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Biomedical subjects

J S Logan

Publications and source records attributed to J S Logan.

At least 55 records · Page 3Linked to original sources
PubMed1994

Mechanisms of injury in porcine livers perfused with blood of patients with fulminant hepatic failure.

Hyperacute rejection of renal and cardiac xenografts is initiated by the reaction of recipient natural antibodies and complement with endothelial cell antigens of the donor organ. The liver is thought to be less susceptible to this form of rejection; however, the mechanisms underlying its decreased susceptibility are not known. We investigated the organ injury occurring in porcine livers perfused with blood from 4 human subjects with fulminant hepatic failure. Nine porcine livers were perfused via an extracorporeal circuit in order to provide temporary metabolic support. Each porcine liver exhibited metabolic function, and the duration of xenoperfusion ranged from 2 to 5 hr. Histologic examination of the xenoperfused livers revealed focal hepatocellular necrosis, prominent infiltration of neutrophils, and, in 7 of 9 cases, periportal and centrilobular hemorrhage and thrombosis. Immunopathology demonstrated minimal or no human IgM and IgG along the small vessels and sinusoidal surfaces. Trace deposits of human IgM were observed along the luminal surfaces of large blood vessels in most cases. Trace deposits of C3 were noted in 2 of 9 livers; however, C4, iC3b, C5b, properdin, and the membrane attack complex were not detected. Human anti-porcine natural antibody titers decreased less than expected during the perfusions. Serum CH50, C3, and C4 levels were low before each procedure and decreased slightly with perfusion. One patient perfused 2 porcine livers and a human liver. The human liver had focal hepatocellular necrosis, trace deposits of IgM, no deposits of complement, and an infiltrate consisting of neutrophils; however, the neutrophil influx was less than that observed in the xenoperfused livers. To further evaluate the effects of alloperfusion, venovenous bypass was established in 2 pigs and the extracorporeal circuit was utilized to perfuse 2 porcine livers. The alloperfused porcine livers had focal hepatocellular necrosis and a minimal infiltrate of neutrophils. There were no deposits of porcine IgM, IgG, or complement components. In conclusion, although the porcine livers perfused by human blood sustained structural damage, the time course, the absence of immune deposits, and the findings of similar, albeit less severe, lesions in the alloperfused livers suggest that the pathogenesis of tissue injury in the xenoperfused livers differs from that of hyperacute rejection and may be related to the action of recipient neutrophils.

Adult↗
PubMed1994

An isologous porcine promoter permits high level expression of human hemoglobin in transgenic swine.

We describe isologous promoter replacement as an approach to permit high level expression of human hemoglobin in transgenic swine. We linked the human beta globin genomic coding region to the porcine beta globin promoter and used this fusion gene in an expression construct containing the human beta locus control region and the human alpha and epsilon genes to produce transgenic pigs. The highest level of expression was 24% human (32g/liter) and 30% human alpha/pig beta hybrid (40g/liter) hemoglobin in one transgenic pig. This pig was bred to a non-transgenic animal resulting in the transmission of high level human hemoglobin expression to 5 of 12 progeny.

Animals↗
PubMed1993

Transgenic animals: beyond 'funny milk'.

The expression of therapeutically useful proteins in transgenic animals is a field of biotechnology that is now coming of age. Over the past few years, significant progress has been made in the expression of proteins in milk. More recently, the expression of proteins in blood and tissues (e.g. animal organs for transplantation to humans) has greatly expanded the potential applications of transgenic animals in medicine and biotechnology.

Animals↗
PubMed1993

Training Japanese listeners to identify English /r/ and /l/. II: The role of phonetic environment and talker variability in learning new perceptual categories.

Two experiments were carried out to extend Logan et al.'s recent study [J. S. Logan, S. E. Lively, and D. B. Pisoni, J. Acoust. Soc. Am. 89, 874-886 (1991)] on training Japanese listeners to identify English /r/ and /l/. Subjects in experiment 1 were trained in an identification task with multiple talkers who produced English words containing the /r/-/l/ contrast in initial singleton, initial consonant clusters, and intervocalic positions. Moderate, but significant, increases in accuracy and decreases in response latency were observed between pretest and posttest and during training sessions. Subjects also generalized to new words produced by a familiar talker and novel words produced by an unfamiliar talker. In experiment 2, a new group of subjects was trained with tokens from a single talker who produced words containing the /r/-/l/ contrast in five phonetic environments. Although subjects improved during training and showed increases in pretest-posttest performance, they failed to generalize to tokens produced by a new talker. The results of the present experiments suggest that variability plays an important role in perceptual learning and robust category formation. During training, listeners develop talker-specific, context-dependent representations for new phonetic categories by selectively shifting attention toward the contrastive dimensions of the non-native phonetic categories. Phonotactic constraints in the native language, similarity of the new contrast to distinctions in the native language, and the distinctiveness of contrastive cues all appear to mediate category acquisition.

Acoustic Stimulation↗
PubMed1993

Production of human hemoglobin in transgenic swine: an approach to a blood substitute.

Many significant challenges have to be met before a clinically useful hemoglobin-based blood substitute can be developed. A major issue is the choice of a production system. Transgenic swine have several features that appear to be suited to the abundant production of human hemoglobin. Here we show that authentic human hemoglobin can be made in transgenic pigs and purified by simple ion-exchange chromatography. The purified hemoglobin can be modified for testing and use as a blood substitute.

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↗