Biomedical subjects

D W Walker

Publications and source records attributed to D W Walker.

At least 19 recordsLinked to original sources

PubMed1992

Chronic ethanol consumption reduces the neurotrophic activity in rat hippocampus.

The effect of chronic ethanol treatment (CET) for 21-26 weeks on the neurotrophic activity contained in the rat hippocampus (HPC) was determined with a bioassay in cultures of dissociated dorsal root ganglion cells (DRG) obtained from E7-8 chick embryos. Extracts of the HPC from CET or pair-fed control rats were used as experimental media, and neuronal survival and neurite-outgrowth of DRG cultures were determined. Both neuronal survival (-25%) and neurite-outgrowth (-50%) were reduced in the presence of HPC extracts from CET rats relative to controls. These data suggest that CET reduces the neurotrophic content of the HPC which may result in damage to septohippocampal neurons.

Animals↗

PubMed1992

Developmental changes in hindlimb muscles and diaphragm of sheep.

In this study, plasma thyroxine, contractile and histochemical (adenosinetriphosphatase and NADH) characteristics of soleus (SOL), medial gastrocnemius (MG), and extensor digitorum longus (EDL) were examined in 140-day-gestation fetal sheep and in 2-, 5-, and 30-day-old lambs and adult ewes. Electrophoretic separation of myosin heavy chains was also done on all muscles and the diaphragm. There were no differences in the twitch contraction and relaxation times of MG and EDL at the different ages; in contrast SOL contraction times were significantly shorter in the fetus and newborn than in the adult. Fast glycolytic fibers first appeared in EDL, MG, and diaphragm at 5, 30, and 5 days after birth, respectively. The proportion of slow oxidative fibers decreased after birth and with postnatal development in EDL, whereas they increased in MG and diaphragm. Plasma thyroxine concentrations were higher in the fetus and day-old lambs than in 2-, 5-, and 30-day-old lambs or adult sheep. It is suggested that contractile specialization of the fast-twitch diaphragm, MG, and EDL is largely achieved in utero and is probably mediated by thyroid hormone. In contrast, SOL changed postnatally, probably influenced by the altered neural drive.

Aging↗

PubMed1991

Binding of [125I]-insulin-like growth factor-1 (IGF-1) in brains of Alzheimer's and alcoholic patients.

Patients with chronic alcoholism and/or Alzheimer's disease suffer from degenerative changes in the cerebral cortex and hippocampus. To investigate possible changes in IGF-1 receptor binding sites in brain tissue of patients with these pathological conditions, the binding of [125I]-IGF-1 was determined in tissues obtained from control, Alzheimer's and/or patients with a history of alcoholism. The four experimental groups examined consisted of patients from similar age groups. Specific binding of [125I]-IGF-1 to cerebral cortical membranes from Alzheimer's patients had significantly more binding sites than age-matched controls, alcoholic patients and alcoholic patients with Alzheimer's disease. Regression analyses indicated that there were no significant differences in [125I]-IGF-1 binding in cerebral cortex with regard to age of patients (1.1% of total variance with a range of 52 to 92 years). Likewise, the time interval between death and autopsy contributed only 1.4% to the total variance in IGF-1 binding. No statistical differences in [125I]-IGF-1 binding were noted in hippocampal tissue from the various patient groups. Thus, human IGF-1 binding sites in cerebral cortex and hippocampus appear to be relatively stable for a number of variables. The increase in cerebral cortical [125I]-IGF-1 binding sites could be due to upregulation of IGF-1 receptors resulting from a decrease in IGF-1 levels in Alzheimer's patients.

Alcoholism↗

PubMed1991

Effect of feeding on the diurnal rhythm of plasma cortisol and adrenocorticotrophic hormone concentrations in the pregnant ewe and sheep fetus.

