bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternatives to platelet transfusions in the management of platelet dysfunction or thrombocytopenia
Authors: KICKLER THOMAS S. 
Published: September 2006

SUMMARYAlternatives to platelet transfusions are important in preventing the adverse events associated with platelet transfusions. The use of platelet alternatives has not been extensively compared with platelet transfusions, although studies suggest that bleeding can be controlled and transfusions prevented. A variety of pharmacologic agents are available, which generally work by augmenting different hemostatic mechanisms. In addition to pharmacologic agents, recombinant activated factor VII is available for controlling inherited qualitative platelet disorders such as Glanzmann’s thrombasthenia. For the treatment of chemotherapy‐induced thrombocytopenia, the use of growth factors may shorten the duration of thrombocytopenia and prove to be an approach for reducing or preventing platelet transfusions. Although interesting research has been carried out for several decades in the aim of developing a platelet substitute, it is unlikely that a platelet substitute will be available for clinical use in the near future.
Pathogen inactivation of platelets
Authors: McCULLOUGH JEFFREY 
Published: September 2006

SUMMARYThe AIDS epidemic greatly increased patients’ and the public’s fear of blood transfusion and resulted in major increased efforts to reduce the risk of transfusion‐transmitted diseases. Testing strategies have been very effective in reducing the risk of transfusion‐transmitted diseases. However, the current approaches have shortcomings: (i) they apply only to known pathogens and not to other presently unknown infectious agents; (ii) they are reactive to new transmissible diseases and thus accept that some patients may be harmed before preventive measures can be implemented; (iii) they do not prevent bacterial contamination; (iv) they do not prevent transmission of other known or unknown infectious agents; and (v) they result in an excessive loss of otherwise suitable donors. Several approaches have been developed to inactivate pathogen in cellular blood components and plasma. Two companies are developing methods that are highly effective for pathogen inactivation, and toxicities of the methods seem to be minimal and not of clinical importance. The in vitro function and in vivo effectiveness of pathogen‐inactivated platelets are clinically acceptable. These exciting developments raise the possibility of a paradigm shift in our approach to reducing the risk of transfusion‐transmitted diseases.
The assessment of platelet function
Authors: TANAKA KENICHI A. 
Published: September 2006

SUMMARYPlatelet activation is involved in physiological hemostasis and in a variety of thromboembolic events leading to stroke, myocardial ischemia, and other organ dysfunction. Apart from congenital platelet dysfunction, acquired platelet defects are increasingly common in patients due to the widespread use of antiplatelet agents. Newer antiplatelet agents targeting platelet glycoprotein IIb–IIIa and adenosine‐5′‐diphosphate receptors inhibit platelet activation, and therefore assessing platelet inhibition may be important to prevent major bleeding, especially before a surgical intervention. In the past decade, the knowledge from genotypic analyses and prospective outcome studies suggested inter‐patient variability in the therapeutic response to antiplatelet therapies, which further stresses the need for individual platelet testing. In managing bleeding patients, platelet transfusion may be better guided by the use of platelet function tests because transfusion therapy is costly and potentially harmful if administered inappropriately. Basic understanding of the hemostatic roles of platelets, etiologies of platelet defects, and characteristics of current platelet assessment methods should help physicians who manage complex coagulation issues in critically ill patients.
Current controversies about the indications for platelet transfusion with a focus on patients with hematological malignancies
Authors: COLLINS GRAHAM , MURPHY MICHAEL F. , STANWORTH SIMON J. 
Published: September 2006

SUMMARYThis article discusses current platelet transfusion practice and compliance with guidelines for platelet transfusions. It then focuses on the evidence for platelet transfusion practice in patients with hematological malignancies. In particular, the review addresses two main topics central to a policy of prophylactic platelet transfusion:1 What is the evidence to indicate if platelet transfusions should be given to prevent bleeding as compared with a strategy aimed to use platelet transfusions when bleeding occurs?2 If platelet transfusions are given to prevent bleeding, how good is the evidence to indicate what is the appropriate threshold level of platelet count?
Essential Roles of Monocytes in Stimulating Human Peripheral Blood Mononuclear Cells with
Lactobacillus casei
To Produce Cytokines and Augment Natural Killer Cell Activity
Authors: Shida Kan , Suzuki Tomomi , Kiyoshima-Shibata Junko , Shimada Shin-ichiro , Nanno Masanobu 
Published: September 2006

