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Biomedical subjects

J Armstrong

Publications and source records attributed to J Armstrong.

At least 91 records · Page 5Linked to original sources
PubMed1996

Interleukin-1 beta in coronary arteries of patients with ischemic heart disease.

Interleukin-1 beta (IL-1 beta) is known to have a number of effects on the different cell types present within coronary arteries. In this study we identified the location and phenotype of cells containing IL-1 beta in human coronary artery specimens from patients suffering from either coronary atherosclerosis or cardiomyopathy and correlated the presence of IL-1 beta with disease severity. Luminal endothelial cells, adventitial vessel wall cells, and macrophages were double labeled immunohistochemically for IL-1 beta protein and a cell type-specific monoclonal antibody for either endothelial cells or macrophages. In situ hybridization was performed to locate the presence of IL-1 beta mRNA within the coronary artery wall. In this study IL-1 beta protein was found to be increased in the adventitial vessel walls of atherosclerotic coronary arteries compared with coronary arteries from nonischemic cardiomyopathic hearts. This increase was directly proportional to the severity of coronary atherosclerosis. IL-1 beta protein was also detected in luminal endothelium and macrophages of atherosclerotic coronary arteries and coronary arteries from nonischemic cardiomyopathic hearts. IL-1 beta mRNA was found in luminal endothelial cells, adventitial vessel endothelial cells, and macrophages. We conclude that IL-1 beta is produced by endothelial cells and macrophages in coronary arteries from ischemic hearts and to a lesser extent from nonischemic cardiomyopathic hearts.

Adult↗
PubMed1996

Identification of a novel member of the Rab8 family from the rat basophilic leukaemia cell line, RBL.2H3.

We describe the cloning of a cDNA from the rat basophilic leukaemia cell line (RBL.2H3) encoding a novel member of the Rab family of small GTP binding proteins. The novel clone, which we call Rab8b, is most highly related to the Rab8 family with substantial divergence in the variable C-terminal domain. Northern blot analysis reveals highest levels of expression of Rab8b in the spleen, testis and brain, which is in marked contrast to the tissue distribution of Rab8. The Rab8b cDNA was modified to introduce a c-myc epitope tag at the extreme N terminus of the protein, and transient transfection studies were performed to analyse the intracellular localization of Rab8b by confocal microscopy. Transient expression of the c-myc/Rab8b fusion protein in both PC12 and RBL.2H3 cells shows staining of both the plasma membrane and ill-defined vesicular structures, and in the case of RBL.2H3 cells appears to induce striking outgrowths of the plasma membrane.

Amino Acid Sequence↗
PubMed1996

Intensity resolution and subjective magnitude in psychophysical scaling.

Several successful theories of psychophysical judgment imply that exponents of power functions in scaling tasks should covary with measures of intensity resolution such as d' in the same tasks, whereas the prevailing metatheory of ideal psychophysical scaling asserts the independence of the two. In a direct test of this relationship, three prominent psychophysical scaling paradigms were studied: category judgment without an identification function, absolute magnitude estimation, and cross-modality matching with light intensity as the response continuum. Separate groups of subjects for each scaling paradigm made repeated judgments of the loudnesses of the pure tones that constituted each of two stimulus ensembles. The narrow- and wide-range ensembles shared six identical stimulus intensities in the middle of each set. Intensity resolution, as measured by d'-like distances, of these physically identical stimuli was significantly worse for the wide-range set for all three methods. Exponents of power functions fitted to geometric mean responses, and in magnitude estimation and cross-modality matching the geometric mean responses themselves, were also significantly smaller in the wide-range condition. The variation of power function exponents, and of psychophysical scale values, for stimulus intensities that were identical in the two stimulus sets with the intensities of other members of the ensembles is inconsistent with the metatheory on which modern psychophysical scaling practice is based, although it is consistent with other useful approaches to measurement of psychological magnitudes.

Adult↗
PubMed1995

Membrane traffic. Is the Golgi complex?

A protein which acts specifically to target vesicles within the Golgi complex, rather than to or from it, has recently been described. But does this open the way to understanding intra-Golgi membrane traffic?

Endoplasmic Reticulum↗
PubMed1995

Characterization of a human adenovirus 5: rabies glycoprotein recombinant vaccine reisolated from orally vaccinated skunks.

An infectious recombinant human adenovirus which carries the rabies glycoprotein gene and accompanying SV40 control elements can be given orally to skunks to immunize them against rabies. We have looked for adenovirus in the feces and oral fluids of animals that have been given this recombinant and have obtained 111 virus positive samples from 16 test animals. DNA from these virus isolates was examined for possible mutations. One possible insertion mutation was detected by SmaI restriction endonuclease analysis of genomic DNA. Further analysis by HaeIII restriction and nucleotide sequencing of polymerase chain reaction products encompassing the whole SV40-rabies insert revealed that this isolate contained an insert of the 72 base pair sequence found in the SV40 promoter region. A second mutation, in which 54 base pairs were deleted from within the rabies glycoprotein gene, was also detected in two independent isolates from one skunk.

