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Biomedical subjects

J M Harris

Publications and source records attributed to J M Harris.

At least 163 records · Page 9Linked to original sources
PubMed1989

Vascular prosthetic infection with Staphylococcus epidermidis: experimental study of pathogenesis and therapy.

To determine whether a slime-producing strain of Staphylococcus epidermidis was capable of producing acute infection of a prosthetic vascular graft, 5 cm segments of knitted Dacron were implanted in the infrarenal aortic position of dogs in three groups of animals. These included a control group (no graft contamination), a contaminated group that received a graft soaked in an S. epidermidis solution (untreated group), and a contaminated group in which perioperative antibiotics (three doses of cefamandole, 100 mg/kg) were administered (prophylaxis group). In all the animals reexploration and graft removal were performed at 10 days, with replacement of the defect being achieved with a new uncontaminated graft. These animals underwent exploration a third time after an additional 10-day period. S. epidermidis was not grown from the control animals (n = 7) but was cultured in 44% of the prophylaxis group (n = 9) and 88% of the untreated group (n = 16) during at least one of the operative procedures (chi 2 = 15.859; p less than 0.001). The pathologic features of acute S. epidermidis infection were best seen in the untreated animals and included anastomotic disruption (56%), periaortic hematoma, and lymphadenopathy (94%). Microscopic examination of the aortic tissues revealed extensive infiltrates of leukocytes, macrophages, and foreign body giant cells with aortic necrosis. These features were less prominent in the prophylaxis animals. We conclude that S. epidermidis is capable of producing acute graft infection with perigraft inflammation and anastomotic disruption. The administration of perioperative antibiotics reduced but did not abolish these effects of bacterial contamination of prosthetic vascular grafts.

Animals↗
PubMed1989

Postendocytotic sorting of the ligand for the polymeric immunoglobulin receptor in Madin-Darby canine kidney cells.

The polymeric immunoglobulin receptor (pIg-R) is responsible for the receptor-mediated transcytosis of polymeric immunoglobulins (IgA and IgM) across various epithelia. We have expressed the cDNA for the pIg-R in Madin-Darby canine kidney (MDCK) cells and found that this system mimics that found in vivo (Mostov, K. E., and D. L. Deitcher. 1986. Cell. 46:613-621). We have now investigated the postendocytotic pathway of the ligand for the pIg-R. After a 5-min internalization at the basolateral surface, approximately 45% of internalized ligand recycles to the basolateral medium and 30% is transcytosed to the apical medium. We have also examined why transcytosis of ligand is unidirectional, going only from basolateral to apical, but not from apical to basolateral. Several factors could explain this, such as proteolytic cleavage of the pIg-R at the apical surface, decreased apical endocytosis of ligand, or an intracellular sorting event. In this report, we show that the protease inhibitor, leupeptin, inhibits the cleavage of the pIg-R but does not alter the unidirectionality of transcytosis. In addition, we demonstrate that there is a significant amount of apical endocytosis of ligand (70% of that observed basolaterally). Finally, we demonstrate that apically endocytosed ligand can return only to the apical surface. Thus, once ligand reaches the apical surface, it is "trapped" and cannot return to the basolateral surface. We propose that the unidirectionality of transcytosis is the result of intracellular sorting, and that this results from a signal(s) present on the pIg-R.

Animals↗
PubMed1989

Acute non-infectious arthritis of the hip in rheumatoid arthritis: synovial membrane findings.

A case of acute hip pain in rheumatoid arthritis is presented, with synovial membrane findings. A patient with classical rheumatoid arthritis suffered three unusual bouts of sudden, severe but transient hip pain. The hips were clinically normal between these episodes. The clinical picture on two of these occasions strongly suggested septic arthritis. Although the synovial fluid was highly inflammatory, cultures were negative. The synovial membrane showed mild lining cell hyperplasia, vascular congestion, and scattered inflammatory cells, predominantly lymphocytes. These findings were not compatible with either pyogenic infection or longstanding rheumatoid arthritis. The clinical and pathological features of acute non-infectious arthritis of the hip appear to delineate a distinct syndrome.

