Biomedical subjects

M Jenkins

Publications and source records attributed to M Jenkins.

At least 37 records · Page 2Linked to original sources

PubMed1999

Fas is expressed early in human thymocyte development but does not transmit an apoptotic signal.

We investigated the expression and function of Fas on human thymocytes prepared from fetal and pediatric tissue specimens and from SCID-hu Thy/Liv grafts. Unlike mouse thymocytes, human thymocytes exhibited a pattern of Fas expression skewed to immature cells, in that the highest expression was seen on double negative thymocytes and on intrathymic T progenitor cells. Fas expression was intermediate on double positive human thymocytes, and low or negative on mature single positive CD4 and CD8 medullary thymocytes. In spite of this relatively abundant surface expression, cross-linking of Fas with agonist mAb was incapable of triggering an apoptotic signal in human thymocytes. Apoptotic signaling was not enhanced by treatment with cycloheximide, nor by restoring a cosignaling milieu by addition of thymic stromal cells. Mouse thymocytes were induced to apoptosis by cross-linked recombinant soluble human Fas ligand both in vitro and in vivo, though human thymocytes were also resistant to this mode of receptor ligation. Membrane-bound Fas ligand also induced apoptotic death in murine thymocytes but not in human thymocytes. Human thymocytes were as sensitive as Jurkat cells, however, to apoptosis induced by TNF-alpha, suggesting that these cells have a signaling defect before activation of the earliest caspases. These data demonstrate a durable and specific resistance of human thymocytes to apoptosis induced through Fas receptor engagement, and reveal significant species-specific differences in the biology of thymocyte-programmed cell death.

Animals↗

PubMed1999

Histopathologic evaluation of an expanded polytetrafluoroethylene-nitinol stent endoprosthesis in canine iliofemoral arteries.

PURPOSE: The authors assess a new ePTFE-nitinol stent for its long-term patency, healing, and properties of endothelialization. MATERIALS AND METHODS: Adult greyhounds (n = 18) underwent bilateral iliofemoral placement of an endoprosthesis (Hemobahn) consisting of a nitinol stent lined with an ultrathin expanded polytetrafluoroethylene (ePTFE) material. Histologic and quantitative morphometric analyses were performed on devices explanted at 2 weeks and 1, 3, 6, and 12 months. The source of endothelialization was examined in four additional devices modified by sealing either the proximal and distal ends or the entire graft with poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP), a nonporous laminate to prevent potential transgraft endothelial cell migration. RESULTS: Device patency assessed with both intravascular ultrasound and histologic study showed minimal arterial stenosis, irrespective of implant duration. The neointima at less than 3 months consisted of fibrin and inflammatory infiltrate; at later time points, it was composed of mostly smooth muscle cells. Flow surfaces were more than 75% endothelialized by 3 months, which was nearly complete by 6 months. Modified endoprostheses entirely enveloped with FEP resulted in endothelialization of only the proximal and distal ends; the middle regions showed nonocclusive thrombi. Conversely, devices wrapped proximally and distally showed nearly complete endothelialization. CONCLUSIONS: This ePTFE-nitinol endoprosthesis demonstrated long-term patency at up to 1 year after implantation and showed early and nearly complete endothelialization by 6 months. The design promoted rapid endothelialization of flow surfaces, particularly in the midregion of the device possibly by transgraft migration.

Alloys↗

PubMed1999

Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy.

Injected antigen-loaded immature monocyte-derived dendritic cells (DCs) may be incapable of migrating from skin to draining lymph nodes for antigen presentation. The in vivo migratory capacity of intradermally administered immature monocyte-derived DCs was therefore investigated during a phase I/II clinical trial for metastatic melanoma. DCs cultured from adherent monocytes in the presence of autologous serum, granulocyte-macrophage colony stimulating factor and interleukin-4 were pulsed with antigen and labelled with technetium-99m hexamethylpropylene-amineoxime (99mTc-HMPAO) ex vivo, then injected intradermally. A 99mTc-HMPAO control containing an equivalent amount of radioactivity was injected into the opposite thigh. The pelvis was then imaged with a gamma camera. The DCs were characterized as immature by functional and phenotypic analysis. Labelled DCs travelled to the draining inguinal lymph nodes within 10 min, and the draining lymph nodes were clearly outlined up to 4 h after injection. Free NmTc outlined draining lymph nodes after 10 min but was cleared from the nodes within 1 h. Thus, immature human monocyte-derived DCs migrate rapidly to and remain in draining lymph nodes after intradermal injection for immunotherapy.

