Search PubMed⌕ Search

Biomedical subjects

L G Davis

Publications and source records attributed to L G Davis.

At least 55 records · Page 3Linked to original sources
PubMed1988

Identification in rodents and other species of an mRNA homologous to the human beta-amyloid precursor.

The isolation and sequencing of the core peptide (beta-amyloid) found in the plaques of patients with Alzheimer's disease has allowed the identification of a cDNA for the precursor protein. Using a human cDNA clone for this beta-amyloid material, we have identified an homologous mRNA (3.8 kb) in brain tissue obtained from 8 additional species. We have also determined its distribution in 7 brain regions and 12 organs obtained from rodents. A prominent, second mRNA species (2.2 kb) has been identified in rat non-neuronal tissues. The beta-amyloid gene is amply expressed in the brain of all vertebrates tested and in most rodent organs, indicating that it encodes a highly conserved and ubiquitous protein.

Alzheimer Disease↗
PubMed1988

Immunocytochemical localization of the precursor protein for beta-amyloid in the rat central nervous system.

Two rabbit polyclonal antibodies generated against different portions of the amyloid precursor protein were used to localize this protein in normal rat brain. Light and electron microscopic immunohistochemical localizations demonstrate that the protein is widely distributed throughout the neuraxis, with the highest concentrations of immunoreactive neurons occurring in the olfactory bulb, cerebral cortex, septum-diagonal band, globus pallidus, cerebellum, and hippocampus. Immunoreactive astrocytes are also present in the cerebral cortex in relation to both neurons and capillaries. However, immunoreactivity was not observed within the endothelium of the cerebral vasculature. These data demonstrate that the beta-amyloid precursor is widely distributed in the CNS and provide further insight into the cellular elements that may be involved in the neuropathological changes associated with Alzheimer's disease.

Amyloid↗
PubMed1988

Implementing drug education in schools: an analysis of the costs and teacher perceptions.

This study examined conditions in which two substance abuse prevention curricula were implemented in three Oregon school districts. Data related to teachers' involvement were collected from on-site interviews in 21 schools using a 43-item personal interview questionnaire with a stratified random sample of 44 teachers of drug education. Information provided by district program coordinators included details of inservice training, and financial costs to implement the Here's Looking at You, Two, (HLAY, II) and Starting Early curricula with 4,325 students. Teacher perceptions related to their responsibility for implementing the program, the quality of the curriculum, quality of the inservice, quality of the implementation procedures, and degree of teacher compliance for teaching the curricula. Results from teacher interviews and time and financial costs analysis could prove useful to school districts, building administrators, and teachers who plan to implement school-based drug education programs.

Attitude↗
PubMed1988

Exemplary school health education: a new charge from HOT districts.

School health education is generally regarded as instructional programs for students. Such programs have limited impact, especially when the social environment is inconsistent with instructional messages. A study of Oregon school districts reveals that some school personnel have gone beyond curricula in their school education programs. Exemplary districts addressed noninstructional issues, most notably staff development programs and food service offerings. In doing so, they have changed not only the social context of the schools, but their ability to directly influence a greater number of Health Objectives for the Nation.

Attitude to Health↗
PubMed1988

Do only the healthy intend to participate in worksite health promotion?

Few companies or organizations involved in health promotion have addressed the major question of whether they are reaching the employees with the greatest health needs or those who could benefit most from these efforts. The popular view that only individuals who are already physically fit and healthy participate in worksite wellness programs was critically examined. Data from 523 survey respondents at the University of Oregon were analyzed to determine whether employees differed on health-related characteristics and their interest in attending a worksite health promotion program. Comparisons between program participant "intenders" and "nonintenders" revealed that both groups had similar lifestyle habits, preventive health practices, and health status profiles. Significant differences were more related to age and perceptions about their physical and emotional health status. Implications for health risk reduction program planning in the work setting are discussed.

Attitude to Health↗
PubMed1987

Neuropeptide modulation of apomorphine-induced stereotyped behavior.

The nucleus accumbens contains many neuropeptides whose functions are presently unknown. The purpose of this study was to determine the extent to which these neuropeptides act in conjunction with the mesolimbic dopamine system. Microinjections of cholecystokinin, neurotensin, met-enkephalin, somatostatin, bombesin, as well as glutamate and muscimol, were made into the medial nucleus accumbens after systemic injection of apomorphine. Cholecystokinin and neurotensin, in nanogram doses, potentiated apomorphine-induced stereotypy. Met-enkephalin reduced, while somatostatin and bombesin were without effect on, apomorphine-induced stereotypy. In addition, both glutamate and muscimol potentiated this effect. These results suggest that several neuropeptides and amino acids act in the nucleus accumbens to modulate apomorphine-induced stereotyped behaviors.

Animals↗
PubMed1987

Expression of rat brain excitatory amino acid receptors in Xenopus oocytes.

