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Biomedical subjects

A L Taylor

Publications and source records attributed to A L Taylor.

At least 73 records · Page 4Linked to original sources
PubMed1984

Acute anthracycline cardiotoxicity. Comparative morphologic study of three analogues.

Chemotherapeutic use of anthracycline antibiotics is limited by their cardiotoxic effects. A potential solution to this problem is the development of anthracycline analogues retaining antitumor efficacy but without cardiac toxicity. An isolated perfused rabbit heart model was used to compare the nature and extent of early ultrastructural effects on the myocyte of three anthracycline analogues purported to have lesser cardiotoxicity than Adriamycin (doxorubicin). Seventeen rabbit hearts were perfused with oxygenated Krebs-Ringer bicarbonate buffer at 39 degrees C containing either Adriamycin (4 mg/L), daunomycin (10.6 mg/L), aclacinomycin (8 mg/L), or rubidazone (17.6 mg/L). For comparison, three hearts each were exposed to phosphoramide mustard (14.7 mg or 25 mg/L) or 4-hydroperoxy cyclophosphamide (24 mg or 17 mg/L), two active congeners of cyclophosphamide, an agent interacting with DNA differently than the anthracyclines and which is known to be cardiotoxic in high dose. Two hearts were exposed to dactinomycin (0.1 mg or 0.2 mg/L) which intercalates with DNA in a manner similar to the anthracyclines but which is not cardiotoxic. Ten control hearts were perfused with oxygenated buffer solution only. Light microscopic study disclosed no differences between treated and control hearts. Electron microscopic examination showed a striking and distinctive clumping of nuclear chromatin with clearing of chromatin from the nuclear membrane in all anthracycline treated hearts but in no hearts treated with 4-hydroperoxy cyclophosphamide, phosphoramide Mustard, dactinomycin, or control hearts. The nuclear effects of the four anthracycline analogues were indistinguishable. Thus, all anthracycline analogues studied produced acute nuclear alterations which were distinctive from the changes produced by other DNA interactive chemotherapeutic agents. The relationship of the distinctive anthracycline nuclear changes to the late cardiomyopathy requires further definition.

Aclarubicin↗
PubMed1983

Involvement of Escherichia coli K-12 DNA polymerase I in the growth of bacteriophage Mu.

We examined several aspects of bacteriophage Mu development in Escherichia coli strains that carry mutations in the polA structural gene for DNA polymerase I (PolI). We found that polA mutants were markedly less efficient than PolI wild-type (PolI+) strains in their capacity to form stable Mu lysogens and to support normal lytic growth of phage Mu. The frequency of lysogenization was determined for polA mutants and their isogenic PolI+ derivatives, with the result that mutants were lysogenized 3 to 8 times less frequently than were PolI+ cells. In one-step growth experiments, we found that phage Mu grew less efficiently in polA cells than in PolI+ cells, as evidenced by a 50 to 100% increase in the latent period and a 20 to 40% decrease in mean burst size in mutant cells. A further difference noted in infected polA strains was a 10-fold reduction in the frequency of Mu-mediated transposition of chromosomal genes to an F plasmid. Pulse labeling and DNA-DNA hybridization assays to measure the rate of phage Mu DNA synthesis after the induction of thermosensitive prophages indicated that phage Mu replication began at about the same time in both polA and PolI+ strains, but proceeded at a slower rate in polA cells. We conclude that PolI is normally involved in the replication and integration of phage Mu. However, since phage Mu does not exhibit an absolute requirement for normal levels of PolI, it appears that residual PolI activity in the mutant strains, other cellular enzymes, or both can partially compensate for the absence of normal PolI activity.

Bacteriophage mu↗
PubMed1983

Extensive myocardial fiber disarray in aortic and pulmonary atresia. Relevance to hypertrophic cardiomyopathy.

