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Biomedical subjects

W Walker

Publications and source records attributed to W Walker.

At least 37 records · Page 2Linked to original sources
PubMed1997

Role of transesophageal echocardiography in the clinical management of a patients with a giant coronary artery aneurysm.

Transthoracic echocardiography (TTE) has substantial limitations for the study of abnormalities of the coronary tree. Transesophageal echocardiography (TEE) allows a more complete examination of the coronary arteries, particularly the proximal segments. This report describes the use of TEE after cardiac catheterization in the clinical management of a patient with unstable angina. While angiography first showed the giant aneurysm of the left circumflex coronary artery. TEE, by revealing an active thrombus of the lumen, prompted an immediate surgical resolution.

Aged↗
PubMed1997

Comparison of the effects of interleukin-1 alpha, interleukin-1 beta and interferon-gamma-inducing factor on the production of interferon-gamma by natural killer.

Interferon-gamma inducing factor (IGIF) is a recently identified cytokine which stimulates the production of interferon-gamma (IFN-gamma) by T cells and enhances natural killer (NK) cell cytolytic activity. Protein fold recognition, structure prediction and comparative modeling have revealed that IGIF is a member of the interleukin (IL)-1 cytokine family and has prompted the designation IL-1 gamma. Here we report functional similarities between members of the IL-1 family by comparing the effects of IL-1 alpha, IL-1 beta and IGIF on NK cell production of IFN-gamma. All three IL-1 types enhanced NK cell production of IFN-gamma when induced by IL-2 or IL-12, although at high concentrations (> 10 ng/ml), IGIF was five- to tenfold more potent than IL-1 alpha or IL-1 beta. This effect correlated with enhanced levels of mRNA for IFN-gamma when NK cells were stimulated with IGIF plus IL-12. In contrast to IL-12 and IL-2, the ability of IGIF to stimulate NK cell production of IFN-gamma was not increased by IL-1 alpha or IL-1 beta. The ability of IGIF to enhance IFN-gamma production was independent of the type I and type II IL-1 receptors or the IL-1R accessory protein. Together, these results identify IGIF as a potent stimulator of NK cell production of IFN-gamma and demonstrate that the effect of IGIF on NK cell production of IFN-gamma is similar to that of IL-1 alpha and IL-1 beta but distinct from that of IL-12.

Adjuvants, Immunologic↗
PubMed1997

Innate immunity to Toxoplasma gondii is influenced by gender and is associated with differences in interleukin-12 and gamma interferon production.

Given that differences between the sexes in relative susceptibility to parasitic infections have been noted, this study further elucidates the mechanisms responsible by demonstrating that male SCID mice are more resistant than female mice to infection with Toxoplasma gondii and that this difference correlates with enhanced innate immune responses in these animals. Male SCID mice exhibited longer survival times, lower parasite burdens, and less severe pathological changes postinfection. An immunological basis for these differences is demonstrated in that these animals produced interleukin-12 more rapidly and exhibited higher levels of gamma interferon earlier postinfection.

Animals↗
PubMed1996

Lipid vesicle-entrapped influenza A antigen modulates the influenza A-specific human antibody response in immune reconstituted SCID-human mice.

This study was designed to investigate the capacity of purified influenza antigen in the presence and absence of adjuvant to induce human antibody responses in human-PBL-SCID mice. Non-ionic surfactant vesicles (NISV) were used as adjuvant as they have been shown to promote the development of Th1 responses in mouse studies. Human peripheral blood lymphocyte-SCID mice were inoculated with either purified influenza antigen (A/Texas, H3N2) or influenza antigen entrapped in NISV. Both vaccinated groups produced significantly higher plasma levels of influenza-specific human IgG when individually compared with non-vaccinated controls. However, similar comparisons revealed that specific IgM levels were significantly higher only in the group challenged with purified antigen. Further analysis of IgG subclasses also demonstrated an adjuvant-dependent dichotomy in the responses of the vaccine groups when compared with non-vaccinated controls. Thus, only influenza-specific IgG1 antibodies (associated with Th1 responses in humans) were significantly increased above control levels using antigen with adjuvant, while both this subclass and antigen-specific IgG4 (Th2 associated) were significantly increased with antigen alone. These results illustrate the suitability of this model for use in human vaccination studies and demonstrates that influenza antigen applied with NISV selectively promotes only Th1 responses, unlike free antigen which also promotes Th2 responses in vivo.