Xenopus laevis oocytes when injected with rat brain mRNA synthesize neuronal receptors that can be analyzed electrophysiologically. After a post-injection incubation period of 24-72 hours, L-glutamic acid, kainic acid and quisqualic acid caused a dose dependent (10-100 microM) depolarization of the oocyte membrane. The voltage and conductance changes associated with kainate activation were distinguishable from those seen for L-glutamate or quisqualate. There was no response to L-aspartate application and an inconsistent response to N-methyl-D-aspartate. Upon fractionation of the mRNA on sucrose gradients, transcripts greater than 2 Kb in length were obligatory for the synthesis of excitatory amino acid receptors. The electrophysiological response of injected oocytes exposed to L-glutamate was similar to that of native oocytes when exposed to muscarinic agents. This similarity may reflect the activation of the same ionophore and suggests that the active mRNA fraction for glutamate responsiveness either encodes for a binding protein that can be assembled along with native ion channels into the oocyte membrane or encodes for a glutamate binding site with a similar channel.

Amino Acids↗
PubMed1987

Reduction of dopamine receptor activity differentially alters striatal neuropeptide mRNA levels.

We have investigated the effect of dopamine receptor blockade on striatal proenkephalin mRNA and protachykinin mRNA by Northern gel analysis and by in situ hybridization histochemistry. Chronic haloperidol treatment resulted in a 3.5 fold increase in striatal proenkephalin mRNA and a 30% decrease in protachykinin mRNA (no apparent change in alpha-tubulin mRNA was observed). The changes in mRNA levels for protachykinin and proenkephalin were uniform throughout the caudate-putamen of the rat as determined by in situ hybridization histochemistry. The results imply that altering receptor-mediated neurotransmitter functions can lead to profound, specific, and long-lasting alterations in neuronal gene expression.

Animals↗
PubMed1987

Pharmacokinetics and tolerance of desciclovir, a prodrug of acyclovir, in healthy human volunteers.

Because of the incomplete absorption of acyclovir (ACV) when given orally in humans, efforts have been made to develop a prodrug of ACV that would be better absorbed from the gastrointestinal tract and then converted in vivo to ACV. One such compound, desciclovir (DCV), is converted to acyclovir in vivo by xanthine oxidase. We gave each of 13 healthy volunteers 250 mg (about 3.25 mg/kg of body weight) of DCV orally thrice daily for 10 days, collected serial plasma and urine specimens, and measured DCV and ACV concentrations. The absorption of DCV was at least 75%, and almost two-thirds of the administered oral dose was recovered in the urine as ACV. Peak ACV levels in plasma were about 5 micrograms/ml and were reached in less than 1 h. The levels of ACV achieved in plasma were of the same magnitude as those reported for subjects given intravenous ACV at a dose of 2.5 mg/kg and approximately 10-fold higher than levels attained after administration of 200 mg of oral ACV every 4 h as measured in previous studies. The half-life of DCV was 0.85 +/- 0.16 h, compared with 2.6 +/- 0.5 h for ACV, indicating rapid conversion of DCV to ACV. There was no substantial increase in ACV levels in plasma on day 11 compared with day 2. No serious or consistent adverse effects were noted. In particular, the creatinine level in serum did not significantly rise in any subject and remained within the normal range in all.

Acyclovir↗
PubMed1986

Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

Synthetic oligonucleotide probes can be easily obtained and used, in contrast to cDNA cloning to develop probes, and thus the present study was carried out to determine whether such probes could also be useful for in situ hybridization. A 24-base synthetic oligonucleotide complementary to part of the alpha-melanocyte-stimulating hormone (alpha-MSH) coding region of proopiomelanocortin (POMC) mRNA was 5'-end-labeled by using [gamma-32P]ATP with T4 polynucleotide kinase or was 3' tailed by using [alpha-32P]dATP or [3H]dCTP with terminal deoxynucleotidyltransferase. Blot analysis of pituitary poly(A)+ RNA showed that the oligonucleotide hybridized to a single species with a molecular size of approximately 1200 nucleotides, consistent with that determined previously for POMC mRNA. The oligonucleotide, regardless of labeling method, hybridized to cells in the pituitary intermediate lobe, but not in the posterior lobe. Only the 3H-labeled probe gave resolution of individual pituitary anterior lobe cells. The specificity of the hybridization was determined by showing that the intermediate lobe signal was blocked by prehybridization of the tissue with unlabeled alpha-MSH oligonucleotide probe. Furthermore, the hybridized probe exhibited a sharp sigmoid curve when melted off. Finally, the oligonucleotide probe detected, in situ, the haloperidol-induced elevation of intermediate lobe POMC mRNA. Thus, the oligonucleotide probe exhibited hybridization in an anatomically and biochemically specific manner, and it detected a tissue-specific change in mRNA levels in situ.

Animals↗
PubMed1986

Glucocorticoid sensitivity of vasopressin mRNA levels in the paraventricular nucleus of the rat.

