Search PubMed⌕ Search

Biomedical subjects

A Willis

Publications and source records attributed to A Willis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of glaucoma and aging on photopic and scotopic motion perception.

PURPOSE: To examine the effects of primary open-angle glaucoma and normal aging on visual sensitivity for targets known to bias responses from the magnocellular visual processing stream. METHODS: Contrast sensitivity was measured for the detection and direction discrimination of low-spatial-frequency (0.5 cyc/deg), drifting (4-24 Hz) sinusoidal gratings in 15 patients with glaucoma (mean age, 58.7 years), 14 age-matched control subjects (mean age 55.8 years), and 10 young control subjects (mean age, 24.4 years). As a control, sensitivity was measured for the detection of stationary stimuli. Stimuli of 4.7 degrees square were presented at either 0 degrees eccentricity or at 20 degrees along the nasal horizontal meridian, under both photopic and scotopic levels of lighting. RESULTS: Across a wide range of conditions, the ability to detect and discriminate visual motion declined significantly (P < 0.05) with increasing age, whereas the ability to detect stationary patterns was generally unaffected. The rate of decline was adequately described by a simple linear function. Control studies showed that the age-related motion sensitivity losses could not be attributed solely to decreases in retinal illuminance associated with increasing age. Of note, however, there were no significant differences in mean sensitivity between glaucoma and age-matched control groups for any of the conditions used. CONCLUSIONS: Even under conditions believed to bias the response of the visual system to the magnocellular pathway, glaucoma subjects could not be reliably differentiated from control subjects on the basis of mean sensitivity to motion stimuli. The findings have two broad implications: first, that substantial neural loss specific for motion perception occurs during the processes of normal aging, and second, that sensitivity to motion targets per se may not be a useful indicator of neural integrity in the early stages of glaucoma.

Adult↗
PubMed1998

Separate colour-opponent mechanisms underlie the detection and discrimination of moving chromatic targets.

Current opinion holds that human colour vision is mediated primarily via a colour-opponent pathway that carries information about both wavelength and luminance contrast (type I). However, some authors argue that chromatic sensitivity may be limited by a different geniculostriate pathway, which carries information about wavelength alone (type II). We provide psychophysical evidence that both pathways may contribute to the perception of moving, chromatic targets in humans, depending on the nature of the visual discrimination. In experiment 1, we show that adaptation to drifting, red-green stimuli causes reductions in contrast sensitivity for both the detection and direction discrimination of moving chromatic targets. Importantly, the effects of adaptation are not directionally specific. In experiment 2, we show that adaptation to luminance gratings results in reduced sensitivity for the direction discrimination, but not the detection of moving chromatic targets. We suggest that sensitivity for the direction discrimination of chromatic targets is limited by a colour-opponent pathway that also conveys luminance-contrast information, whereas the detection of such targets is limited by a pathway with access to colour information alone. The properties of these pathways are consistent with the known properties of type-I and type-II neurons of the primate parvocellular lateral geniculate nucleus and their cortical projections. These findings may explain the known differences between detection and direction discrimination thresholds for chromatic targets moving at low to moderate velocities.

Adaptation, Physiological↗
PubMed1998

Use of complete eluted peptide sequence data from HLA-DR and -DQ molecules to predict T cell epitopes, and the influence of the nonbinding terminal regions of ligands in epitope selection.

In diseases with a strong association with an HLA haplotype, identification of relevant T cell epitopes may allow alteration of the pathologic process. In this report we use a reverse immunogenetic approach to predict possible HLA class II-restricted T cell epitopes by using complete pool sequencing data. Data from HLA-DR2(B1*1501), -DR3(B1*0301), -DQ2(A1*0501, B1*0201), and -DQ8(A1*0301, B1*0302) alleles were used by a computer program that searches a candidate protein to predict ligands with a relatively high probability of being processed and presented. This approach successfully identified both known T cell epitopes and eluted single peptides from the parent protein. Furthermore, the program identified ligands from proteins in which the binding motif of the HLA molecule was unable to do so. When the information from the nonbinding N- and C-terminal regions in the pool sequence was removed, the ability to predict several ligands was markedly reduced, particularly for the HLA-DQ alleles. This suggests a possible role for these regions in determining ligands for HLA class II molecules. Thus, the use of complete eluted peptide sequence data offers a powerful approach to the prediction of HLA-DQ and -DR peptide ligands and T cell epitopes.

Amino Acid Sequence↗
PubMed1997

Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2).

