Search PubMed⌕ Search

Biomedical subjects

K A Rickard

Publications and source records attributed to K A Rickard.

At least 73 records · Page 4Linked to original sources

Lung fibroblasts produce chemotactic factors for bronchial epithelial cells.

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair and morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts and bovine bronchial epithelial cells and determined that fibroblast-conditioned medium has chemotactic activity for bronchial epithelial cells. This activity was nondialyzable, heat labile, pepsin labile, acid stable, lipid inextractable, and eluted from Sephadex G-150 column chromatography in the high-molecular-weight range. DEAE-Sephacyl ion exchange and gelatin-Sepharose affinity chromatography revealed two peaks containing chemotactic activity, one of which may be fibronectin, since it binds to gelatin, reacts in a specific immunoassay, and is inhibited of chemotactic activity by anti-fibronectin antiserum, and another of which does not appear to be fibronectin, since it does not bind to gelatin nor react in the immunoassay. Thus lung fibroblasts can produce at least two chemotactic factors for bronchial epithelial cells that may play a role during lung tissue repair and morphogenesis by modulating bronchial epithelial cell migration.

Animals↗

Bronchial epithelial cells produce lung fibroblast chemotactic factor: fibronectin.

The interaction between the epithelial cells and the subjacent mesenchymal cells in the airway is thought to play a major role during tissue repair after airway injury and lung morphogenesis. To evaluate this interaction, we cultured human lung fibroblasts, and bovine and human bronchial epithelial cells, and determined that bronchial epithelial cell-conditioned medium has a chemotactic activity for lung fibroblasts. This activity had the characteristics of protein: it was nondialyzable, heat-labile, pepsin-labile, acid-stable, and lipid-inextractable. Molecular sieve chromatography on Sephadex G-150 and affinity chromatography on gelatin-Sepharose revealed that there was one peak of chemotactic activity in high molecular weight range, which bound to gelatin, thus suggesting that the chemotactic factor might be fibronectin. Production and secretion of fibronectin into the culture media were demonstrated by biosynthetic incorporation of radioactive amino acid into fibronectin followed by immunoprecipitation on SDS-PAGE and autoradiography. Release into the culture medium was confirmed by ELISA. The identity of fibronectin as the chemotactic activity was confirmed by the addition of antifibronectin antibody to the conditioned medium, which inhibited chemotaxis in dose-dependent manner. Thus, bronchial epithelial cells produce fibronectin which can function as a chemotactic factor for lung fibroblasts. This production of fibronectin by bronchial epithelial cells may play an important role in regulating interaction between the bronchial epithelial cells that line the lumenal surface of the bronchial epithelial wall and the mesenchymal fibroblasts that underlie the bronchial epithelial basement membrane.

Antibodies↗

Physiological changes during liver transplantation.

Thirteen patients who received liver transplants at the National Liver Transplant Unit between January 1986 and March 1987 were studied with extensive monitoring and frequent intraoperative biochemical and haematological profiles. Anaesthetic technique was standardised for all patients. Retrospective analysis of this data confirms that patient homeostasis is most disturbed at the time of revascularisation of the donor liver. In this series, revascularisation was associated with marked changes in all measured haemodynamic parameters (arterial blood pressure, cardiac index, heart rate, and filling pressures). There was also a significant fall in pH with revascularisation, followed by a gradual rise during the final phases of the operation. Potassium levels often rose sharply with revascularisation but then decreased during the rest of the operative period. Ionised calcium levels did not change significantly at any stage; however, all patients were given calcium intraoperatively. Coagulation profiles were often abnormal preoperatively. The transplant procedure was associated with further abnormalities in both coagulation and fibrinolysis. Patient temperatures were maintained at normal levels throughout the procedure.

Adolescent↗

Lack of improved growth outcome related to nonnutritive sucking in very low birth weight premature infants fed a controlled nutrient intake: a randomized prospective study.

The effect of nonnutritive sucking during gavage feeding on nutritional outcome and gastrointestinal transit time was evaluated in 18 premature appropriate for gestational age infants whose birth weights were less than or equal to 1,400 g and gestational ages were less than or equal to 30 weeks. Infants were randomized to a treatment (nonnutritive sucking infants received a pacifier for 30 minutes with each feeding, 12 times per day until they reached a weight of 1,500 g, eight times per day thereafter) or control (no pacifier) group. The nine nonnutritive sucking (five girls, four boys) and nine control (five girls, four boys) infants were treated for 14 days. Infants were without medical complications and were fed a single premature formula by intermittent gastric gavage at exactly 120 kcal/kg/d throughout the study period. Weight gain, linear growth, subscapular and triceps skinfold, and arm circumference accretions were assessed weekly. Serum proteins (albumin, prealbumin, retinol-binding protein, and transferrin) were measured weekly. Gastrointestinal transit times were measured weekly using carmine red markers. In contrast to previous studies, these data indicate no apparent effect of nonnutritive sucking on growth outcome, serum proteins, or gastrointestinal transit time in growing, very low birth weight infants when nutrient intake was controlled. In a subgroup of eight boys (four nonnutritive sucking, four control), energy and fat excretions were determined from 72-hour fecal collections and energy expenditure was estimated from six-hour cumulative heart rate measurements. Neither excretion of fat and calories nor estimated energy expenditure was affected significantly by nonnutritive sucking in this subgroup of baby boys. Fat excretion correlated well (r = .987) with energy excretion.

