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Biomedical subjects

B K Davis

Publications and source records attributed to B K Davis.

At least 19 recordsLinked to original sources

Kinetics of rapid RNA evolution in vitro.

A rapidly acquired partial resistance to the replicase antagonist, ethidium bromide (EB), seen by Spiegelman and coresearchers in Q beta RNA variants competitively replicating under defined conditions in vitro, reflected existence of a pool of mutant RNA molecules, preadapted to EB, and their cross-propagation from the pre-EB optimum species, MDV-1, and from other kindred variants, some of which remained undetected, according to this quantitative analysis of midivariant RNA replication kinetics. DNAlike features of their evolution, such as the cloning of variants from an MDV-1 subtype and a compliance with the fundamental theorem of natural selection, resulted from the suppression, both real and apparent, of intrinsic RNA heterogeneity through sampling and detection methods, and also by the ascendency of self-propagation over cross-propagation with advancement of a superior variant. The deficit in mean polymer fitness, compared with optimum levels, determines the lower limit of this heterogeneity. Stability conditions for frequency equilibrium and strategies for counteracting viral drug resistance have been considered.

Biological Evolution

Variations in polymer fitness at elevated mutation rates.

Two series expressions were obtained that give the first and second order rates of change in population fitness during competitive replication at elevated mutation rates. At their zero-error limit, the respective power series reduces to the second (Fisher's theorem) and third moments of the fitness distribution. The first series maximized the variation in mean polymer fitness, for a given amount of population covariance. From experimental results reported by Spiegelman's group on evolution in vitro among Q beta RNA variants, it was demonstrated: (i) terms in the (second) series fall-off at a rate broadly equal to the replicase error (epsilon congruent to 10(-4); (ii) the rate of change in mean RNA fitness (polymer formation rate constant) corresponds to the variance in fitness; and (iii) agreement exists between second order rate changes in fitness and the third moment (skewness) regression line, extending over 20 successive replication reactions. The impact of these findings on the standard model of evolution has been discussed.

Biological Evolution

The behavioral effects of bilateral middle cerebral artery hemorrhagic ischemia in rat.

After learning position discrimination in a T-maze water escape task, rats had either a 2 mm section of the middle cerebral artery removed bilaterally (bMCA) or they received a sham operation. Beginning on the day of surgery either total brain gangliosides (50 mg kg-1) or saline were administered daily for five days. Of the several measures of neurological function that were tested, only a temporary deficit in grasping with the front paws was observed in bMCA damaged rats. Ganglioside treatment normalized this practical function. Memory of the preoperative habit was not influenced by bMCA damage, but acquisition of a reversal of this habit was compromised. Ganglioside treatment did not influence this deficit. Acquisition of a spatial alternation strategy was influenced by neither the bMCA lesion nor the ganglioside treatment. The preservation that accompanies bMCA interruption might serve as a useful model of the functional declines that accompany stroke and frontal lobe damage.

Animals

Photo-activation of resin cements through porcelain veneers.

The purpose of this study was to determine the effects of porcelain opacity, chemical catalyst, and exposure time on polymerization of light-activated resin-composite cements. Samples of microfill and hybrid composites, with and without catalyst (i.e., dual-cure and visible-light-activated), were polymerized by exposure to visible light through porcelain discs of different opacities. Microhardness testing (KHN) was used to compare degree of cure for each material at various exposure times. Porcelain opacity did not significantly affect hardness. However, the results indicated that a chemical catalyst and prolonged curing times might be essential for clinical success.

Analysis of Variance

Studies on the mechanism of capacitation. II. Evidence for lipid transfer between plasma membrane of rat sperm and serum albumin during capacitation in vitro.

1. Evidence has been provided for the transfer of phosphatidyl[14C]choline and [3H]cholesterol between bovine serum albumin and cauda epididymal rat spermatozoa in Krebs-Ringer bicarbonate medium, which can promote sperm capacitation. 2. An analysis of the lipid composition in both albumin and spermatozoa revealed that phospholipid levels decreased in the protein and increased by roughly comparable amounts in sperm cells during incubation in vitro. 3. Cholesterol (free + ester) increased in albumin and decreased in spermatozoa. Changes in the amount of esterified cholesterol were solely responsible for the increase associated with albumin, whereas whole sperm cell extracts showed a significant decline in free cholesterol. 4. The composition of albumin-bound fatty acids did not alter appreciably as a result of incubation with spermatozoa. 5. Rates of [14C]palmitic acid utilization by spermatozoa suggest that lipid synthesis accounted for less than 5% of the changes observed under the conditions of this study. 6. These results are interpreted as broadly supporting our previous proposal that lipid exchange between albumin and sperm cells is implicated in sperm capacitation in vitro. Specifically, the results are compatible with the idea that a decreased cholesterol/phospholipid ratio in the sperm plasma membrane facilitates this transformation.

