infected with L. panamensis released high amounts of NO upon estrogen exposure (P=0.05), and addition of the iNOS inhibitor L-N6-(1-iminoethyl) lysine blocked the induction of NO production (P=0.02). Infected, nonpregnant females treated with estrogen showed a higher percentage of cells producing NO at the infection site than controls (P=0.001), which correlated with lower parasite burdens (P=0.036). Cultured macrophages or neutrophils from estrogen-treated hamsters showed significantly increased NO production and Leishmania killing compared with untreated controls. iNOS was identified as the likely source of estrogen-induced NO in primed and naïve macrophages, as increased transcription was evident by real-time PCR. Thus, the innate defense against Leishmania infection is heightened during pregnancy, at least in part as a result of estrogen-mediated up-regulation of iNOS expression and NO production.
Behavior of Singlet Oxygen in Vitamin E Emulsion
Authors: Ohara Keishi , Origuchi Takashi , Kawanishi Kanako , Nagaoka Shin-ichi 
Published: March 2008

Abstract
The decay rate constant of the phosphorescence of singlet oxygen (1O2) was measured in a vitamin E (VE) emulsion system by single-photon counting. The results suggest that the 1O2 emission mainly occurs around the oil droplets of VE rather than in the bulk solution.
Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy
Authors: Bailey Kerry Smith , Dewey Curtis W. , Boothe Dawn M. , Barone Georgina , Kortz Gregg D. 
Published: March 2008

Abstract
Objective—To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy.
Design—Open-label, noncomparative clinical trial.
Animals—12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital.
Procedures—Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded.
Results—Median maximum serum levetiracetam concentration was 25.5 μg/mL, median minimum serum levetiracetam concentration was 8.3 μg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of ≥ 50%). Two cats had transient lethargy and inappetence.
Conclusions and Clinical Relevance—Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.
Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs
Authors: Davis Michael S. , Davis William C. , Ensign Wayne Y. , Hinchcliff Kenneth W. , Holbrook Todd C. , Williamson Katherine K. 
Published: March 2008

Abstract
Objective—To determine the effects of training and sustained submaximal exercise on hematologic values in racing sled dogs.
Design—Cohort study.
Animals—39 Alaskan sled dogs bred for endurance racing.
Procedures—Blood samples were collected prior to initiation of a 7-month training regimen (n = 39), after completion of the training regimen (19), and after completion of an 1,100-mile race (9), and a CBC, differential cell count, and flow cytometry for leukocyte surface antigens were performed.
Results—Both training and exercise caused significant decreases in PCV and hemoglobin concentration and significant increases in total WBC count. In contrast, training and exercise were not found to have significant effects on absolute numbers or fractions of CD4+ or CD8+ lymphocytes, other than a significant increase in the fraction of CD8+ lymphocytes associated with training.
Conclusions and Clinical Relevance—Results suggested that training and exercise induced changes in several hematologic values in racing sled dogs. Extracellular fluid volume expansion was the likely explanation for the training-induced decrease in PCV, and acute blood loss secondary to gastrointestinal tract bleeding was likely responsible for the decrease in PCV associated with acute exercise.
Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma
Authors: Simon Daniela , Moreno Sol Naranjo , Hirschberger Johannes , Moritz Andreas , Kohn Barbara , Neumann Stephan , Jurina Konrad , Scharvogel Stefan , Schwedes Claudia , Reinacher Manfred , Beyerbach Martin , Nolte Ingo 
Published: March 2008

Abstract
Objective—To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin.
Design—Nonrandomized controlled clinical trial.
Animals—114 dogs with lymphoma.
Procedures—Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n = 87) or doxorubicin alone (27).
Results—63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage ≤ and dogs with a high BUN concentration at the time of initial diagnosis were significantly less likely to have a complete remission. No significant difference in remission or survival time could be demonstrated between treatment groups. Incidence of hematologic and gastrointestinal tract toxicoses did not differ between treatment groups, with the exception that vomiting was more common among dogs treated with the multiagent protocol.
Conclusions and Clinical Relevance—In this population of dogs, we were not able to identify any significant difference in remission or survival times between dogs with lymphoma treated with a continuous, multiagent chemotherapeutic protocol and dogs treated with a short-term single-agent protocol involving doxorubicin.
Arthropathy caused by a lead bullet in a dog
Authors: Barry Sabrina L. , Lafuente M. Pilar , Martinez Steven A. 
Published: March 2008

