Biomedical subjects

J N Davis

Publications and source records attributed to J N Davis.

At least 73 records · Page 4Linked to original sources

PubMed1989

Species differences in the localization and number of CNS beta adrenergic receptors: rat versus guinea pig.

The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of [125I]cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions 1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, 2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and 3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.

Adrenergic beta-Antagonists↗

PubMed1989

Biochemical and genetic analysis of Salmonella typhimurium and Escherichia coli mutants defective in specific incorporation of selenium into formate dehydrogenase and tRNAs.

Mutation of a single gene, referred to as selA1 in Salmonella typhimurium and as selD in Escherichia coli, results in the inability of these organisms to insert selenium specifically into the selenopolypeptides of formate dehydrogenase and into the 2-selenouridine residues of tRNAs. The mutation does not involve transport of selenite into the cell or reduction of selenite to selenide since both mutant strains synthesize selenocysteine and selenomethionine from added selenite and incorporate these selenoamino acids non-specifically into numerous proteins of the bacterial cells. Complementation of the mutation in S. typhimurium with the selD gene from E. coli indicates functional identity of the selA1 and selD genes. Although the selA1 gene maps at approximately 21 min on the S. typhimurium chromosome and the selD gene at approximately 38 min on the E. coli chromosome, only a single gene in wild-type S. typhimurium hybridized to the E. coli selD gene probe. Transformation of the mutant Salmonella strain with a plasmid bearing the E. coli selD gene restored formate dehydrogenase activity, 75Se incorporation into formate dehydrogenase seleno-polypeptides and [75Se]seleno-tRNA synthesis. Transformation with an additional plasmid carrying an E. coli formate dehydrogenase selenopolypeptide-lacZ gene fusion showed that the selD gene allowed readthrough of the UGA codon and synthesis of beta-galactosidase in the Salmonella mutant.

Aldehyde Oxidoreductases↗

PubMed1988

Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients.

We conducted a double-blind pilot study of 8 patients with established cerebral infarction to evaluate the effect of a single dose of amphetamine on recovery of motor function using the Fugl-Meyer scale. Four patients received amphetamine; the rest were given placebo. All underwent a session of physical therapy. Patients treated with amphetamine obtained greater increments in motor scores than the controls. Along with animal studies, these findings may allow the development of a pharmacological approach to stroke rehabilitation.

Aged↗

PubMed1988

DSP-4 treatment produces abnormal tyrosine hydroxylase immunoreactive fibers in rat hippocampus.

DSP-4 has been used as selective toxin for central norepinephrine (NE) systems. The depletion of NE by DSP-4 is though to result from neurotoxic destruction of locus coeruleus terminals and axons. We have used tyrosine hydroxylase immunocytochemistry (TH-IR), silver stains for neural degeneration, and electron microscopy to examine the morphological effects of DSP-4 treatment on the rat hippocampus. Animals survived for either 2 or 5 weeks after DSP-4 treatment. DSP-4 depleted hippocampal norepinephrine levels to 15% of control values. Abnormally enlarged TH-IR fibers were found in the hippocampus of DSP-4-treated animals. No evidence of fiber degeneration was found following light or electron microscopic examination of the dentate hilus in DSP-4-treated animals. These data suggest that DSP-4 treatment does not destroy NE terminals, but may produce an intraneuronal lesion leading to an accumulation of TH and a depletion of norepinephrine within the terminal fields.

Animals↗

PubMed1988

Development of brain beta-adrenergic receptors after neonatal 6-hydroxydopamine treatment.

We used [125I]-cyanopindolol in vitro autoradiography and neonatal 6-hydroxydopamine treatment to study the development of beta-adrenergic receptor subtypes in rat brain. Brain regions receiving locus coeruleus innervation, such as cerebral cortex and cerebellum, displayed low receptor densities at birth and increased in density rapidly during the second and fourth weeks postnatally. By contrast, regions which receive little innervation from the locus coeruleus, such as substantia nigra, striatum, and globus pallidus, displayed relatively high beta-receptor densities even at birth. The striatum appeared to be an exception to these generalizations. 6-Hydroxydopamine administration was associated with an increase in the densities of beta-receptor subtypes and, unexpectedly, with a change in the proportions of the two subtypes. These data support the view that innervation determines the ontogenetic patterns of some receptors in brain.

Animals↗

PubMed1988

Physician prescribing patterns following hospital admission for ischemic cerebrovascular disease.

Functional recovery after brain injury in laboratory animals is influenced by a variety of drugs. Yet, the impact of currently prescribed drugs on recovery after human stroke remains largely unexplored. From the Duke-VA Stroke Registry, we found 77% of patients admitted to either the university hospital or the Veterans Administration hospital with cerebral infarction were taking medications at the time of their stroke. Ninety-five percent of these patients were receiving medication at the time of discharge. Antihypertensives were the most commonly prescribed agents in the study population, and platelet antiaggregants were second. Sixty-four percent of patients had a change in their antihypertensive regimens. The number of patients prescribed sedative-hypnotic agents doubled over the first 48 hours after hospital admission. The choice of a therapeutic agent for a given clinical indication may have important implications for rehabilitation of the stroke patient.

