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Biomedical subjects

P K Baker

Publications and source records attributed to P K Baker.

13 recordsLinked to original sources
PubMed1994

Hairy cell interactions with extracellular matrix: expression of specific integrin receptors and their role in the cell's response to specific adhesive proteins.

Integrin/extracellular-matrix interactions are central to the migration, localization, and subsequent function of lymphocytes within tissues. In hairy cell leukemia (HCL) the malignant cells display a highly characteristic tissue distribution in which interactions with extracellular matrix (ECM) are often prominent. Therefore, we used HCL as a model in which to investigate the poorly understood integrin/ECM interactions that underlie the migratory behavior of malignant B lymphocytes. Using a combined approach involving immunocytochemistry, flow cytometry, and immunoprecipitation analysis, hairy cells (HCs) were shown to have a consistent and distinctive phenotype (mainly alpha 4 beta 1, alpha 5 beta 1, alpha v beta 1, and alpha v beta 3). Furthermore, functional studies utilising adhesion assays, time-lapse video-microscopy and image analysis showed that the HCs displayed very specific adhesive behaviour in response to relevant adhesive protein ligands. HCs were able to adhere to different extents on all the adhesive proteins examined, but, on laminin and collagen, binding was weak with little cytoplasmic spreading. In contrast, the cells showed strong adhesion both to fibronectin (FN) and to vitronectin (VN). On FN, the cells spread extensively with nonpolarized cytoplasmic projections, whereas on VN cytoplasmic projections were markedly polarized. This polarized morphology was shown to reflect cell motility. Investigation of the role of individual integrin receptors in the cell movement response suggested that alpha v beta 3 is the major integrin responsible for this motile behavior. These results are discussed in relation to the limited previous data on leukemic and activated B-cell integrins, and we suggest that the HC integrins play a significant role in the characteristic behavior of HCs within tissues.

Actin Cytoskeleton↗
PubMed1994

The function of c-fms in hairy-cell leukemia: macrophage colony-stimulating factor stimulates hairy-cell movement.

Hairy cells (HCs) and some activated B cells express high levels of macrophage colony-stimulating factor (M-CSF) (CSF-1) receptor, but the functional effects of the cytokine on B cells have not been previously identified. Using video microscopy, image analysis, and migration assays, M-CSF was shown to induce chemokinetic and chemotactic movement of HCs. This movement response involved transition to a highly mobile, rounded cell form and was accompanied by distinctive changes in F-actin polymerization and distribution. Furthermore, the M-CSF-induced motility was substantially modified by the adhesive protein used as a substratum and involved qualitative changes in the function of the alpha v beta 3 integrin of HCs. It is suggested that the findings are relevant to the pathophysiology of hairy-cell leukemia (HCL) in particular, and to the biology of B-cell migration in general.

Actins↗
PubMed1994

Autologous bone marrow transplantation for myeloma patients using PNA- and CD19-purged marrow rescue.

A new method of in vitro bone marrow purging using a lectin and monoclonal antibody in combination has been used for the first time in vivo. Two patients with advanced myeloma were treated with high-dose melphalan and total body irradiation and then rescued with autologous bone marrow which had been purged in vitro to remove malignant cells by using a combination of a plasma cell-binding lectin (peanut agglutinin, PNA) and the anti-B lymphocyte monoclonal antibody anti-CD19, bound to magnetised microspheres. Both patients showed rapid engraftment of the purged bone marrow and remain well 36 and 46 months later with normal bone marrow morphology, although one patient still has a low level of circulating paraprotein. This is a promising form of therapy for what has been an invariably fatal condition.

Adult↗
PubMed1993

Musculoskeletal origins of chronic pelvic pain. Diagnosis and treatment.

Musculoskeletal dysfunctions often contribute to the signs and symptoms of chronic pelvic pain and in many cases may be the primary cause. The traditional team approach to chronic pelvic pain has not, however, routinely included a practitioner skilled in musculoskeletal examination and treatment. Characteristics of musculoskeletal pain are reviewed as are specific dysfunctions commonly found to produce lower abdominal and pelvic floor pain. A screening examination is presented to assist the gynecologic physician in identifying patients who may benefit from physical therapy.