Adult↗

PubMed1999

A comparison of the plasma disappearance of iohexol and 99mTc-DTPA for the measurement of glomerular filtration rate (GFR) in diabetes.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy. GFR is most commonly measured by the plasma clearance of radioisotopes, however, use of iohexol, a non-ionic radiocontrast medium, is a recently described alternative and has shown good agreement with inulin clearance. A one-compartment model is used for calculating GFR in most Australian centres but a two-compartment model is more accurate. AIMS: To set up a non-radioisotopic method for assessment of GFR using iohexol, and to compare this with the currently used 99mTc-diethylene-triamine-penta-acetic acid (DTPA) method. Secondly, to compare GFR results using an unmodified one-compartment model with a one-compartment model subjected to the Brochner-Mortensen modification. METHODS: Twenty-one patients with diabetes had assessment of GFR with simultaneous measurements of 99mTc-DTPA and iohexol plasma clearance. Plasma clearance was determined by the slope intercept method and then modified according to the Brochner-Mortensen equation. Plasma iohexol concentrations were determined by capillary electrophoresis. RESULTS: There was no significant difference between iohexol and 99mTc-DTPA derived GFR values, difference 4.3+/-7.7 mL/minute (mean+/-SD). This was despite 99mTc-DTPA protein binding demonstrated in the range of 5-10%. Comparison of GFR results using an unmodified one-compartment model with a Brochner-Mortensen corrected one-compartment model showed higher GFR values with the former, in the range of 20-30% for GFR values > 100 mL/minute. CONCLUSION: Iohexol provides an efficient alternative to radioisotopic methods for serial measurement of GFR in diabetic patients with hyperfiltration, incipient and overt nephropathy. A one-compartment model with its inherent overestimation of GFR should be replaced by the Brochner-Mortensen modified one-compartment model.

Adult↗

PubMed1998

Prevention of peripheral tolerance by a dendritic cell growth factor: flt3 ligand as an adjuvant.

Injections of soluble proteins are poorly immunogenic, and often elicit antigen-specific tolerance. The mechanism of this phenomenon has been an enduring puzzle, but it has been speculated that tolerance induction may be due to antigen presentation by poorly stimulatory, resting B cells, which lack specific immunoglobulin receptors for the protein. In contrast, adjuvants, or infectious agents, which cause the release of proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 1beta in vivo are believed to recruit and activate professional antigen-presenting cells to the site(s) of infection, thereby eliciting immunity. Here we show that administration of Flt3 ligand (FL), a cytokine capable of inducing large numbers of dendritic cells (DCs) in vivo, (a) dramatically enhances the sensitivity of antigen-specific B and T cell responses to systemic injection of a soluble protein, through a CD40-CD40 ligand-dependent mechanism; (b) influences the class of antibody produced; and (c) enables productive immune responses to otherwise tolerogenic protocols. These data support the hypothesis that the delicate balance between immunity and tolerance in vivo is pivotally controlled by DCs, and underscore the potential of FL as a vaccine adjuvant for immunotherapy in infectious disease and other clinical settings.

Adjuvants, Immunologic↗

PubMed1998

Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage hematopoiesis in vivo.

