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Biomedical subjects

A Wood

Publications and source records attributed to A Wood.

At least 127 records · Page 7Linked to original sources
PubMed1985

Effects of conditioned medium upon proliferation, deoxynucleotide metabolism, and antimetabolite sensitivity of promyelocytic leukemic cells in vitro.

In order to investigate the interaction of factors from leukocyte-conditioned medium with leukemic cells, effects of an ammonium sulfate-precipitated conditioned medium concentrate were tested upon HL-60 cells. This preparation increased tritiated thymidine incorporation into DNA of HL-60 cells markedly, an effect which was found to be attributable in large part to greater thymidine accumulation in the intracellular nucleotide triphosphate pool. A modestly expanded population of DNA synthetic phase cells was also demonstrated by flow cytometry. Similar effects were noted of the K562 and KG-1 cell lines and were also demonstrable with giant cell tumor-conditioned medium. These effects were not demonstrable with a purified preparation of granulocyte-monocyte colony-stimulated factor. Because of the altered pattern of nucleotide metabolism noted, the effect of the conditioned medium concentrate upon 5-fluorouracil sensitivity was tested. Following continuous 24-h exposure to 5-fluorouracil at 5 X 10(-6) M, tritiated thymidine incorporation of HL-60 cells increased in parallel with depletion of endogenous thymidylate. Conditioned medium concentrate markedly sensitized cells to this effect of 5-fluorouracil and also increased growth retardation, cytotoxicity, and cell cycle arrest as assessed by flow cytometry. These studies thus demonstrated marked effects of a factor in conditioned medium on deoxynucleotide uptake and metabolism of the HL-60 line. These effects occurred in conjunction with, but were relatively more marked than, effects upon cell cycle distribution and were found to influence chemotherapy sensitivity.

Cell Cycle↗
PubMed1985

Origin and immunological hyporeactivity of canine alveolar lymphocytes.

Autochthonous canine thoracic duct lymphocytes were isolated, labelled with 111indium and injected intravenously. Direct sampling showed that the label passed from blood to lymph within 25 hr. By gamma camera imaging, the initial accumulation of 111In the liver and spleen was followed by a striking increase in lymph node associated activity between 24-36 hr. Although initial lung-associated counts were low, a bicarbonate-induced non-specific inflammation of the right lung induced a rapid and selective accumulation of labelled lymphocytes (ratio right to left lung 8:1). Cell suspensions lavaged from the alveolar surface showed only a 9% response to phytohaemagglutinin (PHA) compared to peripheral blood lymphocytes (PBL). The addition of unfractionated lavage cells to PBL caused a macrophage-dependent suppression of mitogen responsiveness. However, macrophage depletion of alveolar lavage cells did not restore the lymphocyte response to PHA. Similarly, the frequency of alloreactive precursors of cytolytic lymphocytes (CTL) was almost 10-fold less in alveolar lymphocytes compared to PBL. Thus, bronchoalveolar lavage provides a technique by which viable cells may be recovered in significant numbers from the alveoli and should be invaluable for the investigation of lung allograft rejection.

Animals↗
PubMed1984

An analysis of in vivo cell migration during teleost fin morphogenesis.

In the teleost embryo the pectoral fin bud initially displays an apical ectodermal ridge along its entire distal margin. The ridge subsequently becomes transformed into an apical fold as the distal ectodermal epithelium grows and folds to enclose an extracellular space between the apposed basal surfaces of the epithelium. Collagen fibrils up to 2 micron in diameter, termed 'actinotrichia', are deposited along the proximo-distal axis in two (dorsal and ventral) arrays. The actinotrichia are aligned parallel to one another with a regular spacing along the greater part of their length. Mesenchymal cells migrating distally from the base of the fin bud encounter the dorsal and ventral arrays of actinotrichia and move between them apparently using the fibrils as a substratum. The entire structure is transparent and, using the killifish Aphyosemion scheeli, we have investigated the migration of the mesenchymal cells between 135 and 220 h of development, using Nomarski interference contrast microscopy and time-lapse video recording. The number of cellular processes per cell increased significantly during the period of observation. These processes could be graded according to their diameters. Processes of diameter greater than 2 micron were not usually aligned along actinotrichia and arose at any aspect of the cell body. In contrast, processes with diameters less than 2 micron appeared to be confined to the distal aspects of the migrating cells and showed an increasing tendency to become aligned as development progressed. Time-lapse video recordings revealed that such aligned processes move faster (mean speed 17.98 (+/- 2.25) micron/h) than non-aligned processes (mean speed 4.66 (+/- 0.67) micron/h). Whole cell translocation was generally slower than rates of process movement: the lowest mean value (1.52(+/- 0.36) micron/h) was recorded between 135 and 160 h of development rising to a maximum mean rate (4.72(+/- 0.42) micron/h) between 195 and 220 h; the period of the fastest rate of cell translocation correlated with maximum process alignment along actinotrichia. Thin 1 micron plastic sections revealed that, generally, aligned processes were in close association with the surface of the actinotrichial fibrils and not the spaces between them.