Immunocytochemical studies have shown that adrenalectomy produces changes in the content and distribution of [arginine-8]vasopressin (AVP) immunoreactivity in the paraventricular nucleus of the hypothalamus. The purpose of this study was to determine whether manipulation of adrenal hormones affects the levels of AVP mRNA. In situ hybridization assays with highly specific synthetic oligodeoxyribonucleotide probes and immunocytochemistry were used to detect the distribution of AVP mRNA and AVP-immunoreactive perikarya. AVP mRNA is codistributed with AVP immunoreactivity in the posterior magnocellular subdivision of the paraventricular nucleus and its accessory nuclei, the supraoptic nucleus and the suprachiasmatic nucleus. In adrenalectomized rats, the density and distribution of the hybridization signal were increased in the paraventricular nucleus; a 2-fold increase in the area comprising the signal was observed. At the cellular level, silver grains were detected in corticotropin-releasing-factor-immunoreactive neurons throughout the medial parvocellular subdivision of the paraventricular nucleus. No changes were seen in the distribution of AVP mRNA in the supraoptic or suprachiasmatic nuclei. Treatment with dexamethasone prevented the increase in AVP mRNA produced by adrenalectomy. In contrast, adrenalectomy did not alter the hybridization signal obtained with a probe for alpha-tubulin mRNA. These results suggest, at the cellular level, that adrenalectomy induces a glucocorticoid-sensitive stimulation of AVP mRNA synthesis in the central nervous system. Thus, considerable plasticity in gene expression is retained in the hypothalamus of the adult rat.

Adrenalectomy↗
PubMed1985

Structure-activity studies with carboxy- and amino-terminal fragments of neurotensin on hypothalamic neurons in vitro.

The purpose of this study was to determine the structural requirements for the activity of neurotensin (NT1-13) on preoptic/anterior hypothalamic (POAH) neurons in vitro. Standard explant culture electrophysiological techniques were employed. NT was administered to POAH cultures through the superfusion fluid, or, to the vicinity of individual neurons by pressure ejection (0.5-10 psi) from micropipettes. Computer-generated, peri-event histograms were used to quantitate neuronal responses. Pressure ejection of NT1-13 (50 pM to 1 microM) consistently produced an excitatory effect on 30 of 42 neurons. The remaining cells were either inhibited or unaffected. Application of the C-terminal hexapeptide, NT8-13, but not the N-terminal octapeptide, NT1-8 (less than or equal to 1 mM), produced an excitatory response in 21 of 30 neurons, but was less potent than NT1-13. Application of an N-acetylated NT8-13 fragment (NTAC8-13) produced a response that was similar to that produced by NT8-13. The excitatory effects of NT1-13 and NT8-13 were maintained in medium which effectively blocked synaptic transmission (0 mM Ca2+/12 mM Mg2+ 1 mM EGTA). These data indicate that the C-terminal hexapeptide, but not the N-terminal octapeptide, produces a dose-related, excitatory effect on single neurons in the POAH in vitro. The persistence of these effects in Ca2+-free medium supports a postsynaptic site of action for these peptides.

Action Potentials↗
PubMed1985

In situ hybridization of putative somatostatin mRNA within hypothalamus of the rat using synthetic oligonucleotide probes.

The distribution of mRNA with high sequence homology to somatostatin mRNA within the periventricular hypothalamus of rat was assessed using in situ hybridization techniques with synthetic oligodeoxyribonucleotide probes, complementary to the 3' coding region of rat somatostatin mRNA. The probes (22- and 24-mers) were 5'-end labeled using T4 polynucleotide kinase and gamma-32P-ATP. They were used either individually or after ligation with T4 DNA ligase to form a 46-mer. Serial tissue sections (less than 10 microns) were taken from the level of the preoptic/anterior hypothalamus through the paraventricular hypothalamus. In situ hybridizations were conducted at room temperature in hybridization buffer. Neurons immunoreactive with antiserum raised against somatostatin were identified in alternate sections using standard immunocytochemical procedures. The anatomical location of the hybridization signal was determined by autoradiography. Our results show that the peri- and paraventricular hypothalamus is rich in transcripts putatively coding for somatostatin and that these transcripts are co-distributed with neurons immunoreactive with antisomatostatin immunoglobulin.

Animals↗
PubMed1985

The application of enzyme-linked immunosorbent assays (ELISA) to neuropeptides.

Procedures are presented for routine evaluation of antibody specificity, titre, and quantitation of antigen levels in tissue extracts without the use of radiolabeled probes. A colorimetric, enzyme-linked immunosorbent assay (ELISA) is described for general use with neuropeptides, using neurotensin as a primary example. These assays use rabbit anti-neurotensin immune serum which is colorimetrically identified after combination with an alkaline phosphatase-conjugated, affinity purified, goat anti-rabbit IgG and reaction with the chromogenic substrate, p-nitrophenyl phosphate. Because the principle of these methods can be adapted for use with various proteins and neuropeptides, they should find widespread applicability in neurobiology.

Alkaline Phosphatase↗