Myocardial fiber disarray is a distinctive histopathologic finding seen in asymmetric hypertrophic cardiomyopathy. We studied 14 hearts with aortic atresia and intact interventricular septum, six hearts with pulmonic atresia and intact interventricular septum, eight normal infant hearts matched for age of the study hearts, and one nonadult heart with hypertrophic cardiomyopathy and asymmetric hypertrophy and quantitatively analyzed tissue sections through both ventricles and the septum. Normal hearts had an average overall fiber disarray of 8.7% (range 3.8-17%) of the left ventricle including septum. Hearts with pulmonary atresia had an overall disarray of 70.4% (range 13-97%) of the entire right ventricle, and those with aortic atresia 62.1% (range 26-97%) of the left ventricle. The one infant heart with hypertrophic cardiomyopathy showed 15.5% disorder of the left ventricular free wall, 75% disorder of the septum and 47% overall myocardial fiber disarray. Thus, while quantitative criterion distinguished normal from abnormal hearts, they did not distinguish among the various pathologic states. Although extensive myocardial fiber disarray is not exclusive to, or pathognomonic of, hypertrophic cardiomyopathy, it is a useful finding taken in the context of the overall disease. The sensitivity and specificity of this isolated morphologic observation as an indication of hypertrophic cardiomyopathy may be misleading.

Aortic Valve↗
PubMed1982

Growth of bacteriophage Mu in Escherichia coli dnaA mutants.

In one-step growth experiments we found that bacteriophage Mu grew less efficiently in nonreplicating dnaA mutants than in dnaA+ strains of Escherichia coli. Phage development in dnaA hosts was characterized by latent periods that were 15 to 30 min longer and an average burst size that was reduced by 1.5- to 4-fold. The differences in phage Mu development in dnaA and dnaA+ strains were most pronounced in cells infected at a low multiplicity and became less pronounced in cells infected at a high multiplicity. Many of these differences could be eliminated by allowing the arrested dnaA cells to restart chromosome replication just before infection. In continuous labeling experiments we found that infected dnaA strains incorporated 5 to 40 times more [methyl-3H]thymidine than did uninfected cells, depending on the multiplicity of infection. DNA-DNA hybridization assays showed that greater than 90% of this label was contained in phage Mu DNA sequences and that only small amounts of the label appeared in E. coli sequences. In contrast, substantial amounts of label were incorporated into both host and viral DNA sequences in infected dnaA+ cells. Although our results indicated that phage Mu development is not absolutely dependent on concurrent host chromosomal DNA replication, they did strongly suggest that host replication is necessary for optimal growth of this phage.

Bacteriophage mu↗
PubMed1982

Acute adriamycin cardiotoxicity: morphologic alterations in isolated perfused rabbit heart.

Adriamycin is an antitumor agent whose use is limited by cardiac toxicity resulting in a late congestive cardiomyopathy. The time course of the cardiac changes and whether they are due to direct effect of the drug on the myocyte is unknown. The purpose of this study was to determine the very early changes in subcellular structure caused by adriamycin in an isolated, perfused, working heart. Eighteen rabbit hearts were perfused with oxygenated Krebs-Ringer-bicarbonate buffer at 39 degrees C. containing either 1, 2, 4, or 8 mg. per liter of adriamycin for periods of 30 to 150 minutes; 10 controls were perfused with buffer only. Light microscopic study of sections through both ventricles revealed no differences between treated and control hearts. Electron microscopy showed a striking and distinctive central clumping of nuclear chromatin in all 18 hearts exposed to adriamycin, but in no controls; this nuclear change was more marked with increasing dose of drug, but not with longer durations of perfusion. In 15 of 18 hearts sarcomeres and mitochondria were normal, and in 15 of 18 mild cytoplasmic vacuolization was present. In contrast, of 10 control hearts nuclei in seven were normal, and three showed some focal peripheral clumping of chromatin; seven had normal sarcomeres and mitochondria, and three showed mild cytoplasmic vacuolization. Thus, exposure of the isolated rabbit heart to adriamycin results in acute and distinctive nuclear alterations, with associated mild cytoplasmic changes. To what extent these nuclear effects mediate subsequent myocyte degeneration or dysfunction remains to be determined.

