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Biomedical subjects

W Parker

Publications and source records attributed to W Parker.

At least 19 recordsLinked to original sources

N-terminal domain of Avena phytochrome: interactions with sodium dodecyl sulfate micelles and N-terminal chain truncated phytochrome.

Phytochrome is the ubiquitous red light photoreceptor present in plants. Properties of the 6-kDa end terminal region of phytochrome A (PHYA from etiolated Avena) have been investigated by the use of synthetic polypeptide fragments corresponding to that region. This region of the phytochrome A protein has been viewed as a possible functional site due to the large differences in the sequence's conformation and exposure between the Pr (red light-absorbing form) and Pfr (far-red light-absorbing, gene-regulating form) species of phytochrome A. Hydrophobic moment calculations reveal amphiphilic helical potential in this section of the protein, consistent with the folding of the N-terminal region onto a hydrophobic chromophore/chromophore pocket. A large N-terminal synthetic peptide also demonstrated helical folding in the presence of SDS micelles. This experimental evidence indicates that the N-terminal alpha-helical folding upon conversion of the regulatorily inactive Pr to the active Pfr form of phytochrome A is likely driven at least in part by amphiphilic helix stabilization. Further, the large synthetic peptide was spectrally demonstrated to interact with phytochrome A lacking the N-terminal region. The formation of this nativelike complex may provide us with a tool for both biophysical and physiological studies on the mechanism of phytochrome A signal transduction.

Edible Grain

Protein structures in SDS micelle-protein complexes.

Sodium dodecyl sulfate (SDS) is used more often than any other detergent as an excellent denaturing or "unfolding" detergent. However, formation of ordered structure (alpha-helix or beta-sheet) in certain peptides is known to be induced by interaction with SDS micelles. The SDS-induced structures formed by these peptides are amphiphilic, having both a hydrophobic and a hydrophilic face. Previous work in this area has revealed that SDS induces helical folding in a wide variety of non-helical proteins. Here, we describe the interaction of several structurally unrelated proteins with SDS micelles and the correlation of these structures to helical amphiphilic regions present in the primary sequence. It is likely that the ability of native nonordered protein structures to form induced amphiphilic ordered structures is rather common.

Animals

Migraine and the vestibular system in adults.

The purpose of this paper is to explore the relationships between migraine and the vestibular system in adults. A review of the literature on migraine reveals that paroxysmal vertigo is not uncommonly associated with migraine in various temporal relationships with headache and/or other neurologic symptoms. Vertigo (or nonvertiginous dizziness) may be the chief presenting complaint sometimes masking less dramatic symptoms causing patients to be directed to an otolaryngologist. Meticulous family, past personal, and present history are necessary to produce the information leading to suspicion of the association of paroxysmal vertigo with the migraine diathesis. A careful prospective study of a large neurotologic population seems indicated to further define this relationship leading to diagnostic and therapeutic benefits. Sixteen cases are presented, six of them in detail.

Humans

Location of helical regions in tetrapyrrole-containing proteins by a helical hydrophobic moment analysis. Application to phytochrome.

Helical regions in many tetrapyrrole proteins are highly amphiphilic, one side interacting with a hydrophobic core and another side interacting with the polar solvent. The mean helical hydrophobic moment is a measure of amphiphilicity of a helix. Helical regions in myoglobin, the alpha and beta subunits of C-phycocyanin, and cytochrome c can be distinguished from nonhelical regions by use of a hydrophobic moment analysis. 24 of 27 (89%) of the helical regions in these proteins were located by this analysis. Calculations were also performed on chymotrypsin, ribonuclease, and papain, which do not possess as pronounced a hydrophobic core as the tetrapyrrole-containing proteins. Less than 50% of the helical regions were correctly located, indicating a lack of amphiphilicity in the helices of these proteins. The hydrophobic moment analysis was also used to predict helical regions in phytochrome, the ubiquitous photoreceptor in plants. Additionally, this analysis is used to quickly locate internal hydrophilic residues which may be functionally important. The distribution of hydrophobic moments from a random sequence was determined so that qualitative and to some extent quantitative comparisons between different amphiphilic helices may be made.

Amino Acid Sequence

Spectral perturbations and oligomer/monomer formation in 124-kilodalton Avena phytochrome.

