[3H] pirenzepine selectively identifies a high affinity population of muscarinic cholinergic receptors in the rat cerebral cortex

The specific binding of [³H] pirenzepine was investigated in homogenates of rat cerebral cortex, cerebellar cortex, and heart. Specific binding of [³H] pirenzepine in the cerebral cortex as defined by displacement with atropine sulfate (1μM) was of high affinity (K_d = 4–10 nM, receptor density = 1.06 pmoles/mg protein), stereoselective, and competitive with drugs specific for the muscarinic receptor. In contrast, few [³H] pirenzepine binding sites were demonstrated in cerebellar and heart homogenates.     

Muscarinic receptor binding in the mouse heart: the selective modulatory effect of fluoride ion on agonist binding

The effect of fluoride ion on the binding of the specific muscarinic agonist ligand [³H]c is methyldioxolane ([³H]CD) to the mouse cardiac muscarinic receptor was investigated. Utilizing equilibrium ligand binding experiments, sodium fluoride (10mM) was shown to decrease [³H]CD binding, measured at a concentration of 2 nM, by 52%. Studies with several different ions demonstrated that the reduction in [³H]CD binding was a specific effect of fluoride. This fluoride modulation was selective for agonist binding, as no effect of fluoride on the binding of the muscarinic antagonist [³H](?) quinuclidinyl benzilate (QNB) was observed.     

Hypothesis test for causal explanations in human pathology: evaluation of pulmonary edema in 181 autopsied patients with leukemia

Symbolic logic, as used in the formal theory of scientific explanation proposed by Hempel and Oppenheim, has been suggested as the basis for automated medical diagnosis. In human autopsy pathology the determination of cause-and-effect relationships is a major area subject to logical analysis. We propose a modification of the Hempel-Oppenheim schema in which the logical relationships must only be satisfied “much” of the time, as determined by binomial significance tests. The analysis employs “certainty levels” logic with a more limited consistency requirement than classical logic. The analysis is applied to a series of 181 autopsied patients with leukemia in an attempt to determine a possible role of chemotherapeutic agents in the etiology of pulmonary edema. Among 51 patients who had received cytosine arabinoside (Ara-C) within 30 days of death, there was significantly more unexplained moderate or massive pulmonary edema than among patients with no or remote therapy (p<0.001). The results suggest that a symbolic logical analysis combined with a binomial significance test can elucidate cause-and-effect relationships observed at autopsy, especially when there are multiple possible explanations for the same effect.     

Soluble mediators produced by a human continuous B-lymphoblastoid cell line

The Ebstein-Barr virus-transformed human lymphoblastoid cell line PGLC-33H releases a migration inhibitory factor (MIF) of MW ~ 20,000 daltons. This MIF may appear free in serum-free culture supernatants or may be associated with a carrier material as a complex of MW ~ 60,000 daltons, from which the MIF can be dissociated. The free form of MIF possesses, or is associated with a suppressor activity for pokeweed mitogen-induced immunoglobulin synthesis. This suppressor activity is heat (56 °C) and acid pH stable but 2-mercaptoethanol sensitive and cannot be attributed to α-interferon or lymphotoxin.     

Race,privilege and the growing class divide

When Wilson argued back in 1978 that by the mid-twentieth century social class mattered more for getting ahead than race, he launched a rigorous scholarly debate about the relative importance of race and class that continues to this day. Since the 1970s, the gap between the black middle class and the black poor has widened, lending credibility to Wilson's claim, but also raising new research questions for scholars to ponder. In this essay, I suggest that extending Wilson's model to include a new period, encompassing the last twenty-five years, would help to illuminate more recent structural advantages that contribute to class privilege in American society as well an emerging fault line within the black middle class.     

Building on Bedrock: William Steel Creighton and the Reformation of Ant Systematics, 1925–1970

Ideas about the natural world are intertwined with the personalities, practices, and the workplaces of scientists. The relationships between these categories are explored in the life of the taxonomist William Steel Creighton. Creighton studied taxonomy under William Morton Wheeler at Harvard University. He took the rules he learned from Wheeler out of the museum and into the field. In testing the rules against a new situation, Creighton found them wanting. He sought a new set of taxonomic principles, one he eventually found in Ernst Mayr's Systematics and the Origin of Species. Mayr's ideas tied together a number of themes running through Creighton's life: the need for a revised taxonomy, the emphasis on fieldwork, and the search for a new power center for ant taxonomy after Wheeler died. Creighton's adoption of Mayr's ideas as part of his professional identity also had very real implications for his career path: field studies required long and intensive studies, and Creighton would always be a slow worker. His method of taxonomy contrasted sharply not only with Wheeler's but also with two of his younger colleagues, William L. Brown and E. O. Wilson, who took over Wheeler's spot at Harvard in 1950. The disputes between these men over ant taxonomy involved, in addition to questions of technical interest, questions about where and how best to do taxonomy and who could speak withthe most authority. Creighton's story reveals how these questions are interrelated. The story also reveals the importance of Mayr's book for changes occurring in taxonomy in the middle of the twentieth century. This revised version was published online in July 2006 with corrections to the Cover Date.     

