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Biomedical subjects

J S Murray

Publications and source records attributed to J S Murray.

At least 37 records · Page 2Linked to original sources
PubMed1995

Social support for siblings of children with cancer.

This descriptive study investigated nursing interventions used by pediatric oncology nurses to provide social support to siblings of children with cancer. The study was guided by House's conceptualization of social support which includes components of emotional, instrumental, informational, and appraisal support. A sample of 250 randomly selected pediatric oncology nurses were mailed the Sibling Social Support Questionnaire (SSSQ), developed by the researcher, to determine what interventions they use in clinical practice to provide social support to siblings of children with cancer. With 134 nurse respondents, the SSSQ demonstrated high internal consistency (Cronbach's alpha of .95). Results indicated that the two most frequently used nursing interventions to provide social support to siblings are: (1) encouraging parents to spend time with their other children and (2) providing honest responses to questions asked by siblings.

Adult↗
PubMed1994

Major histocompatibility complex regulation of T helper functions mapped to a peptide C terminus that controls ligand density.

The functional status (Th1- versus Th2-like) of CD4 T cells primed against human collagen type IV (hCol IV) or a single 30mer peptide from the alpha 2 chain of this molecule is predicted by the major histocompatibility complex (MHC) class II (I-A) genotype of the responding mice. H-2s mice elicit Th1-like cell-mediated responses to these antigens, whereas Th2-like humoral responses are primed in H-2b,d,k mice. We now report that the ability of MHC to dictate T helper function in this system depends upon a single amino acid of the minimal alpha 2(IV) peptide. The C terminus of this minimal (12mer) peptide is -G-G-P-K, which is predicted to form a beta-turn. The present data demonstrate that the terminal lysine (K) stabilizes the immunogens full biological effects necessary for exclusive cell-mediated responses in H-2s mice. The lysine-truncated (11mer) peptide with otherwise identical sequence effectively primes T helper function in both H-2b and H-2s genotypes. Most importantly, our direct analysis of these peptides' presentation by live antigen-presenting cells (APC) reveals that the 12mer is bound at a log higher density on H-2s APC than on H-2b APC, and that the 11mer is presented at an equally low relative density on APC from both genotypes. In vitro analyses of 12mer/11mer cross-reactive Th clones demonstrate that I-As restricted clones require about 1-2 log lower doses of 12mer peptide than 11mer peptide to stimulate equivalent thymidine incorporation and cytokine release. By contrast, I-Ab-restricted (12mer/11mer cross-reactive) Th clones show no preference for the 12mer and require relatively high peptide doses similar to those required to stimulate the I-As clones with the 11mer peptide. Thus, the peptide dose requirements of Th clones reflect the high density of presentation associated with the 12mer: I-As ligand. Taken together, the results directly support the role of ligand density as an important control point in the functional decision of CD4 T cells.

Amino Acid Sequence↗
PubMed1994

Calculated surface electrostatic potentials of molecular sieve models containing SiO4, AlO4, and PO4 units.

Surface electrostatic potentials have been computed at the ab initio HF/STO-5G* level for two model systems: a fragment of a zeolite channel wall; and a fragment composed of SiO4, AlO4 and PO4 units. The potential above the SiO4 network is negative everywhere, despite these units commonly being regarded as electrically neutral. In marked contrast, the AlO4 and PO4 units introduce strongly negative and positive regions, respectively, giving rise to a much more heterogeneous surface potential.

Aluminum Compounds↗
PubMed1993

Functional CD4 T cell subset interplay in an intact immune system.