ABSTRACT

We examined the effect of a probiotic strain,
Lactobacillus casei
strain Shirota, on cytokine production and natural killer (NK) cell activity in human peripheral blood mononuclear cells (PBMNC). The cellular mechanisms of immunoregulation by
L. casei
strain Shirota were also investigated.
L. casei
strain Shirota stimulated PBMNC to secrete interleukin-12 (IL-12), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-10. However, depletion of monocytes from PBMNC eliminated the induction of these cytokines.
L. casei
strain Shirota was phagocytosed by monocytes and directly stimulated them to secrete IL-12, TNF-α, and IL-10. IFN-γ production was diminished by the addition of anti-IL-12 antibody to the PBMNC cultures. Purified T cells, but not NK cells, produced IFN-γ effectively when stimulated with
L. casei
strain Shirota in the presence of monocytes, indicating that monocytes triggered by
L. casei
strain Shirota help T cells to produce IFN-γ through secreting IL-12. In addition, NK cell activity and CD69 expression on NK cells increased after cultivation of PBMNC with
L. casei
strain Shirota. When monocytes were depleted from PBMNC,
L. casei
strain Shirota did not enhance NK cell activity. These results demonstrate that monocytes play critical roles in the induction of cytokines and following the augmentation of NK cell activity during the stimulation of human PBMNC with
L. casei
strain Shirota.
Stimulation of Human Monocytes with the Gram-Positive Vaccine VectorStreptococcus gordonii
Authors: Ciabattini Annalisa , Cuppone Anna Maria , Pulimeno Rita , Iannelli Francesco , Pozzi Gianni , Medaglini Donata 
Published: September 2006

ABSTRACTStreptococcus gordoniiis a bacterial vaccine vector which has previously been shown to activate dendritic cells in vitro and to induce local and systemic immune responses in vivo. In the present study, human monocytes (THP-1 cell line and peripheral blood monocytes) were characterized following interaction withS. gordonii. Treatment of human monocytes withS. gordoniibut not latex beads induced a clear up-regulation of CD83, CD40, CD80, and CD54 and the down-regulation of CD14. Furthermore, bacterial treatment stimulated an increased expression of Toll-like receptor 5 (TLR5), TLR6, and TLR7, production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta, and reduction of the phagocytic activity. This work shows that the immunostimulatory activity ofS. gordoniiis not restricted to induction of dendritic-cell maturation but also affects the differentiation process of human monocytes.
Development and Validation of a Fourfold Multiplexed Opsonization Assay (MOPA4) for Pneumococcal Antibodies
Authors: Burton Robert L. , Nahm Moon H. 
Published: September 2006

ABSTRACT

Opsonophagocytic killing assays (OPAs) are essential for developing and improving pneumococcal vaccines. There is a need for a high-throughput, reliable, standardized, and fully characterized OPA for pneumococcal antibodies. To meet the need, we have developed and characterized a fourfold multiplexed OPA (MOPA4) against 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) of pneumococci. Thirteen target bacteria were made resistant to only one of the following antibiotics: optochin, streptomycin, spectinomycin, and trimethoprim. Following optimization of assay conditions, accuracy of MOPA4 was determined by testing 30 sera from old adults in the MOPA4 and the single-serotype assays. The opsonization titers obtained with both assays agreed well (
r
2
> 0.95). Although 22 (out of 390; ∼6%) results differed more than twofold, the differences were not reproducible. The assay was specific: preabsorbing test sera with homologous polysaccharide (PS) completely abrogated opsonic activity, but a pool of unrelated PS (5 μg/ml of each) had no effect. Intra- and interassay coefficients of variation were 10 and 22%, respectively. MOPA4 results were unaffected by having different target pneumococcal serotypes in each assay group. Also, HL60 cell-to-bacteria ratios could be varied twofold without affecting the results. We conclude that MOPA4 is sensitive, accurate, specific, precise, and robust enough for large-scale clinical studies. Furthermore, MOPA4 should allow evaluation of multivalent pneumococcal vaccines with the limited volume of serum typically available from young children.
Unique Model of Dormant Infection for Tuberculosis Vaccine Development
Authors: Kashino Suely S. , Ovendale Pamela , Izzo Angelo , Campos-Neto Antonio 
Published: September 2006

ABSTRACTMost individuals exposed toMycobacterium tuberculosisbecome infected but hinder the infectious process in dormant foci, known as latent tuberculosis. This limited infection usually stimulates strong T-cell responses, which provide lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant ofMycobacterium tuberculosisrecapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of α-crystallin. Mice challenged with the mutant and inoculated with streptomycin for ∼3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses toM. tuberculosisantigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulentM. tuberculosis. Therefore, infection of mice or other animals (e.g., guinea pigs) withM. tuberculosisstrain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of anM. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine.
Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against
Haemophilus influenzae
Type b in Human Adult Volunteers
Authors: Toraño Gilda , Toledo Maria E. , Baly Alberto , Fernandez-Santana Violeta , Rodriguez Francisco , Alvarez Yunia , Serrano Teresita , Musachio Alexis , Hernandez Ibis , Hardy Eugenio , Rodríguez Arlene , Hernandez Hector , Aguilar Aristides , Sánchez Raydel , Diaz Manuel , Muzio Verena , Dfana Jorgelina , Rodríguez Maria C. , Heynngnezz Lazaro , Verez-Bencomo Vicente 
Published: September 2006

