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Biomedical subjects

W A Harris

Publications and source records attributed to W A Harris.

108 records · Page 6Linked to original sources

Effect of synthetic cannabinoids on elevated intraocular pressure.

Two chemical derivatives of delta-1-tetrahydrocannabinol were evaluated in a randomized, double-masked study, administered as a single oral dose to a group of ocular hypertensive patients. One of the compounds (BW146Y) was found to have a significant intraocular pressure lowering effect that was independent of orthostatic blood pressure changes, although such changes did occur in some patients. The other compound (BW29Y) was ineffective in lowering intraocular pressure at the doses tested. Psychological and performance parameters were measured, and except for a time production test among the BW29Y group, these parameters were not significantly affected by the test drugs. Patients receiving both drugs experienced mild subjective side effects.

Benzopyrans↗

The effects of eliminating impulse activity on the development of the retinotectal projection in salamanders.

The California newt Taricha torosa manufactures tetrodotoxin, a blocker of voltage-sensitive sodium channels and therefore of action potentials.The newt's own nervous system is insensitive to this toxin. Grafting an embryonic eye to the newt from a tetrodotoxin-sensitive species, the Mexican axolotl, blocks action potentials in the retinal ganglion cells of the transplanted eye. Neuroanatomical and electrophysical techniques demonstrate that while such ganglion cells are incapable of firing impulses, they develop normally, grow axons to the host tectum, terminate in the appropriate neuropil layers, form synapses, and project to the tectum retinotopically. Furthermore, they develop these apparently normal projections even in competition with electrically active axons from a host eye.

Action Potentials↗

Regions of the brain influencing the projection of developing optic tracts in the salamander.

Eye primordia from the Mexican axolotl or the California newt were transplanted into hosts of either species. These "third" eyes often developed an optic nerve that penetrated the host brain and made one of three central projections: bilateral to the dorsal thalami, tecta, and basal optic nuclei; ipsilateral to the same areas; or ipsilateral into the cord. The type of projection made by a transplanted eye seemed to depend on where its nerve first entered the brain. The optic fibers that reached the visual centers of the midbrain were organized retinotopically in the optic tectum and mediated visually-guided behavior.

Ambystoma↗

Lysophosphatidyl choline facilitates labeling of CNS projections with horseradish peroxidase.

Previously, it has been difficult to label sensory terminations in the CNS by back-filling peripheral sensory nerves with horseradish peroxidase (HRP), apparently because the amount of HRP transported along the axons is insufficient. Labeling of central sensory projections in axolotls and frogs can be improved by agents known to disrupt membranes. Of those tested, L-alpha-lysophosphatidyl choline is the most effective. The addition of this detergent ot the HRP solution dramatically increases both the number of axons labeled and the density of label within single axons.

Ambystoma↗

Apparent effect of ascorbic acid medication on semen metal levels.

The apparent effect of ascorbic acid therapy for nonspecific spermagglutination on semen levels of ascorbic acid as well as macro- and micrometals was determined in 20 men (ages 25 to 38). Pretreatment diagnosis was based on infertility and relatively low ratings in sperm density, motility, motility index, and semen volume, and were associated with large numbers of abnormal sperm, sperm precursors, and leukocytes. The pretreatment levels of ascorbic acid, sodium, iron, potassium, zinc, manganese, lead, magnesium, and copper were measured in each patient's semen and compared with levels following 60 days of dietary vitamin C supplementation (1.0 gm/day). Analysis of the vitamin C preparation prescribed revealed that each subject was given an impure ascorbic acid medication to supplement a normal diet. Therefore, the significant increases in levels of ascorbic acid and metals in semen following therapy could not be attributed to ascorbic acid alone, nor, similarly, the improved physical parameters of each subject's semen following therapy; no apparent spermagglutination and restored fertility may be due to the interaction of ascorbic acid with cations found in semen.

Adult↗

Prognosis for life in patients with diabetes: relation to severity of retinopathy.

In a group of 709 individuals with diabetes diagnosed prior to age 50 and followed for five to thirteen years a strong inverse relationship was demonstrated between the severity of the retinopathy at the initial visit and survival. Survival in patients with no retinopathy or with microaneurysms only was little different from that of the general population (five-year rate .99, SE .01). The five-year survival rate for patients with more severe nonproliferative retinopathy, characterized by the presence of hemorrhages and/or exudates, but without new vessels or vitreous hemorrhage (B2), was .81 (SE .04), and that for patients with proliferative retinopathy (PDR) was .56 (SE .03). After adjustment for age at diagnosis of diabetes, duration of diabetes and sex, the differences in survival between these three groups were highly statistically significant. Impairment of visual acuity was also shown to be inversely related to survival. The five-year survival rate for patients with visual acuity of 20/200 or worse in each eye was .42 (SE .05). In patients with B2 retinopathy there was a weak but statistically significant trend towards decreasing survival with increasing duration of diabetes. In patients with PDR survival decreased with increasing duration up to 20 years, but then improved for patients with 20 years or more of diabetes.

Adolescent↗

Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process.

