Biomedical subjects
Publications and source records attributed to R Martin.
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The purpose of this work was to define, in this laboratory, the conditions of most general utility for the metabolic activation of chemicals to mutagens in the mouse lymphoma L5178Y cell tk+tk- ----tk-tk- assay. The approach used was to optimize the generation of non-toxic concentrations of NADPH from NADP glucose-6-phosphate (G6P) and G6P dehydrogenase, then use that system to examine the effects of increasing concentrations of Aroclor-1254-induced Fischer 344 male rat liver post-mitochondrial supernatant fluid (S9) upon the mutagenicity of chemicals. The promutagens were 2-acetylaminofluorene, cyclophosphamide, dimethylnitrosamine, methanol, 3-methylcholanthrene and procarbazine. It was determined that: (i) cell population growth was reduced at NADPH concentrations of greater than or equal to 1 mM; (ii) to ensure a maximum conversion of NADP to NADPH the G6P/NADP ratio should be two or greater; (iii) excess G6P (2.5 mM) is not harmful to the cells; (iv) toxicity due to S9 was observed at 12.5 mg whole liver equivalents (WLE)/ml (i.e. 50 microliters of a 25% liver S9 preparation per ml); (v) concentrations of S9 between 2.5 and 7.5 mg WLE/ml appeared to be adequate for the activation of the six promutagens to demonstrably mutagenic products.
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As part of a research program that aims to develop an explicit acoustic basis for a single-word intelligibility test, an initial attempt to characterize the formant trajectories and segment durations of seven test words produced by 30 normal speakers is described. These characterizations are referred to as "acoustic signatures." The data indicate that: (1) formant trajectories show two sex effects, namely, that females are more variable as a group than males and tend to have greater slopes for the transitional segment of the second-formant trajectories and that these effects are consistent across words; (2) Bark transformations of the frequency data do not seem to eliminate the interspeaker differences in formant trajectories, nor do they eliminate either of the sex effects described above; and (3) segment durations have different variabilities depending on the syllabic structure of the word; no sex effect was noted here. The discussion focuses on the appropriate form for the acoustic signatures, as well as factors that should be considered in selecting words for signature development. To demonstrate the potential application of these data, formant trajectory and segment duration data from 18 speakers with amyotrophic lateral sclerosis and varying degrees of dysarthria are compared to the acoustic signature for the word wax.
In Escherichia coli, nonsense suppression at UAA codons is governed by the competition between a suppressor tRNA and the translational release factors RF1 and RF2. We have employed plasmids carrying the genes for RF1 and RF2 to measure release factor preference at UAA codons at 13 different sites in the lacI gene. We show here that the activity of RF1 and RF2 varies according to messenger context. RF1 is favored at UAA codons which are efficiently suppressed. RF2 is preferred at poorly suppressed sites.
Rotaviruses were detected in 163 of 916 (17.8%) specimens collected from children under 3 years of age with gastroenteritis in Vellore, South India, between August 1983 and July 1985. Rotaviruses were detected throughout the study period, with a peak prevalence in December to February (winter) and June to August (southwest monsoon season). A total of 117 rotavirus strains were tested for subgroup, serotype, and rotavirus double-stranded RNA electrophoretic migration pattern; 24.8% of the strains were subgroup I, 69.2% were subgroup II, and 6.0% were neither subgroup I nor subgroup II. Subgroup I and II strains were circulating concurrently throughout the study. Of the 117 rotavirus strains, 32 (27.4%) were serotyped; 15 were serotype 1, 3 were serotype 2, 2 were serotype 3, and 12 were serotype 4. Three serotypes were circulating concurrently during the periods of peak rotavirus prevalence. In 100 of the 117 strains (85.4%) an RNA pattern was detected. One unusual subgroup I group A rotavirus with a long migration pattern and four atypical rotaviruses serologically related to group C were also detected.
A prospective study was performed over a 4.5-year period to determine the ability of a sputum Gram stain to predict the cause of community-acquired bacterial pneumonia. A blood culture isolate, rather than a sputum culture, served as the reference standard to provide precise identification of the etiologic agent. The study population comprised 59 bacteremic adults who expectorated a valid sputum sample. Data are presented that indicate that a physician, aided by the morphology of the stained sputum, could theoretically select appropriate monotherapy approximately 94% of the time when selective, defined criteria for the microbiology of valid sputum are met. Three of the five patients with pneumonia caused by Haemophilus influenzae, however, had sputum stains that suggested alternative pathogens. This study reaffirms that the Gram-stained sputum is a reliable, but not infallible, guide to direct initial antibiotic therapy in adults with community-acquired bacterial pneumonia.
Intracardiac and great artery blood flow velocities were recorded by pulsed and continuous wave Doppler ultrasound in 18 children aged between eight months and four years (mean 25 months) who had undergone anatomical correction of transposition of the great arteries in the first month of life. Postoperative peak flow velocities across the mitral valve and in the ascending aorta were not significantly different from those in an age matched control population, but tricuspid flow velocities were higher than normal. Aortic regurgitation was detected in only one of the eighteen patients, a markedly lower frequency than that reported after two stage anatomical correction. Peak velocities in the pulmonary artery were higher than normal, and in most cases there was some degree of stenosis of the pulmonary artery at the site of anastomosis.
The maximal glucocorticoid responsiveness and the adaptation degree are reduced in old rat liver as demonstrated by cortisol stimulation of RNA polymerases. Nevertheless the concentration of unoccupied 3H-dexamethasone binding sites in molybdate-stabilized cytosol of adrenalectomized old animals is significantly increased in comparison with young adult rats. The KD constants showed an increasing tendency, but not a significant one. In the molybdate-free cytosol the results are similar. First studies of the binding kinetics in the molybdate-free system showed a sigmoidal saturation curve in the cytosol of young adult rats, but usual hyperbolic saturation kinetics in the cytosol of old animals. The Hill coefficient was 1.0 +/- 0.1 for old and 1.9 +/- 0.3 for young animals. The binding of activated 3H-dexamethasone receptor complexes to liver nuclei showed no significant age-dependent differences in binding kinetics, acceptor site concentration or affinity. Attention must be paid to altered glucocorticoid receptor binding in the cytosol and in nuclei as a potential cause of changes in hormone-induced gene expression at the pretranscriptional level.
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Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.