Biomedical subjects

D W Walker

Publications and source records attributed to D W Walker.

At least 109 records · Page 6Linked to original sources

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↗

PubMed1989

Modulation of the responses of fetal sheep to adrenergic stimulation by adrenal demedullation and chemical sympathectomy.

The responses to sympathetic stimulation of fetal sheep adrenal-demedullated or sympathectomised by infusion of guanethidine sulphate have been studied. Sympathetic responses in such denervated or sympathectomised fetuses was studied by intravenous infusion of adrenaline or noradrenaline at about 0.4 micrograms/min per kg. This infusion increased plasma concentration 100-200 fold and there was no significant difference between the control fetuses and those in the vasrious treatment groups. Catecholamine infusions at these rates normally have little effect upon fetal blood gas and pH values, but in adrenal-demedullated fetuses adrenaline infusion drepressed fetal arterial PO2 by 4-6 mmHg (P less than 0.05). The heart rate and blood pressure responses to catecholamine infusion in sympathectomised fetuses was, as expected, much increased. Similar observations were made on adrenal-demedullated fetuses, an unexpected finding, and this is taken to illustrate loss of the adrenal medulla is associated with enhanced responsiveness to adrenergic stimulation in peripheral tissues. The majority of the endocrine and metabolic responses, as reflected in fetal plasma concentrations of ACTH, cortisol, insulin, glucose, lactate and fatty acids, to catecholamine infusion were similarly much enhanced by adrenal-demedullation and chemical sympathectomy. Of particular note was a substantial increase in the responsiveness of the fetal adrenal, as reflected in plasma cortisol, to stimulation by ACTH, a change that usually induces labour, but not so in the present sheep. The results on increased sensitivity in adrenal-demedullated fetuses are discussed in relation to likely tissue mechanisms mediating the changes.

Adrenal Glands↗

PubMed1989

Effect of thyroidectomy on cardiovascular responses to hypoxia and tyramine infusion in fetal sheep.

Fetal sheep were thyroidectomized at 80 days' gestation and reoperated at 118-122 days for insertion of vascular catheters. The effects of hypoxaemia and intravenous tyramine infusion on plasma catecholamine concentrations, blood pressure and heart rate were then determined in experiments at 125-135 days' gestation. Age matched intact fetuses were also studied. Thyroidectomy was associated with increased concentrations of noradrenaline, adrenaline and dopamine in some thoracic and abdominal organs, increased noradrenaline concentrations in the cerebellum, and decreased adrenaline concentrations in the hypothalamus, cervical spinal cord, and superior cervical and inferior mesenteric ganglia. Arterial pressure was significantly lower in the thyroidectomized fetuses (34.0 +/- 0.15 mmHg) than in intact fetuses (44.7 +/- 0.2 mmHg; p less than 0.001). In contrast, plasma noradrenaline concentrations were significantly higher in the thyroidectomized fetuses (2.04 +/- 0.25 ng/ml) compared to the intact fetuses (0.99 +/- 0.08 ng/ml; P less than 0.001). In the intact fetuses there was a significant increase in plasma noradrenaline concentration and blood pressure during hypoxaemia, and bradycardia at the onset of hypoxaemia. In contrast, in the thyroidectomized fetuses hypoxaemia did not cause significant change in plasma catecholamine concentrations, blood pressure or heart rate. Infusion of tyramine produced a 1.9-fold increase of plasma noradrenaline in thyroidectomized fetuses compared to a 9.2-fold increase in the intact fetuses (P less than 0.05). Tyramine infusion caused a similar proportional increase of blood pressure in both thyroidectomized and intact fetuses. Heart rate decreased during the tyramine-induced hypertension in the intact fetus, but increased in the thyroidectomized fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Alterations and recovery of dendritic spine density in rat hippocampus following long-term ethanol ingestion.

Neuronal loss and dendritic pathology are often observed in humans and animals after long-term ethanol ingestion. It is not known, however, if surviving but damaged neurons can recover normal structure during ethanol abstinence. We quantified dendritic spine density in two neuronal populations in rat hippocampus to investigate whether reversibility from the cellular neurotoxic sequelae of chronic ethanol exposure was possible. Male Long-Evans rats were maintained for 20 weeks on an ethanol-containing liquid diet. Controls were pair-fed a liquid diet with sucrose substituted isocalorically for ethanol. One-half of each group was sacrificed at the end of the 20-week treatment and one-half was given a 20-week ethanol-free recovery period period to sacrifice. Analysis of rapid Golgi material revealed a decreased spine density in CA1 pyramidal cells that increased to control level during abstinence, and an increased spine density in dentate gyrus granule cells that was reduced toward control level during abstinence. Thus, despite the fact that chronic ethanol exposure produced differential initial effects, the return toward normal spine density in each region is consistent with the concept of neuronal recovery and reorganization during abstinence from ethanol.