Adenoviruses, Human↗
PubMed1995

Public opinion regarding end-of-life decisions: influence of prognosis, practice and process.

The purpose of this study was to examine the effect of changing key factors in survey questions on public opinion regarding end-of-life decisions. These factors were: (a) patient prognosis (likely vs unlikely to recover from the illness); (b) end-of-life practice (foregoing treatment vs assisted suicide vs euthanasia); and (c) and decision making process (competent patient vs incompetent patient based on living will vs incompetent patient based on family wishes). A representative quota sample of 2019 Canadians 18 years of age or older were surveyed using a 13-item questionnaire with 12 items eliciting attitudes towards end-of-life decisions. The questions were systematically varied according to three key factors; patient prognosis, end-of-life practice and decision making process. One item assessed whether respondents had completed a living will. In the case of a decision to forgo life-sustaining treatment in a competent patient, public approval was 85% if the person was unlikely to recover and 35% if the person was likely to recover. In the case of a competent patient unlikely to recover, public approval was 85% for forgoing life-sustaining treatment, 58% for assisted suicide, and 66% for euthanasia. In the case of forgoing life-sustaining treatment for a patient unlikely to recover, public approval was 85% for a competent patient, 88% for an incompetent patient who had expressed his/her wishes in advance through a living will, and 76% for an incompetent patient based on a family's request. The influence of these key factors was similar in other cases examined. Ten percent of Canadians said they had completed a living will. It was concluded that patient prognosis has a major effect, end-of-life practice a moderate effect, and decision making process a minor effect on public opinion regarding end-of-life decisions.

Adult↗
PubMed1995

The dental phenotype in familial adenomatous polyposis: diagnostic application of a weighted scoring system for changes on dental panoramic radiographs.

A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (< 1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of approximately 68% was obtained. If all positive findings were considered as significant, sensitivity was increased to approximately 82% but the specificity was reduced to approximately 88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, approximately 68% of the affected subjects had significant changes, and approximately 18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.

Adenomatous Polyposis Coli↗
PubMed1993

Post-translational processing of Schizosaccharomyces pombe YPT5 protein. In vitro and in vivo analysis of processing mutants.

SpYPT5p is a member of the rab/YPT small GTP-binding protein family, which is believed to be involved in the regulation of intracellular trafficking. The protein sequence terminates with a CXC motif, and in our previous report (Newman, C. M. H., Giannakouros, T., Hancock, J. F., Fawell, E. H., Armstrong, J., and Magee, A. I. (1992) J. Biol. Chem. 267, 11329-11336) we have shown that SpYPT5p is prenylated both in vivo and in vitro, where geranylgeranylation was confirmed, and carboxyl-methylated. In order to dissect the role of prenylation of each cysteine, we have generated C-terminal mutants where either one or both cysteine(s) were replaced by serine and expressed them in vitro in reticulocyte lysates and in vivo in transfected COS cells. Our results suggest that both cysteines of the CXC motif are prenylated but that the rate of prenylation of the two cysteines is different. The upstream cysteine was found to be preferentially prenylated in reticulocyte lysates unless cytosol from COS cells was added. A separate activity could therefore be required for prenylation of the second cysteine, or the presence of an additional factor is needed to allow accumulation of doubly prenylated SpYPT5p. However, the modification of the upstream cysteine is not a prerequisite for the prenylation of the other. Furthermore, gene replacement in Schizosaccharomyces pombe revealed that each cysteine of the CXC motif can individually support function. Carboxyl methylation occurred only on protein which had been prenylated on the C-terminal cysteine and was required for efficient membrane binding in vitro.

Base Sequence↗
PubMed1993

The management of the clinically positive neck as part of a larynx preservation approach.

PURPOSE: For patients with squamous cell carcinoma of the head and neck with palpable neck node metastases, the standard management of the neck usually involves neck dissection and postoperative neck irradiation. A strategy of larynx preservation with induction chemotherapy and radiation therapy has been utilized for patients with locally advanced resectable cancer of the larynx, hypopharynx, and oropharynx. For patients treated in this non-surgical manner for the primary site, the optimal management of the clinically positive neck has not been clarified. To determine whether response to induction chemotherapy could help to select patients in whom neck dissection could be omitted in favor of definitive radiation therapy alone, we have analyzed our prospective larynx preservation experience. METHOD AND MATERIALS: Between 1983-1989, 80 patients were entered onto larynx preservation protocols involving 1-3 cycles of cisplatin based chemotherapy followed by radiation therapy with or without neck dissection. There were 54 patients with clinically positive necks to treatment, of whom 44% (24/54) had a complete response, and of whom 20% (11/54) had a partial response to chemotherapy in the neck. In 22 of these 35 patients with clinically positive necks who achieved a major neck response to chemotherapy, radiation therapy (median 66 Gy) was used as the only subsequent treatment of the neck. RESULTS: At a median follow-up of 25 months (range 7-83 months), neck control for this subset is 91% (20/22). Neck failure occurred in 20% (1/5) of patients with a partial response to chemotherapy treated without neck dissection and 6% (1/17) of node positive with a complete response. CONCLUSION: These results suggest that patients with clinically palpable cervical nodal metastases who have a complete response to chemotherapy and receive high dose radiation therapy have excellent neck control and may not need neck dissection. Further experience will be required to confirm these preliminary data and to determine if patients who achieve a partial response in the neck after induction chemotherapy can be treated with radiation therapy without neck dissection.

