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M Pagel

Publications and source records attributed to M Pagel.

34 records · Page 2Linked to original sources
PubMed1993

Seeking the evolutionary regression coefficient: an analysis of what comparative methods measure.

Two alternative classes of comparative statistical method differ in the way that the comparative data are used to test for an association between two quantitative traits. Directional comparative methods use reconstructions of the ancestral character states to calculate the changes between ancestral and descendant conditions along the branches of the phylogenetic tree. The set of changes in two or more traits is used to test for evidence of correlated evolution. Cross-sectional techniques do not estimate changes along the branches of the tree, but rather make comparisons across the tips of a phylogeny, or between pairs of extant taxa (or between their higher nodes). These methods, then, study the association between pairs of traits representing the contemporary endpoints of evolution. The best known of the cross-sectional techniques, the species regression, simply regresses the species values of one variable onto those of another. However, it is shown here analytically that directional and cross-sectional methods, despite making very different use of the data, estimate precisely the same evolutionary parameter: the association between the changes in two variables along the branches of the phylogenetic tree. Thus, comparative statistical techniques are able to recover the historical trends of evolution, that is, the ways in which evolution has proceeded along the branches of the phylogenetic tree, from analysis of the variation among the contemporary species of a phylogeny. This means that the choice between the two alternative traditions of comparative study cannot be based upon what the different methods purport to measure, but rather must be based upon the statistical properties of particular methods. In the light of this result, it is discussed here whether there are statistical reasons to prefer some methods over others.

Animals↗
PubMed1993

Honest signalling among gametes.

The gametes of many lower eukaryotic organisms emit pheromones that attract gametes of the opposite mating type or sex. Gametes move or grow in the direction of the highest pheromone concentration, suggesting that the strength of the pheromonal signal is used to infer proximity, or that the strongest signal is most likely to be notice. Here I offer a new explanation of pheromonal signalling and chemotaxis in gametes. I show that pheromonal signals can be interpreted as sexually selected traits that honestly advertise variation in quality among gametes, given that signals are costly to produce and that gametes compete; by 'quality' I refer to some aspect of a gamete's fitness. A gamete's preference for a mating partner, then, is predicted to vary with the quality of a prospective partner as inferred from the strength of its signal. This view can explain characteristics of the signalling and mate selection behaviours of gametes that are not predicted by models of mate choice based on proximity or 'passive attraction' to the strongest signal. These include repeated partner exchanges, escalated exchanges of mating pheromones, and rejection of gametes that signal at low levels.

Animals↗
PubMed1992

Variation across species in the size of the nuclear genome supports the junk-DNA explanation for the C-value paradox.

The amount of DNA in the nuclear genome (the DNA C-value) of eukaryotes varies at least 80,000-fold across species, and yet bears little or no relation to organismic complexity or to the number of protein-coding genes. This phenomenon is known as the C-value paradox. One explanation for the C-value paradox attributes the size of the nuclear genome to 'junk' (typically non-coding) genetic elements that accumulate until the costs to the organism of replicating excess DNA select against it. Across species, organisms that develop at a slower rate should tolerate more junk DNA. Alternatively, junk DNA may function as a nucleo-skeleton to maintain the volume of the nucleus at a size proportional to the volume of the cytoplasm in the cell. Across species, the DNA C-value is predicted to vary with the nuclear and cytoplasmic volumes of cells. Previous studies have not been able to distinguish between the skeletal-DNA and junk-DNA explanations for the C-value paradox. We report a study of DNA content in 24 salamander species which does. The size of the nuclear genome is correlated with developmental rate even after the effects of nuclear and cytoplasmic volume have been removed. However, genome size is not correlated with cytoplasmic volume after controlling for developmental rate. These results support the view that junk DNA accumulates in the nuclear genome until the costs of replicating it become too great, rather than that it functions as a nucleo-skeleton.

Animals↗
PubMed1987

Depressive thinking and depression: relations with personality and social resources.