Aged↗

PubMed1987

The distribution of beta-1- and beta-2-adrenergic receptors of normal and reeler mouse brain: an in vitro autoradiographic study.

The densities of beta-1 and beta-2-adrenergic receptors in normal and reeler mice brains were compared using in vitro autoradiography. For the most part, the regional distribution of the beta-receptor subtypes in mouse brain was similar to that of rat [Rainbow et al. (1984) Proc. natn. Acad. Sci. U.S.A. 81, 1585-1589]. The most striking differences in beta-adrenergic receptor localization between the mouse and rat brain were in the superficial layer of the superior colliculus and the bed nucleus of stria terminalis. The superficial layer of the mouse superior colliculus had high densities of beta-1 receptors and much lower densities of beta-2 receptors, while the superficial layer of the rat superior colliculus had moderately high densities of beta-2 and lower densities of beta-1 receptors. The mouse bed nucleus of stria terminalis had greater densities of beta-1 receptors than beta-2 receptors. This structure in the rat possessed roughly equivalent densities of beta-1 and beta-2 receptors. In general, the distributional pattern of beta-1 and beta-2 receptors in the reeler mouse brain matched that of the normal mouse brain. In regions which neuronal malpositioning had been reported, such as the cerebral cortex, hippocampus, and cerebellum, beta-1 and beta-2 receptors were still present in proportions similar to normal mice; however, the pattern of beta-receptors within each of these regions was altered. The beta-receptor subtypes in these structures showed an abnormal radial distribution similar to the abnormal radial positioning of neurons in these structures.

Animals↗

PubMed1986

Hippocampal sympathetic ingrowth in rats and guinea pigs: quantitative morphometry and topographical differences.

Sympathetic ingrowth is an unusual neural rearrangement in response to damage of the septohippocampal pathway in which peripheral noradrenergic nerves grow into the hippocampal formation. Hippocampal ingrowth has been extensively studied in rats and has been suggested to be regulated by the mossy fibers of the dentate granule cells, hippocampal interneurons, or glial cells. Sympathetic ingrowth was found to occur in both rats and guinea pigs; however, a discrepancy between the species was observed in the topographical distribution of sympathetic ingrowth. Ingrowth fibers were found in the dentate hilus and area CA3 of guinea pigs and rats. However, in the guinea pig fibers extended into area CA1. Quantitative estimates of fiber number confirmed these observations and identified significant differences between the species in the intrahippocampal lamellar distribution of ingrowth fibers. The topographical differences in sympathetic ingrowth could not be explained by differences in the distribution of the mossy fibers (Timms stain), cholinergic septal afferents (anterograde HRP), or in hippocampal interneurons (GAD-immunoreactive neurons). These species differences are challenging to current theories concerning the regulation of sympathetic ingrowth and may provide a useful model for testing further hypotheses about axonal guidance and target selection.

Animals↗

PubMed1986

Localization of alpha 1-adrenergic receptors in normal and weaver mouse brain with in vitro 125I-HEAT autoradiography.

Using 125I-HEAT, a specific alpha 1-adrenergic antagonist, we have autoradiographically localized alpha 1-adrenergic receptors in the normal and weaver mutant mouse. Highest levels of binding in both the normal and weaver mouse were seen in the dorsal thalamus, external plexiform layer of the olfactory bulb and intermediate layers of the frontoparietal cortex. These results essentially parallel those found in the rat, with some differences in the cortical pattern that are attributable to differences between the cytological organization in the two species. Reduced levels of binding in the agranular weaver cerebellum as compared to normals indicated that binding in the normal cerebellum was to receptors on granule cell dendrites.

Adrenergic alpha-Antagonists↗

PubMed1986

Changes in the noradrenergic innervation of the area dentata after axotomy of coeruleohippocampal projections or unilateral lesion of the locus coeruleus.

Lesions of the septal region result in a significant decrease in the norepinephrine content of the area dentata. Over a period of one year, norepinephrine levels return to normal, presumably due to the proliferation of remaining locus coeruleus fibers. Unilateral lesions of the locus coeruleus produce reductions in [3H]norepinephrine uptake values of about 70% and 30% in the ipsilateral and contralateral area dentata, respectively. By 12 weeks after lesion, the noradrenergic fiber density in the contralateral area dentata is within the range of control measurements, whereas the area dentata ipsilateral to the lesion remains significantly depleted of noradrenergic fibers. At 26 weeks postlesion, no further change was observed in the noradrenergic fiber density of either area dentata. These results are interpreted in light of the hypothesis that locus coeruleus axon proliferation is induced by axotomy and represents the expansion of intact collaterals of damaged fibers.

Animals↗

PubMed1986

Peripheral sympathetic ingrowth can alter metabolic activity within the hippocampal formation.

After cholinergic denervation of the hippocampal formation, peripheral sympathetic fibers arising from the superior cervical ganglia grow into the dentate gyrus and CA3 region; the functional significance of sympathetic ingrowth into the hippocampal formation is unknown. Utilizing electrical stimulation of the preganglionic trunk in combination with 2-deoxy-D-[3H]-glucose fine-grained autoradiograms, we demonstrated an alteration of hippocampal glucose metabolism, suggesting that this neuronal rearrangement makes functional connections within the hippocampus.