The effects of two different feeding regimes on the 24 h profiles of maternal and fetal plasma cortisol and adrenocorticotrophic hormone (ACTH) concentrations were studied in eight pregnant ewes between 123 and 144 days of gestation. Once daily-fed ewes (n = 4) received 1 kg of lucerne-chaff at 11.00 h, and multi-fed ewes (n = 4) received 100-200 g of lucerne-chaff at 09.00, 11.00 and 13.00 h and then 150 g until 09.00 h the following day. There were significant differences between the two feeding groups in the 24 h profile of maternal plasma osmolality; once daily feeding at 11.00 h was associated with a peak in maternal plasma osmolality at 15.00 h whereas maternal plasma osmolality reached plateau levels at around 17.00 h in the multi-fed group. There were also differences between the two feeding groups in the 24 h profiles of maternal and fetal plasma glucose. Maternal and fetal plasma glucose reached peak concentrations at 19.00 h in the once daily-fed ewes in contrast to the multi-fed group, where a plateau in maternal and fetal plasma glucose was reached between 19.00 h and 09.00 h the following day. A significant diurnal variation in the plasma concentrations of cortisol was present in the once daily-fed ewes from 123 days gestation and in their fetuses after, but not before, 135 days gestation. Plasma cortisol peaked at 11.00 h in the ewes and at 13.00 h in the fetuses of this group. In the once daily-fed group there was also a significant diurnal variation in maternal and fetal plasma ACTH; plasma ACTH concentrations were highest at 11.00 h in the ewes aged between 123 and 144 days and in fetuses after 135 days gestation. In the multi-fed group, whilst ACTH was highest at 09.00 h in the ewes and at 13.00 h in the fetuses, there was no significant diurnal variation in the plasma concentrations of cortisol in the ewes or fetuses of this group at any stage between 123 and 144 days gestation.

Adrenocorticotropic Hormone↗

PubMed1991

Effects of different lighting regimes on daily hormonal and behavioural rhythms in the pregnant ewe and sheep fetus.

1. We have studied the effect of altering the time of darkness during a 12 h photoperiod on the diurnal rhythms of maternal and fetal plasma melatonin and prolactin concentrations and fetal breathing movements (FBMs) in the late pregnant sheep. 2. Four ewes were exposed to a 'normal' 12 h light-12 h dark regime with lights off at 19.00 h. Eight ewes were exposed to an 'altered' 12 h light-12 h dark regime with lights off at 11.00 h. FBMs were recorded continuously and 2 hourly maternal and fetal blood samples taken during 24 h experiments between 120 and 138 days gestation. 3. Plasma melatonin concentrations were higher during the hours of darkness in the ewes and fetuses in both the normal and altered groups; i.e. altering the time of darkness was associated with a shift in the timing of the daily increase in melatonin concentrations in the mother and fetus. 4. In the fetuses, the mean 24 h plasma prolactin concentration was higher in the altered lighting group (28.8 +/- 6.1 micrograms/l) compared to the normal lighting group (13.0 +/- 3.9 micrograms/l). There was no difference, however, between groups in the daily variation of fetal plasma prolactin concentrations, which were higher at 17.00-01.00 h than at 05.00-19.00 h. Thus, altering the time of darkness did not change the timing of the daily plasma prolactin rhythm in the fetus. 5. Under the normal lighting regime maternal plasma prolactin concentrations were higher at 17.00-19.00 h (i.e. from 2 h before lights off) than at 09.00-11.00 h. In contrast, under altered lighting, plasma prolactin concentrations were higher at 01.00-07.00 h (i.e. 2-8 h after lights on) than at 09.00 h. 6. In the normal lighting group the incidence (min/h) of FBMs were highest at 16.00-21.00 h and reached a minimum at 05.00-06.00 h. In contrast, in the altered lighting group the incidence of FBMs was lowest at 19.00-20.00 h and reached a maximum at 11.00-12.00 h. 7. The results suggest that the light-dark cycle influences the diurnal modulation of FBMs, but not the daily variation of fetal plasma prolactin concentrations. The role of plasma melatonin concentrations, and evidence for a photo-inducible phase of increased prolactin secretion in the fetus, is discussed.

Animals↗

PubMed1990

Characterization of a human apolipoprotein E gene enhancer element and its associated protein factors.

