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Biomedical subjects

D Litchfield

Publications and source records attributed to D Litchfield.

8 recordsLinked to original sources

Solution structure of the tetrameric minimum transforming domain of p53.

We report the solution structure of the minimum transforming domain (residues 303-366) of human p53 (p53tet) determined by multidimensional NMR spectroscopy. This domain contains a number of important functions associated with p53 activity including transformation, oligomerization, nuclear localization and a phosphorylation site for p34/cdc2 kinase. p53tet forms a symmetric dimer of dimers that is significantly different from a recent structure reported for a shorter construct of this domain. Phosphorylation of Ser 315 has only minor structural consequences, as this region of the protein is unstructured. Modelling based on the p53tet structure suggests possible modes of interaction between adjacent domains in full-length p53 as well as modes of interaction with DNA.

Amino Acid Sequence

Analysis of thirty-two patients with Schatzki's ring.

Schatzki's ring is a distinct anatomical entity associated with hiatal hernia; however, its significance is unclear. Thirty-two patients with a radiologically demonstrated Schatzki's ring were compared with 32 patients with hiatal hernia and no Schatzki's ring. Schatzki's ring was confirmed on endoscopy in 59 percent of patients. Seventy-five percent of patients with Schatzki's ring presented with dysphagia compared with 41 percent of control patients (p less than 0.01). Heartburn and regurgitation were less frequent than in control subjects (38 percent versus 91 percent, p less than 0.0001). Schatzki's ring patients were found to have a lower incidence of proven gastroesophageal reflux on 24-hour pH monitoring. Those with proven reflux were found to have a more efficient lower esophageal sphincter than control patients. Sixty-two percent of Schatzki's ring patients without proven reflux had a history of chronic ingestion of drugs known to be damaging to the esophageal mucosa, whereas only 26 percent of patients with reflux had this history. This was found in 16 percent of controls. Sixty-two percent of Schatzki's ring patients without reflux responded to a single dilatation compared with 37 percent of those with reflux. These findings suggest an etiologic relationship between pill lodgement and Schatzki's ring in patients without reflux and indicate that different therapy should be employed in these patients.

Adult

Synthesis in vitro of rat brown adipose tissue 32 000 Mr protein.

The synthesis of the mitochondrial inner membrane 32 000 Mr protein from rat brown adipose tissue was examined. Polysomes from the tissue were translated in a reticulocyte lysate protein-synthesizing system and newly-synthesized protein isolated with a monospecific antibody against the 32 000 Mr protein. The newly-synthesized protein had the same relative molecular mass as the mature protein. It was taken up by mitochondria isolated from Chinese hamster ovary cells into a form resistant to trypsin.

Adipose Tissue, Brown

Average evoked potentials and amplitude modulation.

Average auditory evoked potentials (AEPs) to amplitude modulated (AM) linear voltage ramps within a limited intensity range were investigated in a group of 4 subjects. Increasing linear voltage ramps evoked the familiar vertex potential; the average AEP to decreasing ramps was difficult to measure because of its small amplitude. The amplitude of the average AEP to increasing ramps depended on the tone that preceded it. The average amplitude was largest when the tone preceding the onset of the ramp was constant and decreased in amplitude when the slope of the preceding tone deviated from zero either in the positive or negative direction with the positive slope having the more marked attenuating effect. The standard deviation (S.D.) of the distributions of reaction times to stimulus onset correlated negatively with the average AEP amplitude. The attenuation of the averaged AEP appeared to be related to the uncertainty of the subjects as to when the various types of stimuli occurred. The above findings on AM ramp stimuli closely parrellel our previously reported findings on frequency modulated ramp stimuli.

Acoustic Stimulation

Averaged evoked potentials and frequency modulation.

Frequency modulated (FM) auditory stimuli result in average vertex potentials similar to the usual auditory average evoked potential (AEP). For stepwise increase or decrease in tone frequency the AEPs are similar. For FM stimuli modulated by pulses of different durations 'on' responses are evoked by the transition of the stimulus from the longer duration to the shorter duration frequency tone while 'off' responses result when the frequency transition is from the shorter to the longer duration tone. Ramp modulation of the stimulus frequency results in average evoked responses; the amplitude of these responses is proportional to the slope of the ramp as well as the frequency of the tone that precedes the ramp. Thus, if the tone preceding the ramp is also a ramp but of smaller slope the AEP is attenuated and with sufficiently large slope the AEP can be completely extinguished. No AEPs were obtained at the offset of ramp modulated stimuli. The standard deviation (S.D.) of the reaction time (RT) distributions to stimulus onset indicate that the AEP amplitude is inversely proportional to the S.D. values. Thus, the attenuation phenomena appeared to be related to the uncertainty of the subject as to the exact time the stimulus occurred, both of which seem to be the result of sensory difficulty to the type of stimuli used. AEPs to negative ramps were smaller than AEPs to positive ramps; this may be on account of the psychological inequality between the stimuli.

Acoustic Stimulation