It is still uncertain whether multilineage hematopoietic progenitor cells are affected by human immunodeficiency virus-1 (HIV-1) infection in vivo. The SCID-hu Thy/Liv model is permissive of long-term multilineage human hematopoiesis, including T lymphopoiesis. This model was used to investigate the effects of HIV-1 infection on early hematopoietic progenitor function. We found that both lineage-restricted and multilineage hematopoietic progenitors were depleted from grafts infected with either a molecular clone or a primary isolate of HIV-1. Depletion of hematopoietic progenitors (including CD34(+) cells, colony-forming units in methylcellulose, and long-term culture-initiating cells) occurred several days before the onset of thymocyte depletion, indicating that the subsequent rapid decline in thymocyte numbers was due at least in part to loss of thymocyte progenitors. HIV-1 proviral genomes were not detected at high frequency in hematopoietic cells earlier than the intrathymic T-progenitor cell stage, despite the depletion of such cells in infected grafts. Proviral genomes were also not detected in colonies derived from progenitor cells from infected grafts. These data demonstrate that HIV-1 infection interrupts both lineage-restricted and multilineage hematopoiesis in vivo and suggest that depletion of early hematopoietic progenitor cells occurs in the absence of direct viral infection.

Animals↗

PubMed1998

Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection.

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

Adult↗

PubMed1998

Identification and characterisation of a dense granule-associated protein in Neospora caninum tachyzoites.

Neospora caninum is an apicomplexan parasite which is morphologically and ultrastructurally very similar to Toxoplasma gondii. In order to identify molecules involved in host cell entry and subsequent modification of the parasitophorous vacuole, a polyclonal antiserum directed against N. caninum tachyzoites was raised in a rabbit. Subcellular fractionation of tachyzoites was performed using the non-ionic detergent Triton-X-114. Membrane fractions were analysed by immunoblotting using the polyclonal antiserum. One of the immunoreactive protein bands had a mol. wt of 33,000 and was subsequently named Nc-p33. Affinity-purified anti-Nc-p33 antibodies were used to characterise this polypeptide using SDS-PAGE, isoelectric focusing, Western blot analysis and immuno-EM. Nc-p33 was found in two isolates of N. caninum (NC-1 and Liverpool), but could not be detected in T. gondii tachyzoites. Immunogold EM revealed that Nc-p33 constituted a dense granule-associated protein, and Western blotting demonstrated that Nc-p33 was most likely identical to the recently described antigen NCDG1. Shortly after invasion, this dense granule protein was targeted to the parasitophorous vacuole membrane, and, at later timepoints after infection, was also found on the parasitophorous vacuolar network. This suggested that Nc-p33 could play a functional role in the modification of the parasitophorous vacuole and its membrane.

Animals↗

PubMed1998

Thumb joint flexion. What is normal?

The purpose of this study was to measure the amount of active flexion from a neutral position in normal thumb metacarpophalangeal and interphalangeal joints and compare the results with previously published reports. One hundred and nineteen subjects (238 thumbs) volunteered to have active flexion of the metacarpophalangeal (MP) and interphalangeal (IP) joints of the thumb measured with a computerized Greenleaf goniometer by a certified hand therapist. The mean MP flexion was 59 degrees and IP flexion was 67 degrees. The results of this study suggest that the accepted normal values of thumb flexion should be reconsidered, particularly as a guide for determining impairment.

Adolescent↗

PubMed1998

The naming deficit in early Alzheimer's and vascular dementia.

Patients with early Alzheimer's disease (AD) were compared to normal controls and patients with early vascular dementia (VaD) on their naming errors using the Boston Naming Test (H. Goodglass & E. Kaplan, 1983). All naming errors were classified into three general error categories: visuoperceptual, semantic, and phonemic. Semantic errors were further classified into coordinate errors (responses that belong to the same semantic category as the target words), superordinate errors (responses that belong to a broader semantic category than the target word), and functional-circumlocutory errors (circumlocutions and responses that functionally describe the target word). The findings indicated that AD participants display more overall naming errors than VaD participants, although the pattern of general errors was similar between the patient groups. However, the qualitative difference between the patient groups was observed within the semantic errors because the AD group made more superordinate errors.

