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J L Harrison

Publications and source records attributed to J L Harrison.

36 records · Page 2Linked to original sources
PubMed1990

The TraT lipoprotein as a vehicle for the transport of foreign antigenic determinants to the cell surface of Escherichia coli K12: structure-function relationships in the TraT protein.

The TraT protein is a surface-exposed lipoprotein, specified by plasmids of the IncF group, that mediates serum resistance and surface exclusion. The structure and function of the TraT protein determined by plasmid R6-5 was probed by genetic insertion of a foreign antigenic determinant, the C3 epitope of polio virus, at residues 61, 125, 180, 200 or 216 of the protein. The chimaeric proteins were transported to the outer membrane and, in three cases, immunoassays with an anti-C3 monoclonal antibody indicated that the C3 epitope was exposed on the cell surface. Three of the hybrids, with insertions at residues 125, 180 and 200, assembled into the trypsin-resistant oligomeric form characteristic of the wild-type protein, which suggested that these regions are not involved in TraT subunit:subunit interactions. Additionally, the hybrid protein carrying the C3 epitope at position 180 functioned in a genetic suppression assay and retained partial surface-exclusion activity. Thus, its localization, folding and organization does not appear to be grossly altered from that of the wild-type protein. Applications of the protein for the transport of foreign antigenic determinants to the cell surface are discussed.

Amino Acid Sequence↗
PubMed1990

Ultrastructure of phagocytosed Paracoccidioides brasiliensis in nonactivated or activated macrophages.

Transmission electron microscopy was used to study ultrastructures in Paracoccidioides brasiliensis yeast cells after ingestion by nonactivated or cytokine-activated murine peritoneal macrophages. Yeast cells ingested by nonactivated macrophages had typical bi- and trilayered cell walls, plasma membranes, mitochondria, nuclei, vacuoles, etc., which remained intact for 24 h of coculture. In contrast, yeast cells ingested by activated macrophages exhibited abnormal mitochondrial ultrastructures within 4 h of interaction. Subsequent events that occurred were the formation of several clear vacuoles per cell, disintegration of the cytoplasm, and development of empty cells with intact walls. These findings provide, for the first time, insights into stepwise damage to fungal cells by activated macrophages (of particular interest in this instance because of prior evidence that the damage is due to nonoxidative mechanisms) and give possible clues regarding fungicidal mechanisms.

Animals↗
PubMed1989

Aggregated platelets enhance adherence of Candida yeasts to endothelium.

The adherence of Candida albicans yeasts to human umbilical vein endothelium to subendothelial extracellular matrix (ECM) was investigated. Yeasts added to confluent endothelium in citrated platelet-poor plasma adhered on the average of 1 colony forming unit (cfu) per culture well. When platelets were added as platelet-rich plasma, a significant increase of yeast adherence was not seen. However, when endothelium was contracted by treatment with 2 mM EDTA, resulting in exposure of ECM, yeast adherence was increased to 10 cfu/well. When platelets were added with these yeasts, the number of adhering yeasts was further increased to 23 cfu/well (P less than .01). This represented an increase in adherence of yeasts of 230%. When the endothelial cells were completely removed and ECM exposed, platelets were found to likewise augment yeast adherence. Platelets, when added to the ECM, formed aggregates to which the yeasts firmly adhered. Likewise, when platelets were aggregated by adenosine diphosphate and mixed with yeasts, yeasts were shown to bind avidly to aggregated platelets, whereas yeasts did not adhere to unactivated, discoid platelets. Thus, exposed subendothelial ECM induces the aggregation of platelets and yeasts bind avidly to these platelet aggregates.

Blood Platelets↗
PubMed1986

Electron-microscopic observations of the Coccidioides immitis parasitic cycle in vivo.

BALB/c mice were inoculated by intranasal challenge with viable arthroconidia of C. immitis and in-vivo morphogenesis of the fungal pathogen was investigated by electron-microscopic examination of pulmonary lavage and cryofractured lung specimens. Samples were prepared at intervals over an 11-day period. Stages of spherule and endospore development were easily identified by scanning and thin-section electron microscopy. Details of morphogenesis of the pathogen in vivo closely resemble developmental aspects reported from in-vitro studies.

Animals↗
PubMed1983

Adherence and penetration of vascular endothelium by Candida yeasts.