Immunization with human collagen IV has been shown to lead to the selective activation of Th-1 and Th-2-like cells in vivo depending on the I-A genotype of the mice. Mice expressing I-As generate Th-1 cells, and mice expressing I-Ab generate Th-2 cells after immunization. We examined the response of (bxs)F1 hybrid mice to determine the types of CD4 T cell activated. We found that Th-1-like responses dominated, in that CD4 T cells from human collagen IV-primed mice displayed good proliferative responses and little ability to induce antibody formation, and secreted IFN-gamma and not IL-5. Most of the Th-1-like activity of F1 hybrid T cells was I-As restricted. Inhibition of Th-1 cell priming using anti-I-As antibody administered with the priming Ag in vivo revealed Th-2-like activity, in that the CD4 T cells now secreted IL-5 and not IFN-gamma and induced antibody formation. Additional studies indicated that anti-IFN-gamma treatment in vivo also revealed Th-2 cells, suggesting that I-As-restricted CD4 T cells producing or controlling the production of IFN-gamma suppress Th-2 priming.

Animals↗
PubMed1993

D-arabitol metabolism in Candida albicans: studies of the biosynthetic pathway and the gene that encodes NAD-dependent D-arabitol dehydrogenase.

Candida albicans produces large amounts of the pentitol D-arabitol in culture and in infected mammalian hosts, but the functional and pathogenic significance of D-arabitol in C. albicans is not known. In this study, we sought to elucidate the pathway by which C. albicans synthesizes D-arabitol and to identify and characterize key enzymes in this pathway. C. albicans B311 produced D-[14C-1]arabitol from [14C-2]glucose; this finding implies on structural grounds that D-ribulose-5-PO4 from the pentose pathway is the major metabolic precursor of D-arabitol. NAD- or NADP-dependent pentitol dehydrogenases catalyze the final steps in D-arabitol biosynthesis in other fungi; therefore, lysates of C. albicans B311 were tested for enzymes of this class and were found to contain a previously unknown NAD-dependent D-arabitol dehydrogenase (ArDH). The ArDH structural gene was cloned by constructing a new D-arabitol utilization pathway in Escherichia coli. The C. albicans ArDH gene expressed in E. coli and Saccharomyces cerevisiae an enzyme that catalyzes the reaction D-arabitol + NAD <-->D-ribulose + NADH; this gene was present as a single copy per haploid genome, and its deduced peptide sequence was homologous with sequences of several members of the short-chain dehydrogenase family of enzymes. These results suggest that (i) C. albicans synthesizes D-arabitol by dephosphorylating and reducing the pentose pathway intermediate D-ribulose-5-PO4 and (ii) ArDH catalyzes the final step in this pathway.

Amino Acid Sequence↗
PubMed1992

Major histocompatibility complex (MHC) control of CD4 T cell subset activation. II. A single peptide induces either humoral or cell-mediated responses in mice of distinct MHC genotype.

CD4 T cells activated in vivo in response to human collagen type IV (hCol IV) resemble either T helper type 1 (Th1) or Th2 cells depending on the major histocompatibility complex (MHC) class II genotype of the responding mice. H-2s mice were shown to selectively activate Th1-like cells, releasing interleukin (IL 2 and interferon-gamma in response to hCol IV, whereas H-2b.d mice were shown to selectively activate Th2-like cells, releasing IL 4 and IL 5 in response to hCol IV. These results suggested that MHC class II regulated the type of effector function observed during an immune response. It was of interest to determine if the functional difference observed between the CD4 T cells of the two strains was due to the presentation of different peptides of the hCol IV molecule by the two MHC class II molecules. The present results demonstrate that a single peptide of the collagen IV molecule will elicit a Th1-like response in H-2s strains and Th2-like responses in H-2b.d strains, as was observed when using the intact hCol IV molecule. Furthermore, the failure to generate Th1-like responses in H-2b.d could be overcome by increasing the dose of this peptide in vitro. Compared to H-2s, the Th1-like response in H-2b required 100 times the amount of peptide to reelicit an equivalent response. These data suggest that a single peptide of hCol IV can control the type of effector response observed.

Amino Acid Sequence↗
PubMed1990

Measurement of association constants in ELISA. Reactions between solid-phase antibody and fluid-phase biotinylated antigen.