Energy Metabolism↗

Post bone marrow transplant sera and persisting mast cell colonies.

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.

Blood Physiological Phenomena↗

Identification and characterization of human hemopoietic mast cell colonies.

Persisting mast cell colonies from human bone marrow and cord blood cells grown in semisolid agar cultures for over 56 days have been positively identified and characterized using morphology and cytochemistry. Mast cells demonstrated the following features: Cytoplasmic granules frequently contained the specific and characteristic papyrus rolls (transmission electron microscopy); mature cells were positive to the mouse monoclonal antibody YB5.B8 specific for human mast cells (raised against acute myeloid leukemia cells) and RPA-M1 specific for human monocytes but negative to the human basophil monoclonal antibody Bsp-1; morphologically the cells were large (diameter 20-25 micron), deeply basophilic, and contained granules that measured up to 2 micron in diameter (May-Grünwald-Giemsa stain); the presence of heparin by the thrombin clotting time and positive staining with toluidine blue and alcian blue; the presence of histamine by a positive fluorescent o-phthalaldehyde stain; the presence of IgE receptor sites with human IgE and a rabbit anti-human IgE second antibody; and a unique zone of lysis around mast cell colonies occurred when cultured on peripheral blood feeder layers in agar plates that was not present around monocytic, neutrophilic, or eosinophilic colonies under the same culture conditions. Our results identify the cells in persisting colonies as mast cells and describe some specific characteristics that distinguish these cells from basophils.

Bone Marrow Cells↗

Persisting colonies in agar cultures containing serum from patients with CML in blastic transformation.

Addition of serum from patients with chronic myeloid leukemia (CML) in both chronic phase and blastic transformation, to agar cultures of normal human marrow cells stimulated the growth of persisting colonies (day 35) containing either eosinophils or mast cells. Chronic phase serum stimulated an 800% increase in the total number of these colonies of which only 16% were mast cells. Serial studies using serum from 2 patients demonstrated that the proportion of mast cells increased during the progression to blastic transformation. The emergence of a greater proportion of persisting mast cell colonies and a decrease in absolute number of eosinophil colonies in agar cultures of normal marrow cells containing serum from patients with CML coincides with the emergence of blastic transformation and suggests that a significant change occurs in the absolute and relative concentration of hemopoietic growth factors in these patients.

Bone Marrow Cells↗

Australian hemophiliac recipients of voluntary donor blood products longitudinally evaluated for AIDS. A clinical and laboratory study, 1983-1986.

One hundred and sixty-one Australian patients with hereditary bleeding disorders comprising hemophilia A (120), hemophilia B (18), von Willebrand's disease (16), and seven symptomatic female hemophilia A or B carriers were screened for clinical and serological evidence of exposure to HTLV-III/LAV/ARV/HIV infection. During the previous five years (1979-1984) they had been treated almost exclusively with blood products derived from Australian voluntary donors. The prevalence of HTLV-III antibodies in 1985 was 45%, with the highest frequency being in those with severe hemophilia A (78%) and the lowest in patients with hemophilia B (6%). Antibody positivity correlated with a reduced absolute T helper (T4) cell numbers and/or an inverted T4:T8 ratio. Lymphadenopathy was detected in 23 subjects but only 13 had an abnormal T cell ratio. Comparison of seropositivity and T4:T8 ratios in 32 patients studied in 1983 and again in 1985 suggested that T4 cell deficiency reflected HTLV-III exposure rather than being a predisposing factor for infection with the virus. Individual patients showed considerable fluctuation in T cell subsets over a 12 month period of follow-up, but as a population there was a slight trend with time towards diminishing T4:T8 ratio only in the antibody positive hemophilia A patients of mild to moderate severity. Three (2%) of the 161 patients screened to date have developed confirmed AIDS with fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The value of nutrition support in children with cancer.

A positive stance towards nutrition support of the child with cancer assures potential for normal growth, development, and quality of life during extended oncologic treatment. Data from recent studies of children with cancer (advanced neuroblastoma, Wilms' tumor) demonstrate the importance of integrating nutrition staging, assessment, and support into treatment protocols. Patients with solid tumors and lymphomas who are malnourished at diagnosis have a poor outcome when compared to nourished counterparts. Enteral nutrition (intensive nutrition counseling and favorite, nutritious foods) is effective in low nutritional risk groups but ineffective in preventing or reversing protein-energy malnutrition in high nutritional risk groups. For high-risk groups, central parenteral nutrition is a relatively short-term, but important, support measure which allows children to grow despite extended periods of intense oncologic treatment. The patient's nutritional course may affect bone marrow suppression and the ability to tolerate aggressive chemotherapeutic treatment. Although treatment tolerance may be improved with nutrition support, adequacy of primary oncologic treatment outweighs other supportive factors as a determinant of ultimate survival.

