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J H LaVail

Publications and source records attributed to J H LaVail.

11 recordsLinked to original sources

cis and trans regulation of tissue-specific transcription.

Analysis of both the cis-regulatory sequences which control globin gene switching as well as the trans-acting factors which bind to these sequences to elicit a differential, developmentally regulated response has lent insight into the general mechanisms responsible for tissue-specific gene regulation. We show here that the chicken adult beta-globin gene promoter sequences are intimately involved in competitive interaction with the beta/epsilon-globin enhancer to regulate differentially epsilon- versus beta-globin gene transcription. Secondly, we show that the family of GATA transcription factors directs gene regulation in a variety of discrete cell types, and describe potential cellular target genes for each member of the GATA factor family, as well as potential mechanisms whereby multiple GATA factors expressed in a single cell might be used to elicit differential transcriptional activities.

Animals

A quantitative assay of retrograde transported HSV in the trigeminal ganglion.

The relationship between the dose of Herpes simplex virus type 1 (HSV) inoculated in the cornea and the amount of actively replicating virus recovered from mouse trigeminal ganglion cells 5 d after corneal scratch and inoculation was investigated with a tissue culture plaque assay. A dose response curve of productive viral replication was obtained. The estimated dose of HSV that produces half-maximal recovery of virus within the ganglion was 9.15 x 10(3) plaque forming units per eye, and the maximal amount of HSV recovered was 1.34 x 10(4) pfu per ganglion. This definition of infectivity as a function of dose will be useful for studying the effects of potential inhibitors of the binding, uptake, and transport of HSV by productively or latently infected trigeminal neurons.

Animals

Herpes simplex viral infection of the mouse trigeminal ganglion. Immunohistochemical analysis of cell populations.

Several distinct populations of sensory neurons in the ophthalmic region of the mouse trigeminal ganglion have been identified by their reactivity to antibodies raised against substance P (SP), calcitonin gene-related peptide (CGRP), cell-surface glycoconjugates SSEA3 and LD2, and the plant lectin, Bandeiraea simplicifolia lectin 1, isolectin 4 (BSIL4). Thirty-six percent of the neurons in the ophthalmic portion of the mouse trigeminal ganglion express CGRP and 17%, SP. All neurons that express SP also express CGRP. Forty percent of the neurons in the ophthalmic region of the ganglion are recognized by monoclonal antisera to SSEA3, and 66% of this population also express the neuropeptides SP or CGRP. The neuronal population recognized by BSIL4 is identical to the population with the LD2 epitope. This population of cells (BSIL4/LD2) does not express the SSEA3 glycoconjugate and is largely nonpeptidergic. All four populations of sensory neurons (SP, CGRP, SSEA3, and LD2/BSIL4) can be infected by herpes simplex virus (HSV). However, the relative proportion of SSEA3- and LD2/BSIL4-labeled cells that were infected productively with HSV was much less than expected based on the relative size of the populations of these neurons in the ophthalmic region of the ganglion.

Animals

Ultrastructural immunocytochemical localization of herpes simplex virus (type 1) in trigeminal ganglion neurons.

Four days after corneal inoculation of mice with herpes simplex (type 1) virus (HSV), infected trigeminal ganglion cells with and without calcitonin gene-related peptide (CGRP) antigenicity were examined by electron microscopy in sections treated with colloidal gold labeled antibodies. Cells that contain CGRP were identified by the dense gold labeling of small vesicles about 100 nm in diameter. Adjacent thin sections were stained using an indirect colloidal gold immunocytochemical technique to reveal HSV-1 antigens. In CGRP-positive neurons, HSV antigens were located over both nuclear and cytoplasmic compartments. HSV label was found over cytoplasmic vesicles that were significantly larger than those labeled with anti-CGRP antisera; the HSV-containing vesicles ranged in profile diameter from less than 170 to greater than 400 nm. There was no overlap in the distribution of the two labels. Thus, for this time period, the organelles involved in transport of the endogenous neuropeptide and HSV appear to remain discrete. Furthermore, there was no significant difference in the distribution of HSV in CGRP-reactive and CGRP-negative trigeminal ganglion cells. Thus, there is no indication of a preferential distribution or limited replication of HSV in CGRP-positive neurons.