Alcoholism↗

PubMed1988

Ethanol exposure following unilateral entorhinal deafferentation alters synaptic reorganization in the rat dentate gyrus: a quantitative analysis of acetylcholinesterase histochemistry.

The phenomenon of reactive synaptogenesis in the dentate gyrus following partial deafferentation was used to assess quantitatively the effects of ethanol exposure on neuronal plasticity. Adult male Long-Evans rats received unilateral lesions of the entorhinal cortex, followed by 40 days of dietary ethanol exposure. Synaptic reorganization of the commissural/associational (C/A) and cholinergic (primarily septal) afferents was evaluated in the dentate gyrus processed for acetylcholinesterase (AChE) histochemistry. The widths and optical densities of several laminae in the molecular layer were measured using a computer-based digital imaging system. The degree of reorganization was assessed by comparing the lesioned side to the unlesioned side in each animal (difference scores were calculated). In the exposed blade of the dentate gyrus, the lesion-induced expansion of the C/A width was reduced significantly in the ethanol group. However, in the buried blade, there was an actual shrinkage of the C/A zone in the ethanol group. There was also a tendency for less "clearing" or lightening of the AChE staining in the C/A zone of both blades. On the lesioned side, the ethanol group also displayed a significantly greater condensation or darkening of the AChE staining in the proximal outer molecular layer than the pair-fed control group. The supragranular layer of both blades ipsilateral to the lesion was reduced in width in the ethanol group. These results indicate that exposure to ethanol following partial deafferentation disrupts the normal pattern of synaptic reorganization in the dentate gyrus.

Acetylcholinesterase↗

PubMed1988

Diurnal rhythms in plasma melatonin concentrations in the fetal sheep and pregnant ewe during late gestation.

We have measured plasma melatonin (MT) concentrations in the pregnant ewe and fetal sheep during 24-h periods between 114 and 142 days gestation. There was a clear diurnal rhythm in the plasma MT concentrations in both the ewe and fetus from 114 days gestation. Blood samples were also collected from the pregnant ewe and fetus during the day every 2-3 days from 112 days gestation to term. There was no gestational age trend in maternal or fetal day time plasma MT concentrations during late pregnancy. To establish whether there was transplacental transfer of MT, pregnant ewes were injected with [3H]MT, and total radioactivity (disintegrations per min) was measured in maternal and fetal arterial plasma and in amniotic fluid collected before and for 1 h after the [3H]MT injection. Two minutes after [3H]MT injection, radioactivity was detected in both maternal and fetal sheep plasma. Extraction of fetal plasma with chloroform indicated that [3H]MT accounted for 48.0 +/- 7.2 (SE) % of total radioactivity at 2 min after the injection. In one pregnant ewe infused with unlabeled MT (0.3 microgram/ml saline.min for 20 min) maternal and fetal plasma MT concentrations increased within 6 min after the start of the MT infusion. We conclude that there is a diurnal rhythm in the plasma concentrations of MT in the fetal lamb and pregnant ewe between 114 and 142 days gestation, and that MT crosses the ovine placenta from the maternal to the fetal circulation. Therefore, the MT present in the fetal sheep circulation may be solely of maternal origin or it may be derived from both fetal and maternal sources.

Animals↗

PubMed1988

The role of the adrenal medulla and peripheral sympathetic nerves in the physiological responses of the fetal sheep to hypoxia.