Adjuvants, Immunologic↗
PubMed1996

Long-term sequelae of hearing impairment in congenital hypothyroidism.

Hearing loss and its functional consequences were evaluated retrospectively in children with congenital hypothyroidism. From a cohort of 101 children followed longitudinally to evaluate newborn screening, 75 with previous hearing tests were studied. Fifteen (20%) were found to have hearing problems. Of these, nine had unilateral or sensorineural loss mostly at high frequencies, five had a conductive loss, and one had both problems. Hearing impaired children differed from children with normal hearing in age of treatment onset (22 vs 14 days) but not disease severity or duration. A comparison of language and auditory processing skills at ages 3, 5, and 7 years revealed that early speech was delayed in hearing impaired children, whereas deficits persisted in later receptive language and auditory discrimination skills. Comparing hearing impaired children and children with normal hearing with matched control subjects at grade 3 showed that hearing impaired children were poorer readers because of less adequate phonologic processing skills.

Child↗
PubMed1996

Planning for a community-based hypertension control program in the inner city.

Uncontrolled hypertension is a significant problem among African-Americans residing in inner city environments. To help address the problem, we are developing community-based hypertension control programs in African-American communities located in Milwaukee, Wisconsin and Chicago, Illinois. The Milwaukee program focuses on an entire, diverse inner city area, while the Chicago program is targeted to several more homogeneous African-American neighborhoods. The investigators hypothesize that the success of a hypertension control program will depend on carefully tailoring the educational approaches to the specific characteristics of the target area. Therefore, the study areas that have been selected differ with regard to community size and diversity, community 'stressors' (poverty, unemployment, crime, etc), and types of organizations which are present in the community. This paper describes the background and the rationale for community hypertension control programs in the inner city. The initial approaches to establishing the program by developing interfaces with the community and the gathering of baseline data through household surveys are described.

Community Medicine↗
PubMed1995

Modulation of Tax and PKA-mediated expression of HTLV-I promoter via cAMP response element binding and modulator proteins CREB and CREM.

Nuclear proteins of the human peripheral blood T lymphocytes that bind to the CREs located within three 21-bp repeat enhancers of the HTLV-I promoter belong to the CREB/CREM family of bZIP transcription factors. It has been shown previously that Tax enhances transactivation of these CREs by direct interactions with the bZIP domain of the transcription factors to stabilize DNA-binding. We show that CREB and CREM bind all three CRE sequences of the HTLV-I promoter which are important determinants in Tax-elicited transactivation as well as PKA-mediated activation of the HTLV-I promoter. Tax and PKA activate transcription from a HTLV-I-LTR CAT reporter plasmid transfected to NIH 3T3 cells, and CREM attenuates the activation. In the context of a GAL4 CREB fusion protein in which the DNA-binding bZIP domain of CREB is replaced by GAL4 binding domain, a single amino acid substitution of serine-133, phosphorylated by PKA and critical for the transactivation function of CREB, attenuates both Tax and PKA-mediated transcriptional responses. These observations suggest that Tax enhances CREB-mediated transactivation of the HTLV-I promoter by a mechanism apart from, and/or in addition to, the reported stabilization of DNA-binding by interaction with the bZIP domain of CREB.

3T3 Cells↗
PubMed1995

Antibody responses to Toxoplasma gondii antigen in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient mice reproduce the immunological status of the lymphocyte donor.

