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Biomedical subjects

D Ford

Publications and source records attributed to D Ford.

At least 127 records · Page 7Linked to original sources

Blood grouping with monoclonal anti-N antibodies.

Four monoclonal antibodies (N1, N3, N4 and N5) with specificity for the N blood group have been produced from fusions in which human erythrocytes were used as the immunizing stimulus. N1 and N3 differed from N4 and N5 with regard to their serological specificities and pH optima. Antibody N3 has been assessed for its suitability as a blood grouping reagent by testing 10,767 blood donors in parallel with Vicia graminea anti-N lectin or rabbit anti-N. There was complete correlation between the results obtained with the monoclonal and conventional reagents providing strong evidence that N3 is a reliable and potent blood grouping reagent.

Antibodies, Monoclonal↗

Bone marrow transplantation for malignant histiocytosis in childhood.

This report describes a girl who was diagnosed with malignant histiocytosis at the age of 5 years. The disease was controlled initially with chemotherapy for 3 years and had then recurred with meningeal involvement on three occasions. Four years and 8 months from diagnosis, bone marrow transplantation (BMT) was undertaken from an HLA-identical and mixed lymphocyte culture (MLC) nonreactive brother after conditioning with VP-16-213 5 mg/kg/day X 2, cyclophosphamide 60 mg/kg/day X 2, and total body irradiation 200 rad twice daily to a total dose of 1000 rad delivered at 7 rad/minute. At the time of transplant, the disease was in remission. Currently, more than 48 months after the transplant, the child remains free of disease, with a normally functioning donor marrow and with no evidence of graft versus host disease. This is the first recorded case of BMT in the treatment of malignant histiocytosis. The outcome in this patient in late-stage disease suggests that BMT could be considered early in management as definitive therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Histochemical fiber composition of lumbar back muscles in the rabbit.

The present study of the back muscles of the rabbit, using enzyme histochemical techniques and stereological methods, was undertaken with the view to gaining a better understanding of the fiber-type make-up of the lumbar musculature of this animal. The muscles considered were the multifidus, sacrospinalis and the intertransversarii between levels L5 and L6. Gross examination reveals that the multifidus and the sacrospinalis form the bulk of the lumbar musculature and that these muscles appear white. Between and deep to these two muscles are the red intertransversarii. Histochemically the multifidus and the sacrospinalis are also similar in their fiber-type composition, mostly types IIA and IIB and the percentage of connective tissue that they contain. The intertransversarii, in contrast, are for all practical purposes composed of only type-I fibers. The intertransversarii contain significantly more connective tissue than the other two muscles. It may be concluded that the bulk of the lumbar musculature of the rabbit is phasic while the intertransversarii, containing only type-I fibers and a high percentage of connective tissue, are postural muscles.

Adenosine Triphosphatases↗

Precursor frequency of antigen-specific T cells: effects of sensitization in vivo and in vitro.

Limiting dilution analysis (LDA) of primary lymphocyte cultures was used to determine the frequency of keyhole limpet hemocyanin (KLH)-specific precursors in the peripheral blood of unimmunized individuals. The KLH-specific precursor frequencies ranged from 1:150,000 to 1:340,000. In contrast, frequencies of KLH-specific cells in the blood from immune donors ranged from 1:25,000 to 1:42,000. LDA of KLH-stimulated primary cultures indicated that the frequency of KLH-specific cells increased with time in culture reaching a four- to fivefold expansion relative to the frequency obtained prior to culture. The data presented suggest that the enhanced kinetics of secondary T-cell responses observed after in vitro sensitization are due to a decrease in the proportion of lymphocytes which exhibit a suppressor phenotype.

Adult↗

In-vivo effects of prostaglandin E1 and lysine-bradykinin on rat salivary secretions elicited by parasympathomimetic stimulation.

Intravenous injections of either prostaglandin E1 or lysine bradykinin (kallidin) modified the secretory response of the submandibular, parotid and sublingual glands of the rat to intravenous infusions of acetylcholine. The two substances caused reductions (of from 16 to 67 per cent) in salivary flow rates when administered in concentrations ranging from 10 to 50 micrograms/kg body weight. The effect lasted for 20-30 min, followed by a return to pre-injection levels and in general, depended on the concentration of the secretory stimulator and on the dose of test substance used. In the submandibular and sublingual gland, both substances generally caused a concomitant increase in the salivary Na+ concentrations. This effect depended on the concentrations of acetylcholine and of test substance and varied from 10 to 117 per cent. The effect was more marked in submandibular saliva. Absolute increases in salivary Na+ concentration were not observed in the parotid gland, but the reductions in salivary Na+ concentrations (from 2.5 to 31.7 per cent) were smaller and did not parallel the simultaneous reduction in flow rate, which was between 16.4 and 60.4 per cent. As both kinins and prostaglandins are present in the glands and may be activated as a result of secretory or metabolic activity, the results suggest that they act as modulators of the secretory response to cholinergic stimulation. The divergent effects on flow rate and on salivary Na+ concentration suggest that kinins and prostaglandins have specific and independent effects on acinar and duct cells.