Adolescent↗
PubMed1992

Effective concentration of bone marrow mononuclear cells using density gradient separation within an automated cell separator.

An effective method for concentrating bone marrow is described. Concentration was achieved using an intermittent flow cell separator. Elimination of mature haemopoietic cells was enhanced by the addition of a density separation medium (Ficoll-metrizoate) which was then removed by washing. All procedures were undertaken using the cell separator, this allowed for standardization of procedure and less manipulation which is associated with enhanced mononuclear cell recovery and less risk of microbial contamination. Mature granulocytes were depleted by 86.8% and red cells by 97.7% whilst mononuclear cells showed a 49% recovery. Marrows processed in this way and subsequently purged and/or cyropreserved were shown to successfully engraft when reinfused.

Bone Marrow Transplantation↗
PubMed1992

A method for clinical purging of myeloma bone marrow using peanut agglutinin as an anti-plasma cell agent, in combination with CD19 monoclonal antibody.

Previous studies have shown that the lectin peanut agglutinin (PNA) binds bone marrow plasma cells in the majority of patients with myeloma and does not bind to normal haemopoietic progenitors. This lectin has been used in combination with anti-CD19 monoclonal antibody (moAb) in a system for purging myeloma bone marrow. This has now been scaled up for application to ex vivo treatment of large volumes of bone marrow suitable for autologous bone marrow transplantation. Four bone marrow harvests from patients with myeloma containing 9.5 +/- 4.9% plasma cells were depleted of erythrocytes and mature granulocytes by Ficoll separation using the Haemonetics V50 cell separator. The mononuclear fraction was then purged with magnetic beads coated with PNA and anti-CD19 moAb. The system proved highly efficient with removal of all detectable plasma cells and CD19+ cells. Average mononuclear cell recovery following purging was 71% of the concentrated marrow with 78% yield of CFU-GM. Normal progenitor recovery related to patients' weight is predicted to be adequate for haemopoietic reconstitution following ablative chemoradiotherapy. This system is therefore feasible for large-scale clinical purging.

Adult↗
PubMed1991

Continuous flow cell separator use for bone marrow processing.

Many techniques have been described for processing bone marrow prior to transplantation, purging or cryopreservation. Effective techniques incorporate centrifugation and, or, density separation to produce an ideal marrow concentrate. We report on the use of a continuous flow cell separator (COBE Spectra) for marrow processing. Preliminary results indicate that the improved technology incorporated in this machine together with the new algorithm control of its collection functions allows for rapid collection of an ideal marrow concentrate. The addition of an inert sedimenting agent prior to processing enhances differential mononuclear cell collection and elimination of red blood cells and granulocytes. By this technique a volume depletion of 87% was achieved with recovery of 76.4% mononuclear cells and 86.5% CFU-GM progenitor cells. Marrow processed in this manner has been successfully transplanted; patients receiving such marrow show no delay in engraftment and their grafts have been sustained.

Bone Marrow Cells↗
PubMed1988

Ascaris suum antigens incorporated into liposomes used to stimulate protection to migrating larvae.

Four- to 8-week-old SPF pigs were immunized, using antigens of Ascaris suum incorporated into liposomes, via intestinal cannula or orally. Avridine was also incorporated in the liposomes in one experiment and interleukin-2 (IL-2) injected into pigs in another experiment. A priming dose of embryonate eggs (80-470 eggs/pig) were given in four of six experiments. Compared to control animals, the greatest protection of pigs to migrating ascarid larvae from a challenge dose of 10,000 embryonated eggs occurred where pigs received (1) a priming dose of eggs plus second-stage ascarid larval wall incorporated into liposomes, with or without avridine or IL-2, or (2) a priming dose of eggs plus ascarid intestinal aminopeptidase incorporated into liposomes with IL-2. The degree of protection was not statistically significant due, in part, to the variability in the responses of animals in the same treatment groups and the small number of animals per group. In general, only low titers of specific serum antibodies were detected and specific antibodies were not detected in the intestinal washing.