The mechanisms by which social supports and personality variables may buffer against psychopathology are not well understood. We studied depression, depressive cognitions, social supports, and self-esteem in a sample of 68 spouse-caregivers of patients with Alzheimer's Disease in an attempt to identify possible buffering mechanisms of the latter two variables. Specifically, we hypothesized that the well-known relation of depressive cognitions to depression would vary as a function of satisfaction with social supports and with level of self-esteem. Hierarchical multiple regression analyses conducted to predict depression revealed significant and independent main effects for depressive cognitions (p less than .01), social supports (p less than .025), and self-esteem (p less than .001), with depressive cognitions associated with higher depression and the other two variables associated with reduced depression (R2 = .53 for the three main effects). In addition, the relation of depressive cognitions with depression varied substantially depending on the level of social supports (p less than .01); caregivers with high levels of depressive cognitions had high levels of depression only if social supports were low (R2 = .61 including interaction). Self-esteem and depressive cognitions showed a similar interaction, but it failed to reach significance. Analyses to determine whether self-esteem and social supports were directly associated with lower depressive cognitive activity yielded a main effect for self-esteem only (p less than .03). Thus, whereas social supports and self-esteem were directly associated with lower depression, only the social supports variable was further associated with reduced depression because it apparently buffered the impact of depressive thinking. Self-esteem was also indirectly associated with lower depression via its relation with lower depressive thinking. Implications of our results for cognitive theories of depression and for the psychosocial mechanisms of stress buffering are discussed.

Adult↗
PubMed1984

Prediction of pregnancy complications: an application of the biopsychosocial model.

This paper describes a pilot study of biomedical and psychosocial risk and the outcome of pregnancy. Ninety-three pregnant women completed four instruments to identify three types of psychosocial risk: life events, family function and social support. Biomedical risk was identified through analysis of self-reported health histories and hospital records. Information on complications of pregnancy was obtained from hospital delivery records. Further complications data were obtained by a home interview at 6 weeks postpartum. In the sample studied, from an agricultural-university community in Eastern Washington, biomedical risk alone was not substantially related to complications. Psychosocial risk was related to both delivery and postpartum complications. Family function was the best single psychosocial predictor. The interaction between family function and biomedical risk also predicted complications reliability. A total of 11% of variance in postpartum complications could be explained jointly by biomedical and psychosocial risk. The results of the study suggest that psychosocial risk assessment alone and in interaction with biomedical risk assessment will offer significant improvement in the identification of women who may experience pregnancy complication.

Adult↗
PubMed1983

Inability of dimethyl sulfoxide and 5-fluorouracil to open the blood-brain barrier.

The inability of most chemotherapeutic agents to adequately penetrate the blood-brain barrier (BBB), in either normal brain or tumor-infiltrated brain, is a major factor limiting the use of chemotherapy in central nervous system malignancy. This barrier, however, can be opened in a reversible manner by the intra-arterial administration of hyperosmotic agents such as mannitol. It has been suggested that the intravenous administration of dimethyl sulfoxide (DMSO) or 5-fluorouracil (5-FU) can accomplish the same thing in a less invasive manner. We have not been able to confirm these findings. DMSO was administered to 25 rats intravenously at concentrations ranging from 25 to 90% or into the internal carotid artery at a concentration of 30%. The penetration of methotrexate, Evans blue-albumin, and hexosaminidase A was then evaluated at intervals ranging from 1.5 to 3.5 hours after administration. Significant barrier opening was not observed in animals receiving intravenous DMSO. Barrier modification, albeit generally modest, was obtained in animals receiving intracarotid DMSO, but this may have been the result of grand mal seizures, inasmuch as 5 of 6 of these animals had such seizures. Several of the animals receiving i.v. DMSO also had seizures, and all animals developed varying degrees of hematuria. Similarly, 5-FU was administered at a dose of 30 mg/kg i.v. and the permeability of the BBB to either Evans blue-albumin or methotrexate was evaluated. No increased permeability of the BBB to these two markers was observed. In summary, osmotic BBB opening in our hands remains the most consistent and reliable means available to open the BBB in a reversible fashion. Neither intravenous DMSO nor 5-FU seems to increase the delivery of chemotherapy or protein tracer to the central nervous system, and the use of DMSO can result in seizures and hematuria.

Animals↗
PubMed1982

Effects of oxygen administration on the manifestation of acetate intolerance in dialysis patients.

