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Biomedical subjects

W A Harris

Publications and source records attributed to W A Harris.

At least 37 records · Page 2Linked to original sources
PubMed1999

Giant eyes in Xenopus laevis by overexpression of XOptx2.

Overexpression of XOptx2, a homeodomain-containing transcription factor expressed in the Xenopus embryonic eye field, results in a dramatic increase in eye size. An XOptx2-Engrailed repressor gives a similar phenotype, while an XOptx2-VP16 activator reduces eye size. XOptx2 stimulates bromodeoxyuridine incorporation, and XOptx2-induced eye enlargement is dependent on cellular proliferation. Moreover, retinoblasts transfected with XOptx2 produce clones of cells approximately twice as large as control clones. Pax6, which does not increase eye size alone, acts synergistically with XOptx2. Our results suggest that XOptx2, in combination with other genes expressed in the eye field, is crucially involved in the proliferative state of retinoblasts and thereby the size of the eye.

Albinism↗
PubMed1999

The effect of ascorbic acid supplementation on the nicotine metabolism of smokers.

BACKGROUND: The relationship of serum ascorbic acid (AA) levels and excretion of nicotine metabolites was determined in 75 men who smoked at least one pack of cigarettes per day. METHODS: The subjects were randomly divided into three groups of 25 each who received a placebo, 200 mg of supplementation, or 1000 mg of supplementation of AA per day for 1 month. Baseline and weekly serum AA levels were determined and simultaneous estimates of urinary excretion of nicotine metabolites as cotinine equivalents (CE). RESULTS: The group mean serum AA levels in the placebo group decreased 13% after 2 weeks; the group mean serum levels of the supplemented groups increased significantly after 1 week (P </= 0. 001) and remained elevated over 100% per week from baseline throughout the study. There was a progressive increase in urinary CE excretion in the placebo group. In the supplemented groups, group mean CE excretion decreased an average of 5% weekly in the 200-mg group and an average of 33% weekly in the 1000-mg group. Pearson's correlation between serum AA and urine CE excretion was significant (r = -0.7980, P </= 0.0003). CONCLUSIONS: Body levels of AA affect the level of urinary nicotine metabolites. The results of this study indicate that dietary levels of AA are inversely correlated to urinary excretion of nicotine metabolites and may be due to suppressed: (1) nicotine intake by smokers who smoked fewer cigarettes or inhale less deeply, (2) nicotine metabolism, or (3) both.

Adult↗
PubMed1999

Amniotic fluid B12, calcium, and lead levels associated with neural tube defects.

The group mean differences and relationships between folate, B12, calcium, lead, and methionine levels in amniotic fluid from 29 non-NTD and 11 NTD pregnancies (15-20 weeks' gestation age) were determined. The study population was predominantly Hispanic in both groups (48% in non-NTD and 36% in NTD group) with an average maternal age of 29 years in the non-NTD group and 24 years in the NTD group; and, an average gestation age of 18.5 weeks in the non-NTD and 17.5 weeks in the NTD group. The folate, B12, lead, calcium, and methionine levels of the two groups were compared by Student's t-test and by Pearson's correlation. The NTD levels were lower for calcium (p< or =0.0001), B12 (p< or =0.001), and methionine (P< or =0.001); but, the lead level was higher (p< or =0.0001). A negative correlation was observed between lead and both B12 (p< or =0.007) and methionine (p< or =0.02).

Adult↗
PubMed1999

The effect of ascorbic acid supplementation on the blood lead levels of smokers.

BACKGROUND: The study subjects were 75 adult men (20 to 30 years of age), who smoked one pack of cigarettes per day (minimum) and had no clinical signs of ascorbic acid deficiency or lead toxicity. None had a history of industrial exposure to lead, and the blood-lead levels were anticipated to be below 1.45 micromol/L, the minimum blood level associated with toxicity symptoms. METHODS: The men were randomly assigned to three study groups of 25, and each group was provided a four-week supply of one level of daily ascorbic acid supplements (placebo, 200 mg or 1000 mg of ascorbic acid). We measured baseline and weekly serum and urine ascorbic-acid levels as well as blood and urine lead levels. The weekly group means and variations of the measured data were statistically compared by means of ANOVA and Pearson's correlation. RESULTS: The serum ascorbic-acid levels of the groups receiving ascorbic acid increased significantly after one week (p< or =.001). There was no effect of placebo or 200 mg ascorbic-acid supplementation on the blood or urine lead levels. However, there was a 81% decrease in blood-lead levels in the 1000 mg ascorbic acid group after one week of supplementation (p< or =.001). CONCLUSIONS: Daily supplementation with 1000 mg of ascorbic acid results in a significant decrease of blood-lead levels associated with the general population. Ascorbic acid supplementation may provide an economical and convenient method of reducing blood-lead levels, possibly by reducing the intestinal absorption of lead.

Adult↗
PubMed1999

Amniotic fluid amino and nucleic acid in normal and neural tube defect pregnancies. A comparison.