Acute Disease↗
PubMed1989

Septic arthritis of the shoulder in adults.

Septic arthritis of the shoulder is uncommon in adults. We reviewed the cases of eighteen patients who were followed for a minimum of one year. The patients ranged in age from forty-two to eighty-nine years. All but one patient had at least one serious associated disease. Eight patients had had an injection or aspiration of the shoulder before development of the infection. All but one patient had had a delay in diagnosis. At the time of admission to the hospital, the erythrocyte sedimentation rate was always elevated, but the body temperature and white blood-cell count were not. After treatment, the functional result was usually poor: only five patients regained forward flexion to 90 degrees or more, eight patients had no active motion of the glenohumeral joint, and two patients died. Arthrotomy appeared to afford a better result than did repeated aspiration.

Adult↗
PubMed1988

Cell separation by immunoaffinity partitioning with polyethylene glycol-modified protein A in aqueous polymer two-phase systems.

Previous work has shown that polyethylene glycol (PEG)-bound antibodies can be used as affinity ligands in PEG-dextran two-phase systems to provide selective partitioning of cells to the PEG-rich phase. In the present work we show that immunoaffinity partitioning can be simplified by use of PEG-modified Protein A which complexes with unmodified antibody and cells and shifts their partitioning into the PEG-rich phase, thus eliminating the need to prepare a PEG-modified antibody for each cell type. In addition, we provide a more rigorous test of the original technique with PEG-bound antibodies by showing that it is effective at shifting the partitioning of either cell type of a mixture of two cell populations.

Animals↗
PubMed1988

Interleukin-2-induced production of interferon-gamma by resting human T cells and large granular lymphocytes: requirement for accessory cell factors, including interleukin-1.

Between 5 and 20% of normal human lymphocytes were found to synthesize interferon-gamma (IFN-gamma) in primary cultures with recombinant interleukin-2 (rIL-2). After 22 hr, IFN-gamma-producing cells included CD5+ T lymphocytes, CD16+ large granular lymphocytes (LGL), and a population of CD5-, CD16- blast cells. Only a small proportion (0-7%) of IFN-gamma-synthesizing cells expressed HLA-DR. The production of IFN-gamma by all rIL-2-responding lymphocyte subsets was shown to require the presence of DR+ accessory cells, probably including nonadherent, esterase-negative monocytes and/or dendritic cells. Accessory cell function in lymphocyte preparations depleted of DR+ cells, or in purified (greater than or equal to 95%) suspensions of LGL, was fully replaced either by addition of 2% autologous, adherent monocytes or by monocyte culture supernatant. The activity of monocyte supernatant was greatly reduced by treatment with antiserum specific for human interleukin-1 beta (IL-1 beta), although a combination of rIL-1 beta and rIL-2 failed to stimulate IFN-gamma production in DR- lymphocytes. These results indicate that rIL-2-induced IFN-gamma synthesis in both T cells and LGL requires the synergistic activity of IL-1, and possibly of one or more other monokines, as yet unidentified.

Antigen-Presenting Cells↗
PubMed1988

A double-blind, placebo-controlled comparison of the efficacy of standard and individually titrated doses of theophylline in patients with chronic asthma.