An enhancer element in the 5' flanking region of the human apolipoprotein E gene, known as upstream regulatory element 1 (URE1), has previously been implicated in the expression of this gene. The URE1 element, which spans nucleotides -193 to -124 of the 5'-flanking region of the human apolipoprotein E gene, contains two sequences that bind to nuclear proteins, as determined by the DNase I footprinting assay. In the present study of URE1, we have characterized these sequences further. Deletion of one of the footprint sequences, at nucleotides -161 to -141, reduced URE1 enhancer activity substantially. A 30-base pair oligonucleotide that included this protein-binding sequence was able, by itself, to act as an enhancer. This sequence, termed the positive element for transcription (PET), was demonstrated by gel retention analysis to bind at least two protein factors, one of which is the transcription factor Sp1. Sp1 appeared to be the only protein required for the enhancer activity of PET to be manifested. In vitro transcription assays showed that the PET sequence was necessary for efficient transcription directed by the apoE promoter and that the PET sequence was the dominant regulatory element in the apoE promoter. Gel filtration chromatography and PET oligonucleotide-affinity chromatography were used to isolate a second PET-binding factor, a Mr = 55,000 protein, from HeLa cell nuclear extracts. It appeared to compete with Sp1 for a common binding site in the PET sequence, but it was not required for enhancer activity. The second footprint sequence in URE1, at nucleotides -184 to -173, also bound Sp1, but it was not required for enhancer activity. A third Sp1-binding region was located at a proximal GC box element (nucleotides -54 to -45). This region had no enhancer activity, but it was required for maximum transcriptional activity of the apoE promoter. Thus, the regulation of apoE gene expression is influenced by different protein-binding sequences, with transcription factor Sp1 playing major roles in both basal promoter activity and enhancer activity.

Animals↗

PubMed1990

Maternal pinealectomy alters the daily pattern of fetal breathing in sheep.

We have investigated the effect of pinealectomy of the pregnant ewe on the 24-h pattern of fetal breathing activity during late gestation. Fetal breathing movements were recorded during 24-h periods on 18 occasions in 5 pinealectomized ewes and on 24 occasions in 6 pineal-intact ewes between 120 and 145 days gestation. All ewes were fed once daily between 1000 and 1300 h and were kept under a light-dark cycle 12:12 h. There was no significant difference in the mean hourly incidence of fetal breathing movements between the pineal-intact (27.2 +/- 0.5 min/h) and pinealectomized (25.5 +/- 0.6 min/h) groups. However, there was a significant difference in the 24-h profiles of fetal breathing movements in the two groups. The peak incidence of fetal breathing occurred between 1900 and 2000 h in the pineal-intact ewes and between 1200 and 1300 h in the pinealectomized ewes. We conclude that maternal pinealectomy alters the daily pattern of a fetal behavioral pattern and that maternal melatonin may therefore provide the fetus with information about time of day.

Animals↗

PubMed1990

Effect of feeding regimen on diurnal variation of breathing movements in late-gestation fetal sheep.

There is a diurnal variation in the mean incidence and amplitude of fetal breathing movements (FBMs) in sheep after approximately 120 days gestation. To determine whether this variation is caused by diurnal fluctuations in plasma glucose or prostaglandin (PG) concentrations, we studied two groups of pregnant sheep fed either once daily at 1100 h or every 2 h for 24 h. Maternal and fetal blood samples were taken every 2 h from 0900 to 0900 h the next day for assay of plasma glucose and PGE2 and PGF2 alpha concentrations. FBMs were recorded throughout the 24 h. The mean fetal plasma glucose concentrations of the once-daily and multifed groups were not different, but there was a significant difference between the two groups in the 24-h pattern of fetal glucose concentrations. In the once-daily fed group, plasma glucose concentrations reached a peak 8 h after maternal feeding and then declined, whereas in the multifed group, fetal plasma glucose concentrations reached a plateau and were constant from 1300 to 0900 h the next day. Fetal plasma PGE2 and PGF2 alpha concentrations did not show a significant change with time of day in either group. There was a significant diurnal variation in the incidence and amplitude of FBMs in each of the two feeding groups, and the 24-h pattern of FBMs did not differ significantly between groups. Therefore it would appear that the diurnal variation of FBMs is not a consequence of the maternal feeding regimen or diurnal changes in plasma glucose or PG concentrations.