ABSTRACT

Since 1989, we have been involved in the development of a vaccine against
Haemophilus influenzae
type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.
Isolation of High-Affinity Single-Chain Antibodies against
Mycobacterium avium
subsp.
paratuberculosis
Surface Proteins from Sheep with Johne's Disease
Authors: Berger Sven , Hinz Dominik , Bannantine John P. , Griffin J. Frank T. 
Published: September 2006

ABSTRACT

Johne's disease, caused by infection with
Mycobacterium avium
subsp.
paratuberculosis
, causes significant economic losses to the livestock farming industry. Improved investigative and diagnostic tools—necessary to understand disease processes and to identify subclinical infection—are much sought after. Here, we describe the production of single-chain antibodies with defined specificity for
M. avium
subsp.
paratuberculosis
surface proteins. Single-chain antibodies (scFv) were generated from sheep with Johne's disease by cloning heavy-chain and lambda light-chain variable regions and expressing these in fusion with gene III of filamentous phages. Two scFv clones (designated SurfS1.2 and SurfS2.2) were shown to be immunoreactive against
M. avium
subsp.
paratuberculosis
surface targets by flow cytometry, and immunoblotting identified specificity for a 34-kDa proteinase-susceptible determinant. Both antibodies were cross-reactive against
Mycobacterium avium
subsp.
avium
but nonreactive against
Mycobacterium bovis
or
Mycobacterium phlei
cells and were shown to be capable of enriching
M. avium
subsp.
paratuberculosis
cells by a factor of approximately 10
6
-fold when employed in magnetic bead separation of mixed
Mycobacterium
sp. cultures. Further, magnetic bead separation using SurfS1.2 and SurfS2.2 was capable of isolating as few as 10
3
M. avium
subsp.
paratuberculosis
cells from ovine fecal samples, indicating the diagnostic potential of these reagents. Finally, inclusion of SurfS1.2 or SurfS2.2 in in vitro broth culture with
M. avium
subsp.
paratuberculosis
indicated that surface binding activity did not impede bacterial growth, although colony clumping was prevented. These results are discussed in terms of the potential use of single-chain phage display monoclonal antibodies as novel diagnostic reagents.
The Selective Value of Bacterial Shape
Authors: Young Kevin D. 
Published: September 2006

SUMMARY
Why do bacteria have shape? Is morphology valuable or just a trivial secondary characteristic? Why should bacteria have one shape instead of another? Three broad considerations suggest that bacterial shapes are not accidental but are biologically important: cells adopt uniform morphologies from among a wide variety of possibilities, some cells modify their shape as conditions demand, and morphology can be tracked through evolutionary lineages. All of these imply that shape is a selectable feature that aids survival. The aim of this review is to spell out the physical, environmental, and biological forces that favor different bacterial morphologies and which, therefore, contribute to natural selection. Specifically, cell shape is driven by eight general considerations: nutrient access, cell division and segregation, attachment to surfaces, passive dispersal, active motility, polar differentiation, the need to escape predators, and the advantages of cellular differentiation. Bacteria respond to these forces by performing a type of calculus, integrating over a number of environmental and behavioral factors to produce a size and shape that are optimal for the circumstances in which they live. Just as we are beginning to answer how bacteria create their shapes, it seems reasonable and essential that we expand our efforts to understand why they do so.
Genetics ofStreptomyces rimosus, the Oxytetracycline Producer
Authors: Petković Hrvoje , Cullum John , Hranueli Daslav , Hunter Iain S. , Perić-Concha Nataša , Pigac Jasenka , Thamchaipenet Arinthip , Vujaklija Dušica , Long Paul F. 
Published: September 2006

SUMMARYFrom a genetic standpoint,Streptomyces rimosusis arguably the best-characterized industrial streptomycete as the producer of oxytetracycline and other tetracycline antibiotics. Although resistance to these antibiotics has reduced their clinical use in recent years, tetracyclines have an increasing role in the treatment of emerging infections and noninfective diseases. Procedures for in vivo and in vitro genetic manipulations inS. rimosushave been developed since the 1950s and applied to study the genetic instability ofS. rimosusstrains and for the molecular cloning and characterization of genes involved in oxytetracycline biosynthesis. Recent advances in the methodology of genome sequencing bring the realistic prospect of obtaining the genome sequence ofS. rimosusin the near term.
The Bacterial Cytoskeleton
Authors: Shih Yu-Ling , Rothfield Lawrence 
Published: September 2006