Aged↗

PubMed1998

Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance.

BACKGROUND: Some clinicians link chronic disease in certain patients to 'food intolerance'. This is currently diagnosed by exclusion dieting, a time-consuming and tedious technique. It has been claimed that IgE/IgG4 antibody testing is a rapid and valid method of determining food intolerance. OBJECTIVE: To determine the test/retest reliability of IgE/IgG4 antibody testing as a diagnostic tool. METHODS: Blinded testing of duplicate blood samples from nine patients with suspected food intolerance was undertaken by tertiary referral centre using the services of a commercial laboratory. The proportions of consistent and inconsistent results for tests of 95 different foods were analysed. RESULTS: Test/retest reliability was low. Even though the study method systematically overestimated kappa, this value never exceeded 0.51, regardless of the statistical model used. All but one patient had a greater number of inconsistent results than had been prespecified as an unacceptable level of disagreement. In one case, 50 out of 95 test results were inconsistent on retest. CONCLUSIONS: We found no evidence that IgE/IgG4 antibody testing as performed by this laboratory is a reliable diagnostic tool.

Allergens↗

PubMed1998

Assessment of pelvic stabilization devices for improved field reproducibility.

The aim of this study was to evaluate the improvement in patient comfort and field positional accuracy provided by a new pelvic stabilization system when delivering multiple field radiotherapy to the pelvis. The Pelvic Cradle (BEHTS Manufacturing, Brisbane, Qld, Australia) is a stabilization device that provides reproducible patient positioning and levelling. Ninety patients were randomized into three groups. The first group was treated using the Pelvic Cradle, the second group was treated using current stabilization practices, and the third group was treated using the Pron Pillo (Chattanooga Pharmacal Company, USA) and current stabilization practices. Port films were assessed for field displacement in the lateral and cranio-caudal directions. A patient survey was used to evaluate the patient's perception of comfort while receiving treatment. When compared to the control group, the pelvic cradle group demonstrated a 48% improvement in the mean lateral deviation from 3.8 mm to 2.0 mm (P < 0.001) and a 36% improvement in the mean cranio-caudal deviation from 3.9 mm to 2.5 mm (P < 0.001). The Pelvic Cradle was found to provide an improved level of field positional accuracy while maintaining patient comfort.

Aged↗

PubMed1998

Prospective comparison of temperature guided microwave and radiofrequency catheter ablation in the swine heart.

Microwave energy has been proposed as an alternative to radiofrequency energy for use during catheter ablation procedures. The purpose of this study was to prospectively compare, in an animal model, the lesion size associated with temperature guided catheter ablation using either microwave or radiofrequency energy. Eleven swine underwent catheter ablation with either radiofrequency (N = 4) or microwave energy (N = 7). In each animal catheter ablation was performed at 7-15 sites. At each site energy was delivered for 60 seconds using closed loop feedback temperature control to achieve a target temperature of 70 degrees C. Cardiac catheterization was performed before and after ablation. Animals were sacrificed approximately one month following the ablation procedure. Analysis of lesion size demonstrated that overall lesions created using radiofrequency energy were larger than those created using microwave energy. In the ventricle, lesions created using microwave energy were longer, but had a similar width and depth as those created using radiofrequency energy. An important relation was observed between the depth of lesions created using microwave energy and catheter stability, as evidenced by the temperature profile. Overall, lesions created using microwave energy are smaller than those created using radiofrequency energy. Catheter stability has an important impact on lesion size.

Animals↗

PubMed1998

Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI.

In this study, 12 patients over age 60 with depression with moderate to severe subcortical hyperintensities (SH) localized to the periventricular white matter were identified by quantitative MRI. Using the California Verbal Learning Test, they were compared with 12 age-, education-, and severity-matched patients with depression with minimal white matter changes on specific aspects of memory performance. Patients with cortical lesions, neurologic or systemic illness affecting cognition, and history of substance abuse were excluded. Patients in the group with high SH showed reduced use of semantic encoding strategies (p < 0.05), reduced learning efficiency (p < 0.05), and a greater discrepancy between free recall and recognition discriminability (p < 0.05) than their low SH counterparts. This pattern of performance on memory tasks is similar to that found in previous studies to be associated with subcortical degenerative disorders such as Huntington's and Parkinson's diseases. Geriatric patients with depression with SH may represent a subgroup with greater subcortical involvement, with associated cognitive and functional decline.