In studies on the role of the peripheral sympathetic system during fetal life the effects of adrenal demedullation or chemical sympathectomy on the responses of the fetal sheep to hypoxaemia have been studied. Fetal sheep of 127-138 days gestation were either adrenal demedullated by injection of acid formalin into the adrenal medulla, chemically sympathectomised by chronic treatment with guanethidine sulphate, or subjected to both manipulations. None of these treatments had any effect upon resting heart rate and blood pressure, or blood gas status. Hypoxia was induced by giving the pregnant ewe 9% O2 and 3% CO2 in N2 to breathe for 60 min. This depressed fetal PO2 by about 30% in the intact and all but the adrenal-demedullated, chemically-sympathectomised fetuses, where the fall was about 50%. Similarly in this group of fetuses there was a sharp fall in plasma pH contrasting with little change in the other fetuses. Adrenal demedullation blocked completely the hypoxia-induced rise in fetal plasma adrenaline, and reduced that of noradrenaline to 10% of normal, implying that during hypoxia most of the plasma elevation of catecholamines is of adrenal origin. In contrast, and possibly to compensate for the blunted catecholamine response, plasma AVP increases during hypoxia were substantially enhanced by adrenal demedullation. Fetal hypoxia was associated normally with a fall in heart rate and rise in blood pressure. Adrenal demedullation had no effect on the heart rate changes, thought to be a reflex response to rise in blood pressure, but abolished the rise in blood pressure during hypoxia. Chemical sympathectomy, in contrast, abolished the fall in heart rate even though blood pressure rose. This shows clearly that reflex changes in heart rate during hypoxia can be uncoupled from those in blood pressure. Turning to the endocrine effects of demullation, cortisol and ACTH responses to hypoxia were much increased, whilst those of insulin were depressed. During chemical sympathectomy these responses were much accentuated in the case of cortisol and ACTH but depressed for insulin. A feature of these effects was that the endocrine changes in the adrenal-demedullated fetuses, whilst initially high, were not sustained for the 60 min of hypoxia. The same was true of the fetal matabolic responses to hypoxia reflected in plasma glucose, lactate and non-esterified fatty acids. Most of the results in this study are consistent with the proposal that in the fetus adrenal catecholamines are important in sustaining responses to hypoxia, but not normally initiating them.

Adrenal Medulla↗

PubMed1988

Effects of increased core temperature on breathing movements and electrocortical activity in fetal sheep.

Core temperature of fetal sheep was raised by perfusing warm water through a loop implanted into the abdomen, or into the stomach via the oesophagus. Raising fetal temperature by 0.8-2 degrees C was associated with an increase in amplitude and incidence of breathing movements, and an increase in the proportion of breathing movements that occurred during high voltage electrocortical (ECoG) activity. Fetal hyperthermia was maintained for 8 h, but the augmentation of breathing movements did not last for more than 2-3 h. The results indicate that changes of maternal temperature caused by hot weather, exercise, fever, and possibly diurnal changes of body temperature could alter the amplitude and pattern of fetal breathing movements.

Animals↗

PubMed1987

Structure and expression of the human apolipoprotein A-IV gene.

We have isolated the human apolipoprotein (apo) A-IV gene from a cosmid library and determined its complete nucleotide sequence. The gene contains three exons of 162, 127, and 1180 nucleotides separated by two introns of 357 and 777 nucleotides. A sequence polymorphism has been identified in the 3' noncoding portion of the third exon. The human apoA-IV gene lacks an intron in the area encoding the 5' nontranslated region of its mRNA, which distinguishes it from all the other human apolipoprotein genes whose sequences are known. Comparison matrix analysis of the human apoA-IV gene sequence revealed evidence for an ancestral 11-nucleotide repeat unit that spans the third exon. These repeated sequences are much more highly conserved than those present in either rat apoA-IV or in any other human apolipoprotein. Optimal alignments of the 5' flanking regions of the rat and human apoA-IV genes disclosed multiple deletions in the rat sequence as well as a highly conserved region of 90 nucleotides (90% sequence identity) located within 170 nucleotides of the start site of transcription. The 5' flanking regions of the human and rat apoA-IV genes were ligated to the bacterial chloramphenicol acetyltransferase gene, then transfected into different cultured cells. The apoA-IV gene sequences elicited preferential expression of chloramphenicol acetyltransferase activity when introduced into intestinally derived Caco-2 cells and liver-derived Hep-G2 cells, consistent with the tissue specificity of the native gene. Analysis of deletion mutants of the human apoA-IV 5' flanking region indicated that regions from -293 to -233 and from -127 to -60 upstream of the transcription start site contain sequences required for maximum gene expression. These findings on the structure and expression of rat and human apoA-IV should prove useful in studying the control of the apoA-IV gene.

Amino Acid Sequence↗

PubMed1987

Peripheral and brain tissue catecholamine content in intact and anti-NGF-treated fetal sheep.