In a prospective double-blind study. 12 patients were dialyzed four times each with nasal oxygen (O2) and 4 times each with air throughout acetate dialysis. Fewer symptoms (p less than 0.01), improved postdialysis task performance (p less than 0.04) and a tendency for less mean blood pressure drop (p less than 0.07 two-sided) were noted on O2 dialyses than on air dialyses. The rate of acetate metabolism was increased during O2 dialyses since serum acetate levels were significantly lower at 2, 3 and 4 h. Significant hypoxemia was demonstrated in 10 of these patients on acetate dialysis without O2. These results clearly demonstrate that: (1) prevention Of hypoxemia during dialysis reduces acetate intolerance, and (2) compromised tissue O2 availability may be partly responsible for dialysis morbidity.

Acetates↗
PubMed1981

Delivery of hexosaminidase A to the cerebrum after osmotic modification of the blood--brain barrier.

The present studies were undertaken to evaluate the possibility that hexosaminidase A, the enzyme deficient in Tay--Sachs disease, could be effectively delivered to brain. Previous studies from our laboratory have shown that hypertonic mannitol can be used to osmotically produce reversible disruption of the blood--brain barrier in animals (rat and dog) and man without significant neurotoxicity and that such barrier modification significantly increases the delivery of cytoreductive chemotherapy agents to selected areas of brain. By using the rat model of blood--brain barrier modification and radiolabeled enzyme, increased hexosaminidase A delivery to brain has been demonstrated in more than 85 animals. The time of injection of hexosaminidase A after blood--brain barrier disruption is critical for maximum delivery. Rapid (over 30 sec) intra-arterial administration of hexosaminidase A immediately after blood--brain barrier disruption resulted in a marked increase in enzyme delivery to the brain when compared with controls without prior barrier disruption. When the enzyme was administered 15-20 min after barrier disruption, approximately 50% less hexosaminidase A was delivered; when given 60-120 min after barrier modification, the amount delivered was the same as in control animals. This critical time course is very different than that seen in trials of low molecular weight chemotherapeutic agents (methotrexate and adriamycin). These preliminary studies suggest that hexosaminidase A can be delivered to the brain by blood--brain barrier modification and may be indicative of the potential for enzyme replacement in patients who hae Tay--Sachs disease.

Animals↗
PubMed1981

Pharmacology and toxicity of intracarotid adriamycin administration following osmotic blood-brain barrier modification.

The effect of reversible blood-brain barrier modification on the delivery of Adriamycin to the brain was studied in a rodent and canine model. Pharmacokinetic and physiological studies were done in these animals after a wide range of doses of Adriamycin (0.1 to 1.0 mg/kg) were administered into the carotid artery following osmotic barrier modification with mannitol. In the absence of barrier modification, no immunoreactive Adriamycin was detected in the cerebrum; whereas, following barrier modification, up to 4.5 micrograms of drug and/or metabolites per g of brain were found. Optimum tissue levels of Adriamycin and metabolites were achieved following barrier modification when the drug was administered by either bolus or slow continuous (15-min) infusion. Immunoreactive drug was identified in brain for up to 6 hr after administration. Significant functional neurotoxicity occurred at all dose levels, even at 0.1 mg/kg, a level at which Adriamycin concentration in the brain was below the level of detectability. Neuropathological examination revealed the presence of necrosis and hemorrhagic infarcts. Thus, these pharmacological and toxicity studies suggest that Adriamycin (or its metabolites) may produce significant clinical neurotoxicity when even small amounts penetrate the blood-brain barrier.

Animals↗
PubMed1979

The influence of acetate versus bicarbonate on patient symptomatology during dialysis.

The effect of large-surface area dialysis (LS) using dialysate containing both acetate and bicarbonate (LS-C) on a patient's symptomatology was compared with that noted with acetate (LS-A) or bicarbonate (LS-B) in the dialysis fluid. Patients experienced significantly more symptoms and deterioration of objective performance test scores with both LS-A and LS-C than LS-B. Furthermore, a correlation was seen between plasma acetate level at the end of dialysis and decrement in the performance test scores. The results suggest that accumulation of acetate rather than acute alteration in acid-base status is primarily responsible for the morbidity.

Acetates↗