Acetylcholine↗

Analysis of vertebral muscle obtained during surgery for correction of a lumbar disc disorder.

Biopsies of erector spinae (sacrospinalis) and multifidus muscles were taken, in a precise manner, adjacent to lumbar vertebra 5, from 18 patients aged 28-73, suffering from acute lumbar disc disorders. The respective muscle fiber characteristics were assessed histologically and histochemically using ATPase and NADH staining procedures. A 'strength factor' component was developed for each muscle by combining measurements of fiber area and fiber type, to introduce a functional indication of force. No obvious signs of muscle pathology were evident histologically or histochemically. While a large difference in muscle characteristics may exist on opposite sides of the vertebral column in individual subjects, these differences do not appear to be related to the side of the disc protrusion. It is therefore suggested that muscle obtained from patients suffering from disc protrusion can be used as representative of normal muscle.

Adult↗

Sensitization of human lymphocytes in vitro. Kinetics and specificity of the response to hemocyanins.

In vitro primary sensitization of human peripheral blood T-cells to hemocyanins was detected during a 12-14 day culture period with antigen (KLH or HCH)-pulsed macrophages. Primed T-cells proliferate in secondary culture (2-3 days) when restimulated with antigen presented by macrophages. The kinetics of primary sensitization and secondary responsiveness are interrelated and are dependent on the antigen doses employed. Antigen-induced proliferation of cells sensitized in vitro is identical to proliferation of T-cells from immunized donors in terms of antigen specificity and the clonal nature of the response to antigen. Through the use of thymidine suicide techniques, distinct populations of cells responding to KLH or HCH can be demonstrated using cells from actively immunized donors or cells that have been sensitized in vitro to both hemocyanins.

Dose-Response Relationship, Immunologic↗

Endothelial cell presentation of antigen to human T cells.

Activation of human T cells requires presentation of antigen by Ia (HLA-DR in man) bearing cells of the mononuclear phagocytic series (macrophages, MO, and more recently Langerhans cells, dendritic cells, and vascular endothelial cells. Since T cells must cross endothelial barriers to enter extravascular tissues during immune reactions, we investigated the role of endothelial cells in antigen presentation. Endothelial cells were cultured from human umbilical veins and identified by classic morphology and specific markers (factor VIII related antigen, and so on). Antigen-pulsed endothelial cells were used to present antigen to MO-depleted human T cells; activation was assessed by 3H-thymidine uptake. The HLA-DR compatible endothelial cells were as effective as MO in reconstituting MO-depleted T-cell responses. The endothelial cell reconstituted responses were antigen specific, HLA-DR restricted, and blocked by monoclonal antibodies to HLA-DR framework structures. Moreover, the T-cell responses were clonal with respect to HLA-DR. A monoclonal antibody completely eliminated MO reconstitution of the MO-depleted response without diminution of endothelial cell reconstitution of the same response. Fibroblasts and smooth muscle cells cultured from the same umbilical veins could not reconstitute the MO-depleted T-cell response. These data indicate that endothelial cells play an important and distinctive role in lymphocyte triggering.

Antigens↗

Di- and tri-methoxystyryl derivatives of heterocyclic nitrogen compounds.

A series of mono-, di-, and trimethoxystyryl derivatives of heterocyclic nitrogen compounds were prepared to test the N-O-O triangulation hypothesis of Zee-Cheng and Cheng. Of 29 free bases submitted for KB cell culture test, only 2-(3,4-methylenedioxystyryl)benzoxazole and 4-(2,5-dimethoxystyryl)cinnoline were active (ED50 of 4 microgram/ml or less). Methiodide salts were more potent: 8 of 14 were active. 2-(2,4,6-Trimethoxystyryl)quinoline methiodide and 4-(2,4,5-trimethoxystyryl)quinoline methiodide had ED50 of 0.4 and 0.9 microgram/ml, respectively. The methiodides of 2-(2,3,4-, 4-(2,4,5-, 4-(2,4,6-, and 2,4-bis-(2,4,6-trimethoxystyryl)quinoline and 1-(2,4,6-trimethoxystyryl) isoquinoline and the propiodide of 4-(2,4,6-trimethoxystyryl)quinoline were active against P388 leukemia. Several of the active compounds do not conform to the dimensions of the Zee-Cheng and Cheng triangle.