These studies describe the production of specific antibodies in human peripheral blood lymphocyte-reconstituted severe-combined immunodeficient (PBL-SCID) mice following vaccination with antigen from the protozoan parasite Toxoplasma gondii. To determine the effect of previous exposure of the lymphocyte donor to antigen, human-PBL-SCID animals were created by transferring peripheral blood lymphocytes from either a single T. gondii-seronegative or a single seropositive donor. These reconstituted animals were subsequently inoculated with T. gondii soluble tachyzoite antigen (STAg) entrapped within non-ionic surfactant vesicles as an immunological adjuvant. Animals were bled at pre-determined time points post-vaccination and the expression of human anti-STAg antibodies in the plasma determined by enzyme-linked immunosorbent assay. Human antibodies specific for STAg were readily inducible in both groups of reconstituted animals, although the pattern of isotype production differed markedly between groups. The response in animals reconstituted with lymphocytes from the T. gondii-seronegative donor consisted primarily of IgM and subsequently of IgG (predominantly IgG1). In animals reconstituted with lymphocytes from the seropositive donor, no parasite-specific IgM could be demonstrated. The detectable response to STAg consisted entirely of human antibodies of the IgG isotype (IgG1), indicative of a memory-type response. These results mimicked exactly the antibody responses that would be expected had the lymphocyte donors been directly challenged with either the antigen or the live infectious agent, demonstrating that the immune system within these animals is functional and reproducible with regard to both the primary and secondary responses of the human donors.

Animals↗
PubMed1995

The development of a novel immunotherapy model of human ovarian cancer in human PBL-severe combined immunodeficient (SCID) mice.

The reported ability of SCID mice to accept xenografts of both human tumors and peripheral blood lymphocytes (PBL) provides the potential for the development of novel immunotherapy models in these animals. This study describes the development of a novel small animal model of human ovarian cancer. This was achieved by engrafting a human ovarian cancer cell line (Ovan-4) into the peritoneal cavity of immunodeficient SCID and immune reconstituted human PBL-SCID mice. When transplanted to SCID mice this cell line exhibited growth characteristics similar to the clinical disease observed in patients with implantation of metastatic nodules onto the interior surface of the peritoneal wall. Reconstituted human PBL-SCID mice challenged with identical numbers of Ovan-4 cells exhibited a significant increase in survival time, suggesting a role for cells of the human immune system in preventing the development of this type of malignancy in vivo. Furthermore, vaccination of human PBL-SCID mice against Ovan-4 produced tumour-specific human antibodies in the serum of these animals. Animals reconstituted with CD8-depleted PBL exhibited increased serum immunoglobulin levels and produced enhanced anti-Ovan-4 activity after vaccination. Subsequent challenge of these animals with Ovan-4 revealed a further increase in survival time. These results suggest that human antibodies may have a role in immunity against ovarian cancer and could be of therapeutic value in this type of disease.

Animals↗
PubMed1994

Psychological development of technology-dependent children.

Reviewed the psychosocial and developmental challenges faced by technology-dependent children, their families, and their caregivers. Previous literature which has examined psychological outcome in children with repeated hospitalizations is presented. Psychosocial implications for programs addressing the needs of technology-dependent children are discussed.

Child↗
PubMed1994

The in vivo production of specific human antibodies by vaccination of human-PBL-SCID mice.

Human-PBL-SCID animals were created by intraperitoneal (i.p.) transfer of human peripheral blood lymphocytes (PBL) or PBL depleted of CD8-expressing lymphocytes (CD8dL). Analysis of human immunoglobulin levels in these animals revealed that severe combined immunodeficiency (SCID) mice receiving CD8dL produced significantly higher levels of serum human immunoglobulin than those receiving PBL. In an attempt to induce antigen-specific human antibodies these human-PBL-SCID animals were vaccinated with soluble protein antigen [ovalbumin (OVA)] entrapped within liposomes as an immunological adjuvant. Vaccination produced antigen-specific human IgM and IgG in human-PBL-SCID mouse serum. The use of liposomes as adjuvant and the reconstitution of animals with CD8dL together enhanced the OVA-specific immune response as evidenced by the detection of significantly increased serum antibody titres. In the CD8dL reconstituted group, solid tumours of human B-cell origin became detectable in the peritoneal cavity of animals at 8-10 weeks post-reconstitution. These tumours were readily established in vitro and subsequent analysis of culture supernatants showed that these malignant cells continue to secrete human antibodies specific for the original immunizing antigen in vitro. We believe this vaccination of the human-PBL-SCID mouse to produce antigen-specific human antibodies, may find use in the future production of human monoclonal antibodies and in the testing and development of novel vaccine/adjuvant systems.

