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J C Howard

Publications and source records attributed to J C Howard.

At least 73 records · Page 4Linked to original sources
PubMed1989

Cost-related variables: a pilot study.

The advent of prospective payment systems prompts nurses to examine cost-related factors in demonstrating savings resulting from quality care. The clinical nurse specialist plays an active role in the examination of variables influencing costs for patients within the specialty. This pilot study utilized a retrospective chart audit of 142 women falling within Diagnostic-related Group 355 (non-radical hysterectomy, age less than 70 years, without comorbid condition or complication) during 1985 to identify demographic, illness/treatment-related, and discharge variables related to charge variance. Independent (length of stay, p less than 0.001 and previous admission, p = 0.066) predictors of charge variance were found among the 14 variables studied. The value of the research as a model for other practitioners is discussed.

Costs and Cost Analysis↗
PubMed1988

Mosaic pattern and lineage analysis in chimeras.

Mammalian chimeras have been used in a number of developmental studies over the years. A major limitation in these studies has been the lack of in situ procedures for establishing mosaic pattern in the tissues of these animals. Recently, a number of procedures have become available for the histochemical demonstration of mosaicism in chimeras. These include the elucidation of various enzymes, receptors, or surface antigens, which have variant expression between strains. The observation of pattern in organs of mosaic animals can suggest possible modes of organogenesis and organ maintenance. Experimentation with such animals can be used to establish some mechanisms of pathogenesis as well.

Animals↗
PubMed1988

Employee assistance programs in the hospital industry.

The health care literature describes the industry's need for employee assistance programs (EAPs). New research results show the degree to which EAPs are used in the industry and ways to determine their success.

Counseling↗
PubMed1988

Studies in the rat of antibody-sensitized and N-ethylmaleimide-treated erythrocyte clearance by the liver: effects of immune complex infusion and complement activation.

The function of the hepatic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide (NEM)-treated erythrocytes and erythrocytes sensitized with a rat IgG2a monoclonal antibody (R2/15S) directed against the rat RT1Aa class I antigen. The clearance of the antibody-sensitized erythrocytes was biphasic, with the initial phase being rapid and complement dependent. This clearance was entirely hepatic and could be reduced or prevented by the infusion of cobra venom factor (CVF), complement fragments or small amounts of immune complexes, prepared either at equivalence or 10-fold antigen excess. NEM-treated cells were removed rapidly from the circulation of normal rats (t 1/2 6.2 +/- 0.4 min) and their clearance rate was not influenced by complement depletion. Most of the cells accumulated in the liver, although a small proportion (17%) was removed by the spleen. Immune complexes formed at equivalence or heat-aggregated human gamma globulin (HAGG) delayed the removal of these cells from the circulation, although significantly larger amounts of HAGG were required to do this. Antigen-excess immune complexes had no effect.

Animals↗
PubMed1987

Audit of serum theophylline concentrations in patients from general practice.

From the repeat prescription register of a British general practice, 37 patients regularly taking theophylline preparations were identified. Measurement of their serum theophylline concentration showed that less than 25% of these patients were achieving a theophylline concentration in the therapeutic range. Reasons for this are discussed.

Adolescent↗
PubMed1986

Characterization of tryptophan transport in human placental brush-border membrane vesicles.