OBJECTIVE: To explore the relationship between fetal amino acids (AAs), which are the components of structural proteins and nucleic acids, and the changes associated with neural tube defects (NTD). STUDY DESIGN: Ten weekly amniotic fluid (AF) samples from normal pregnancies (non-NTD) and 10 from NTD pregnancies between 16 and 20 weeks' gestational age were analyzed for AAs, and the weekly average for the non-NTD and NTD groups was determined. The group mean levels were compared by ANOVA. RESULTS: The weekly group mean levels of methionine, serine and aspartic acid were significantly lower than the weekly group mean levels of the other AAs. The group mean levels of methionine were significantly lower for NTD than for non-NTD pregnancies. CONCLUSION: The mean methionine level in NTD pregnancies was the only AA alteration in NTD. Although the AF levels of the non-NTD pregnancies showed that the levels of serine, aspartic acid and methionine were 3- to 19-fold lower than those of the other AAs, only methionine is essential. Consequently, methionine is rate limiting with respect to the role of structural proteins and nucleic acids in the fetus.

Amino Acids↗
PubMed1998

A critical window for cooperation and competition among developing retinotectal synapses.

In the developing frog visual system, topographic refinement of the retinotectal projection depends on electrical activity. In vivo whole-cell recording from developing Xenopus tectal neurons shows that convergent retinotectal synapses undergo activity-dependent cooperation and competition following correlated pre- and postsynaptic spiking within a narrow time window. Synaptic inputs activated repetitively within 20 ms before spiking of the tectal neuron become potentiated, whereas subthreshold inputs activated within 20 ms after spiking become depressed. Thus both the initial synaptic strength and the temporal order of activation are critical for heterosynaptic interactions among convergent synaptic inputs during activity-dependent refinement of developing neural networks.

Animals↗
PubMed1998

The genetic sequence of retinal development in the ciliary margin of the Xenopus eye.

The ciliary marginal zone is a perpetually self-renewing proliferative neuroepithelium at the perimeter of the retina in amphibians and fish. In the ciliary marginal zone (CMZ), cells are spatially ordered with respect to cellular development, deep stem cells being most peripheral and differentiating retinal progenitors being most central. This spatial gradient in the CMZ recapitulates embryonic retinogenesis and provides a powerful system to examine the relative order of gene expression during this process. A number of neurogenic and proneural genes have been described to have interacting roles in the development of the vertebrate nervous system, and so it is of major importance to put these genes in a hierarchical pathway. In no other system yet described are the developmental stages of neurogenesis arrayed so clearly in a spatial pattern as in the CMZ. We have therefore taken advantage of this system, using double in situ hybridizations on cross sections of the CMZ, to compare the spatial patterns of 15 proneural, neurogenic, and other genes involved in early and late phases of retinal development. In addition, we have positioned these expression patterns with respect to cell division. What emerges from this work is a spatial ordering of gene expression that predicts a genetic hierarchy governing vertebrate retinogenesis. By injecting messenger RNA for some of these genes into blastomeres of the Xenopus embryo and examining the effects on expression of the putative downstream genes, we have been able to corroborate some of the relationships between genes predicted to act sequentially.

Animals↗
PubMed1998

Properties of ectopic neurons induced by Xenopus neurogenin1 misexpression.

We have examined cells cultured from ectoderm-misexpressing Neurogenin1 (Ngn1) to describe better the extent to which this gene can control aspects of neuronal phenotype including motility, morphology, excitability, and synaptic properties. Like primary spinal neurons which normally express Ngn1, cells in Ngn1-misexpressing cultures exhibit a motility-correlated behavior called circus movements prior to neuritogenesis. Misexpression of NeuroD also causes circus movements and later neuronal differentiation. GSK3beta, which inhibits NeuroD function in vivo, blocks both Ngn1-induced and NeuroD-induced neuronal differentiation, while Notch signaling inhibits only Ngn1-induced neuronal differentiation, confirming that NeuroD is downstream of Ngn1 and insensitive to Notch inhibition. While interfering with NeuroD function in ventral ectoderm inhibits both circus movements and neuronal differentiation, such inhibition in the neural plate inhibits only neuronal differentiation, suggesting that additional factors regulate circus movements in the neural ectoderm. Ngn1-misexpressing cells extend N-tubulin-positive neurites and exhibit tetrodotoxin-sensitive action potentials. Unlike the majority of cultured spinal neurons, however, Ngn1-misexpressing cells do not respond to glutamate and do not form functional synapses with myocytes, suggesting that these cells are either like Rohon-Beard sensory neurons or are not fully differentiated.

Animals↗
PubMed1998

Comparison of sperm viability with seminal plasma metal levels.

This study compares the semen levels of lead (Pb), cadmium (Cd), and aluminum (Al) in relation to live sperm in semen samples from 64 apparently healthy men. The measured levels were separated into live sperm count tertiles (<25% [18 subjects], 25-50% [26 subjects], and >50% [20 subjects]). The mean +/- SD for each group was calculated, and the difference between the means of the high and low tertiles were compared by ANOVA. Significant differences were observed between the high and low live sperm groups for Pb (p < 0.01) and Al (p < 0.05), but not Cd. Spearman's rank correlation between sperm viability and the semen plasma metal levels showed a direct relation to Mg (p < 0.05). However, there was an inverse relation to lead (p < 0.001), cadmium (p < 0.01), and aluminum (p < 0.01). There was no significant correlation between Ca and Zn. Linear regression between the live sperm counts and semen level of the three metals show that metal levels were inversely correlated with the percentage of live sperm (p < 0.001, < 0.01). Apparently, the presence of these metals in the environment and in seminal plasma exerts a toxic effect on sperm.