Animals↗
PubMed1983

Assessment of liver function using fasting bile salt concentrations in psoriasis prior to and during methotrexate therapy.

To determine if fasting bile salt concentrations are an accurate indicator of pre-existing and methotrexate-induced liver disease in patients with psoriasis, the plasma concentrations of conjugated cholate, chenodeoxycholate and sulpholithocholate were measured in 18 patients being assessed for methotrexate therapy and 21 receiving long-term therapy. The results were compared with other liver function tests and liver histology. The liver function tests were a poor indicator of occult liver disease and, whilst fasting bile salts appeared more sensitive, they were still unreliable and inadequate for the clinical assessment of the hepatopathy associated with psoriasis. The reasons for these discrepancies are discussed.

Adult↗
PubMed1983

Pharmacokinetic study of methyl glyoxal-bis-guanylhydrazone (methyl-GAG).

Using a paired ion exchange high pressure liquid chromatographic assay, pharmacokinetic evaluation of methyl glyoxal bis guanylhydrazone (methyl-GAG) was performed in nine male New Zealand albino rabbits following administration of a single intravenous bolus dose of 50 mg/kg B.W (550 mg/m2 BSA). Blood samples were collected before and at intervals of 5, 10, 15, 30 min and 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after administration of the drug. The analysis of experimental data indicates a three compartment open model with first order elimination from the central compartment described by the equation Cpt = A.e-alpha t + B.e-beta t + C.e-gamma t, where A, B, C, are 107.985, 4.785, and 0.763 micrograms/ml, respectively. alpha, beta, gamma, are 5.466, 0.487, and 0.030 h-1, respectively, and T1/2 alpha, beta, gamma are 7.6, 85.3 min and 23.1 h, respectively. The mean volume of distribution in the central compartment Vc was 0.44 liters (1)/kg, volume of distribution Vdarea 30.326 1/kg, and the total body clearance 0.9097 1/kg/h. The existence of a long terminal plasma half life of methyl-GAG reported previously in human studies was also confirmed in experimental animals and may explain the cumulative toxicity of this drug.

Animals↗
PubMed1983

Distinctive patterns of cAMP-binding proteins and their relationship to hemopoietic cellular differentiation.

In order to clarify distinctions among cAMP-binding protein patterns present in hemopoietic cells of the various major lineages, we have studied extracts from 18 human cell lines by photoaffinity labelling with 8-azido [32P]cAMP, followed by SDS-polyacrylamide gel electrophoresis and autoradiography. Four major cAMP-binding protein bands were noted. These occurred in five recognizable patterns of combinations, each of which was restricted to cells of particular lineages. A distinctive pattern was found in the pluripotent stem cell line K562, confirming its unusual nature compared with other lines committed to myeloid or lymphoid differentiation. Three patterns were noted among the pre-B and early and late B cell lines studied, which may thus define sequential stages of differentiation of this series. These studies indicate the utility of cAMP-binding proteins as a biochemical differentiation marker system. The variety of phenotypes noted further suggests a role for them in the development or expression of specialized cellular functions.

Affinity Labels↗
PubMed1983

Intravenous cyclosporine kinetics in renal failure.

Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.

Chromatography, High Pressure Liquid↗
PubMed1983

Evidence for a slowing in trimethoprim resistance during 1981--a comparison with earlier years.

Two thousand seven hundred bacterial strains, isolated during 1981 from urine specimens both from patients in hospital and general practice, were examined for resistance to trimethoprim. The incidence of such resistance was 13% in the hospital isolates and 5.8% in the general practice strains. High level resistance (MIC greater than 1 mg/ml) was present in 75-90% of the resistant strains. With the exception of Staphylococcus epidermidis and Proteus mirabilis, almost all the trimethoprim-resistant strains were also resistant to sulphonamide. In 410 strains from sputum specimens the incidence of resistance was 5.4%. Disc testing for the determination of sensitivity of urine isolates is best carried out using a 5 micrograms disc, while for sputum isolates our present experience indicates that a 1.25 micrograms disc is most appropriate. Our results indicate that the rate of increase in the acquisition of resistance to trimethoprim appears to have slowed down compared with the period 1975-1977, and that almost all this resistance is now high level. The introduction of trimethoprim alone for therapeutic use appears to have little if any effect on the incidence of trimethoprim resistance.