Animals↗

Ultrastructural localization of cations in the rat pars distalis under various experimental conditions.

Modifications of the pyroantimonate technique were used to localize intracellular sites of bound cations in the pars distalis of normal and hypothyroid rats and in rats with increased levels of plasma calcium. In the normal animal, cations were localized within most intracellular organelles and sometimes on the membranes involved in exocytosis. The amount of bound cations within pituitary intracellular organelles was considerably augmented in rats injected intravenously with calcium chloride. However, in the thyroidectomy cells of hypothyroid rats, the amount of cation precipitate appeared to be selectively increased in the dilated rough endoplasmic reticulum (RER). The calcium chelator, EGTA, and X-ray microprobe analysis revealed the presence of calcium in cation deposits.

Animals↗

Effects of sulfuric acid aerosol on cardiopulmonary function of dogs, sheep, and humans.

Submicronic aerosol of sulfuric acid (H2SO4) originates from the burning of fossil fuels and discharge of vapor from the automobile engine equipped with the catalytic converter. This study was conducted to determine whether brief exposure to this aerosol in high concentrations adversely affects the cardiopulmonary system. In all studies, submicronic aerosol of sodium chloride was used as a control. Anesthetized dogs that breathed H2SO4 aerosol in concentrations up to 8 mg per m3 showed no effects on respiratory resistance, static lung compliance, and functional residual capacity. A 4-hour exposure to H2SO4 aerosol (4 mg per m3) produced no significant changes in mechanics of breathing, functional residual capacity, pulmonary and systemic arterial blood pressures, cardiac output, heart rate, and arterial blood gas tensions. Conscious sheep that breathed H2SO4 aerosol in concentrations up to 14 mg per m3 for 20 min had no alteration of tracheal mucous velocity in an immediate 3-hour follow-up period or 5 to 10 days later. Conscious sheep that breathed H2SO4 aerosol (4 mg per m3) for 4 hours had no significant alteration of tracheal mucous velocity immediately and 2 hours thereafter. Both normal and asthmatic adults breathing H2SO4 aerosol in concentrations up to 1 mg per m3 for 10 min showed no significant alteration of lung volumes, distribution of ventilation, ear oximetry, dynamic mechanics of breathing, oscillation mechanics of the chest-lung system, pulmonary capillary blood flow, diffusing capacity, O2 consumption, and pulmonary tissue volume. No delayed effects in pulmonary function nor exacerbation of bronchial asthma were observe during a follow-up period of a few weeks. The present study indicates that single exposure to submicronic H2SO4 aerosol does not produce an immediate or a delayed adverse effect on cardiopulmonary function in anesthetized dogs, conscious sheep, and normal and asthmatic adults.

Aerosols↗

Assessment of inherent fluctuations of mitotic and labelling indices of human tumours.

A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours.

Cell Count↗

Defibrination of normal human blood in vitro: a method giving a high recovery of untraumatized cells.

A new automatic apparatus is described for the defibrination of blood in vitro at laboratory temperature which results in only small (less than 10%) losses of white cells. Freshly-drawn blood is mixed smoothly at high speed (greater than 1200 rpm) and fibrin is removed rapidly as formed. The apparatus is designed to produce minimum mechanical trauma to the blood. Subsequent in vitro incubation of red cells, granulocytes and lymphocytes demonostrated their viability to be comparable with cells obtained by other methods of defibrination.

Blood Cells↗

Histocompatibility antigens in Graves' disease.

Histocompatibility antigen typing was undertaken in 100 Caucasian patients with Graves' disease (autoimmune thyrotoxicosis) and in 100 healthy Caucasian blood donors. Standard lymphocyte microcytotoxicity methods were used to tests for the presence of 22 HL-A antigens in all subjects. There was a significant difference between the groups in respect of the HL-A 8 antigen which was present in 40 patients and in 25 controls (P less than 0-0023). There was no significant difference between the patients and controls with respect to the frequency of occurrence of any of the other HL-A antigens tested.

Adult↗