Animals↗

PubMed1990

Catecholamine neurons in fetal brain: effects on breathing movements and electrocorticogram.

We investigated the effect of increasing the synaptic concentration of catecholamines released from central pathways on breathing movements and electrocortical (ECoG) activity in fetal sheep in utero. In 11 trials (9 fetuses) intravenous infusion of the noradrenergic uptake inhibitor desipramine (DMI) resulted in an initial increase in the incidence of breathing movements from 47.8 +/- 2.2%/h to a maximum of 77.9 +/- 5.5%/h (P less than 0.05) followed by a subsequent decrease to 18.8 +/- 2.7%/h (P less than 0.05), which was associated with a decrease in the incidence of low-voltage ECoG activity. Mean breath amplitude also increased after DMI infusion from 5.8 +/- 0.2 mmHg to a peak of 8.9 +/- 0.9 mmHg (P less than 0.05). In five fetuses, intravenous injection of the alpha 1-receptor antagonist prazosin 30 min after the start of the DMI infusion blocked the increase of breath amplitude observed when DMI was given alone. Intracisternal infusion of 6-hydroxydopamine (6-OHDA, which causes an initial displacement of transmitter stores followed by a neurotoxic action) in six fetuses caused an increase in mean breath amplitude from 6.6 +/- 0.3 mmHg (control) to 22.3 +/- 5.5 mmHg (P less than 0.05) and a prolonged episode of breathing movements (168.5 +/- 47.2 min). The incidence of low-voltage ECoG activity was also increased significantly. A second infusion of 6-OHDA, 2 days after the first, had no effect on breathing movements or ECoG activities. The two treatments with 6-OHDA also resulted in a significant reduction in the response to intravenous infusion of DMI, indicating that endogenous release of norepinephrine had been reduced by the neurotoxin. These results suggest that 1) there is normally some tonic release of norepinephrine from central pathways, but this release is insufficient to stimulate sustained fetal breathing, and 2) accumulation in the synaptic cleft of catecholamines from central neurons is able to stimulate fetal breathing and promote low-voltage ECoG activity. Possible mechanisms that normally limit the activity of central catecholamine pathways before birth are discussed.

Animals↗

PubMed1990

Effect of hyperthermia on thyroid structure in the late gestation fetal lamb.

This study examined the effect of hyperthermia in late gestation on fetal thyroid structure. Mild heat stress (increase of ewe's rectal temperature to 40.4 degrees C) caused significant changes of fetal thyroid structure. Intra-follicular colloid area was significantly larger in the heat-stressed group (2,532 +/- 181 microns2) compared to a control group where rectal temperature of the ewe was within the normal range (1,660 +/- 188 microns2; p less than 0.01). Epithelial cell height was significantly reduced (2.5 +/- 0.19 vs. 4.8 +/- 0.26 microns; p less than 0.01). Fetal plasma glucose concentrations were significantly lower in the heat-stressed group (0.7 +/- 0.07 mmol/l) compared to the non-heated group (1.0 +/- 0.11 mmol/l; p less than 0.05). We suggest that the fetal thyroid gland in sheep is responsive to environmental temperature changes and is important in the neuroendocrine regulation of fetal body temperature. Fetal hypoglycaemia may also contribute to the changes in fetal thyroid gland by altering the peripheral utilization of thyroid hormone. Such changes, if prolonged, may contribute to the decreased rate of fetal growth and maturation associated with chronic heat stress in sheep.

Animals↗

PubMed1990

Polypeptides constituting the antigenic basis for identification of Rickettsia sibirica species by the standard serotyping method for spotted fever group rickettsiae.