The characteristics of tryptophan uptake in isolated human placental brush-border membrane vesicles were investigated. Tryptophan uptake in these vesicles was predominantly Na+-independent. Uptake of tryptophan as measured with short incubations occurred exclusively by a carrier-mediated process, but significant binding of this amino acid to the membrane vesicles was observed with longer incubations. The carrier-mediated system obeyed Michaelis-Menten kinetics, with an apparent affinity constant of 12.7 +/- 1.0 microM and a maximal velocity of 91 +/- 5 pmol/15 s per mg of protein. The kinetic constants were similar in the presence and absence of a Na+ gradient. Competition experiments showed that tryptophan uptake was effectively inhibited by many neutral amino acids except proline, hydroxyproline and 2-(methylamino)isobutyric acid. The inhibitory amino acids included aromatic amino acids as well as other system-1-specific amino acids (system 1 refers to the classical L system, according to the most recent nomenclature of amino acid transport systems). The transport system showed very low affinity for D-isomers, was not affected by phloretin or glucose but was inhibited by p-azidophenylalanine and N-ethylmaleimide. The uptake rates were only minimally affected by change in pH over the range 4.5-8.0. Tryptophan uptake markedly responded to trans-stimulation, and the amino acids capable of causing trans-stimulation included all amino acids with system-1-specificity. The patterns of inhibition of uptake of tryptophan and leucine by various amino acids were very similar. We conclude that system t, which is specific for aromatic amino acids, is absent from human placenta and that tryptophan transport in this tissue occurs via system 1, which has very broad specificity.

Amino Acids↗
PubMed1986

Studies in cobra venom factor treated rats of antibody coated erythrocyte clearance by the spleen: differential influence of red blood cell antigen number on the inhibitory effects of immune complexes on Fc dependent clearance.

The splenic component of the mononuclear phagocyte system (MPS) was investigated in decomplemented rats by determining the clearance from the blood of erythrocytes coated with a monoclonal antibody (R3/13). The infusion of immune complexes (IC), prepared at 10-fold antigen excess, at an appropriate time during the erythrocyte clearance produced a significant increase in the T1/2 of the antibody coated cells. Immune complexes formed with the F(ab')2 fragment of the rabbit antibody did not have any significant effect. A positive correlation was seen between the dose of immune complex infused and the degree of inhibition of erythrocyte clearance. The influence of red cell antigen number on the behaviour of erythrocytes sensitized with R3/13 was studied by comparing the clearance of DA and (DA X PVG) F1 erythrocytes. F1 erythrocytes, with only half the number of specific antigens on their surface that bind R3/13 antibody were cleared much more slowly (82 +/- 2.6 min, mean +/- s.e.) by the spleen than the DA erythrocytes (44 +/- 1.5 min P less than 0.001). Both cell suspensions were equally susceptible to inhibition by soluble IC. These studies show that the number of specific antigens on the red cell surface influences the rate at which sensitized cells are removed by splenic macrophage Fc receptors but not their susceptibility to inhibition by IC. Our results draw attention to a major defect in the use of autologous erythrocytes coated with anti-rhesus (D) immunoglobulin to assess macrophage Fc receptor function in man.

Animals↗
PubMed1986

Studies in the rat of antibody-coated and N-ethylmaleimide-treated erythrocyte clearance by the spleen. I. Effects of in vivo complement activation.

The splenic component of the mononuclear phagocyte system (MPS) was investigated in the rat using N-ethylmaleimide-treated erythrocytes (NEM) and erythrocytes coated with a monoclonal IgG2b antibody (R3/13) directed against the rat RT1Aa major histocompatibility antigen. Both cell suspensions were removed by the spleen, and their clearance times were significantly longer in splenectomized animals. The mean clearance times for the NEM-treated cells in both normal and cobra venom-treated rats were similar (19.1 +/- 1.1 min and 19.0 +/- 1.0 min, respectively) but differences were seen between the clearance of R3/13 antibody-sensitized cells in these two groups (normal rats 38.3 +/- 2.8 min and CVF-treated rats 51.7 +/- 4.2 min, P less than 0.02). Different receptors were also involved in the removal of these cells; in normal animals recognition entailed interaction with complement receptors, whereas in CVF-treated animals this was implemented by Fc receptors. Complement activation prolonged the clearance rates of both R3/13 cells and NEM cells in normal animals, but the effect of complement activation on the clearance of NEM-treated cells was achieved via changes in splenic blood flow. When this was prevented from taking place no effect was seen on the clearance of NEM cells, although the clearance of R3/13 cells was inhibited by the complement fragments generated by complement activation.

