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Biomedical subjects

Robert Baker

Publications and source records attributed to Robert Baker.

At least 19 recordsLinked to original sources
PubMed2003

Correlated discharge among cell pairs within the oculomotor horizontal velocity-to-position integrator.

In the oculomotor system, temporal integration of velocity commands into position signals may depend on synaptic feedback among neurons of a bilateral brainstem cell assembly known as the "neural integrator." Both ipsilateral excitatory and contralateral inhibitory projections between eye position-related integrator cells are hypothesized as a substrate for positive feedback supporting integration. Presence of feedback interactions should be evident in cross-correlation functions of neuron pairs. Here, unilateral and bilateral paired recordings were obtained during fixation behavior from neurons in goldfish brainstem area I, a key element of the integrator. During fixations, discharge of most unilateral pairs, composed of cells with eye position sensitivities of the same sign, was positively correlated with lag of 0-10 msec (n = 11 of 14 significant). Typically, a very narrow peak (mean half-width <4 msec) near zero lag was observed. Discharge of bilateral pairs, composed of cells with position sensitivities of the opposite sign, was either negatively correlated with lag of 0-10 msec (n = 5 of 13 significant) or not correlated. Troughs in negative correlations always had minima between 3 and 5 msec lag. These results are consistent with the feedback hypothesis of temporal integration, highlighting excitation unilaterally and inhibition bilaterally. Absence of visual input did not weaken correlations, but other sources of correlated input extrinsic to area I were not ruled out. Triplet recordings revealed that unilateral pairwise correlations were primarily independent. Correlation between unilateral pairs systematically decreased with increasing eye position, demonstrating that synchrony is not necessary for persistent activity at high firing rates.

Action Potentials↗
PubMed2003

Practical synthesis of D- and l-2-cyclopentenone and their utility for the synthesis of carbocyclic antiviral nucleosides against orthopox viruses (smallpox, monkeypox, and cowpox virus).

Highly efficient and practical methodology for the syntheses of D- and l-4,5-O-isopropylidene-2-cyclopentenone (9 and 22), versatile intermediates for the synthesis of carbocyclic nucleosides, have been developed via a ring-closing metathesis reaction from d-ribose in eight steps. The utility of D- and l-4,5-O-isopropylidene-2-cyclopentenone is demonstrated by their application for the preparation of D-cyclopentyl-6-azauridine 12 and D-cyclopentenyl-5-halocytosine nucleosides (33-35) using Mitsunobu reaction to introduce pyrimidine bases as potential antiviral agents. Preliminary antiviral activity against orthopox viruses (smallpox, monkeypox, and cowpox virus) of the synthesized nucleosides are described.

Antiviral Agents↗
PubMed2003

History dependence of rate covariation between neurons during persistent activity in an oculomotor integrator.

Persistent firing in response to a brief stimulus is a neural correlate of short-term memory in a variety of systems. In the oculomotor neural integrator, persistent firing that encodes eye position is maintained in response to transient saccadic eye-velocity commands. To a first approximation, firing rates in the integrator vary linearly with eye position. Thus, viewed across many cells, the pattern of persistent firing in the integrator may be constrained to a unique line of stable states. Here this idea was tested by examining the relationship between firing rates of simultaneously recorded neurons. Paired recordings were obtained in awake goldfish from neurons in hindbrain area I, an essential part of the horizontal eye-position integrator. During spontaneous eye movements consisting of sequential fixations at different horizontal positions, the pair relationship between the majority of cells on the same side of the integrator was not unique: for a given rate of one cell, the rate of the paired cell assumed different values that depended systematically on the preceding saccade history. This finding suggests that the set of persistent firing states that encode eye position is not constrained to a unique line, and that models with stable states restricted to a such a line need to be modified accordingly.

Action Potentials↗
PubMed2003

Aerosolized cidofovir is retained in the respiratory tract and protects mice against intranasal cowpox virus challenge.

We employed a murine model to test the concept of using an aerosolized, long-acting antiviral drug to protect humans against smallpox. We previously showed that a low dose of aerosolized cidofovir (HPMPC [Vistide]) was highly protective against subsequent aerosolized cowpox virus challenge and was more effective than a much larger dose of drug given by injection, suggesting that aerosolized cidofovir is retained in the lung. Because the nephrotoxicity of cidofovir is a major concern in therapy, delivering the drug directly to the respiratory tract might be an effective prophylactic strategy that maximizes the tissue concentration at the site of initial viral replication, while minimizing its accumulation in the kidneys. In the present study, we found that treating mice with aerosolized (14)C-labeled cidofovir ((14)C-cidofovir) resulted in the prolonged retention of radiolabeled drug in the lungs at levels greatly exceeding those in the kidneys. In contrast, subcutaneous injection produced much higher concentrations of (14)C-cidofovir in the kidneys than in the lungs over the 96-h time course of the study. As further evidence of the protective efficacy of aerosolized cidofovir, we found that aerosol treatment before or after infection was highly protective in mice challenged intranasally with cowpox virus. All or nearly all mice that were treated once by aerosol, from 2 days before to 2 days after challenge, survived intranasal infection, whereas all placebo-treated animals died.

Administration, Intranasal↗
PubMed2002

Bioethics and history.