The antigens of Rickettsia sibirica, Rickettsia rickettsii, and Rickettsia conorii were examined by Western immunoblots and the standard immunofluorescent serotyping assay with mouse anti-Rickettsia sibirica serum that is used for determining the species identification of spotted fever group rickettsiae. Serum was employed prior to absorption and after absorption with purified native or heated Rickettsia sibirica. The unabsorbed antiserum, the antiserum absorbed with heated Rickettsia sibirica and the antibodies eluted from native Rickettsia sibirica recognized two antigenic polypeptides of Rickettsia sibirica (130 and 118 kDa), Rickettsia rickettsii (151 and 133 kDa), and Rickettsia conorii (136 and 113 kDa), respectively when examined in native state, not denatured by heat. The antiserum absorbed with native Rickettsia sibirica reacted most strongly with one polypeptide of Rickettsia sibirica (118 kDa), Rickettsia rickettsii (133 kDa), and Rickettsia conorii (136 kDa); at the endpoint of the immunofluorescence assay there was minimal reactivity with the 130 kDa polypeptide by immunoblotting. Both Western immunoblots and immunofluorescence assay showed that the antiserum absorbed with native Rickettsia sibirica reacted with homologous and heterologous antigens at a much lower titer than did the antiserum that was not absorbed. However, the titers of reaction with Rickettsia sibirica, Rickettsia rickettsii, or Rickettsia conorii were not diminished by absorption of the native antiserum with heated Rickettsia sibirica. The antibody eluted from native Rickettsia sibirica reacted by immunofluorescence with all the rickettsiae at a higher dilution than the antibody eluted from heated Rickettsia sibirica.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effect of hyperthermia on the plasma concentrations of prolactin and cortisol in the fetal lamb and pregnant ewe during late gestation.

Exposing pregnant sheep to an ambient temperature of 43 +/- 1 degree C for 8 h was associated with a 1-1.5 degrees C increase of maternal and fetal core temperatures, and a 11-fold and 3-5 fold increase in maternal and fetal plasma prolactin concentrations respectively. Hyperthermia did not change maternal or fetal plasma cortisol concentrations. We conclude that maternal and fetal hyperprolactinaemia may occur in late pregnancy during hyperthermic conditions and that the increase in fetal plasma prolactin is due to either increased secretion or decreased metabolic clearance of prolactin in the feto-placental compartment.

Animals↗

PubMed1989

Biocytin: a versatile anterograde neuroanatomical tract-tracing alternative.

Biocytin, a naturally occurring low molecular weight analog of biotin, was evaluated as a neuroanatomical tract-tracing marker in the adult rat brain. Since it retains high-affinity binding to avidin, biocytin can be labelled with avidinylated visualization reagents. Iontophoretic or pressure injections resulted in filling of cell bodies and dendrites around the injection site and their efferent axonal processes and boutons. Retrogradely labelled neurons were occasionally observed at a distance but only with large injections. Anterograde tracing with biocytin is successful even in animals that are quite old, in contrast to lectins and HRP conjugates, and offers advantages in delivery, tissue processing, selection of light and/or electron microscopic labels, time to obtain results, and cost over many conventional tracers.

Alkaline Phosphatase↗

PubMed1989

Effect of inhibiting prostaglandin synthesis in pregnant sheep with 4-aminoantipyrine under normothermic and hyperthermic conditions.

Infusion of the prostaglandin synthetase inhibitor 4-aminoantipyrine at a rate of 20 mg/min via the fetal tarsal vein during normothermic conditions (ambient temperatures = 24 degrees C) significantly decreased the concentrations of prostaglandins E2 and F2 alpha in maternal and fetal arterial plasma and in uterine and umbilical vein plasma. The infusion was associated with a small but significant rise in fetal temperature and a fall in fetal arterial pH. Respiratory alkalosis developed in fetuses during hyperthermia by raising the ambient temperature to 43 degrees C for 8 hours. In contrast, infusion of 4-aminoantipyrine during hyperthermia produced fetal metabolic acidosis as indicated by a fall in fetal pH and an increase in PaCO2, even though the ewe remained hypocapnic. Four of the 10 fetuses died during or shortly after the 4-aminoantipyrine infusion during hyperthermia. These results indicate that uteroplacental prostaglandin synthesis is essential to allow the fetus to adapt to an increase in body temperature and suggests that prostaglandin synthetase inhibitors should be used with caution during pregnancy.

Ampyrone↗

PubMed1989

Neither chronic exposure to ethanol nor aging affects type I or type II corticosteroid receptors in rat hippocampus.