Two genes in Drosophila, rdgA and rdgB, which when defective cause retinal degeneration, were discovered by Hotta and Benzer (Hotta, Y., and S. Benzer. 1970. Proc. Natl, Acad. Sci. U. S, A. 67:1156-1163). These mutants have photoreceptor cells that are histologically normal upon eclosion but subsequently degenerate. The defects in the rdgA and rdgB mutants were localized by the study of genetic mosaics to the photoreceptor cells. In rdgB mutants retinal degeneration is light induced. It can be prevented by rearing the flies in the dark or by blocking the receptor potential with a no-receptor-potential mutation, norpA. Vitamin A deprivation and genetic elimination of the lysosomal enzyme acid phosphatase alsoprotect the photoreceptors of rdgB flies against light-induced damage. The photopigment kinetics of dark-reared rdgB flies appear normal in vitro by spectrophotometric measurements, and in vivo by measurements of the M potential. In normal Drosophila, a 1-s exposure to intense 470-nm light produces a prolonged depolarizing afterpotential (PDA) which can last for several hours. In dark-reared rdgB mutants the PDA lasts less than 2 min;; it appears to initiate the degeneration process, since the photoreceptors become permanently unresponsive after a single such exposure. Another mutant was isolated which prevents degeneration in rdgB flies but which has a normal receptor potential. This suppressor of degeneration is an allele of norpA. It is proposed that the normal norpA gene codes for a product which, when activated, leads to the receptor potential, and which is inactivated by the product of the normal rdgB gene.

Acid Phosphatase↗

Genetic dissection of the photoreceptor system in the compound eye of Drosophila melanogaster.

Three mutations which eliminate specific types of photoreceptors in Drosophila were characterized. Of the eight photoreceptors in each facet, two mutations delete the outer six (R 1-6). The third eliminates R 7, one of the two central photoreceptors. Double mutants can be constructed in which only photoreceptor R 8 is present. The spectral sensitivities, photopigments, and behavioural properties of these mutants were investigated. R 1-6 have two sensitivity peaks, near 350 and 470 nm. These receptors contain a rhodopsin with these absorption peaks. It interconverts with a metarhodopsin that absorbs around 570 nm. R 7 is a U.V.-receptor, containing rhodopsin that absorbs around 370 nm and interconverts with a metarhodopsin which absorbs around 470 nm. R 8 is a non-adapting blue-receptor with a third type of rhodopsin. The properties of these photopigments explain the different sensitivities and spectral adaptation phenomena of the various photoreceptors. All the photoreceptors have input into phototaxis. Spectral analysis of this behaviour provides evidence for integration of the input from the different photoreceptors.

Animals↗

Effect of three proteinaceous foreign materials on infected and subinfected wound models.

A model was devised to determine the effects of several foreign bodies (microcrystalline collagen hemostat (MCCH), blood clot, catgut suture) on S. aureus wound contamination and wound infection. In a subinfected wound model, MCCH, when compared with the other foreign bodies, showed an increase in the number of wounds classified as "contaminated," but 84 percent of these wounds yielded bacterial counts below the level accepted for biologically significant wound infection (10 to the 5th power bacteria per gram tissue). The number of "infected" wounds was not significantly greater than the number found in the uninoculated control group. In the infected wound model, all groups of inoculated animals showed significant infections. The severity of the wound infection was unaffected by the presence of catgut suture, clotted blood, or MCCH. Higher levels were not seen for the MCCH animals than for the inoculated control animals. We did not see in these experimental wound studies with MCCH a significant aggravation of wound contamination or wound infection during the 48 hour period following inoculation with varying dose levels of S. aureus. Further studies would be necessary to determine the possible bacteriological response after 48 hours.

Animals↗

Levator tuck: a simplified blepharoptosis procedure.

A simplified technique for tucking the levator palpebrae superioris aponeurosis and muscle in the correction of blepharoptosis is described. The anterior (skin) approach is used and no special instruments are required. The advantages of this procedure are discussed, including preservation of the normal anatomy as much as possible, minimum dissection and minimum edema. A preliminary number of cases are reported. It is believed that this technique is useful in cases of acquired blepharoptosis and in congenital blepharoptosis with good levator function.

Anesthesia, General↗

Conditioned behavior in Drosophila melanogaster.

Populations of Drosophila were trained by alternately exposing them to two odorants, one coupled with electric shock. On testing, the flies avoided the shock-associated odor. Pseudoconditioning, excitatory states, odor preference, sensitization, habituation, and subjective bias have been eliminated as explanations. The selective avoidance can be extinguished by retraining. All flies in the population have equal probability of expressing this behavior. Memory persists for 24 hr. Another paradigm has been developed in which flies learn to discriminate between light sources of different color.

Animals↗

Homing behaviour of axons in the embryonic vertebrate brain.

In embryonic nervous systems, growing axons must often travel long distances through diverse extracellular terrains to reach their postsynaptic partners. In most embryos, axons grow to their appropriate targets along particular tracts or nerves, as though they were following guidance cues confined to specific pathways. For example, in all vertebrates, axons from the retina invariably grow to the tectum along the well-defined optic tract. Yet, transplant experiments demonstrate that retinal axons make tectal projections even though they enter the brain at locations which are distinctly off the optic tract. Only recently has it become possible to label discreet growing projections in the embryonic vertebrate brain. Thus, it is not yet known whether displaced retinal axons grow directly towards the tectum or find it accidently, through random extension. To resolve this question, pioneering axons from normal and transplanted eyes in embryonic Xenopus were labelled using a short-survival horseradish peroxidase (HRP) method, and their orientation during growth was quantitatively assessed. The finding that the ectopic fibres head towards their distant targets implies that guidance cues are not restricted to specific pathways but are distributed throughout the embryonic brain. The significance of this result is discussed with respect to the ontogeny and evolution of the visual pathway.

Animals↗