Anthropometry↗

Plasma lactoferrin in patients with neutropenia.

This study examines the role of plasma lactoferrin in the assessment of neutropenia. In particular, we have studied lactoferrin as an inhibitor of granulopoiesis and as an indicator of the size of the total blood granulocyte pool (TBGP). Plasma lactoferrin concentration was determined in a heterogeneous group of 30 patients with neutropenia. Serial plasma lactoferrin levels in a patient with cyclic neutropenia correlated with the cycles of the neutrophil count. Patients with splenomegaly had a grossly elevated lactoferrin:neutrophil ratio. Most chronic idiopathic neutropenia patients had no real clinical problems and a normal plasma lactoferrin level. The results provide further evidence to support the concept that plasma lactoferrin indicates the size of the TBGP and the lactoferrin: neutrophil ratio indicates the degree of granulocyte margination. There was no evidence to suggest that lactoferrin acting as a feedback inhibitor of granulopoiesis caused neutropenia in these patients.

Agranulocytosis↗

Nutritional support of children with neoplastic diseases.

There are numerous factors promoting the development of PEM in the child with cancer. Some of these factors are related to the tumor, many to the treatment itself, and some to failure of recognition of PEM. Not all children with cancer are at great risk for the development of PEM. These patients must be monitored and supported with comprehensive enteral programs. Children who have developed or are at risk for PEM must be identified and supported with CPN or PPN plus CEN during early intensive periods of treatment and during the later phases of abdominal radiotherapy, operative resection of tumor, or relapse. The decision to institute CPN must be based not only on the child's current nutritional status but also on the nature of the therapy he or she is soon to receive and the likelihood that he or she will be able to maintain an adequate intake during that therapy. Realistic goals must be set for nutritional support. The value of nutritional intervention lies in its ability to correct or prevent the development of adverse effects related to PEM. This support is hoped to contribute to improved tolerance of therapy, increased energy to complete normal day-to-day activities, and an improved sense of well-being for the child. If these goals have been accomplished, then the nutritional therapy has been successful.

Anthropometry↗

Management of splenectomy failures in chronic immune thrombocytopenic purpura: role of accessory splenectomy.

Accessory splenic tissue was demonstrated in four of eight patients with chronic immune thrombocytopenic purpura investigated following post-splenectomy relapses. Time from initial splenectomy to relapse of thrombocytopenia ranged from immediately to eight years and post-splenectomy changes were present on the peripheral blood films of all patients at time of relapse. Three scanning techniques were employed to demonstrate and localise residual splenic tissue. Conventional 99mTc scans were positive in three of the four patients whilst 99mTc-heat damaged red cell scans and computerised tomographic scans were each positive in three out of three patients including the one patient in whom a conventional 99mTc scan was negative. Histological confirmation of splenic tissue was obtained in all cases with the weights of the accessory spleens ranging from 0.6 g to 2 g. Two patients responded to accessory splenectomy and, without immunosuppressive therapy, have remained well with normal platelet counts for over four years. There was no correlation between length of initial remission and the response to removal of the accessory spleen. The presence of a functioning accessory spleen should be considered in all patients with chronic ITP who fail to respond to, or relapse following, initial splenectomy.

Adult↗

Advances in nutrition care of children with neoplastic diseases: a review of treatment, research, and application.

Within the last decade, significant advances have been made both in treating children with cancer and in providing proper nutrition support. Oncologic treatment and nutrition research and their application to the nutrition care of children with cancer are reviewed. Quality nutrition care is now possible because of an improved understanding of (a) the prevalence and significance of protein-energy malnutrition (PEM) in high-risk groups, (b) the staging and assessment of nutritional status, and (c) the efficacy and limitations of nutrition support options. Nutrition staging, assessment, and support should be integrated into treatment protocols for children with neoplastic diseases. Common risk factors for the development of PEM have been identified from serial monitoring of newly diagnosed children with a variety of tumors. Certain tumor types and their treatment can be classified within either low or high nutritional risk groups. A comprehensive nutrition program (intense nutrition counseling, favorite nutritious foods) is preferred for low nutritional risk groups but is ineffective in preventing or reversing PEM in high-risk groups. For high-risk patients, central parenteral nutrition (CPN) is the method of choice as a relatively short-term but important support measure that allows children to withstand long intervals of intense treatment during periods of growth and development. Current data suggest that bone marrow suppression may be attenuated and treatment tolerance improved with the use of CPN in selected children with advanced cancer (e.g., acute nonlymphocytic leukemia or advanced neuroblastoma).

Child↗