Both chronic exposure to ethanol and aging are reported to result in a loss of hippocampal pyramidal neurons and an elevation in plasma corticosteroid concentration. Aging has also been reported to result in a reduction in corticosterone receptors and corticosterone-concentrating cells in the hippocampus. Since these aging-associated effects have been hypothesized to be due to the cumulative exposure to corticosteroids over the life span, in the present studies, we investigated the hypothesis that corticosteroids play a similar role in the loss of hippocampal neurons during chronic ethanol ingestion. In contrast to our expectations, when a liquid diet containing either ethanol or sucrose was administered to male Long-Evans rats for 20-24 weeks, a period of treatment found previously to result in hippocampal neuronal loss, there were no ethanol-associated effects on the specific binding of [3H]-aldosterone to Type I or of [3H]dexamethasone to Type II receptors in cytosol derived from either whole hippocampus or dorsal versus ventral hippocampus. Allowing the rats to withdraw from the chronic ethanol exposure for 12 weeks also failed to reveal any ethanol-associated effects on corticosteroid receptor concentrations in the hippocampus. The basal morning concentrations of corticosterone in blood plasma were not affected by any of these treatments. In view of these null findings we next investigated the effects of aging on hippocampal corticosteroid receptors in male Long-Evans and Fischer 344 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1989

Effects of hyperthermia on fetal and maternal plasma prostaglandin concentrations and uterine activity in sheep.

The exposure of pregnant sheep to high ambient temperatures (43 degrees C) for 8 hours, sufficient to significantly elevate maternal and fetal body temperature +2.0 degrees C (p less than 0.001) and +1.9 degrees C (p less than 0.001) respectively, resulted in significant increases in PGE2 plasma concentrations in both the maternal and fetal circulations. Plasma PGF2 alpha concentrations were significantly raised in the fetal circulation but not the maternal during hyperthermia. The increase in prostaglandin concentrations were correlated with the magnitude of the increase in maternal and fetal body temperature. Uterine activity also increased during hyperthermia, probably as a result of the increase in prostaglandin concentrations. We propose that increased synthesis and release of prostaglandins from the uterus and/or placenta is an adaptive response to hyperthermia, and may protect the fetus from the consequences of heat stress.

Animals↗

PubMed1989

Acetylcholinesterase stain intensity variation in the rat dentate gyrus: a quantitative description based on digital image analysis.

Three-dimensional patterns of variation in the intensity of acetylcholinesterase histochemical staining and the width of stain-defined subregions were quantified for the dentate gyrus of the adult male Long-Evans rat. Matched tissue sections sampled through the central hippocampal formation of five rats were measured with a digital image analysis computer system. The width and stain intensity were determined for defined portions of the dentate gyrus related to gross acetylcholinesterase staining patterns and the known distribution of dentate afferents. Normalized values reflecting stain intensity at defined positions within this standardized sampling array were examined to investigate regional differences in acetylcholinesterase distribution along the primary dendritic axis of dentate granule neurons. The data illustrate quantitative differences in the partitioning of acetylcholinesterase as a function of intrahippocampal position. The variation is more pronounced in the septal-temporal axis than the granule cell layer crest-tip axis. Furthermore, the septal-temporal variations in acetylcholinesterase intensity demonstrate some independence according to proximal-distal location within the molecular layer. The results suggest that acetylcholinesterase distribution within the dentate gyrus may reflect local physiological characteristics of those afferent systems related to this enzyme, including but not necessarily limited to those that are specifically cholinergic.

Acetylcholinesterase↗

PubMed1989

Is AIDS a biasing factor in teacher judgment?

This study examined the effect that knowledge of a student having AIDS (Acquired Immune Deficiency Syndrome) would have on regular-education teacher judgment regarding special education placement. Regular-education, third-grade teachers in Indiana were sent one of two psychological reports. The reports were identical except that one report stated that the student had AIDS and the other stated that the student had rheumatic fever. AIDS was not found to be a biasing factor in teachers' judgments regarding special education services.

Acquired Immunodeficiency Syndrome↗