Biomedical subjects
H P Williams
Publications and source records attributed to H P Williams.
A fission yeast kinesin affects Golgi membrane recycling.
We report here an in vivo study of kinesin heavy chain (KHC) functions in yeast. We have identified in Schizosaccharomyces pombe a kinesin motor gene, klp3(+), which has the highest homology to the Neurospora crassa KHC. Using indirect immunofluorescence, HA epitope-tagged Klp3 protein is cytoplasmic and appears as one to a few distinct patches that are coincident with microtubules. The klp3 null allele is viable. In klp3 deleted cells, ER, Golgi and mitochondrial distribution appear normal. Mitochondrial distribution in S. pombe is known to be microtubule-associated. We show that latrunculin A does not cause mitochondria to aggregate, suggesting that mitochondrial distribution in fission yeast, unlike budding yeast, is not dependent upon actin-based processes. Neither latrunculin A nor thiabendazole affects ER or Golgi distribution. We also used the vital dye FM4-64 to visualize the internalization of the dye and its transport to vacuoles in fission yeast in the presence and absence of Klp3. We observed no significant difference between the wild-type and Klp3 null cells in either the dynamics of endocytosis or the distribution and fusion of vacuoles. The drug brefeldin A causes Golgi-to-ER recycling in wild-type fission yeast cells. Although recycling of Golgi to ER after brefeldin A treatment occurs in klp3 null cells, recycling is defective and the distribution pattern we see is different from that observed in the wild-type strain. We conclude that Klp3 plays a role in BFA-induced membrane transport. The nucleotide sequence of S. pombe klp3(+) was submitted to GenBank under Accession No. AF154055.
Effect of anterior capsulotomy on decentration of a two-zone multifocal intraocular lens.
A study was undertaken to determine if can-opener (CO) or continuous curvilinear capsulorhexis (CCC) anterior lens capsulotomy influences decentration of a two-zone multifocal intraocular lens (IOL). Fifty IOLs (25 with polypropylene haptics and 25 with poly[methyl methacrylate] haptics) were implanted following CO, 42 with poly(methyl methacrylate) haptics, following CCC. The extent and direction of decentration was estimated using a photogeometric technique. The haptic material may influence decentration. Continuous curvilinear capsulorhexis was associated with less decentration than CO (0.36 mm and 0.43 mm, respectively). The difference, however, was not statistically significant.
Cocaine euphoria, dysphoria, and tolerance assessed using drug-induced changes in brain-stimulation reward.
The time course of cocaine-induced changes in self-stimulation thresholds were used to evaluate cocaine euphoria and dysphoria as a function of the chronicity of drug treatment, dosage level, and the spacing of injections. It was assumed that cocaine-induced decreases in thresholds were indicative of cocaine euphoria, while increases in thresholds reflected rebound dysphoric responses to cocaine administration. Three experiments were performed using self-stimulating rats implanted with ventral tegmental area electrodes. Cocaine's threshold-lowering effects were evident 15 min postinjection (IP) with thresholds returning to baseline by approximately 3.0 h after treatment. Little evidence for cocaine-induced increases in thresholds was observed during periods of chronic cocaine treatment. However, thresholds were slightly elevated upon withdrawal from chronic cocaine treatment in Experiments 2 and 3. No evidence of tolerance or sensitization to cocaine-induced shifts in thresholds was noted with single daily injections, while multiple daily injections produced tolerance to cocaine's threshold-lowering effects. It is concluded that cocaine's ability to enhance brain-stimulation reward is highly reliable and robust, while decreases in brain-stimulation reward associated with chronic cocaine treatment are less reliable and difficult to demonstrate. The possible influence of drug dosage on the induction of cocaine dysphoria and the ability of various self-stimulation procedures to measure dysphoric effects are discussed.
Cocaine's effects on rate of intracranial self-stimulation.
While some investigators have reported that cocaine increases response rates for brain stimulation reward, others have failed to demonstrate this effect. The present study was designed to evaluate the influence of stimulation parameters, dose of cocaine and operant-dependent response requirements on cocaine's ability to alter self-stimulation rates. Self-stimulation rates were collected on a minute by minute basis for 45 min following IP injections of 0, 5, 15 or 30 mg/kg cocaine HCI. All doses were tested using both nose-poking and lever-pressing operants. It was found that mean lever-pressing rates were significantly increased by 5 mg/kg cocaine, while nose-poking rates were significantly increased by 15 and 30 mg/kg cocaine. Further examination of the pattern of results indicated that the cocaine-induced increases in lever-pressing rate were mainly due to an increase in the time spent self-stimulating, whereas increases in nose-poking were mainly due to increases in nose-poking rate/min within self-stimulation bouts. It was hypothesized that 5 mg/kg cocaine increased lever-pressing by producing response perseveration, while the higher doses increased nose-poking mainly due to the compatibility of the nose-poking response topography with cocaine-induced stereotypies.
England's National Health Service: still a success.
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Evolution, games theory and polyhedra.