Aged↗

PubMed1998

Albumin-binding surfaces: synthesis and characterization.

The nature of the proteinaceous film deposited on a biomaterial surface following implantation is a key determinant of the subsequent biological response. To achieve selectivity in the formation of this film, monoclonal antibodies have been coupled to a range of solid substrates using avidin-biotin technology. Antibody clones varied in their antigen-binding activity following insertion of biotin groups into lysine residues. Biotinylated antibodies coupled to solid substrates via an immobilized avidin bridge retained their biological activity. During immobilization of avidin a significant proportion of the protein molecules were passively adsorbed rather than covalently attached to the surface. This loosely bound material could be removed by stringent elution procedures which resulted in a surface density of 5.4 pmol avidin cm(-2). Although these conditions would be harsh enough to denature monoclonal antibodies, they did not destroy the biotin-binding activity of the residual surface-coupled avidin, enabling the subsequent immobilization of biotinylated antibodies. The two-step immobilization technique allowed the use of gentle protein modification procedures, reduced the risk of surface-induced denaturation and removed loosely bound material from the surface. The versatility of the technique encourages its application to a wide range of immobilization systems where retention of biological activity is a key requirement.

Adsorption↗

PubMed1998

Albumin-binding surfaces: in vitro activity.

Immobilized monoclonal antibodies (Mabs) have been used to attract specific molecules to a solid surface from complex mixtures such as blood, plasma or serum, thereby directing the response to the modified substrate, a key goal in rational biomaterial design. The nature of the Mab dictated the nature of the response: anti-albumin antibodies were used to prevent cell and platelet adhesion in vitro, whilst anti-fibronectin Mabs promoted attachment. Patterned surfaces could be formed, bearing Mabs that generated adhesive and non-adhesive regions. Fibrinogen adsorption from plasma showed a Vroman peak on unmodified control polymer, which was reduced by 64% in the presence of surface-bound anti-albumin Mab. Immobilization of a control Mab reduced fibrinogen adsorption only slightly, implying an albumin-mediated effect. In static tests, platelet adhesion from human platelet rich plasma was significantly reduced by the immobilization of anti-HSA Mab when compared to the untreated FEP surface (p < 0.0001). This effect was also seen with citrated blood flowing through Mab-treated polyurethane tubing at a shear rate of 132 s(-1) (p=0.034). Since platelets and proteins (as blood, plasma or serum) were introduced to the surface simultaneously, the generation of a defined protein film must have been sufficiently rapid as to shape the platelet or cell response.

Antibodies, Monoclonal↗

PubMed1998

On nurses.

Explore the source record for details and available documents.

Health Promotion↗

PubMed1998

Implementation of a clinical information system in nurse-managed care.

The Penn Nursing Network Information System Project is a collaborative effort of practitioners, academic researchers, and a health-care software developer. The Penn Nursing Network, a group of nurse-managed practices owned and operated by the University of Pennsylvania School of Nursing, has taken a leadership role in the project. PNN is developing an information system specific to the needs of nurse-managed care and creating a data warehouse for nursing centres in the Philadelphia region. Important components of this project include the identification of key data elements to represent the problems treated, interventions performed, and outcomes sensitive to the nursing care provided. The Omaha System provided a useful framework for capturing the necessary data elements. However, additional data were needed. In addition, attention was paid to the development of a software program that would complement the workflow of the practitioner while capturing data efficiently. The main goal of the project is development of a longitudinal database reflective of clinical practice, to be used for both research and evaluation.

Clinical Nursing Research↗