We have studied the effects of pH, ionic strength, and hydrophobic fluorescence probes, 8-anilinonaphthalene-1-sulfonate (ANS) and bis-ANS, on the structure of intact (124-kDa) Avena phytochrome. The Pfr form of phytochrome forms oligomers in solution to a greater extent than the Pr form. Hydrophobic forces play a major role in the oligomerization of phytochrome, as suggested by fluorescence and monomerization by bis-ANS. However, electrostatic charges also take part in the phytochrome oligomerization. The partial proteolytic digestion patterns for the Pr and Pfr species are different, but binding of bis-ANS to the phytochrome abolishes this difference and yields an identical proteolytic peptide mapping for both spectral forms of phytochrome. This appears to result from bis-ANS binding at the carboxy-terminal domain, which induces monomerization of phytochrome oligomers. A second bis-ANS binding at an amino-terminal site blocks cleavage sites of trypsin and alpha-chymotrypsin. Bis-ANS especially blocks access of the proteases to the amino-terminal cleavage site that produces an early proteolytic product (114/118 kDa) on SDS gels. The bis-ANS binding does not, however, affect the proteolytic cleavage site that occurs in the hinge region between the two structural domains of phytochrome, the chromophore domain and the C-terminal non-chromophore domain. A chromophore binding site in the Pfr form is apparently exposed for preferential binding of bis-ANS, causing cyclization of the chromophore and bleaching of its absorbance at 730 nm. These observations have been discussed in terms of a photoreversible topographic change of the chromophore/apoprotein during the phototransformation of phytochrome.

Anilino Naphthalenesulfonates

Migraine and the vestibular system in childhood and adolescence.

A review of the literature gives considerable evidence that there are manifestations of migraine involving the vestibular system starting in infancy and proceeding to late life. This paper deals with these manifestations in the first two decades of life. There is evidence that vestibular symptoms are probably caused by involvement at different levels of the system in different cases. Paroxysmal vestibular symptoms may occur in association with headache, temporally independent of headache, or without headache, and may at times be the chief complaint causing the patient to seek help from the otolaryngologist in the latter two instances. Other neurologic symptoms may or may not be present. Meticulous family, past personal, and present history are the sources of information necessary to suspect the association of paroxysmal vestibular symptoms and a migraine diathesis. A prospective study of a large neurotologic population of this age group with recurrent paroxysmal vestibular symptoms seems indicated and may lead to diagnostic and therapeutic benefits.

Adolescent

The dynamics of weight loss after gastric partition for gross obesity.

Energy intake and expenditure have been assessed in patients before gastric partition for gross obesity, 3 months after operation when they were still losing weight and at 12 months when weight loss was complete and stable. Food intake was drastically reduced after surgery and the energy deficit so produced was sufficient to account completely for the weight loss, even when allowance was made for an adaptive reduction in energy expenditure. In a majority of patients, the eventual reduction in expenditure parallels the regression of metabolic rate against body mass index for a population of stable obese patients. However, the reduction in resting metabolic rate was maximal soon after the operation, when weight loss was far from complete. Weight loss stabilized at about 6 months, not due to a further reduction in energy expenditure but because energy intake recovered until the patient was again in energy balance.

Adult

An inherited connective tissue disease in the horse.

The hyperextensible, fragile skin of two related horses was compared with the skin of eight normal horses. Skin sections were examined by light microscopy and transmission electron microscopy. The deep dermal layer of the dorsal abdomen was much thinner in the affected horses, and contained bundles of collagen fibers which were more loosely packed. Within individual fibers, the fibrils were frequently curved and nonparallel rather than straight and parallel. Both of the affected animals had a greater range of fibril diameters than a normal horse. They had some unusually thick fibrils with very irregular outlines in cross-sections, not observed in the normal animal. Other skin samples were subjected to acetic acid extraction, pepsin digestion, amino acid analysis and polyacrylamide gel electrophoresis. In the skin of the two affected horses, the proportion of total extracted collagen which was acid-soluble was twice as high as in two normal horses. Collagen types I and III were present in similar proportions in normal and affected horses, and the collagen chains were of normal molecular weights. The disorder resembles the group described by Minor (Minor RR: Am J Pathol 98: 226, 1980) as 'dominant collagen packing defect I' which has been reported in dogs, mink, and cats, and which shares features with Ehlers Danlos Syndrome I, II, and III in man. The pedigree data available for these horses suggest an autosomal recessive mutation, but are also consistent with autosomal dominant inheritance.

Animals

Neovascular glaucoma following neodymium-YAG laser posterior capsulotomy.

Iris neovascularization and neovascular glaucoma were diagnosed in three diabetic patients following neodymium-YAG laser posterior capsulotomy. Each of the patients had previously undergone an uncomplicated extracapsular cataract extraction with insertion of a posterior chamber lens implant. These occurrences are consistent with the hypothesis that the posterior lens capsule may serve as a protective barrier to a diffusible vasoproliferative factor from the vitreous or retina. Both the beneficial optical effects and the potential adverse effects should be carefully considered prior to performing neodymium-YAG laser posterior capsulotomy in diabetic patients or other patients with ischemia in the fundus. Following neodymium-YAG laser posterior capsulotomy, these eyes should be closely followed up for signs of neovascularization and possible panretinal photocoagulation.

