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Biomedical subjects

P Bryant

Publications and source records attributed to P Bryant.

10 recordsLinked to original sources

Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation.

The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain.

Carcinoma, Transitional Cell

Antiviral and pharmacokinetic properties of C2 symmetric inhibitors of the human immunodeficiency virus type 1 protease.

Specific processing of the human immunodeficiency virus (HIV) gag and gag-pol polyprotein gene products by the HIV protease is essential for the production of mature, infections progeny virions. Inhibitors of HIV protease block this maturation and thus prohibit the spread of HIV in vitro. Previously, we reported a series of novel, symmetric inhibitors of HIV protease designed to match the C2 symmetric structure of the active site of the enzyme. In response to the poor aqueous solubility of those lead compounds, we designed a series of analogs with substantially improved (greater than 10(4) fold) solubility. These inhibitors showed anti-HIV activity in H9 and MT4 cells at 0.05 to 10 microM, and in most cases, they were noncytotoxic at concentrations in excess of 100 microM. Further examination of one inhibitor (A-77003) revealed broad-spectrum activity against both HIV types 1 and 2, including azidothymidine-resistant HIV, in a variety of transformed and primary human cell lines. After administration of the inhibitors to rats, short half-lives and, with two notable exceptions, moderate oral bioavailability were observed. Additional pharmacokinetic studies in dogs and monkeys revealed the potential utility of A-77003 as an intravenous anti-HIV agent.

Amino Acid Sequence

Electromyographic activity of mystacial pad musculature during whisking behavior in the rat.

Cinematographic measurements of whisker movements generated by behaving rats were compared with electromyographic (EMG) activity recorded simultaneously from mystacial pad musculature. Muscle activity consisted of repetitive bursts, each of which initiated a "whisking" cycle consisting of a protraction followed by a retraction. Protraction amplitude and velocity were directly proportional to the amount of EMG activity during forward whisker movement. Overtime, the intensity of muscle discharge determined the set point about which the vibrissae moved; higher levels of muscle activity resulted in a greater degree of overall whisker protraction. These findings are consistent with the known anatomy of the facial musculature and underscore the importance of whisker protraction in the acquisition of tactile information by the vibrissae.

Animals

Young children understanding that looking leads to knowing (so long as they are looking into a single barrel).

3 experiments were conducted to investigate the claim made by Wimmer, Hogrefe, and Perner that 3-4-year-old children do not understand that people gain knowledge about something by looking at it. The first experiment involved a simple forced-choice procedure in which children had to judge which of 2 assistants knew what was inside a box when one of the assistants had looked inside and the other had lifted it up. In this experiment, the children did realize that the assistant who had looked in the box knew its contents. The second experiment followed the Wimmer et al. procedure, but with a simpler question form. The children were just asked to state whether someone knew what was in the box. Again, the children were able to work out that a person who had looked in a box knew what was inside it. In the third experiment, a direct comparison was made between the simpler question and the more complex, double-barreled question asked by Wimmer et al. The children found the more complex question considerably harder. The results of these experiments suggest that, in contrast to the claims made by Wimmer et al., 3- and 4-year-old children do understand that looking leads to knowing, and that their difficulty in the Wimmer et al. study was mainly with the form of the question that they were asked.

Attention

Rhyme, rime, and the onset of reading.

There is recent evidence that children naturally divide syllables into the opening consonant or consonant cluster (the onset) and the rest of the syllable (the rime). This suggests an explanation for the fact that preschool children are sensitive to rhyme, but often find tasks in which they have to isolate single phonemes extremely difficult. Words which rhyme share a common rime and thus can be categorized on that speech unit. Single phonemes on the other hand may only be part of one of these speech units. This analysis leads to some clear predictions. Young children, even children not yet able to read, should manage to categorize words on the basis of a single phoneme when the phoneme coincides with the word's onset ("cat," "cup") but not when it is only part of the rime ("cat," "pit"). They should find it easier to work out that two monosyllabic words have a common vowel which is not shared by another word when all three words end with the same consonant ("lip," "hop," "tip") but the odd word has a different rime than when the three words all start with the same consonant ("cap," "can," "cot") and thus all share the same onset. The hypothesis also suggests that children should be aware of single phonemes when these coincide with the onset before they learn to read. We tested these predictions in two studies of children aged 5, 6, and 7 years. The results clearly support these predictions.

Child

Health policy.

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Health Policy

Circulating erythroid progenitors in the anemia of prematurity.

We studied erythropoiesis in infants with the anemia of prematurity by counting the number of colonies derived from erythroid burst-forming units (BFU-E) in the blood of 11 premature infants before they received transfusions. Colony growth in blood from the infants was compared with growth in blood from adults and umbilical-cord blood from term infants, in the presence of erythropoietin, 0 to 2000 mU per milliliter. Addition of increasing concentrations of erythropoietin resulted in a stepwise increase in the number of colonies derived from BFU-E (P less than 0.0005) of all three groups of subjects. Cultures stimulated with 2000 mU of erythropoietin yielded 28.1 +/- 7.6, 88.0 +/- 19.4, and 121.0 +/- 22.5 bursts (mean +/- SE) per 10(5) cells plated in blood from adults, blood from premature infants, and cord blood, respectively. Although more BFU-E-derived colonies appeared when 200 or 2000 mU were present per milliliter in cultures of the infants' blood and cord blood, the intrinsic responsiveness of BFU-E to erythropoietin was similar in all groups. Although the mean hematocrit was 26 percent, mean serum erythropoietin concentrations (+/- SD) in the infants (20.7 +/- 10.0 mU per milliliter) were not significantly different from those in the adult controls (24.0 +/- 6.5). We conclude that progenitor cells committed to erythroid differentiation are present during the anemia of prematurity, and that the intrinsic responsiveness of the circulating BFU-E pool to erythropoietin is normal. These results implicate inadequate production of erythropoietin as the cause of the anemia of prematurity and suggest that recombinant erythropoietin might provide a therapeutic alternative to transfusion for symptomatic babies with this condition.

Anemia

Demonstration of papillomavirus structural antigen in human urinary bladder neoplasia.

Clear cells showing characteristic features of koilocytotic atypia were found in 41 (82%) of 50 paraffin sections of urinary bladder tumour. Papillomavirus common structural antigen was detected in seven (14%) of the samples using an avidin-biotin peroxidase staining technique. The results suggest a role for the human papillomavirus in the aetiology of urinary bladder neoplasia.

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