SUMMARYIn recent years it has been shown that bacteria contain a number of cytoskeletal structures. The bacterial cytoplasmic elements include homologs of the three major types of eukaryotic cytoskeletal proteins (actin, tubulin, and intermediate filament proteins) and a fourth group, the MinD-ParA group, that appears to be unique to bacteria. The cytoskeletal structures play important roles in cell division, cell polarity, cell shape regulation, plasmid partition, and other functions. The proteins self-assemble into filamentous structures in vitro and form intracellular ordered structures in vivo. In addition, there are a number of filamentous bacterial elements that may turn out to be cytoskeletal in nature. This review attempts to summarize and integrate the in vivo and in vitro aspects of these systems and to evaluate the probable future directions of this active research field.
The Morbidity Associated with Osteochondral Harvest from Asymptomatic Knees for the Treatment of Osteochondral Lesions of the Talus
Authors: Reddy Sudheer , Pedowitz David I. , Parekh Selene G. , Sennett Brian J. , Okereke Enyi 
Published: September 2006

Background Mosaic autogenous osteochondral transplantation has been used to treat large osteochondral defects. Hypothesis There is potential, previously unrecognized donor-site morbidity associated with osteochondral harvest from asymptomatic knees for the treatment of talar osteochondral defect lesions. Study Design Case series; Level of evidence, 4. Methods Fifteen patients underwent mosaic osteochondral transplantation to treat a talar osteochondral defect lesion, with 11 patients available for follow-up. A Lysholm knee score was used to assess donor-site morbidity at a mean follow-up of 47 months (range, 7-77 months). Mean age was 29 years (range, 21-44 years). A single surgical team performed the mosaicplasties. Significance was determined using the Student t test. Results All patients had asymptomatic knees preoperatively. Mean postoperative Lysholm score was 81 (range, 49-100). By Lysholm criteria, 5 rated as excellent, 2 as good, and 4 as poor. No significant difference was detected in terms of the harvest method or the number of grafts obtained from those having an excellent rating versus those having a good/poor rating. Patients rated as good/poor cited knee instability in daily activities as the most common problem. One had knee pain and patellar instability after osteochondral harvest by lateral arthrotomy that required a subsequent lateral retinacular release and tibial tubercle osteotomy. Conclusion This study demonstrates that donor-site morbidity after osteochondral harvest can be significant. In this population, those who experienced a decline in knee function had problems performing activities of daily living. When performing these procedures, the authors recommend that surgeons consider these risks and discuss them with their patients.
Hydrogel Meniscal Replacement in the Sheep Knee
Authors: Kelly Bryan T. , Robertson William , Potter Hollis G. , Deng Xiang-Hua , Turner A. Simon , Lyman Stephen , Warren Russell F. , Rodeo Scott A. 
Published: September 2006

Background Meniscal allograft transplantation has become a viable surgical alternative for a select group of patients with deficient or irreparable menisci. Subjective results are encouraging; long-term success, durability, and safety of allograft meniscal transplantation are uncertain. Purposes To evaluate a novel hydrogel meniscal replacement implant in an ovine model and assess chondroprotective effects of this hydrogel meniscal replacement using several validated outcome measures. Study Design Controlled laboratory study. Methods Fourteen skeletally mature sheep underwent hydrogel meniscal replacement; 45 additional animals had previously undergone 1 of 3 operations: lateral meniscectomy (24), meniscal allograft transplant (17), and sham (4). Animals were sacrificed at 2, 4, or 12 months. Cartilage was assessed by magnetic resonance imaging, gross inspection, biomechanical testing, and semiquantitative histological analysis. Results There were no differences between the sham operation and nonoperated control limbs. Compared with meniscectomy, hydrogel meniscal replacement resulted in significantly decreased cartilage degeneration with all outcome parameters (P < .05). Compared with nonoperated control limbs, hydrogel meniscal replacements demonstrated no significant differences at 2 months in any category. By 4 months, hydrogel limbs demonstrated significantly greater cartilage degeneration than did nonoperated control limbs in all categories. Compared with meniscal allograft transplantation animals, hydrogel meniscal replacements demonstrated no differences at 2 months but had significantly increased cartilage degeneration in the peripheral zone of the tibial plateau at 4 months (P < .05). At 1 year, all hydrogel implants had developed complete radial splits in the posterior third of the implant. Conclusion Although promising preliminary results for hydrogel meniscal replacement were seen at early time points, significant cartilage degeneration and implant failure were seen at 1 year, and overall performance was worse than was allograft transplantation. Improvements in hydrogel material properties and surface characteristics and more accurate size matching may improve outcomes. Clinical Relevance Improvements in the hydrogel material properties and surface characteristics and more accurate size matching may lead to the use of hydrogel implants in humans.