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Biomedical subjects

J S Logan

Publications and source records attributed to J S Logan.

At least 19 recordsLinked to original sources
PubMed1995

Protection of xenogeneic cardiac endothelium from human complement by expression of CD59 or DAF in transgenic mice.

We investigated the ability of membrane-bound human complement regulatory proteins to control complement-driven humoral immune reactions on murine microvasculature. The human complement regulatory proteins CD59 and DAF were expressed using heterologous promoters in a variety of tissues in transgenic mice. Animals expressing these gene products are healthy and exhibit significant levels of endothelial cell expression of CD59 and DAF in cardiac muscle. Transgenic hearts perfused with human plasma exhibited profound reductions in the level of complement deposition compared with nontransgenic controls. We have also produced transgenic pigs that express these two human genes. Our results indicate that expression of complement regulatory proteins can control activation of complement and suggest that these proteins may have therapeutic applications in some inflammatory diseases and in the development of xenogeneic organs for human transplantation.

Animals↗
PubMed1995

In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium.

Many proteins are associated with the outer layer of the cell membrane through a posttranslationally added glycosyl phosphatidylinositol (GPI) anchor. The functional significance of this type of protein linkage is unclear, although it results in increased lateral mobility, sorting to the apical surface of the cell, reinsertion into cell membranes, and possibly cell signaling. Here evidence is presented that GPI-linked proteins can undergo intermembrane transfer in vivo. GPI-linked proteins expressed on the surface of transgenic mouse red blood cells were transferred in a functional form to endothelial cells in vivo. This feature of GPI linkage may be potentially useful for the delivery of therapeutic proteins to vascular endothelium.

Animals↗
PubMed1995

Transgenic expression of human complement regulatory proteins in mice results in diminished complement deposition during organ xenoperfusion.

Complement activation is an essential step in the hyperacute rejection of a vascularized xenograft. Endothelial cell-associated complement regulatory proteins limit complement activation in most settings, but are not able to limit the extensive complement activation that occurs in xenografts, at least in part due to their species specificity. To overcome this problem we and others have sought to express human complement regulatory proteins in the organs of potential donor animals. As an initial step toward evaluating this concept we tested organs from transgenic mice expressing human CD59 and/or decay-accelerating factor (DAF) in two in vitro perfusion systems for the ability to control activation of heterologous complement. In the first system, mouse hearts were perfused on a Langendorff circuit with 50% human plasma. Immunopathologic analysis of heart biopsies revealed deposition of human IgG, IgM, and C4 in both control and transgenic organs. The hearts from mice transgenic for human CD59 had substantially less and in some cases no membrane attack complex (MAC) and hearts from CD59/DAF transgenic mice had substantially less or no C5b and MAC. In the second system, mouse hearts were perfused with baboon blood through arterial lines inserted into baboons. Immunopathologic analysis of serial biopsies revealed the deposition of IgG, IgM, and C4 in control and transgenic hearts. Compared with controls, less MAC was deposited in many CD59-expressing hearts and less C5b and MAC in DAF-expressing hearts. These results demonstrate that human complement regulatory proteins expressed in a xenogeneic organ are able to contribute to the control of complement activation in that organ and support the concept that expression of these human molecules would help protect a xenogeneic organ transplanted into a human.

Animals↗
PubMed1995

Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury.

The susceptibility of xenografts to hyperacute rejection is postulated to reflect in part failure of complement regulatory proteins (CRPs) to control activation of heterologous complement on graft endothelium. To test this concept, transgenic swine expressing the human CRP decay accelerating factor and CD59 were developed using a novel expression system involving transfer of the proteins from erythrocytes to endothelial cells. Hearts from transgenic swine transplanted into baboons had markedly less vascular injury and functioned for prolonged periods compared to hearts from nontransgenic swine. These results indicate that expression of human CRPs in xenogeneic organs may contribute to successful xenografting and suggest that intercellular protein transfer might be a useful approach for expression of heterologous proteins in endothelial cells.

Animals↗
PubMed1992

Production of functional human hemoglobin in transgenic swine.

A construct containing the locus control region (LCR) from the human beta globin locus together with two copies of the human alpha 1 gene and a single copy of the human beta A gene was used to obtain three transgenic pigs. The transgenic pigs are healthy, not anemic, and grow at a rate comparable to non-transgenic littermates. All animals expressed the human genes. However, alpha globin was consistently expressed at higher levels than beta globin. Isolation of the human hemoglobin from both porcine hemoglobin and other non-hemoglobin proteins was accomplished by ion exchange chromatography. The purified porcine derived human hemoglobin exhibited an oxygen affinity similar to that of human derived human hemoglobin.

Animals↗
PubMed1991

On the nature of talker variability effects on recall of spoken word lists.