Fetal lambs were treated with a single dose of anti-mouse nerve growth factor (anti-NGF) at 80 days gestational age. The catecholamine content of tissues was determined at 135 days gestational age. There was a reduction of either norepinephrine, epinephrine, or both, in the thymus, thyroid, atrium (but not ventricle), lung, liver, kidney, and jejunum when compared with age-matched control fetuses. The spleen, ileum, colon, and the adrenal glands were not affected by anti-NGF. In treated fetuses there was a reduction in catecholamine content of the thalamus, hypothalamus, hippocampus, medulla, cerebellum, and cervical spinal cord. These results show that some tissues are sensitive to, and some are refractory to, the action of anti-NGF at 80 days gestation. Also the results suggest that NGF may play a role in the development of catecholamine-containing neurons within the central nervous system.

Animals↗

PubMed1987

Effects of naloxone on breathing movements during hypercapnia in the fetal lamb.

To determine whether endogenous opioids influence the fetal breathing response to CO2 we have investigated the effect of the opiate antagonist, naloxone on the incidence, rate, and amplitude of breathing movements during hypercapnia in fetal lambs in utero. In 20 experiments in six pregnant sheep (130-145 days gestation) hypercapnia was induced by giving the ewe 4-6% CO2-18% O2 in N2 to breathe for 60 min. After 30 min of hypercapnia either naloxone (13 experiments) or saline (7 experiments) was infused intravenously for the remaining 30 min. During hypercapnia breath amplitude increased from 5.8 +/- 0.5 to 9.1 +/- 1.2 mmHg (P less than 0.001), and infusion of naloxone was associated with a further significant increase to 15.7 +/- 1.2 mmHg (P less than 0.001). Naloxone had no effect on the incidence or rate of breathing movements during hypercapnia. After hypercapnia there was a significant decrease in the incidence of fetal breathing movements in the naloxone group (14.7 +/- 3.2%). Infusion of saline during hypercapnia had no effect on incidence, rate, or amplitude of fetal breathing movements. These results suggest that endogenous opioids act to suppress or limit breath amplitude during hypercapnia but do not affect rate or incidence of breathing movements.

Animals↗

PubMed1987

Analysis of fetal breathing in real time using a microprocessor.

A system has been designed using an inexpensive microprocessor to analyze fetal breathing movements on a breath-by-breath basis in real time. An algorithm was developed which would recognize fetal breathing from the changes in tracheal pressure and which was capable of rejecting the artifactual changes caused by fetal or maternal movements. The tracheal pressure signal was digitized (at 51 samples/s), differentiated, and the start and peak of each breath was recognized from the zero-crossing points of the differentiated signal. Each breath was validated for size and shape according to a set of criteria incorporated into the breath recognition algorithm. On acceptance of the pressure change as a valid breath, the inspiratory time, breath amplitude, breath-to-breath interval, and inspiratory effort were calculated and stored in memory. The program was structured so that the microprocessor was able to accept new data and output summarizes of previous data concurrently. More than 95% of breaths in records contaminated with movement artifacts were recognized.

Computers↗

PubMed1987

Diurnal variations in plasma concentrations of cortisol, prolactin, growth hormone and glucose in the fetal sheep and pregnant ewe during late gestation.

We have measured fetal and maternal plasma concentrations of cortisol, prolactin, GH and glucose in samples collected during a 24-h period in 14 animals between 127 and 142 days of gestation. There was a significant increase in both the mean daily plasma cortisol concentration and mean daily coefficient of variation (C.V.) of plasma cortisol concentrations after 135 days of gestation. There was also a significant variation in the fetal plasma cortisol concentrations with a peak occurring at 19.00 h. There was a significant sinusoidal diurnal rhythm in the plasma prolactin concentrations in both the fetal sheep and pregnant ewe and the maximal prolactin concentrations occurred between 19.00 and 23.00 h (fetal) and 21.00 and 01.00 h (maternal). Although no significant diurnal variation was detected in fetal plasma GH concentrations, there was a significant sinusoidal diurnal rhythm in the plasma GH concentrations of the pregnant ewe and the maximal maternal GH concentrations occurred between 21.00 and 01.00 h. Both the fetal and maternal plasma glucose concentrations showed a significant sinusoidal diurnal rhythm. The maximal maternal and fetal glucose concentrations were measured between 21.00 and 01.00 h and between 23.00 and 03.00 h respectively. We have therefore established that diurnal variations in plasma cortisol and prolactin concentrations exist prenatally. Whether the presence of such hormonal rhythms reflects the activity of an endogenous fetal circadian pacemaker remains to be established.

Animals↗