Animals

Effects of eye removal on receptors of alpha-bungarotoxin in the optic lobes of chick brain.

The existence of receptors with high affinity for alpha-bungarotoxin and the pharmacologic properties of a nicotinic ACh receptor has been shown in the optic tectum of chick brain. In the present study eyes were removed from chicks at embryonic day 3 (E3), or at post-hatching day 3 (P3). In both cases, the total number of receptors for I125-alphaBT which developed in the deafferented optic lobe was about 50% of the number in normal lobes.

Animals

Genetic control of retinal ganglion cell projections.

We have assessed the effects of 15 pigmentation mutations on the development of retinal ganglion cell projections in mice in two ways: (1) by analyzing the pattern of innervation of the ipsilateral lateral geniculate nucleus as mapped in autoradiograms of brains of animals killed 12 days after intravitreal injection of 3H-proline into one eye and (2) by determining the ratio of axonally transported radioactive protein in the contralateral and ipsilateral optic tracts after similar intravitreal injections. Analysis of the ratio of transported protein in the two optic tracts provides a new and useful assay of the degree of decussation in experimental animals. The effects of the mutations on eye pigmentation, whole eye melanin content and relative tyrosinase activity also were examined. The degree of ipsilateral innervation generally correlates with the degree of pigmentation of the retinal pigment epithelium and with tyrosinase activity. However, discrepancies have been found in ch and ce mutants. In these animals the pigment epithelium is well pigmented, and the area of ipsilateral innervation in the lateral geniculate nucleus is extensive, despite a high ratio of label in contralateral to ipsilateral optic tracts and low tyrosinase activity. Furthermore, mice heterozygous for the c2J allele have pigmentation and optic projections that are normal even though tyrosinase is reduced to 40% of normal. The few anomalous results suggest that alternative or additional factors may control optic axon projections.

Alleles

A study of the dynamics of retrograde transport and accumulation of horseradish peroxidase in injured neurons.

The phenomenon of retrograde intraaxonal transport of extracellular markers introduced at the level of the axon terminal has been suggested as a possible mechanism of communication between the axon terminal and the neuron cell body. We tested the hypothesis that communication after axotomy might consist of a change in the rate of uptake or of transport of material by injured neurons. Small lesions were made with a needle in one retinal quadrant of chicks and immediately afterwards horseradish peroxidase (HRP) was injected into the vitreous body of the eye. The amount of HRP accumulated by some of the neurons of the isthmo-optic nucleus (ION) which project to the damaged area was clearly different from that of nearby cells which project to the non-damaged portions of the retina. The uninjured cells accumulated enzyme marker beginning at 3.5 h after injection. The injured neurons did not accumulate significant amounts of HRP until between 4 and 6 h after injection. Between 6.75 h and 18 h the injured cells in the ION accumulated greater amounts of HRP than cells in other regions, but by 24 h the cells of the ION in the region of injury contained distinctly less label. This pattern of enzyme accumulation was confirmed by counts of the number of HRP-positive granules within cells of chicks fixed 4, 11.75, 12.25, 27.6 and 72 h after injury. In another series of experiments, the axon terminals of the ION were first exposed to HRP, and 1 h later some of the axons were damaged with a needle. In these cases, there was no difference between the injured and control neurons in the time of first appearance of labeled cells in the ION within the first 4 h after injection of HRP. These findings suggest that injury initially results in a decrease in the uptake of the marker rather than a decrease in the rate of retrograde transport. The amount of marker found in the injured neurons later is greater than that found in the control neurons. This subsequent difference may represent an increase in the rate of uptake, transport, or both or a decrease in the rate of degradation of HRP within the cell body as a response to injury of the axon.

Animals

The retrograde transport method.

After an injection of horseradish peroxidase into the brain, the enzyme product can later be found in cell bodies of neurons which project axons to the injection site. The use of the tracer has now been adapted as a means of identifying neurons on the basis of their efferent fiber projections. In this review particular attention is paid to characteristics of the phenomenon of retrograde transport, such as diffusion of the marker from the injection site and the region of effective uptake, uptake by injured axons of passage as well as by axon terminals and the preterminal portions of axons, and the anterograde movement of peroxidase. The retrograde transport method is compared to the previously available method of retrograde cell degeneration and the advantages and limitations of both techniques are considered.

Animals