Animals↗
PubMed1980

Integration of bacteriophage Mu at host chromosomal replication forks during lytic development.

The target site for bacteriophage Mu integration in a lytic cycle of infection was investigated. DNA synthesis in five Hfr strains of Escherichia coli K-12 was synchronized by amino acid starvation and was allowed to proceed for 0, 8, or 15 min before infection. The Hfr cells were then infected with Mu and were subsequently mated with nonimmune F- recipient cells. Mating was interrupted mechanically at 5-min intervals and samples were assayed for infective centers. Conjugal transfer of Mu was delayed in Hfr strains that have transfer origins 15 map units or more from the E. coli replication origin, and the delays increased as the distance between an Hfr point of origin and the replication origin increased. When a gene A mutant of Mu was used for the infection, no infective centers were generated. Infection with a gene B mutant resulted in infective center formation only after long periods of mating. These data are most consistent with a model in which infecting Mu DNA or its progeny integrate at host chromosomal replication forks.

Bacteriophage mu↗
PubMed1980

Diabetic ketoacidosis. Reassessment of therapeutic "truths".

The diagnosis of diabetic ketoacidosis remains, as always, a bedside clinical exercise. Rapid consideration and exclusion of other conditions associated with altered consciousness that may occur in diabetics, such as lactic acidosis, hyperosmolar states, hypoglycemia, alcohol-related ketosis, and infections, should be routine. Although recent reassessment of therapy has meant more rational and specific action, close attention to the physical and laboratory responses to treatment is equally essential for a successful outcome.

Bicarbonates↗
PubMed1977

The attachment of a retarded child to an inanimate object: translation into clinical utility.

This paper describes the relationship of a moderately retarded boy with autistic features to an inanimate object, relates this relationship to his emotional development, and suggests methods for utilizing observations of his behavior with the object for assessment of cognition. The authors suggest that the object differs only qualitatively from a transitional object. Implications for the evaluation of retarded children include the necessity for approaches identical to those used in evaluating intellectually normal children and interdisciplinary assessment with combinations of behavioral and dynamic techniques. Implications for parent counseling, institutional policies, therapeutic practice, psychological assessment, and personality theory are outlined.

Child↗
PubMed1975

Influence of insertions on packaging of host sequences covalently linked to bacteriophage Mu DNA.

Insertions in bacteriophage Mu DNA have been identified. These insertions are responsible for at least seven X mutations, all of which eliminate essential Mu functions. The insertions are about 800 base pairs long and are located to the left of the cleavage site of restriction endonuclease EcoRI, near the immunity end of Mu DNA. We have found that such insertions cause a reduction in the length of nonhomologous terminal sequences which are seen as split ends in denatured and renatured Mu DNA molecules. These heterogeneous sequences apparently arise from packaging of host DNA from maturation precursors in which Mu and host DNA are covalently linked. We infer that a single Mu genome length is too short to be cut during morphogenesis, and thus some host DNA is packaged into mature virions. Since the insertions increase the length of Mu DNA, they decrease the amount of host DNA needed for packaging.

Chromosome Aberrations↗
PubMed1974

Isolation of heterogeneous circular DNA from induced lysogens of bacteriophage Mu-1.

Covalently-closed circular DNA molecules are formed after induction of phage Mu cts4 and after infection with phage Mu cts4. The circular molecules obtained after induction have a molecular length range from 36.5 to 156.7 kilobases as measured by electron microscopic techniques. These heterogeneous molecules have no consistent correlation to exact multiples of a Mu genome equivalent (37.3 +/- 1.2 kilobases). Direct evidence is given that these molecules contain phage Mu DNA that is covalently linked to other DNA sequences.

Centrifugation, Density Gradient↗