In a recent study, Martin, Mullennix, Pisoni, and Summers (1989) reported that subjects' accuracy in recalling lists of spoken words was better for words in early list positions when the words were spoken by a single talker than when they were spoken by multiple talkers. The present study was conducted to examine the nature of these effects in further detail. Accuracy of serial-ordered recall was examined for lists of words spoken by either a single talker or by multiple talkers. Half the lists contained easily recognizable words, and half contained more difficult words, according to a combined metric of word frequency, lexical neighborhood density, and neighborhood frequency. Rate of presentation was manipulated to assess the effects of both variables on rehearsal and perceptual encoding. A strong interaction was obtained between talker variability and rate of presentation. Recall of multiple-talker lists was affected much more than single-talker lists by changes in presentation rate. At slow presentation rates, words in early serial positions produced by multiple talkers were actually recalled more accurately than words produced by a single talker. No interaction was observed for word confusability and rate of presentation. The data provide support for the proposal that talker variability affects the accuracy of recall of spoken words not only by increasing the processing demands for early perceptual encoding of the words, but also by affecting the efficiency of the rehearsal process itself.

Adult↗
PubMed1991

Training Japanese listeners to identify English /r/ and /l/: a first report.

Native speakers of Japanese learning English generally have difficulty differentiating the phonemes /r/ and /l/, even after years of experience with English. Previous research that attempted to train Japanese listeners to distinguish this contrast using synthetic stimuli reported little success, especially when transfer to natural tokens containing /r/ and /l/ was tested. In the present study, a different training procedure that emphasized variability among stimulus tokens was used. Japanese subjects were trained in a minimal pair identification paradigm using multiple natural exemplars contrasting /r/ and /l/ from a variety of phonetic environments as stimuli. A pretest-posttest design containing natural tokens was used to assess the effects of training. Results from six subjects showed that the new procedure was more robust than earlier training techniques. Small but reliable differences in performance were obtained between pretest and posttest scores. The results demonstrate the importance of stimulus variability and task-related factors in training nonnative speakers to perceive novel phonetic contrasts that are not distinctive in their native language.

Adult↗
PubMed1990

Identification of the origin of the growth hormone-binding protein in rat serum.

GH specifically interacts with a soluble binding protein in serum. The GH-binding protein (GHBP) has been shown to contain the extracellular portion of the cell surface GH receptor (GHR). In rats and mice there is a unique mRNA that encodes the GHBP. This mRNA contains an alternatively spliced exon that replaces the transmembrane and intracellular domains of the receptor with a short hydrophilic carboxy-terminus of 17 and 25 amino acids, respectively, in rats and mice. In humans and other species no mRNAs encoding the GHBP have been identified, suggesting that the GHBP is in these cases a proteolytically processed GHR. In this study a monoclonal antibody (GHBP 4.3) was raised to the rat GHBP using as immunogen a synthetic peptide containing the unique C-terminal 17 amino acids that are not found in the rat GHR. As predicted, this antibody is specific to rat GHBP and does not cross-react with rat GHR. In combination with polyclonal and monoclonal antibodies that recognize both GHBP and GHR, this antibody was used to show that all, or most, of the GHBP in rat serum is indeed derived from the alternatively spliced GHBP mRNA and not from proteolytic processing of the GHR. In addition, endogenous rat serum GHBP was found to exist in two forms, with apparent mol wt of 52 and 44 kDa, arising from a single protein core of 32 kDa by extensive glycosylation. The concentrations of GHBP in male and female rat plasma were also estimated to be 300 and 575 ng/ml, respectively (measured in nonglycosylated GHBP equivalents).

Amino Acid Sequence↗
PubMed1990

Medical impact analysis for the space station.

Since the Space Station Health Maintenance Facility can house only a relatively limited quantity of supplies and equipment, the decisions about what should be included must be based on documented research. In this study, Space Station medical care priorities were determined by a medical impact analysis of two analog populations, U.S. Army and U.S. Navy personnel. Diseases and injuries in the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) were ranked, using a Medical Impact Score (MIS) combining modified incidence rate and a function of disease outcome. The validity of the analysis method was tested by measuring rank order correlation between the two analog populations. Despite virtually identical age and sex distributions, Army and Navy incidence rates differed significantly for half of the ICD-9-CM categories, p less than 0.05. Disability rates differed for 76%, p less than 0.05. Nevertheless, Army and Navy MIS rank orders for categories and sections were not significantly different, p less than 0.001. In critical ways, the Space Station will be a safer environment than Earth. Cardiac events, musculoskeletal injuries, affective psychoses, and renal calculi were among the highest scoring categories.

Accidents, Occupational↗
PubMed1989

The role of smart medical systems in the Space Station.

NASA is developing a Health Maintenance Facility to provide medical equipment and supplies requisite for the Space Station to be launched in the late 1990s. An essential component of this medical facility is a computerized Medical Decision Support System which will expedite medical officers' efforts to maintain the crew's health. The computerized system includes four major functions: 1. A data collection and storage system with a self-contained medical expert scheme for performing treatment protocols. The expert system has 'data driven' and 'time driven' capabilities to facilitate automatic decision-making functions. 2. An integrated medical record and medical 'reference' information management component. 3. An inventory management system for medical supplies and pharmaceuticals. 4. Video, audio, and data communications between the medical officer in the Space Station and ground-based medical personnel. This paper discusses the design of such computerized data collection, communications and expert medical systems as will be developed for use in a Space Station Health Maintenance Facility.

Aerospace Medicine↗