Adult↗
PubMed1998

Eating disorders.

The eating disorders remain perplexing treatment challenges. These disorders are best understood through the clustering of their symptoms and with a multidimensional model. Treatment must follow from the observed symptoms and cannot always follow a standardized course as is done in other psychiatric disorders. CBT is the most efficacious treatment for both AN and BN.

Ambulatory Care↗
PubMed1998

Target selection: invasion, mapping and cell choice.

Recent research has shown that changes in the concentration of particular molecules lead axons to invade their target, and that concentration changes in other molecules at the borders of the target prevent axons from leaving the target area. After invasion, topographic and lamina-specific cues guide axons to the correct location within the target field. At the level of a single cell or part of a cell, the evidence raises the possibility that axon targeting might be a combinatorial affair whereby specific axons compare the relative concentrations of several molecules on the surface of postsynaptic cells in order to choose a particular target. Both proteins and carbohydrates of various classes play major roles in these processes.

Animals↗
PubMed1998

Sequential genesis and determination of cone and rod photoreceptors in Xenopus.

In this study, we addressed the temporal sequence of photoreceptor fate determination in Xenopus laevis by examining a number of key events during early cone and rod development. We compared the relative timing and spatial pattern of cone and rod specification using a number of cell type-specific markers, including probes to a long wavelength-sensitive opsin which is expressed by the major cone subtype. Our results show that cones are initially more numerous, and can arise in less mature regions of the retina than rods, although both types of photoreceptors begin to express their respective opsins at about the same time. We applied these markers to an assay of cellular determination to identify the stages of embryonic development at which the earliest photoreceptor fates are induced in vivo. The relative birth order of the major cone and rod subtypes was revealed by simultaneous labeling with markers of cell proliferation and terminal differentiation. Although there is much temporal overlap between the periods of cone and rod genesis and determination in Xenopus, we could discern that the earliest cones are both born and determined before the first rods. Thus, even in the rapidly developing retina of Xenopus, photoreceptors achieve their identities in a sequential fashion, suggesting that the inductive cues which determine specific photoreceptor fates may also arise sequentially during development.

Amino Acid Sequence↗
PubMed1998

Molecular recapitulation: the growth of the vertebrate retina.

In postembryonic lower vertebrates, the ciliary marginal zone (CMZ) of the retina is a continuously growing zone in the central nervous system. By studying the cellular and molecular biology of the cells in this region, we have discovered that the CMZ can be divided into several zones, from peripheral to central, which reflect different stages of development of retinal stem cells. Based on the behavior of the cells and on the genes expressed in different regions, we propose here that cellular development in the CMZ recapitulates in space what happens in embryonic retinal development in time.

Animals↗
PubMed1997

Myosin functions in Xenopus retinal ganglion cell growth cone motility in vivo.

The role of myosins in Xenopus retinal ganglion cell growth cone motility in the optic tract was studied using two pharmacologic inhibitors with different specificities. 2,3-Butanedione monoxime (BDM) disrupts myosin-actin interactions of all myosins, and ML-7 specifically inhibits activation of myosin II. Both inhibitors caused growth cones to assume a collapsed morphology and decreased growth cone speed. Similar effects were observed in vitro. Interestingly, the effects of the two inhibitors, while similar, were clearly distinguishable, raising the possibility that different myosins may have different functional roles in growth cone motility. BDM caused growth cones to withdraw lamellipodia and some filopodia and eventually to freeze, whereas ML-7 caused total collapse and retraction. Concentrations of BDM and ML-7 that had no effect when applied independently stopped growth cones when applied simultaneously, suggesting that these inhibitors act synergistically on myosin function, thus providing evidence of specificity. These results imply that normal growth cone motility in the molecularly and spatially complex environment of the living brain requires myosin function.

Actins↗
PubMed1997

Regulation of neuronal diversity in the Xenopus retina by Delta signalling.

To generate the variety of mature neurons and glia found in the developing retina, the competence of pluripotent progenitor cells to respond to extracellular signals must be controlled. Delta, a ligand of the Notch receptor, is a candidate for regulating progenitor competence on the grounds that activation of the pathway involving Notch and Delta can inhibit cellular differentiation. Here we test this possibility in the developing Xenopus retina by misexpression of Delta messenger RNA. We find that Delta-misexpressing cells with wild-type neighbours adopt earlier fates, primarily becoming ganglion cells and cone photoreceptors. Progenitors transfected with Delta later in development also produce rod photoreceptors, but not the latest-generated cell types, demonstrating the importance of timing in Delta function. We conclude that Delta signalling in the vertebrate retina is a basic regulatory mechanism that can be used to generate neuronal diversity.

Animals↗