Abstract
Case Description—A 3-year-old spayed female Labrador Retriever was evaluated for progressive lameness of the left forelimb 21 months after being shot in the elbow with a lead bullet.
Clinical Findings—Physical examination findings were consistent with moderate osteoarthritis of the left elbow joint. Orthogonal radiographic views of the elbow revealed multiple metallic fragments in and around the joint space as well as signs of osteoarthritis.
Treatment and Outcome—The elbow joint was evaluated arthroscopically. A lead-based bullet fragment was seen in the lateral synovial compartment and removed in multiple pieces. Excess fibrin and synovium were removed, and microfractures were created in exposed subchondral bone to stimulate neovascularization and fibrocartilage formation. In a follow-up telephone conversation 4 months after surgery, the owner reported a marked improvement in the lameness.
Clinical Relevance—Removal of lead intra-articular foreign bodies may be indicated even if the material is not believed to mechanically interfere with joint motion.
Comparison of tibial plateau angles in dogs with unilateral versus bilateral cranial cruciate ligament rupture: 150 cases (2000–2006)
Authors: Cabrera Sady Y. , Owen Tina J. , Mueller Maureen G. , Kass Philip H. 
Published: March 2008

Abstract
Objective—To compare tibial plateau angle (TPA) in dogs with unilateral versus bilateral cranial cruciate ligament (CCL) rupture, to compare right versus left TPA in dogs with bilateral CCL rupture, and to determine whether TPA can be used to predict whether a dog with unilateral CCL rupture would subsequently rupture the contralateral CCL.
Design—Retrospective case series.
Animals—150 dogs with unilateral (n = 58) or bilateral (92) CCL rupture.
Procedures—Medical records were reviewed and TPA was recorded. Dogs with unilateral CCL rupture that were not known to have ruptured the contralateral ligament were followed up for a minimum of 2 years.
Results—Dogs with unilateral CCL rupture were significantly older (median, 7.0 years) than dogs with bilateral CCL rupture (median, 4.5 years). Median TPA for dogs with unilateral CCL rupture (26°) was not significantly different from median TPA for dogs with bilateral rupture (27° in both the right and left limbs), and right and left TPAs were not significantly different in dogs with bilateral CCL rupture. There was no correlation between TPA and the time interval between diagnosis of the initial and subsequent CCL ruptures in dogs with bilateral CCL rupture.
Conclusion and Clinical Relevance—Results suggested that TPA in the range studied (mostly < 35°) was not a useful predictor of contralateral CCL rupture among dogs with unilateral CCL rupture, although age may be a risk factor for development of bilateral CCL rupture. The incidence of bilateral CCL rupture may be higher than previously reported.
Relationship between Doppler blood pressure and survival or response to treatment in critically ill cats: 83 cases (2003–2004)
Authors: Silverstein Deborah C. , Wininger Fred A. , Shofer Frances S. , King Lesley G. 
Published: March 2008

Abstract
Objective—To evaluate the relationship between Doppler blood pressure (DBP) and survival or response to treatment in critically ill cats.
Design—Retrospective case series.
Animals—83 cats.
Procedures—Medical records from cats admitted to the intensive care unit with at least 2 recorded DBP measurements were included in the study. Hypotension was defined as 1 or more DBP measurements d 90 mm Hg. Change in blood pressure, survival to hospital discharge, heart rate, rectal temperature, PCV, plasma pH, serum ionized calcium concentration, disease process, body weight, age, duration of hospitalization, and catecholamine treatment were also evaluated.
Results—39 cats were included in the hypotensive group, and 44 were consistently normotensive. Overall survival rate was 53% (44/83), with a significantly higher mortality rate in the hypotensive group (64% vs 32%). Among other variables, only low rectal temperature and low PCV were significantly associated with hypotension. Hypotensive cats with an increase in blood pressure of ≥ 20 mm Hg during hospitalization were more likely to survive to discharge (mortality rate, 69% vs 17%).
Conclusions and Clinical Relevance—Hypotensive cats had increased mortality rate with lower rectal temperatures and lower PCV, compared with normotensive critically ill cats. The implications of these findings with regard to treatment remain to be elucidated, but addressing these abnormalities may be appropriate.