The suppression of experimental allergic encephalomyelitis in Lewis rats by treatment with myelin basic protein-cell conjugates

Pretreatment of Lewis rats with guinea pig (GP) myelin basic protein (MBP) coupled to syngeneic spleen leukocytes (SL) suppressed the subsequent induction of experimental allegic encephalomyelitis (EAE) with GP-MBP in Freund's complete adjuvant. The degree of suppression correlated positively with the amount of antigen coupled to the SL. GP-MBP coupled to syngeneic red blood cells (RBC) also resulted in suppression of EAE and the extent of the suppression was related to the dose of cells. These regimens of pretreatment also resulted in a decrease in the in vitro lymphocyte proliferative response to GP-MBP and in the extent of perivascular cuffing in the spinal cord. No decrease in the anti-MBP antibody response was detected in rats pretreated with either GP-MBP-SL or GP-MBP-RBC conjugates. Transfer of lymph node cells from rats pretreated with GP-MBP-RBC resulted in a decrease in disease severity in recipients. It is concluded that prior administration of MBP-cell conjugates is an effective way of suppressing the symptoms of EAE.     

Physics in the Galtonian sciences of heredity

Physics matters less than we once thought to the making of Mendel. But it matters more than we tend to recognize to the making of Mendelism. This paper charts the variety of ways in which diverse kinds of physics impinged upon the Galtonian tradition which formed Mendelism's matrix. The work of three Galtonians in particular is considered: Francis Galton himself, W. F. R. Weldon and William Bateson. One aim is to suggest that tracking influence from physics can bring into focus important but now little-remembered flexibilities in the Galtonian tradition. Another is to show by example why generalizations about what happens when 'physics' meets 'biology' require caution. Even for a single research tradition in Britain in the decades around 1900, these categories were large, containing multitudes.     

Quantitative Assessment of Current Risks to Harlequin Ducks in Prince William Sound,Alaska, from the Exxon Valdez Oil Spill

Harlequin Ducks (Histrionicus histrionicus) were adversely affected by the Exxon Valdez oil spill (EVOS) in Prince William Sound (PWS), Alaska, and some have suggested effects continue two decades later. We present an ecological risk assessment evaluating quantitatively whether PWS seaducks continue to be at-risk from polycyclic aromatic hydrocarbons (PAHs) in residual Exxon Valdez oil. Potential pathways for PAH exposures are identified for initially oiled and never-oiled reference sites. Some potential pathways are implausible (e.g., a seaduck excavating subsurface oil residues), whereas other pathways warrant quantification. We used data on PAH concentrations in PWS prey species, sediments, and seawater collected during 2001–2008 to develop a stochastic individual-based model projecting assimilated doses to seaducks. We simulated exposures to 500,000 individuals in each of eight age/gender classes, capturing the variability within a population of seaducks living in PWS. Doses to the maximum-exposed individuals are ～400–4,000 times lower than chronic toxicity reference values established using USEPA protocols for sea- ducks. These exposures are so low that no individual-level effects are plausible, even within a simulated population that is orders-of-magnitude larger than exists in PWS. We conclude that toxicological risks to PWS seaducks from residual Exxon Valdez oil two decades later are essentially non-existent.     

The priority dispute over the function of the lymphatic system and Glisson's ghost (the 18th-century Hunter-Monro Feud)

Basic Immunology has had only two significant public priority disputes. The first began in the late 1650s and concerned the recognition of the peripheral network of vessels which collects lymph throughout the body. The publication of this major anatomical discovery prompted a priority feud discussed in a previous paper. The subject of this essay is the second dispute which occurred a century later in the late 1750s. It focused on the function of the lymphatic system and precipitated a heated war of words between a young Scotch medical graduate (Alexander Monro) and a noted London anatomist (William Hunter). Their published charges and responses ranged from feigned respect to ad hominen invectives. But in retrospect, the priority claims of both were precluded by the observations and speculations of an Englishman (Francis Glisson) a full century before. The several editions of his work were unknown to Hunter and Monro at the inception of their feud.