Animals

Eosinophilic pyeloureteritis: report of a case.

A case is reported of ureteral obstruction that was owing to eosinophilic pyeloureteritis, a previously unrecorded entity. The microscopic findings of extensive fibrosis and a relatively mild eosinophilic infiltrate were similar to those found in a series of eosinophilic cystitis, which was reported recently from this laboratory. Also, local injury appears to initiate some examples of eosinophilic cystitis and in the present case there was a striking history of injury 1 month before the symptoms of ureteral obstruction.

Adult

Complexity transmission during replication.

The transmission of complexity during DNA replication has been investigated to clarify the significance of this molecular property in a deterministic process. Complexity was equated with the amount of randomness within an ordered molecular structure and measured by the entropy of a posteriori probabilities for discrete (monomer sequences, atomic bonds) and continuous (torsion angle sequences) structural parameters in polynucleotides, proteins, and ligand molecules. A theoretical analysis revealed that sequence complexity decreases during transmission from DNA to protein. It was also found that sequence complexity limits the attainable complexity in the folding of a polypeptide chain and that a protein cannot interact with a ligand moiety of higher complexity. The analysis indicated, furthermore, that in any deterministic molecular process a cause possesses more complexity than its effect. This outcome broadly complies with Curie's symmetry principle. Results from an analysis of an extensive set of experimental data are presented; they corroborate these findings. It is suggested, therefore, that complexity governs the direction of order-order molecular transformations. Two biological implications are (i) replication of DNA in a stepwise, repetitive manner by a polymerase appears to be a necessary consequence of structural constraints imposed by complexity, and (ii) during evolution, increases in complexity had to involve a nondeterministic mechanism. This latter requirement apparently applied also to development of the first replicating system on earth.

Base Sequence

Eosinophilic cystitis. A study of 16 cases.

The authors describe 16 examples of eosinophilic cystitis. Cases were predominately in older men, and usually were associated with other conditions of the bladder or prostate. In contrast, most of the 21 cases reported in the English language were in women and children who had a low incidence of associated bladder conditions, but often had allergic disorders and eosinophilia. It appears that either bladder injury or allergy predisposes to eosinophilic cystitis. The bladder-injury type probably occurs fairly commonly and can be misdiagnosed both clinically and pathologically. In most of the present series, the clinical diagnosis was carcinoma of the bladder, and some biopsy specimens superficially resembled specimens from cases of nonspecific chronic inflammation. There was muscle necrosis in most examples, and significant replacement fibrosis of muscle in all the latter sometimes masquerading as mucosal fibrosis. Giemsa stain for eosinophils and trichrome stain for muscle fibrosis are helpful diagnostic aids. Also, eosinophilic cystitis appears related to allergic cystitis and interstitial cystitis.

Aged

Rate of polymer formation and entropy production during competitive replication.

The rate of increase in the mean polymer formation rate constant during competitive replication by Qbeta RNA variants (Kramer et al., 1974) has been shown to agree statistically with the variance in their formation rate constants. This result demonstrates that Fisher's fundamental theorem of natural selection (Fisher, 1930) can define time variations in the mean rate of synthesis for a heterogeneous population of replicating polymers. It was also revealed that RNA replication, far from equilibrium, accompanied a progressive decrease in the order of the entropy production derivative, with respect to time, that reached a maximum (with the next higher order being zero). Maximization of entropy at equilibrium, in compliance with the second law of thermodynamics, therefore appears as a natural extension of the earlier non-equilibrium pattern of entropy production within the system. The order of the zero-valued entropy production derivative was shown to be determined by the chemical affinity, and its rate of decrease was specified by the mean polymer formation rate constant.

Biological Evolution