Forty adult patients with chronic asthma completed a 3-month double-blind crossover study to compare the effect of sustained-release theophylline given both as a fixed 300 mg twice daily dose (standard) and an individually titrated dose (titrated) with placebo. Theophylline was given in addition to other usual therapy, inhaled bronchodilators, inhaled steroids and, in 12 patients, oral steroids. The 3-month period was preceded by a run-in phase to determine the dose of theophylline which each subject required to achieve peak serum levels of 12-20 mg/litre and trough levels of 8-12 mg/litre. Doses ranged from 300 mg to 700 mg twice daily. Twenty-one patients needed more than the standard dose to achieve satisfactory serum levels. Patients recorded daily peak flow rates and symptom scores and were seen at monthly intervals to measure lung function, check serum theophylline levels and change treatments, which were given in random order. FEV1 was significantly higher for the whole group after standard (2.11 litres) and titrated (2.15 litres) theophylline therapy than after placebo (1.89 litres), as was FVC, but in the large subgroup whose titrated dose was greater than the standard dose, the FEV1 only improved with the titrated dose. Peak flow measurements at home showed the same pattern. Patients taking oral steroids appeared to derive less benefit from theophylline than others. It is concluded that theophylline can usefully be added as a third-line drug in chronic asthma, but that since half the patients are likely only to benefit from a dose greater than 300 mg twice daily, while the other half may have high serum levels above this dose, it is essential to measure serum levels in order to use the drug effectively and safely.

Adult↗
PubMed1988

Prevention of lower extremity stress fractures: a controlled trial of a shock absorbent insole.

A prospective controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities. The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Island, South Carolina. Polymer and standard mesh insoles were systematically distributed in boots that were issued to members of odd and even numbered platoons. The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training. To control for the confounding effects of running in running shoes, which occurred for about one and one-half hours per week for the first five weeks, we also examined the association of age of shoes and cost of shoes with injury incidence. A slight trend of increasing stress injuries by increasing age of shoes was observed. However, this trend did not account for the similarity of rates in the two insole groups. In addition, we observed a strong trend of decreasing stress injury rate by history of increasing physical activity, as well as a higher stress injury rate in White compared to Black recruits. The results of the trial were not altered after controlling for these factors. This prospective study confirms previous clinical reports of the association of stress fractures with physical activity history. The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits. The findings are relevant to civilian populations.

Adolescent↗
PubMed1987

Phase partitioning in space and on earth.

In aqueous solution at low concentrations, the neutral polymers dextran and poly(ethylene glycol) (PEG) rapidly form a two-phase system consisting of a PEG-rich phase floating on top of a dextran-rich phase. Biological particles and macromolecules tend to partition differentially between the phases and the liquid-liquid phase interface in these systems. Bioparticle partitioning has been shown to be related to physiologically important surface properties such as membrane charge or lipid composition. Affinity partitioning into the PEG-rich phase can be accomplished by coupling PEG to a ligand having affinity for specific cells or macromolecules. Subpopulations can be identified or separated using multi-step countercurrent distribution (CCD). Incomplete understanding of the influence of gravity on the efficiency and quality of the impressive separations achievable by partitioning, and appreciation for the versatility of this efficient technique, have led to its study for low-gravity biomaterials processing. On Earth, two-phase systems rapidly demix because of density differences between the phases. In low-gravity, demixing has been shown to occur primarily by coalescence. Polymer surface coatings, developed to control localization of demixed phases in low-g, have been found to control electroosmosis which adversely affects electrophoretic separation processes on Earth and in space. In addition PEG-derivatized antibodies have been synthesized for use in immunoaffinity cell partitioning.

Dextrans↗
PubMed1987

An anchor-minus form of the polymeric immunoglobulin receptor is secreted predominantly apically in Madin-Darby canine kidney cells.

The polymeric immunoglobulin receptor is expressed in a variety of polarized epithelial cells. Newly made receptor travels first to the basolateral surface. The receptor is then endocytosed, transported across the cell in vesicles, and exocytosed at the apical surface. We have now deleted the membrane spanning and cytoplasmic portions of the receptor by site-directed mutagenesis, thus converting the receptor to a secretory protein. When expressed in polarized Madin-Darby canine kidney (MDCK) cells the truncated protein is secreted at both surfaces, with a ratio of apical-to-basal secretion of 3.4. In contrast, when the exogenous secretory protein chicken lysozyme is expressed in these cells, it is released at both sides with a ratio of apical-to-basal secretion of 0.43. (Koder-Koch, C., R. Bravo, S. Fuller, D. Cutler, and H. Garoff, 1985, J. Cell Biol., 43:297-306). Lysozyme is thought to lack a signal that targets it to one surface or the other, and so its secretion may represent a default, bulk flow pathway to both surfaces. When compared with lysozyme, the truncated polymeric immunoglobulin receptor is preferentially secreted apically by a factor of 3.4:0.43 or 7.8. We suggest that the lumenal portion of the polymeric immunoglobulin receptor contains a signal that targets it to the apical surface.