Animals↗
PubMed1986

Studies in the rat of antibody-coated and N-ethylmaleimide-treated erythrocyte clearance by the spleen. II. Effects of immune complex infusion.

The effects of immune complex infusion on the clearance of antibody (R3/13)-coated and NEM-treated rat erythrocytes by the splenic component of the rat mononuclear phagocyte system (MPS) were investigated. Equivalence complexes of BSA-anti-BSA produced a significant delay in the clearance of the NEM cells (pre-infusion T1/2 19.7 +/- 3.9 min, post-infusion T1/2 26.5 +/- 3.8 min, mean +/- SE, n = 6, P less than 0.01), but this effect could be abolished by agents that prevented the changes in the splenic blood flow that followed complement activation. The immune complexes formed in 10-fold antigen excess (mean size 15S) did not delay the clearance of the NEM cells. Clearance of R3/13-coated cells was impaired by the infusion of immune complexes prepared at equivalence. 10-fold antigen excess or complexes prepared with F(ab')2 fragments of rabbit anti-BSA antibody. The inhibition of red cell clearance was independent of changes in blood flow, but the degree of inhibition produced did not correlate well with the dose of immune complex injected.

Animals↗
PubMed1985

Histological demonstration of mosaicism in a series of chimeric rats produced between congenic strains.

Experimental chimeras were produced by aggregating morulae from congenic strains of PVG rats differing in the major histocompatibility complex (RTI). Monoclonal antibodies against variant class I antigens of the two strains were directly conjugated to iodine-125 and applied to tissue sections. Autoradiograms allowed examination of most internal tissues. The proportion of PVG-RTIa cells in the erythrocyte populations of the chimeras varied from 8 to 70 percent, as determined with fluorescence-activated flow cytometry. Digital analysis of autoradiograms demonstrated that the contribution of PVG-RTIa cells to the livers of the chimeras ranged from 34 to 86 percent. Patches of cells of each genotype in the liver were geometrically complex, with large variations in size. The thymus, but not the spleen, showed evidence of oligoclonal development. The adrenal cortex revealed a radially striped pattern, suggestive of clonal expansion of stem cells. With this approach it is possible to measure cell distribution in chimeras through direct histological visualization, which may prove useful in the study of rat organogenesis.

Adrenal Cortex↗
PubMed1985

Antibody density on rat red cells determines the rate of activation of the complement component C1.

It is a common observation that there is variability in the rate of activation of C1, the first component of complement, when bound to immune complexes. The cause of this variation has been investigated with experiments designed to assess separately the effect of antibody, antigen and C1 density. Using 125I-labeled C1 and a rat monoclonal antibody specific for the class I antigen, it has been found that the rate of activation is primarily dependent on antibody density on the cell surface and not on antigen or C1 density. This finding supports the suggestion that direct contact between the C1r2C1s2 subcomponent of C1 and antibody may be required for potentiation of C1 activation.

Animals↗
PubMed1984

The alloantigenic organization of RT1Aa, a class I major histocompatibility complex molecule of the rat.

Over 300 monoclonal IgG alloantibodies have been prepared against RT1Aa , the class I major histocompatibility complex molecule of the DA rat. In this study a combination of techniques is exploited to show that all these antibodies can be allocated to 9 antigenic sites which form a continuous antigenic surface, that is, no site is completely isolated from the rest. The results suggest that techniques for the identification of antigenic sites using competitive inhibition of monoclonal antibody binding are generally valid, in the sense that competition between antibodies appears most commonly to represent competition between combining sites for a structural feature of the antigenic surface. From the distribution of antibodies between sites, it is clear that the RT1Aa molecule has three immunogenic areas against which nearly all the antibodies studied were directed. Of these areas one is both antigenically complex, consisting of four closely spaced sites, and remarkably immunodominant. Antibodies directed at sites between the major areas are extremely rare.

Animals↗
PubMed1984

IgG pair formation on one antigenic molecule is the main mechanism of synergy between antibodies in complement-mediated lysis.