Adjuvants, Immunologic↗
PubMed1994

Human immunoglobulin production in SCID mice following primary sensitisation of human lymphocytes in situ.

We have grafted human peripheral blood mononuclear cells to the peritoneal cavity of SCID mice, exposed them to soluble antigens in the absence of adjuvant and examined their ability to make specific antibody. The effect of in vitro pre-priming of donor cells on antibody production was determined. Human IgM and IgG antibodies were found in the SCID serum following in situ antigenic challenge and there was good evidence of antigen specificity. The total Ig levels and the relative antigen binding ability were diminished by in vitro pre-priming. The results demonstrate that primary human antibodies against antigens to which the donor is probably naive can be generated by in situ sensitisation in SCID mice, but that optimisation for each antigen may be required.

Animals↗
PubMed1993

Prevention of hypoxemia during lumbar puncture in infancy with preoxygenation.

Hypoxemia has previously been reported during lumbar puncture (LP) in infancy. The purpose of this study was to determine whether preoxygenation before the LP would reduce hypoxemia during the procedure in infants. Twenty-one infants (one to 15 weeks of age) undergoing LP for evaluation of possible sepsis were randomly assigned to the control group (12) or treatment group (9). The treatment group was preoxygenated breathing oxygen (FiO2 = 1.0) spontaneously via snug face mask for three minutes prior to being positioned for the LP. The control group spontaneously breathed room air during this interval. Oxyhemoglobin saturation was measured prior to, and continuously during, the LP with pulse oximetry. The groups were comparable in age, resting respiratory rate, baseline saturation, and duration of the procedure. The treatment group developed significantly less desaturation during the procedure than the control group (P < 0.05). We conclude that preoxygenation prior to LP prevents most of the hypoxemia resulting from the procedure in infants.

Female↗
PubMed1993

Mononuclear blood cell magnesium in older subjects: evaluation of its use in clinical practice.

Serum and mononuclear blood cell (MBC) magnesium were measured in 24 healthy community subjects, average age 76 years (67-93), and in 21 ill hospitalized subjects, average age 79 years (65-90). MBC magnesium, expressed as mumol/mg protein, was significantly lower in the in-patient group (P < 0.001), but tended to be higher in the same group when expressed as fmol/cell (not significant). Further samples from community subjects on the same day, and again at 7 days, revealed coefficients of variation for intrasubject analysis of 12% and 22%, respectively (fmol/cell). The equivalent intrasubject values for serum were 2.8% on the same day and 4% at 1 week. MBC magnesium values for inpatients were probably distorted by changes in cell size and cell protein content caused by illness. Biological variability and the effects of illness on the composition and size of cells seem to limit the usefulness of MBC magnesium measurement as a clinical tool for assessment of body magnesium status.

Aged↗
PubMed1992

Monoclonal antibodies to rat liver microsomal cytochrome b5.

Hybridomas obtained by the fusion of spleen cells from rat cytochrome b5-immunized mice with mouse myeloma cells produced five groups of monoclonal antibodies (MAbs) with three mouse immunoglobulin subtypes: IgG1, IgG2b and IgM. All of the MAbs bound strongly to rat cytochrome b5 as measured by radioimmunoassay (RIA). Four clones of MAbs were also strongly immunoreactive with cytochrome b5 when tested by Western blotting, but only one of the MAbs (1-39-2) weakly immunoprecipitated cytochrome b5 in an Ouchterlony double-immunodiffusion test. Two of the MAbs partially inhibited cytochrome b5-mediated NADH cytochrome c reduction catalyzed by liver microsomes (24-36%). Expression of immunodetectable cytochrome b5 was highest in the liver, next highest in the kidney, and quite low in the other tissues examined with MAb 1-17-1 by Western blotting. This MAb recognized homologous cytochrome b5 of human liver microsomes and in homogenates of TK- cells infected with recombinant vaccinia virus encoding human cytochrome b5. These MAbs to cytochrome b5 will be useful for the identification, quantification, and purification of cytochrome b5 from animal and human tissues, and for understanding its role in cytochrome P450 catalyzed drug metabolism and carcinogen activation with respect to tissue, organ and individual differences.

Age Factors↗
PubMed1992

Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow.

Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory.

Bone Marrow↗