Animals↗
PubMed1987

An in vitro study of the properties influencing Staphylococcus epidermidis adhesion to prosthetic vascular graft materials.

This study examines the influence of the properties of various vascular graft materials on the bacterial adherence process of two different strains of Staphylococcus epidermidis (mucous and normucous producing). Dacron grafts (both knitted and woven), Teflon grafts, and Dacron grafts coated with one and two layers of silicone were studied because these materials differ significantly in porosity, hydrophobicity, and surface charge (zeta potential). Graft segments were immersed in 3H-labeled bacteria solution for periods ranging from 5 to 180 minutes and liquid scintillation techniques were used to quantify bacterial adherence. The porous knitted Dacron material had a significantly higher rate of bacterial adherence than either the woven Dacron or Teflon (p less than 0.05). Silicone coating (either one or two layers) reduced adherence by a factor of four for the knitted Dacron (p less than 0.05) and by a factor of two for woven Dacron (p less than 0.05). The mucous producing strain of S. epidermidis displayed significantly better adherence to woven and knitted Dacron than the normucous producing strain, but only when 0.25% dextrose was added to the bacteria solution. These findings indicate that the highly porous knitted Dacron grafts have the highest propensity for bacterial adhesion. Graft materials with the most negative zeta potentials are more resistant to bacterial adherence. Silicone coating of Dacron material significantly changed adherence characteristics, suggesting that this may be a viable strategy for protecting implantable medical devices containing materials to which bacteria readily adhere.

Adhesiveness↗
PubMed1986

Direct antibody rosette-forming reactions using monoclonal markers of lymphocyte subpopulations. Methodology and applications illustrated by investigations with rat pan-T antibodies of the CAMPATH series.

A sensitive direct antibody rosette assay has been developed for the detection of antigens on the lymphocyte cell membrane. Indicator cells for rosette tests were prepared by chromic chloride coupling of rat or mouse monoclonal IgG or IgM anti-lymphocyte antibodies to untreated or trypsinized bovine red blood cells. The monoclonal antibodies used were reactive with a range of cell surface markers which identify various lymphocyte subpopulations, including T cell antigens, HLA class II (Ia-like antigens), Leu-7 (HNK-1) and VEP 13, a determinant of Fc gamma receptors on large granular lymphocytes. Results obtained by direct rosette formation correlated well with those of parallel tests using indirect immunofluorescent antibodies staining. Several applications of the direct antibody rosetting procedure are described in further investigations with a series of pan-T monoclonal (CAMPATH) antibodies. These include the morphological examination of antibody-binding cells in cytocentrifuge smears, the separation of lymphocyte subsets by density gradient centrifugation, and the use of a rosette inhibition assay to identify monoclonal antibodies binding to the same (or closely associated) epitopes of the lymphocyte cell membrane.

Animals↗
PubMed1986

Immuno-affinity partition of cells in aqueous polymer two-phase systems.

Poly(ethylene glycol) (PEG) was covalently coupled to IgG antibody preparations directed against human red blood cells. This modification reduces the tendency of the antibody to agglutinate cells and increases its affinity for the upper phase in dextran-PEG aqueous two-phase systems. These effects are related to the molecular weight of the PEG used for modification and to the number of PEG molecules attached to the antibody. Exposure of human red blood cells to PEG-modified antibody causes a substantial and specific increase in cell partition into the PEG-rich phase in a number of PEG-dextran aqueous two-phase systems. Pertinent phase-system parameters were examined. Following a single incubation with PEG-derivatized antibody, a mixture of sheep and human red blood cells was completely separated in 100 min by a 30-transfer countercurrent extraction using a two phase system which normally offers little resolution.

Animals↗