An ELISA procedure which utilized an avidin-peroxidase amplification reaction to detect and quantify the amount of fluid-phase biotinylated antigen bound to solid-phase antibody was developed to determine antibody association constants. The methodology required is uncomplicated, avoids the use of radioisotopes, and is theoretically amenable for use with any protein which can be biotinylated, and any receptor protein which can be immobilized on plastic wells. A plot of known immobilized biotinylated antigen concentrations, which ranged from approximately 100 ng/ml to 1000 ng/ml, versus avidin-peroxidase conjugate product formation, was used to establish a standard curve from which the amount of antibody-associated antigen in binding assays could be determined. Antibody association constants obtained with this method ranged from 10(5) to 10(9) M-1.

Animals↗
PubMed1990

The use of the electrostatic potential at the molecular surface in recognition interactions: dibenzo-p-dioxins and related systems.

An ab initio self-consistent-field molecular orbital approach was used to compute the electrostatic potentials of dibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two analogues of the latter, and two isomeric benzoflavones on a three-dimensional molecular surface corresponding to the contour of constant electronic density equal to 0.002 electrons/bohr3. The results are discussed in relation to the biological activities of the respective molecules. It is shown that the electrostatic potential graphically depicted on the molecular surface is well suited for the study of recognition interactions, such as are believed to be involved in the initial receptor-mediated step leading to toxicity in the dibenzo-p-dioxins. The surface potential has the advantage of clearly showing steric features that may play a role in understanding the recognition process being investigated.

Computer Graphics↗
PubMed1990

Evidence that the Fc region of autologous rabbit IgG isolated before and after hyperimmunization is structurally different: recognition by rheumatoid factor and monoclonal antibodies.

Autologous hyperimmune (HI) and pre-inoculation (PI) rabbit Fc gamma populations were found to be conformationally different by spectroscopic measurements, and antigenically different by measurements which examined rheumatoid factor (RF) and monoclonal antibody (MoAb) binding specificity for both populations in ELISA. Circular dichroism spectra of HI rabbit Fc gamma (prepared from animals after hyperimmunization with streptococcal vaccine) were both qualitatively and quantitatively different, particularly in the 225-228 nm range, in comparison to both homologous normal and autologous PI Fc gamma. Binding studies in ELISA showed that affinity constants obtained for reactions of both rabbit RF and various murine MoAb with HI IgG and Fc were approximately 10-fold higher relative to those observed for PI IgG and Fc. Enzymatic deglycosylation of HI and PI Fc gamma led to elimination of CD spectral differences. Further, association constants obtained for RF and MoAb reactions with deglycosylated (sialic acid and galactose removed) PI Fc gamma were equivalent to those obtained in the presence of untreated HI Fc gamma. Together, these results suggest the complex oligosaccharide structure of rabbit IgG may play a significant role in the expression of Fc gamma determinants, and alteration of this structure under hyperimmune or other conditions may be related to induction of an RF response.

Animals↗
PubMed1989

MHC control of CD4+ T cell subset activation.

The present results demonstrate that CD4+ T cells activated in the primary in vivo response to antigen produce distinct patterns of cytokines depending upon the MHC class II haplotype of the responding mice. I-As mice were found to selectively activate IL-2/IFN-gamma-producing CD4+ T cells, whereas I-Ab mice exhibited selective activation of IL-4-producing CD4+ T cells in response to collagen IV. The effector response phenotype was found to correlate with the cytokine phenotype of CD4+ T cells activated in vivo; IL-2/IFN-gamma-producing cells giving rise to proliferative (cell-mediated) responses, IL-4-producing cells leading to secondary IgG (humoral) responses. Together the data support the notion that the outcome of a given immune response (e.g., protection vs. onset, tolerance vs. autoimmunity) may be determined in part by the type of CD4+ T cells initially activated by antigen. Moreover, the present experiments demonstrate for the first time that polymorphism in class II MHC can determine such selective activation of different cytokine-producing CD4+ T cell phenotypes.

Animals↗
PubMed1988

Hyperimmunization alters Fc gamma antigenicity. Linkage to glycosylation.

