PubMed Health⌕ Search

Biomedical subjects

P Allaire

Publications and source records attributed to P Allaire.

11 recordsLinked to original sources
PubMed2000

Synaptic interactions regulate gephyrin expression in avian cholinergic neurons in vivo.

Our recent studies of chick parasympathetic ciliary ganglion (CG) neurons demonstrate a unique postsynaptic receptor microheterogeneity - under one presynaptic terminal, excitatory nicotinic acetylcholine receptor (nAChR) clusters and separate inhibitory glycine receptor (GlyR) clusters coexist in distinct membrane microregions. Gephyrin, a peripheral membrane protein that is required for GlyR clustering at synapses in the rodent central nervous system, is also expressed in chick CG neurons where it codistributes with GlyRs, but not nAChRs. We now extend these findings by characterizing the regulation of gephyrin expression in chick CG neurons in vivo. We show that developmental increases in gephyrin transcript levels occur during pre- and postganglionic synapse formation. The increases are induced by both innervation and target tissue interactions, with the target tissues having the greater regulatory influence. The time course of the developmental rise in gephyrin mRNA levels most closely resembles that reported for functional GlyR expression, but not that of functional nAChRs nor GABA(A) receptors. We also demonstrate that gephyrin is concentrated in the postsynaptic density of a subset of synapses on both the ciliary and choroid neurons in the CG and is stably expressed from embryonic to adult stages. Altogether, our results suggest that gephyrin is a synapse organizing molecule that functions to localize GlyRs, but not nAChRs, to discrete postsynaptic membrane microregions in chick CG neurons in vivo.

Animals↗
PubMed2000

Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal.

Fast excitatory synaptic transmission through vertebrate autonomic ganglia is mediated by postsynaptic nicotinic acetylcholine receptors (nAChRs). We demonstrate a unique postsynaptic receptor microheterogeneity on chick parasympathetic ciliary ganglion neurons-under one presynaptic terminal, nAChRs and glycine receptors formed separate but proximal clusters. Terminals were loaded with [3H]glycine via the glycine transporter-1 (GlyT-1), which localized to the cholinergic presynaptic terminal membrane; depolarization evoked [3H]glycine release that was calcium independent and blocked by the GlyT-1 inhibitor sarcosine. Ganglionic synaptic transmission mediated by nAChRs was attenuated by glycine. Coexistence of separate clusters of receptors with opposing functions under one terminal contradicts Dale's principle and provides a new mechanism for modulating synaptic activity in vivo.

Amino Acid Transport Systems, Neutral↗
PubMed1999

Motor feedback physiological control for a continuous flow ventricular assist device.

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open-loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional-integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.

Algorithms↗
PubMed1998

Performance of a continuous flow ventricular assist device: magnetic bearing design, construction, and testing.

A new centrifugal continuous flow ventricular assist device, the CFVAD III, which is fully magnetic bearing suspended, has been developed. It has only one moving part (the impeller), has no contact (magnetic suspension), is compact, and has minimal heating. A centrifugal impeller of 2 inch outer diameter is driven by a permanent magnet brushless DC motor. This paper discusses the design, construction, testing, and performance of the magnetic bearings in the unit. The magnetic suspension consists of an inlet side magnetic bearing and an outlet side magnetic bearing, each divided into 8 pole segments to control axial and radial displacements as well as angular displacements. The magnetic actuators are composed of several different materials to minimize size and weight while having sufficient load capacity to support the forces on the impeller. Flux levels in the range of 0.1 T are employed in the magnetic bearings. Self sensing electronic circuits (without physical sensors) are employed to determine the impellar position and provide the feedback control signal needed for the magnetic bearing control loops. The sensors provide position sensitivity of approximately 0.025 mm. A decentralized 5 axis controller has been developed using modal control techniques. Proportional integral derivative controls are used for each axis to levitate the magnetically supported impeller.

Algorithms↗
PubMed1997

Changes in apoptosis of human polymorphonuclear granulocytes with aging.

Many alterations with aging occur at the cellular and organic levels in the immune system ultimately leading to a decrease in the immune response. Our aim in the present work was to study apoptosis of polymorphonuclear granulocytes (PMN) with aging under various stimulations since apoptosis might play an important role in several pathologies encountered with aging. The PMN of healthy young (20-25 years) and elderly (65-85 years) subjects were examined after 24 h of sterile culture with and without stimulation. The stimulating agents included: phorbol myristate acetate (PMA), hydrogen peroxide (H2O2), N-formyl-methionyl-leucyl phenylalanine (FMLP), granulocyte-macrophage colony stimulating factor (GM-CSF), reduced glutathione (GSH), lipopolysaccharide (LPS) and interleukin 2 (IL-2). Apoptosis was assessed by traditional staining of the plates, by flow cytometric staining and DNA gel electrophoresis. It was found that without stimulation the susceptibility of PMN to apoptosis was slightly increased with aging. Under various stimulations, such as PMA. H2O2, apoptosis was almost 100%, while the treatment by FMLP, oxLDL and GSH did not change its extent in PMN obtained either from young or elderly subjects. Marked age-related changes were observed in the extent of apoptosis under stimulation with GM-CSF, IL-2 and LPS. These agents were able to significantly prevent apoptosis in PMN of young subjects, while only the GM-CSF was able to slightly modulate it in neutrophils of elderly subjects. From these results, we suggest that changes in apoptosis of PMN with aging could play a role in the increased incidence of certain immune system related pathologies of aging, such as cancer, infections and autoimmune disorders.