Two rat IgG2b monoclonal antibodies bound to different epitopes on a offgle RT1Aa antigen molecule synergize in their induction of complement-mediated lysis of the red cells. The mechanism of this synergistic action has been investigated by determining the C1q:IgG relationship on red cells using the fluorescence-activated cell sorter and making use of the considerable variation in antigen density between individual red cells. With a synergistic pair of antibodies, the C1q:IgG ratio was approximately 1 and independent of antibody density per cell, indicating that the antibody molecules are present as closely associated pairs, each pair binding two C1q molecules and thus forming a cyclic tetramer. When one of the antibodies was used alone, the number of C1q molecules bound relative to the amount of antibody was higher than expected from theoretical considerations based on a presumed random distribution of antigen-antibody complex. This result can be explained if there is some mobility of the complex within the membrane. The interpretation of the results gives strong support to the hypothesis that C1q must bind bivalently to rat IgG2b complexes.

Animals↗
PubMed1984

Localized conformational changes induced in a class I major histocompatibility antigen by the binding of monoclonal antibodies.

We describe two monoclonal antibodies, R3/47 and YR1/1, directed against different epitopes of the expressed rat class I major transplantation antigen RT1Aa, that interact with each other so that the binding of one antibody, YR1/1, is greatly enhanced by the binding of the other. The positive interaction between R3/47 and YR1/1 also occurs when using RT1Aa molecules solubilized from cell membranes in detergent. It is therefore unlikely that the molecular environment of the membrane contributes to the interaction. The ability of R3/47 to modify the YR1/1 determinant on the RT1Aa molecule is mediated without any significant loss of potency by highly purified monomeric Fab fragments. This result suggests that the binding of R3/47 to the RT1Aa molecule alters the YR1/1 determinant by initiating a propagated conformational change in the antigen.

Animals↗
PubMed1984

T helper cells required for the in vitro primary antibody response to SRBC are neither SRBC-specific nor MHC-restricted.

These studies address the specificity of the T cells which normally function in the in vitro primary immune response. It is generally accepted that SRBC-specific, MHC-restricted T helper cells become activated both in vivo and in vitro by seeing erythrocyte antigens presented in the context of the MHC antigens of an antigen-presenting cell. At this point, the in vivo and in vitro systems differ. In vivo, the interaction between SRBC-specific B cells and the activated T helper cells is itself also MHC-restricted, whereas in vitro, the T cell-B cell interaction is not MHC-restricted, and may be factor-mediated. It is the first phase of the in vitro response, and actually the specificity of the T cells which function in the in vitro primary response that we are questioning, in these studies. The experimental approach was to deplete antigen-specific T helper cell activity by passage of T cells through irradiated mice in the presence of a high dose of antigen, and collecting thoracic duct cells one day later. Using this protocol, we have confirmed that removal of SRBC-specific T cells ablates the adoptive transfer in vivo response to SRBC. However, the same negatively selected T cell populations were just as potent as control T cells in supporting the in vitro response to SRBC. We confirmed that the T cells removed respond to SRBC in an MHC-restricted manner by removing from an F1 T cell population the cells able to respond to SRBC in association with one parental haplotype. These T cells nonetheless provided equal help for both parental B cell populations in vitro. These experiments show that the MHC-restricted antigen-specific T cell which is required for the in vivo response is not required in the primary in vitro response to erythrocytes. The significance of this is twofold. Firstly, this demonstrates clearly that different T cells are functioning in vitro vs. in vivo. Singer and his colleagues have shown that different B cell subpopulations (Lyb5+ vs. Lyb5-), with differing MHC-restriction requirements, are preferentially activated in vivo and in vitro. Our data says that another difference between the in vivo and in vitro SRBC response is that different T cells are working in the two systems. Understanding exactly which B cell and T cell subpopulations are working within the model system (in vivo or in vitro) that an investigator chooses is obviously of critical importance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