Rabbits were hyperimmunized with streptococcal vaccine to produce hyperimmune (HI) IgG, and both HI IgG and autologous preinoculation (PI) IgG were used to prepare Fc gamma. mAb raised against these, and deglycosylated PI Fc gamma preparations were subsequently used to determine if antigenic differences existed between autologous HI and PI Fc gamma. Although the majority of mAb examined did not discriminate between the two sources of Fc gamma, several mAb exhibited remarkable specificity for autologous HI Fc gamma. We did not detect any mAb which exhibited the converse specificity. Of the mAb chosen for study, all except one appeared specific for determinants located in C gamma 2; the exception specifically reacted with pFc', and did not discriminate between the two Fc preparations. Importantly, partial deglycosylation of autologous PI Fc gamma led to equivalent reactivity with previously HI-specific mAb. The results of this study provide immunologic evidence that abnormal C gamma 2 structures exist prior to and reach serologically detectable levels during the hyperimmune response in these animals, apparently as a result of glycosylation pattern alterations within the Fc region. Such autoantigenic differences could account for the induction of RF under these conditions, and perhaps in certain human arthritic diseases as well.

Alkylation↗
PubMed1981

Teratogenic effects of vitamin A palmitate in Fischer 344 rats.

Prior to employing the Fischer 344 rat in teratology studies, it was considered necessary to establish the responsiveness of this strain to teratogenic agents. Bred Fischer 344 rats were administered 0, 3.2, 32, or 128 mg/kg/day (approximately 1,000, 10,000, or 40,000 USP units per animal) of vitamin A palmitate by gavage on days 6 through 15 of gestation. Maternal toxicity, as evidenced by decreased body weight gain, and decreased food and water consumption, was observed at the 128 mg/kg/day dose level. This dosage level was embryolethal and teratogenic in the Fischer 344 rat. The incidence of fetal resorptions was statistically significantly increased as compared to controls. Among the surviving fetuses, malformations observed included cleft palate, exencephaly, microphthalmia, anophthalmia, hydronephrosis, brachygnathia, pinna anomalies, and great vessel and heart anomalies. Based on these findings, it is concluded that the Fischer 344 rat responded to a known teratogenic agent and hence is appropriate for use in studies designed to evaluate the teratogenic potential of test agents.

Animals↗
PubMed1981

Triethylenemelamine (TEM): dominant lethal effects in Fischer 344 rats.

Male Fischer 344 rats were administered triethylenemelamine orally at dose levels of 0, 0.5 or 1.0 mg TEM/kg/day, five days per week for four weeks. A separate group of males was administered TEM as a single intraperitoneal injection of 0.3 mg/kg. Following treatment, males were mated with two groups of untreated females for a period of one week each. The uterine contents of untreated females were examined for evidence of a dominant lethal effect as manifested in an increase in the average resorption rate. Significant increases in the resorption rate were seen at 0.5 mg/kg/day for the second breeding period, and at 1.0 mg/kg/day for both breeding periods following oral administration. Significant decreases in the number of implantations, and increases in the average pre-implantation loss and resorption rate were observed following intraperitoneal administration. These effects seen in Fischer 344 rats were comparable to results obtained with other strains following a similar treatment regimen.

Animals↗
PubMed1980

2-Isocyanatoethyl methacrylate--an inhalation dominant lethal study in the male Sprague-Dawley rat.

2-Isocyanatoethyl methacrylate (IEM), a monomer, has been developed for use as a component in coating materials. The dominant lethal test was used to evaluate the mutagenic potential of IEM in rats. In this study, male Sprague-Dawley rats were exposed to 0, 25, 80, or 250 ppb of IEM by inhalation for 6 hr/day for 10 weeks (one spermatogenic cycle). After the exposure period, the males were bred with untreated virgin female rats. At approximately mid-gestation, the females were sacrificed and the number of corpora lutea, implantations, and resorptions were recorded. Statistical analysis of these data indicated that the treated males were comparable to control males in all reproductive parameters evaluated. IEM did not affect male fertility or produce dominant lethal mutations in male rats following ten weeks of inhalation exposure to 25, 80 or 250 ppb IEM.

Acrylates↗