Metastatic infection after hematogenous dissemination of Candida species is presumably dependent on the fungus traversing the vascular endothelium. An in vitro model of the earliest events of metastatic Candida infection was developed with whole vascular strips. Freshly obtained porcine blood vessels were secured in a perforated Lucite template that allowed the application of yeasts directly to the endothelial surface. Multiple wells allowed experimental and control observations on the same vascular segments. Adherence to endothelium was greatest with Candida albicans and Candida tropicalis, less with Candida Krusei, and least with Candida parapsilosis, Candida pseudotropicalis, and Torulopsis glabrata. This hierarchy of adherence parallels that in other in vitro systems employing mucosal epithelial cells or fibrin-platelet matrixes and reflects the known virulence of the respective species and their potential for hematogenous dissemination. C. albicans and C. tropicalis yeasts that adhered were capable of directly traversing the endothelial surface before the production of germ tubes. Heat or Formalin-killed yeasts and viridans group streptococci, although adherent, were incapable of vascular penetration, a process presumably attributable to enzymatic digestion of host tissue. Loss of integrity of penetrated endothelial tissue was verified by loss of dye exclusion, lactic dehydrogenase release, and ultramicroscopic changes. These two steps, adherence and penetration, provide direct insight into the earliest events in hematogenous Candida species dissemination and suggest that C. albicans and C. tropicalis yeasts are capable of initiating tissue invasion before germ tubes have had the opportunity to form and participate in the invasive process.

Adhesiveness↗
PubMed1982

Morphogenesis throughout saprobic and parasitic cycles of Coccidioides immitis.

The fungus, Coccidioides immitis, differs from other dimorphic pathogens in that its parasitic stage is a complex morphogenic cycle, raising the question that changes and composition during morphogenesis might influence host responses. As a prelude to examining the interaction of fungal morphogenesis and host responses, the life cycle of this fungus has been examined in greater detail than previously accomplished. During saprobic development, alternating enterothallic arthroconidia are formed as infectious propagules. The outer wall is broken and loosely adherent. Under in vitro conditions supporting the parasitic cycle, multinucleate arthroconidia transform into uninucleate round cells. Rapid, synchronous, nuclear replication is initiated, accompanied by increase in cell mass and deposition of new cell wall substance. As karyokinesis ceases, morphologic differentiation begins with invagination of the inner layers of the spherule wall and then is progressive, eventually segmenting the protoplasm into uninucleate endospores grouped in clusters within a hyaline membrane. Endospores, escaping through a break in the spherule wall, are held in aggregates by fibrils which are stretched and broken as endospores separate. It would seem that rapid production of hundreds of progeny from an original single cell, protected during development by an enclosing spherule wall and then released in clusters, should favor establishment of the fungus in a host, and dynamic changes in the cell wall during morphogenesis should influence the host response.

Cell Membrane↗
PubMed1982

Avulsion of the innominate artery from the aortic arch associated with a posterior tracheal tear.

The management of a patient with avulsion of the innominate artery from the aortic arch associated with a longitudinal tear on the posterior aspect of the trachea is discussed. It is obviously important to make both diagnoses preoperatively to determine priorities in the surgical management. If the airway injury can be managed by tracheal intubation, then it is recommended that the vascular injury be repaired first. If there is a persistent air leak with respiratory distress, then it is necessary to repair the tracheal injury before performing the vascular procedure. In some patients it may be appropriate to treat the tracheal injury nonoperatively.

Accidents, Traffic↗
PubMed1980

Brainstem auditory evoked responses in 200 patients with multiple sclerosis.

Brainstem auditory evoked responses (BAERs) were recorded from 202 patients with definite, probable, or possible multiple sclerosis (MS). Definitions of abnormality were based only on interwave separations and the wave I/wave V amplitude ratio. Thirty-two percent of the patients had abnormal BAERs, and the presence of clinically unsuspected lesions was revealed by BAER abnormalities in 7.4%. Thirty-five percent of the patients who had nystagmus and 53% of those who had internuclear ophthalmoplegia at the time of testing had BAER abnormalities. Forty-five percent of the abnormalities were elicited with stimulation of one ear only, stressing the importance of monaural stimulation. Click rates faster than 10 per second did not reveal abnormalities undetected at slower rates. BAERs were normal by these criteria in patients with labyrinthine diseases and amyotrophic lateral sclerosis. Thus, the BAER in MS can (1) confirm the presence of central lesions in patients with suspected brainstem involvement, (2) document the presence of clinically unsuspected lesions, and (3) be followed over time to provide possible assistance in evaluating the effectiveness of therapeutic measures. The BAER is a useful tool in the diagnosis and management of MS.

Acoustic Stimulation↗
PubMedDate not supplied

Presentation of foreign antigenic determinants at the bacterial cell surface using the TraT lipoprotein.

The TraT protein is an oligomeric outer membrane lipoprotein, specified by plasmids of the IncF group, that is very highly exposed at the bacterial cell surface. We have investigated the feasibility of using the protein as a carrier of foreign antigenic determinants by genetic insertion of the C3 epitope of type 1 poliovirus into defined sites in the protein. Several of the hybrid proteins constructed had features characteristic of the native protein and one in particular retained the ability of function in surface exclusion and genetic suppression assays as well as to assemble into oligomers. Our results suggest that the TraT protein can be used to transport and present foreign antigenic determinants at the cell surface.

Antigens, Viral↗