Adult↗
PubMed1996

Using hybrid magnetic bearings to completely suspend the impeller of a ventricular assist device.

Clinically available blood pumps and those under development suffer from poor mechanical reliability and poor biocompatibility related to anatomic fit, hemolysis, and thrombosis. To alleviate these problems concurrently in a long-term device is a substantial challenge. Based on testing the performance of a prototype, and on our judgment of desired characteristics, we have configured an innovative ventricular assist device, the CFVAD4, for long-term use. The design process and its outcome, the CFVAD4 system configuration, is described. To provide unprecedented reliability and biocompatibility, magnetic bearings completely suspend the rotating pump impeller. The CFVAD4 uses a combination of passive (permanent) and active (electric) magnetic bearings, a mixed flow impeller, and a slotless 3-phase brushless DC motor. These components are shaped, oriented, and integrated to provide a compact, implantable, pancake-shaped unit for placement in the left upper abdominal quadrant of adult humans.

Biocompatible Materials↗
PubMed1989

Effect of prolactin versus growth hormone on islet function and the importance of using homologous mammosomatotropic hormones.

The purpose of this study was to determine the effects of homologous rat PRL (rPRL) and rat GH (rGH) on islet B-cell function in neonatal and adult rat islets in vitro. In neonatal rat islets, exposure to rPRL for more than 24 h was necessary for a stimulatory effect on insulin secretion. By day 4, insulin secretion was 3.8-fold greater in the islets cultured with rPRL. rGH had a modest effect on insulin secretion, and this effect was additive with that of rPRL. Both rPRL and rGH increased islet insulin content and [3H]thymidine incorporation. After removal of rPRL, more than 24 h were necessary to detect a reversal in the level of insulin secretion. In addition, even after 5 days without rPRL the previously treated islets still had elevated levels of insulin secretion. In a dose-response study of rPRL on insulin secretion, a detectable effect was observed at 62.5 ng/ml, with a half-maximal effect of approximately 100 ng/ml. Glucose oxidation by neonatal islets was enhanced by rPRL treatment, but not by rGH treatment. In adult rat islets, exposure to rPRL, but not to rGH, enhanced insulin secretion. In contrast, when using heterologous human GH, results similar to those obtained with rPRL, but not rGH, were observed. The results from these experiments indicate that rPRL and rGH have both individual and shared regulatory effects on rat islets. However, it is rPRL and not rGH that has the primary influence on insulin secretion. When interpreting studies examining the effect of GH and PRL on islet function, it is important to consider whether homologous hormones are used.

Animals↗
PubMedDate not supplied

The CEO as organizational architect: an interview with Xerox's Paul Allaire. Interview by Robert Howard.

As chairman and CEO of the Xerox Corporation, Paul Allaire leads a company that is a microcosm of the changes transforming American business. With the introduction of the first plain-paper copier in 1959, Xerox invented a new industry and launched itself on a decade of spectacular growth. But easy growth led Xerox to neglect the fundamentals of its core business, leaving the company vulnerable to low-cost Japanese competition. Starting in the mid-1980s, Xerox embarked on a long-term effort to regain its dominant position in world copier markets and to create a new platform for future growth. Thanks to the company's Leadership through Quality program, Xerox became the first major U.S. company to win back market share from the Japanese. Allaire describes his efforts to take Xerox's corporate transformation to a new level. Since becoming CEO in 1990, he has repositioned Xerox as "the document company" at the intersection of the worlds of paper-based and electronic information. And he has guided the company through a fundamental redesign of what he calls the "organizational architecture" of Xerox's document processing business. Few CEOs have approached the process of organizational redesign as systematically and methodically as Allaire has. He has created a new corporate structure that balances independent business divisions with integrated R&D and customer operations organizations. He has redefined managerial roles and responsibilities, changed the way managers are selected and compensated, and renewed the company's senior management ranks. And he has articulated the new values and behaviors Xerox managers will need to thrive in a more competitive and fast-changing business environment.

Administrative Personnel↗