The problem of finding an Evolutionary Stable Strategy (ESS) for an animal species is defined. It is shown how such strategies are a subset of the equilibrium solutions for a particular non-zero sum game. These equilibrium solutions are then shown to arise from the vertices of a particular convex polyhedron. A method of finding these equilibrium solutions through the vertices and then the ESS solutions is given. This is illustrated by a number of numerical examples taken from the literature. Finally an alternative approach based on solving a Linear Complementarity Problem is discussed.
Both response effort and current intensity affect self-stimulation train duration thresholds.
Self-stimulation thresholds obtained from rate/intensity functions have often been used to measure brain stimulation reward (BSR) under the assumption that these indices are not contaminated by performance factors. However, very few studies have explicitly examined the effect of performance variables on thresholds. The present experiment examined the joint effects of response effort and current intensity on train duration thresholds. Three levels of stimulation current and lever weightings were factorially combined and train duration thresholds (defined as 50% of maximum response rates) were determined for each condition. It was discovered that changes in both current intensity and response effort produced shifts in thresholds, and that these shifts were of approximately equal magnitude. It was concluded that caution must be exercised when interpreting self-stimulation threshold data since, at least under some conditions, both reward (i.e., train duration) and performance (i.e., effort) manipulations produced similar shifts in self-stimulation response functions.
Manipulation of the iris in extracapsular lens extraction.
Successful extracapsular cataract surgery depends on adequate mydriasis, which will facilitate the anterior capsulotomy and provide a full field of view throughout the operation. The surgeon, especially the neophyte, must recognise which irises may present a difficulty in establishing, maintaining, and reversing mydriasis, with or without the introduction of an intraocular lens. The author describes the preliminary assessment of the iris for disease, previous iris surgery, ease of dilatation, and the place of primary iridectomy. Topical and subconjunctival preoperative mydriatics are assessed, and a practical account of the pharmacological, mechanical, and surgical means of maintaining intra-operative mydriasis is given. The indication for iridectomy in extracapsular lens extraction with or without an intraocular lens is reviewed, and the postoperative manipulation of the iris is described with reference to the problems caused by rebound mydriasis.
Herpes simplex kerato-uveitis and glaucoma.
We present a retrospective study of fifty patients who developed raised intraocular pressure in association with herpes simplex kerato-uveitis. We consider the incidence, clinical features, management and prognosis, and discuss the mechanisms which may be responsible.
Pentachlorophenol distribution in a fresh water ecosystem.
The results of this investigation have shown that PCP persisted in leaf litter and sediments for at least seventeen months following contamination. This persistence provides a potential for continuous contamination of the water column and biological magnification via detritus- and benthic-feeding organisms. An investigation of these factors is presently underway.
Corticosteroids in the management of herpetic eye disease.
The discriminate use of topically applied corticosteroids to modify or abolish the inflammatory response in herpetic stromal keratitis, has, as its objectives, the prevention of visual loss from corneal scarring and disorganization and a lessening of the morbidity associated with this disese. Steroids may be expected to have a profound anti-inflammatory effect in antibody-complement mediated inflammation and are effective in delayed hypersensitivity as in homograft rejection. The equally profound effect of pharmacological vasoconstriction may enable steroids to impede both afferent and efferent pathways in an immunological reflex arc, and they may be expected to reduce inflammation of nonimmunogenic origin. The adverse effects of the misapplication of these potent drugs in herpetic keratitis, in terms of an increase in the rate of complications and in the severity and morbidity of the disease, should be emphasized again.
Objectives in therapy of herpetic eye disease.
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Management of herpetic eye disease.
We define in this paper a rational approach to the management of the various stages of herpetic eye disease. We consider in more detail comparisons between idoxuridine (IDU), trifluorothymidine (F3T), and adenine arabinoside (Ara-a) (derived largely from clinical trials in herpetic ulcers). We discuss metaherpetic ulcers and certain aspects of keratoplasty.
Comparison of the accommodative effects of carbachol and pilocarpine with reference to accommodative esotropia.
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Letter: Gel chromatography in the analysis of 99mTc radiopharmaceuticals.
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Evidence for the presence of hydrogen-bonded secondary structure in angiotensin II in aqueous solution.
Automated tritium-hydrogen exchange measurements have been made on the linear octapeptide Val(5)-angiotensin II amide. All six amide hydrogens of the peptide backbone are observable, and are resolved into three classes according to their exchange rates. The rate of exchange of the slowest class, t(1/2) of 300 min at 0 degrees C (pH 2.5), is compared with that of hydrogens that exchange abnormally slowly in other peptides. It is concluded that these slow hydrogens in angiotensin II are involved in secondary structure with either one or both forming stable, intramolecular hydrogen bonds. This finding demonstrates that linear peptides may have hydrogen-bonded conformations in aqueous solutions. Analysis of the pH dependence of the rate of exchange indicates that one peptide amide hydrogen, namely that of the Asn(1)-Arg(2) peptide bond, is not involved in hydrogen bonding and is freely accessible to the solvent. Thus, the finding of internal hydrogen bonding, together with the assignment of the environment of one peptide bond, places major constraints on the number of allowable conformations of this linear polypeptide hormone.
The outlook for the child with a myelomeningocele for whom early surgery was considered inadvisable.
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