Animals↗
PubMed1987

Bordetella bronchiseptica and toxigenic type D Pasteurella multocida as agents of severe atrophic rhinitis of swine.

Bordetella bronchiseptica and toxigenic type-D Pasteurella multocida were cultured from pigs in each of five herds diagnosed as having severe atrophic rhinitis (AR). B. bronchiseptica alone, P. multocida alone, or both organisms isolated from four herds were inoculated intranasally into 1-week-old gnotobiotic pigs which were necropsied 4 weeks post-inoculation (PI). Nasal turbinate atrophy in B. bronchiseptica-inoculated pigs was moderate to severe, while P. multocida-inoculated pigs had slight to severe atrophy. Pigs inoculated with both organisms had moderate to complete turbinate atrophy. P. multocida was reisolated at necropsy from all pigs receiving the organism except those having no turbinate damage. B. bronchiseptica and P. multocida from a fifth herd were simultaneously inoculated into six naturally farrowed 6-day-old SPF pigs. Necropsy performed 4 weeks PI revealed severe to complete turbinate atrophy. Nasal turbinates were normal for control pigs in both experiments.

Animals↗
PubMed1986

Immunity of swine to Ascaris suum.

Swine were hyperimmunized to Ascaris suum by giving multiple oral inoculations of embryonated eggs. Sera and lymphocyte lysate from these pigs were administered parenterally to 4-week-old pigs. The latter animals were no more resistant to larval migration than control pigs receiving sera or lymphocyte lysate from non-immunized pigs. Other pigs were infected with transmissible gastroenteritis (TGE) virus, allowed to recover and challenged with embryonated ascarid eggs. They likewise were no more resistant to ascarid larval migration than control pigs.

Animals↗
PubMed1986

Blocking of nonspecific IgG in indirect radioimmunoassay for detecting Ascaris suum antigens.

The sensitivity of an indirect radioimmunoassay (IRIA) used for detecting larval body wall (LBW) antigens of Ascaris suum was enhanced by using various blocking agents which prevented nonspecific binding of immunoglobulin G (IgG) or free 125I without preventing binding of specific antibodies to the antigen. The use of blocking agents reduced counts for both positive and negative sera, resulting in an increase in calculated binding ratios (BR) and deltas and, thus, in the sensitivity of the assay. The relative effectiveness of blocking agents, in decreasing order, were turkey serum (TS), rabbit gamma globulin (RGG), rabbit whole serum (RS), bovine serum albumin (BSA), rabbit IgG (RIgG), bovine alpha globulin (BAG), bovine gamma globulin (BGG) and Tween-20.

Alpha-Globulins↗
PubMed1984

A repartitioning agent to improve performance and carcass composition of broilers.

Clenbuterol [benzyl alcohol, 4-amino-alpha-(t-butylamino)methyl-3,5-dichloro] was tested in the finisher ration of broilers in three series of experiments for its effects on performance and carcass characteristics. In Experiment 1, administration of clenbuterol at feed levels of .25, .5, 1, 2, and 4 ppm from 28 to 49 days of age resulted in significant sex combined weight gain improvements at all levels except 4 ppm and significant feed efficiency improvements at all levels tested. Uneviscerated body composition analysis indicated that clenbuterol treatment significantly increased body protein and water content and decreased body fat in female birds. In males, body fat was significantly reduced by 1, 2, and 4 ppm clenbuterol. From these results the 1 ppm level was selected for further testing. In Experiments 2 and 3, clenbuterol fed from 28 to 49 days of age significantly improved sex combined weight gain and feed efficiency and both male and female 49-day weights. Carcass yield was significantly increased in males and females by 1.11 and 1.91 percentage points, respectively. Abdominal fat was significantly reduced by clenbuterol feeding only in females. Carcass analysis indicated that clenbuterol-fed birds had a significantly lower carcass fat content. In Experiments 4 to 7, clenbuterol was administered at 1 ppm in the finishing feed but was withdrawn 3 to 5 days prior to terminal performance and carcass evaluations. Clenbuterol significantly improved sex combined weight gain and feed efficiency, and 49-day weights for both sexes. Carcass yield was significantly increased in males and females by .54 and .98 percentage points, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