Adult↗
PubMed1993

Processing of the small GTP-binding protein SpYPT1p in Schizosaccharomyces pombe and in mammalian COS cells.

SpYPT1p belongs to a family of ras-like GTP-binding proteins which is believed to be involved in the regulation of intracellular vesicular trafficking. We have analyzed the processing of this protein in its natural environment, the fission yeast Schizosaccharomyces pombe, and when expressed in transfected mammalian COS cells. In COS cells SpYPT1p exists in two forms: a cytosolic 24 kDa protein which represents the unprocessed precursor form and a prenylated 23.5 kDa protein which is equally distributed between membranes and cytosol. In contrast, in S.pombe we have been unable to detect any prenylation of the protein, despite the presence of a potential C-terminal CysCys prenylation site. In addition a 23.5 kDa form was localized exclusively in the cytosol and a third membrane-bound 23 kDa form was also detected. Pulse-chase experiments revealed that in S.pombe SpYPT1p is co-translationally or immediately after translation converted to the 23.5 kDa form which is then rapidly processed to the 23 kDa membrane bound form. We have been unable to detect any significant soluble pool of the protein.

Animals↗
PubMed1993

Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus.

Cytolytic T lymphocytes play an important role in host defense against viral infections, including human immunodeficiency virus (HIV). In a phase I clinical trial (protocol 080 of the AIDS Clinical Trials Group), generation of CD8+ effector cells from peripheral blood of patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and safety of autologous adoptive transfer of these cells were evaluated. For therapeutic infusions, CD8+ T cells were purified by positive selection on anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral blood of seven patients. These CD8+ T cells were cultured in the presence of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell cultures established from the seven patients and used for therapy were highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded CD8+ cells had excellent cytotoxic function at the time they were used for therapy, including HIV-specific activity against autologous targets infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and env. Anti-HIV activity of cultured CD8+ cells was significantly higher than that of autologous fresh peripheral blood lymphocytes. Our results show that CD8+ T lymphocytes obtained from peripheral blood of symptomatic HIV-infected patients can be purified, cultured to obtain large numbers of cells with enhanced anti-HIV activity, and safely infused into patients with AIDS as a form of immunotherapy.

AIDS-Related Complex↗
PubMed1993

A phase 1 study of adoptive transfer of autologous CD8+ T lymphocytes in patients with acquired immunodeficiency syndrome (AIDS)-related complex or AIDS.

Based on preclinical studies showing that CD8+ T lymphocytes of human immunodeficiency syndrome (HIV)-infected subjects have anti-HIV activities, a phase 1 study was undertaken to determine the safety and feasibility of infusing in vitro purified, activated, and expanded CD8+ cells as a therapeutic measure in seven patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS. Autologous CD8+ cells were first selectively isolated in monoclonal antibody-coated flasks from peripheral blood mononuclear cells recovered by leukapheresis. They were then cultured and expanded with phytohemagglutinin and recombinant interleukin-2 (rIL-2) before infusion. Five cycles of isolations and infusions of increasing numbers of CD8+ T cells were achieved in five of seven subjects. Five cycles could not be completed in two subjects with AIDS whose CD4+ cell counts were < or = 48/microliters. Infusions of CD8+ cells alone were well tolerated. Four patients received rIL-2 by continuous infusion for 5 days with their final cycle of CD8+ cells. All developed reversible adverse effects attributable to rIL-2. After infusion, 111In-labeled CD8+ cells quickly accumulated in the lungs, with less than 10% of the labeled cells remaining in the circulation. After 24 hours, labeled CD8+ cells were reduced in the lungs, but increased and persisted in liver, spleen, and bone marrow. Four of five patients who were treated with multiple infusions of CD8+ cells have improved or remained clinically stable, and the fifth developed Pneumocystis carinii pneumonia but recovered. This study demonstrated that infusion of autologous, in vitro expanded and activated CD8+ cells was feasible and clinically well tolerated in five of seven subjects with advanced HIV infections.

AIDS-Related Complex↗
PubMed1993

Feelings of Fatness Questionnaire: a measure of the cross-situational variability of body experience.

The Feelings of Fatness Questionnaire (FOFQ) was developed to assess the variability of bodily feelings of thinness-fatness across life situations. The FOFQ, three other conventional measures of perceptual and cognitive-affective body experience, the Beck Depression Inventory, and the Eating Attitudes Test were administered to 132 undergraduate women. The FOFQ demonstrated acceptable construct validity and revealed considerable variation in "felt" body experience across psychosocial contexts. Problems with summary measures of body experience and possible cognitive processes mediating the relationship between context and subjective body experience are discussed.

Adolescent↗