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D G Leonard

Publications and source records attributed to D G Leonard.

44 records · Page 3Linked to original sources
PubMed1987

Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells.

Differential screening of cDNA libraries was used to detect and prepare probes for mRNAs that are regulated in PC12 rat pheochromocytoma cells by long-term (2-week) treatment with nerve growth factor (NGF). In response to NGF, PC12 cells change from a chromaffin cell-like to a sympathetic-neuron-like phenotype. Thus, one aim of this study was to identify NGF-regulated mRNAs that may be associated with the attainment of neuronal properties. Eight NGF-regulated mRNAs are described. Five of these increase 3- to 10-fold and three decrease 2- to 10-fold after long-term NGF exposure. Each mRNA was characterized with respect to the time course of the NGF response, regulation by agents other than NGF, and rat tissue distribution. Partial sequences of the cDNAs were used to search for homologies to known sequences. Homology analysis revealed that one mRNA (increased 10-fold) encodes the peptide thymosin beta 4 and a second mRNA (decreased 2-fold) encodes tyrosine hydroxylase. Another of the increased mRNAs was very abundant in sympathetic ganglia, barely detectable in brain and adrenals, and undetectable in all other tissues surveyed. One of the decreased mRNAs, by contrast, was very abundant in the adrenals and nearly absent in the sympathetic ganglia. With the exception of fibroblast growth factor, which is the only other agent known to mimic the differentiating effects of NGF on PC12 cells, none of the treatments tested (epidermal growth factor, insulin, dibutyryl cyclic AMP, dexamethasone, phorbol ester, and depolarization) reproduced the regulation observed with NGF. These and additional findings suggest that the NGF-regulated mRNAs may play roles in the establishment of the neuronal phenotype and that the probes described here will be useful to study the mechanism of action of NGF and the development and differentiation of neurons.

Animals↗
PubMed1986

Measurement of basilar membrane vibrations and evaluation of the cochlear condition.

The experimental procedure for measuring basilar membrane responses to acoustic signals is described. The surgical procedure developed for opening the cochlea with minimal trauma is presented. Each experiment included sound pressure level measurements to define the input signal, cochlear microphonic (CM) measurements to monitor the cochlear condition, interferometric measurements and histological evaluation of the cochleas. The characteristic frequency (CF) and the sensitivity at CF for the basilar membrane response is correlated with the change of CM response observed in six animals. It is demonstrated that both tuning characteristics are extremely sensitive to cochlear trauma as evidenced by changes of CM.

Animals↗
PubMed1986

Relationship between basilar membrane tuning and hair cell condition.

Basilar membrane tuning characteristics were measured in 15 cats using laser interferometry. The experimental procedures introduced varying degrees of cochlear trauma. Variability from animal to animal was also observed in the characteristic frequency (CF) of tuning, the sensitivity at CF and lower frequencies, and the sharpness of tuning. The changes in the tuning characteristics of the basilar membrane are correlated with the extent of outer hair cell (OHC) damage. These observations lead to the conclusion that the tuning properties in the CF region are predominantly determined by the mechanical properties of the OHC and not the basilar membrane.

Animals↗
PubMed1984

Histological evaluation of damage in cat cochleas used for measurement of basilar membrane mechanics.

Cochleas utilized in basilar membrane vibration measurements were examined histologically using an epon-embedded surface preparation technique. The amount of damage observed at both the apical and basal ends of the cochleas was variable. The apical damage was probably caused by large, low-frequency movements of the basilar membrane. The basal damage was due to trauma produced directly by the surgical and experimental procedure. The sharpness of turning observed in the basilar membrane frequency response was found to be inversely related to the extent of histological damage.

Animals↗
PubMed1978

Prospective analysis of psoriatic arthritis in patients hospitalized for psoriasis.

Among 77 patients hospitalized with psoriasis, 30 (39%) had psoriatic arthritis. Arthiritis was more frequent (P less than 0.05) in those with extensive psoriasis (grades 3 and 4) than in those with less extensive psoriasis (grade 1 and 2). Temporally, flares in skin and joint disease were not closely related. The Moll-Wright classification of psoriatic arthritis into five clinical groups could be loosely applied to our patients. However, sacroiliitis (present in 33% of the patients) was seen in all five groups and was related to HLA-B27 antigen. Although there was no positive correlation between extent of psoriasis and serum urate level, four patients had gout. Mean serum urate level was higher (P less than 0.05) in females with psoriatic arthritis than in females with psoriasis alone. Antinuclear antibodies were found in 6 of 19 patients with psoriatic arthritis and in none of the 11 patients with psoriasis alone.

Adolescent↗
PubMedDate not supplied

Larger trinucleotide repeat size in the androgen receptor gene of infertile men with extremely severe oligozoospermia.

Androgens are significant regulators of human spermatogenesis. Their action is mediated through the androgen receptor (AR), which binds to the androgen responsive element on DNA and regulates gene transcription. Men become infertile with spinobulbar muscular atrophy (Kennedy disease) caused by a trinucleotide repeat expansion, > or = 40 CAG repeats, in the AR gene located on the X chromosome. In this prospective study, we investigated whether the variable size, larger repeats, of this trinucleotide could alter AR function and result in impaired spermatogenesis. A total of 69 infertile men were studied. Clinical and laboratory analysis showed idiopathic, nonobstructive azoospermia in 16 men, extremely severe oligozoospermia in 27 men (< 1 million sperm/mL), and severe oligozoospermia in 26 men (1 to 5 million sperm/mL). Fertile control men (n = 45) were selected by documented paternity proven by linkage analysis. Leukocyte DNA was analyzed by polymerase chain reaction (PCR) amplification across the AR repeat region. Accurate size determination of the PCR product using an ABI 373 DNA sequencer allowed precise calculation of CAG repeat sizes. The AR gene was not analyzed for other types of mutations. The difference in CAG repeat size between infertile men and proven fertile controls was statistically significant, P = .03. Patients with extremely severe oligozoospermia had significantly longer CAG repeat tracts (mean, 25.4 +/- 4.0; P = .0005; range 20-39) than controls (mean, 22 +/- 2.8; range 12-30) or patients with severe oligozoospermia (mean, 22.2 +/- 2.3; range 18-26). None of the 26 infertile men with sperm counts < 1 million/mL had < or = 19 CAG repeats compared with 6 out of 45 controls (13%; P = .06). This study suggests that some men with severe impairment of spermatogenesis have longer trinucleotide repeats in the AR gene. Although direct evidence is missing, lower affinity between androgen and the AR protein or decreased AR protein availability with longer repeats could be responsible for a diminished androgen effect on spermatogenesis. Two of the patients in the extremely severe oligozoospermia group had 35 and 39 CAG repeats, respectively (normal range is 11 to 33). Although not yet considered a mutation, longer trinucleotide repeats are unstable and might either expand or contract between generations. If they expand, conception through the use of intracytoplasmic sperm injection (ICSI), could result in the son of an

Humans↗