Cataract Extraction

Vestibular responses to different caloric stimulus intensities.

Data are presented concerning stimulus response relationships to weak (44 degrees C) and strong (0 degrees C) caloric stimuli. In clinically hypoactive ears the response to the strong stimulus is not equivalent to the response to the weak stimulus for evaluating hypoactivity when using the usual percentage formula. The ratio of responses to strong and weak stimuli in the hypoactive ear is greater than in the better ear. The absolute differences in mean eye speed response to strong and weak stimuli are the same for hypoactive and better ears as for hypoactive and probably normal groups. A hypothetical schema is described to explain these relationships involving alteration of tonic balance between the two ears in the presence of central compensation. The effect of directional preponderance on stimulus response relationships is described. It is suggested that differences in absolute mean eye speed values in group analysis are the true measure of gain due to the stronger stimulus and are more valid for determining stimulus response relationships between stimuli of differing intensities than the ratio of these means. Using this criterion, no evidence of recruitment was found in the ears described. The concept of vestibular recruitment and decruitment in terms of caloric test characteristics is discussed and the appropriateness of these terms is questioned.

Caloric Tests

An approach to quantify central vestibular compensation.

Central vestibular compensation is the ultimate goal for the dizzy patient. Monitoring spontaneous nystagmus and caloric responses are not usually correlated with the patient progress and cannot be objectively documented. On the other hand, Temporal Asymmetry Shift (TAS) is a more accurate and objective measure of central vestibular compensation. Furthermore, its dynamic pattern offers a reliable indicator to differentiate between peripheral and central vestibular dysfunctions.

Adult

Exaggerated acoustic reflex response in a patient with transient facial palsy and hyperacusis.

An unusual acoustic reflex response was documented by immittance recording in a patient with acute facial palsy. The amplitude of the stapedial response to sustained stimulation was reduced when recorded from the affected side, suggesting the facial nerve was affected proximal to the stapedius muscle. In addition, the impedance change at onset of intense acoustic stimulation of the affected side was unusually large, regardless of which stapedius response was recorded. The large change was coincident with the reported hyperacusis in the stimulated ear. This suggested the cochlear nerve as site of involvement of hyperacusis in this case of facial palsy.

Adult

ENG analysis of 150 cases of posterior fossa disease.

Analysis of the ENG records of 150 patients with well substantiated neurologic disease involving the structure of the posterior fossa revealed a high incidence of diminished optic fixation inhibition (DOFI) of caloric induced nystagmus. DOFI is defined as less than 50 percent decrease of speed of the slow phase when eyes are open and fixated. The whole group was subdivided into seven subgroups according to type and location of disease and the incidence of DOFI was found to vary significantly in the different subgroups. The highest incidence was found in the group of cerebellar mass lesions and in the group of degenerative diseases, most of which had cerebellar involvement. A review of the literature reveals work done by others showing that suppression of vestibular reflexes induced by high speed turning and also habituation of caloric induced nystagmus is dependent on optic fixation inhibition (opto-vestibular reflex.). It has been shown that the flocculonodular lobe of the cerebellum has an inhibitory effect on the effects of vestibular activity by both destructive and stimulating techniques. Afferent and efferent pathways between the cerebellum and primary vestibular reflex arcs have been extensively described. It has been shown that cerebellar nodulectomy severely interferes with acquisition of habituation and retention of previously acquired habituation. Since habituation and suprression of vestibular nystamus depend on optic fixation inhibition and equally on the cerebellum, it is reasonable to infer that the opto-vesitubular inhibitory reflex is mediated by the crebellum. The clinical data of the 150 cases were analyzed for correlation of DOFI and other cerebellar signs. This analysis gives a high incidence of correlation: 66 percent of the cases having DOFI also had other cerebellar signs, whereas only 19 percent of cases that did not have DOFI had other cerebellar signs. These data lend further support to the inference that the cerebellum is involved in mediation of the opto-vestibular inhibitory reflex. Under most circumstances visual perception of the environment during movement depends on an inter-reaction between the vestibulo-oculomotor and the opto-vestibular reflexes. Eye movements during head movements are entirely different with eyes closed than with eyes open and fixating. In fact, it can be shown that ocular fixation is far more efficient during head movements than it is during movement of an object with head stationary. It is probable that fixation in the former case is the result of vestibulo-oculomotor slow phase activity modified by the opto-vestibular inhibitory reflex and elimination of the fast phase. A defect in the latter should result in a sense of spatial insecurity during movement by virtue of altered visual perception. The opto-vestibular inhibitory reflex is a central descending reflex probably mediated through the cerebellum. It is easy to test during and ENG. It is essential to normal visual perception during head movement...

Brain Diseases