Standard bioethics textbooks present the field to students and non-experts as a form of "applied ethics." This ahistoric and rationalistic presentation is similar to that used in philosophy of science textbooks until three decades ago. Thomas Kuhn famously critiqued this self-conception of the philosophy of science, persuading the field that it would become deeper, richer, and more philosophical, if it integrated the history of science, especially the history of scientific change, into its self-conception. This essay urges a similar reconceptualization for bioethics, arguing that the analysis of moral change ought to be integral to bioethics (and to ethics generally). It proceeds by suggesting the sterility of the ahistoric, rationalist applied ethics model of bioethics embraced by standard bioethics textbooks. It also suggests the fecundity of alternative conceptions of the bioethics that focus on the history of successful and failed attempts to negotiate moral change, and the history of multifaceted relations between moral philosophy and practical ethics.

Abortion, Legal↗
PubMed1998

A theory of international bioethics: multiculturalism, postmodernism, and the bankruptcy of fundamentalism.

The first of two articles analyzing the justifiability of international bioethical codes and of cross-cultural moral judgments reviews "moral fundamentalism," the theory that cross-cultural moral judgments and international bioethical codes are justified by certain "basic" or "fundamental" moral priniciples that are universally accepted in all cultures and eras. Initially propounded by the judges at the 1947 Nuremberg Tribunal, moral fundamentalism has become the received justification of international bioethics, and of cross-temporal and cross-cultural moral judgments. Yet today we are said to live in a multicultural and postmodern world. This article assesses the challenges that multiculturalism and postmodernism pose to fundamentalism and concludes that these challenges render the position philosophically untenable, thereby undermining the received conception of the foundations of international bioethics. The second article, which follows, offers an alternative model -- a model of negotiated moral order -- as a viable justification for international bioethics and for transcultural and transtemporal moral judgments.

Advisory Committees↗
PubMed1998

A theory of international bioethics: the negotiable and the non-negotiable.

The preceding article in this issue of the Kennedy Institute of Ethics Journal presents the argument that "moral fundamentalism," the position that international bioethics rests on "basic" or "fundamental" moral prinicples that are universally accepted in all eras and cultures, collapses under a variety of multicultural and postmodern critiques. The present article looks to the contractarian tradition of Hobbes and Locke -- as reinterpreted by David Gauthier, Robert Nozick, and John Rawls -- for an alternative justification for international bioethics. Drawing on the central themes of this tradition, it is argued that international bioethics can be rationally reconstructed as a negotiated moral order that respects culturally and individually defined areas of nonnegotiability. Further, the theory of a negotiated moral order is consistent with traditional ideals about human rights, is flexible enough to absorb the genuine insights of multiculturalism and postmodernism, and yet is strong enough to justify transcultural and transtemporal moral judgments, including the condemnation of the Nazi doctors at Nuremberg. This theory also is consistent with the history of the ethics of human subjects experimentation and offers insights into current controversies such as the controversy over changing the consent rule for experiments in emergency medicine and the controversy over exempting certain clinical trials of inexpensive treatments for preventing the perinatal transmission of AIDS from the ethical standards of the sponsoring country.

Bioethics↗
PubMed1998

Negotiating international bioethics: a response to Tom Beauchamp and Ruth Macklin.

Can the bioethical theories that have served American bioethics so well, serve international bioethics as well? In two papers in the previous issue of the Kennedy Institute of Ethics Journal, I contend that the form of principlist fundamentalism endorsed by American bioethicists like Tom Beauchamp and Ruth Macklin will not play on an international stage. Deploying techniques of postmodern scholarship, I argue that principlist fundamentalism justifies neither the condemnation of the Nazi doctors at Nuremberg, nor, as the Report of the Advisory Committee on the Human Radiation Experiments (ACHRE) demonstrates, condemnation of Cold War radiation researchers. Principlist fundamentalism thus appears to be philosophy bankrupt. In this issue of the Journal, Beauchamp and Macklin reject this claim, arguing that I have misread the ACHRE report and misunderstood Nazism. They also argue that the form of post-postmodern negotiated human rights theory that I proffer is adequate only insofar as it is itself really fundamentalist; insofar as I take postmodernism seriously, however, I mire international bioethics in relativism. In this response, I reaffirm my anti-fundamentalism, provide further evidence in support of my reading of the ACHRE report, and defend my post-postmodern version of rights theory. I also develop criteria for a minimally adequate theoretical framework for international bioethics.

Advisory Committees↗
PubMedDate not supplied

The frog as a unique vertebrate model for studying the rhombomeric organization of functionally identified hindbrain neurons.

The segmental organization of cranial nerve efferent, vestibular, and precerebellar neurons of larval ranid frogs is essentially retained in adult frogs, indicating the absence of any substantial postembryonic longitudinal migration of hindbrain neurons in this group. Comparison of the rhombomeric organization of vestibulomotor and branchiomotor pathways across different species suggests that the frog hindbrain blueprint is common to most vertebrates. The unique segmental stability seen in frogs can be used to create a quantitative stereotactic map of the adult brain that mirrors the embryonic and larval rhombomeric framework. Such a map allows the large number of physiologically identified hindbrain neurons in adult frogs to be linked with their underlying genetic specification. Transgenic reporters and antisense knockdown of gene activities suspected of having necessary functions in patterning neurons within specific rhombomeres may allow direct testing of the proposed map.

Animals↗