Bacteria↗
PubMed1983

Biofeedback and relaxation in the treatment of migraine headaches: comparative effectiveness and physiological correlates.

Twenty-seven migraine headache patients were divided into three equal groups which received thermal biofeedback, frontalis EMG biofeedback, or relaxation training. Training was given under "massed" practice conditions (nine sessions per week) and consisted of 18 training sessions and six test-generalisation sessions. While improvements in headaches were observed in all groups, the best improvements took place in the thermal biofeedback group, which had almost complete elimination of migraine attacks by the end of training, and maintained that performance as long as six months after training. Examination of the patterns of skin temperature and EMG changes in the three groups over the course of training also points to a relationship between skin temperature control and reduction in migraine headache symptomatology, and suggests that this relationship is worthy of further investigation.

Adult↗
PubMed1983

Lectin-dependent and lectin-independent activities of human mononuclear cells that modulate the growth of human synovial cells.

Human peripheral mononuclear cells (MC) secrete 2 soluble activities that modulate the growth of human synovial fibroblastic cells. A growth-suppressive, lectin-dependent activity is elaborated by the non-adherent population and its secretion begins before DNA synthesis is initiated in concanavalin-stimulated MC cultures. The elaboration of this activity is partially dependent on the presence of serum and it appears to be distinct from virus-induced human leukocyte interferon. The second activity is secreted spontaneously by the MC, under a variety of culture conditions including supplementation with homologous human plasma, and it enhances the growth of synovial fibroblasts. The rate of secretion of the growth-enhancing activity by the nonstimulated MC approximately parallels that of the inhibitory activity from the stimulated MC cultures. MC from patients with rheumatoid arthritis and from nonaffected individuals secrete similar concentrations of growth-stimulatory activity for the synovial fibroblasts.

Arthritis, Rheumatoid↗
PubMed1982

Early pectoral fin development and morphogenesis of the apical ectodermal ridge in the killifish, Aphyosemion scheeli.

Using scanning electron microscopy it has been found that in the killifish the distal epithelium of the pectoral fin bud forms a morphologically distinct apical ectodermal ridge along its entire distal margin. This ridge is a relatively more prominent feature than its counterpart in various tetrapod systems. At a later stage the ridge becomes folded internally and elongates distally marking the transformation of the ridge into a fin fold. By continued distal growth the fin fold develops into a semicircular swimming-paddle. Collagenous rays or actinotrichia differentiate in a highly ordered arrangement close to the epithelial basement membrane within the space enclosed by this elongating fin fold and apparently support the early swimming-paddle. During the ridge-to-fold transition the fin bud displays a dorsal deflection of approximately 45 degrees and a caudalward rotation about the axis of the fin itself. This change in orientation results in close apposition of the developing fin structure to the flank.

Animals↗
PubMed1982

VM-26 with prednisone and vincristine for treatment of refractory acute lymphocytic leukemia.

Fifty-six children with refractory acute lymphocytic leukemia (ALL) were assessed for remission-induction responses to VM-26 (250 mg/m2 per week) in combination with prednisone (40 mg/m2 per day) and vincristine (1.5 mg/m2 per week). Each child had been treated intensively with steroids, vincristine, daunorubicin and L-asparaginase. In fact, all patients had failed to respond to previous reinduction therapy with prednisone-vincristine or had relapsed while receiving vincristine. Our intent in this study was to test whether or not addition of VM-26 to prednisone-vincristine would overcome clinical resistance to these established agents. Complete remissions were induced in 17 patients (0.30) over 4 to 6 weeks. Five of these children, all clinically unresponsive to prednisone-vincristine alone, had complete remissions that lasted longer than 1 year; two remain in remission for 2 1/2 years and both are now off therapy. Myelosuppression, the most serious treatment complication, was documented in 20 of 26 evaluable patients. The median time to recovery of normal marrow function was 15 days. These results demonstrate further the potential of VM-26 in combined-drug treatment of refractory ALL. Whether the effectiveness of this combination represents potentiation of prednisone and vincristine activity by VM-26 or some other, as yet unidentified interaction, remains to be determined.

Adolescent↗