HLA-DQ8 (A1*0301, B1*0302) and -DQ2 (A1*0501, B1*0201) are both associated with diseases such as insulin-dependent diabetes mellitus and coeliac disease. We used the technique of pool sequencing to look at the requirements of peptides binding to HLA-DQ8, and combined these data with naturally sequenced ligands and in vitro binding assays to describe a novel motif for HLA-DQ8. The motif, which has the same basic format as many HLA-DR molecules, consists of four or five anchor regions, in the positions from the N-terminus of the binding core of n, n + 3, n + 5/6 and n + 8, i.e. P1, P4, P6/7 and P9. P1 and P9 require negative or polar residues, with mainly aliphatic residues at P4 and P6/7. The features of the HLA-DQ8 motif were then compared to a pool sequence of peptides eluted from HLA-DQ2. A consensus motif for the binding of a common peptide which may be involved in disease pathogenesis is described. Neither of the disease-associated alleles HLA-DQ2 and -DQ8 have Asp at position 57 of the beta-chain. This Asp, if present, may form a salt bridge with an Arg at position 79 of the alpha-chain and so alter the binding specificity of P9. HLA-DQ2 and -DQ8 both appear to prefer negatively charged amino acids at P9. In contrast, HLA-DQ7 (A1*0301, B1*0301), which is not associated with diabetes, has Asp at beta 57, allowing positively charged amino acids at P9. This analysis of the sequence features of DQ-binding peptides suggests molecular characteristics which may be useful to predict epitopes involved in disease pathogenesis.

Alleles↗
PubMed1996

Three types of postsynaptic glutamatergic receptors are activated in DMNX neurons upon stimulation of NTS.

While it is widely accepted that parasympathetic activity plays a significant role in cardiovascular, bronchomotor, and gastrointestinal function, little is known about the synaptic control of parasympathetic vagal neurons. In this study, we identified the neurotransmitter(s) and postsynaptic responses in dorsal motor nucleus of the vagus (DMNX) neurons upon stimulation of the nucleus of the solitary tract (NTS). Neurons were visualized in rat brain stem slices, and perforated patch-clamp techniques were used to record postsynaptic currents. NTS stimulation activated glutamatergic currents in DMNX that were separated into N-methyl-D-aspartate (NMDA) and non-NMDA components using D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. The non-NMDA component was further characterized using cyclothiazide and concanavalin A to block desensitization of DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and kainate receptors, respectively. Cyclothiazide increased the postsynaptic amplitude, whereas concanavalin A augmented duration, suggesting kainate, but not AMPA, currents are curtailed by desensitization. High frequency stimulations did not alter synaptic efficacy. In conclusion, this study demonstrates the existence of a monosynaptic glutamatergic pathway from NTS that activates NMDA, kainate, and AMPA postsynaptic receptors in DMNX neurons.

2-Amino-5-phosphonovalerate↗
PubMed1995

Processing of major histocompatibility class I-restricted antigens in the endoplasmic reticulum.

We have introduced long precursor peptides directly into the endoplasmic reticulum (ER) of a mutant cell line (T2-Db) that lacks the ability to transport peptides from the cytosol to the ER in a transporter associated with antigen processing (TAP) dependent way. This was done by expressing various influenza A-derived peptides containing the naturally processed epitope ASNENMDAM (366-374) preceded by the influenza hemagglutinin ER translocation sequence. Peptides derived from these minigenes that became associated with Db were isolated and identified by combined reversed phase liquid chromatography and detection by cytotoxic T lymphocytes. Our results establish that NH2-terminal extensions of at least 40 residues can be trimmed from peptides entering the ER, but that proteolysis of larger proteins may be limited.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Dihydrolipoamide dehydrogenase in the trypanosoma subgenus, trypanozoon.

The enzyme dihydrolipoamide dehydrogenase has been discovered and characterised in four salivarian trypanosomes of the subgenus trypanozoon: Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, and Trypanosoma evansi. The three T. brucei species, which have insect procyclic forms biochemically distinct from their mammalian bloodstream forms, express dihydrolipoamide dehydrogenase in both cell types, but have higher levels in the procyclic forms. Determination of Michaelis constants for the enzyme from each of the three T. brucei species did not reveal any significant kinetic differences between the bloodstream and procyclic enzymes. On Western blots, antibodies raised against dihydrolipoamide dehydrogenase from the stereorarian trypanosome, Trypanosoma cruzi, cross-react strongly with the dihydrolipoamide dehydrogenase from all three T. brucei species; by this method, the relative molecular masses of their dihydrolipoamide dehydrogenases are indistinguishable. Dihydrolipoamide dehydrogenase was purified from both the bloodstream and the procyclic forms of T. b. brucei, and the N-terminal have been sequenced. These sequences are identical to the derived protein sequence of the cloned gene (Else et al., Eur. J. Biochem. 212 (1993) 423-429), but have a nine amino acid N-terminal truncation, giving an N-terminus equivalent to that of T. cruzi dihydrolipoamide dehydrogenase. The T. b. brucei dihydrolipoamide dehydrogenase gene has been expressed in Escherichia coli and the resultant protein purified; its N-terminus is processed in a similar fashion to that in the trypanosome, but with reduced specificity.

Amino Acid Sequence↗