Animals↗

PubMed1985

Retrograde labeling of locus coeruleus neurons after lesion-induced sprouting of the coeruleohippocampal projection.

Locus coeruleus axons have been observed to proliferate and reinnervate targets after the partial removal of normal locus coeruleus inputs. Sixteen weeks after a large electrolytic lesion of the septal region, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections of the dorsal area dentata resulted in the labeling of neurons of the dorsal half of the locus coeruleus. Similar injections made at earlier postlesion times failed to produce visible HRP labeling in the locus coeruleus. These observations are consistent with our previous report of the time course for the noradrenergic reinnervation of the dorsal area dentata after septal lesions. Using double-labeling techniques, we have also demonstrated that collaterals of locus coeruleus axons that originally innervated the dorsal area dentata sprout to reinnervate that region 4 months after a lesion of the septal region. Thus the homotypic compensatory proliferation of locus coeruleus projections appears to be mediated, at least in part, by a pruning effect.

Animals↗

PubMed1985

Differential distribution of locus coeruleus projections to the hippocampal formation: anatomical and biochemical evidence.

Locus coeruleus (LC) fibers in the fornix mainly innervate the septal pole of the dentate gyrus, whereas the cingulum projects to the ventral hippocampal formation to provide LC input to the dentate gyrus. LC fibers in the ventral amygdaloid bundle have a wide-spread distribution, innervating the entire hippocampal gyrus, as well as the mid-septotemporal and temporal regions of the dentate gyrus. The LC fibers of the fornix and ventral amygdaloid bundle do not appear to overlap significantly in the septal pole of the dentate gyrus.

Amygdala↗

PubMed1985

Anatomy of brain alpha 1-adrenergic receptors: in vitro autoradiography with [125I]-heat.

Much useful information on the localization of alpha 1-adrenergic binding sites has been gained by using tritiated radioligands for in vitro autoradiography. However, the iodinated alpha 1-adrenergic antagonist HEAT [( 2-beta (4-hydroxyphenyl)-ethylaminomethyl)-tetralone], BE 2254), a radioligand with high affinity and specificity, provides autoradiographs with a higher signal to noise ratio. This has allowed us to describe the anatomy of these binding sites in much greater detail than previously possible. Regions showing the highest levels of binding include external plexiform layer of the olfactory bulb, layers Va and Vc of frontoparietal cortex, lateral and central amygdaloid nuclei, thalamus, and inferior olive. Other regions were generally less intensely labeled, with the least evidence of labeling in white matter, such as corpus callosum. Some regions (e.g., hippocampus) had only moderate labeling, but the binding appeared in a discrete pattern that reflected the functional organization of the structure. Although the [125I]-HEAT binding sites were distributed in a pattern similar to that previously reported for [3H]-WB 4101 and [3H]-prazosin, the anatomical detail seen with the iodinated ligand is greater. As a result, an association of alpha 1-adrenergic antagonist binding sites with specific layers in the cortex and with some catecholamine-containing nuclei in the brainstem, such as the locus coeruleus, have been seen for the first time.

Animals↗

PubMed1985

Regional distribution of rat brain alpha 1-adrenergic receptors: correlation between (125I)-heat membrane binding and in vitro autoradiography.

[125I]-HEAT has proven useful for in vitro autoradiography as a specific alpha 1-adrenergic radioligand. We compared the binding of [125I]-HEAT to membranes from ten brain regions with the densitometric readings of these regions in autoradiographs. There was an excellent correlation between receptor numbers from membrane binding and relative optical densities from the autoradiography. The affinity of HEAT for binding to membranes from various regions was similar. The results of this direct comparison are further evidence that HEAT binds to alpha 1-adrenergic receptors in lightly fixed tissue sections. A further interesting observation is that in regions with a heterogeneous distribution of binding sites, membrane binding may not reflect the presence of a dense local population of receptors.

Adrenergic alpha-Antagonists↗

PubMed1985

Purification and properties of a quinone-dependent p-nitrophenylphosphatase from Clostridium sticklandii.

A highly specialized phosphatase that depends on both a quinone (e.g., 2-methyl-1,4-napthoquinone) and a sulfhydryl compound for activity was purified to homogeneity from extracts of Clostridium sticklandii. Selective adsorption to Cibacron Blue-Sepharose 4B followed by elution with p-nitrophenylphosphate was an effective enrichment procedure. An affinity matrix containing vitamin K5 (4-amino-2-methyl-1-naphthol) covalently attached to Sepharose 4B selectively retained the enzyme and was also used in its purification. The only known substate for the enzyme, p-nitrophenylphosphate, is hydrolyzed to equivalent amounts of orthophosphate and p-nitrophenol. Although a protein phosphotyrosine residue seemed a likely candidate as the natural substrate, the enzyme failed to hydrolyze 32P-labeled phosphotyrosine residues in casein, in vinculin, or in denatured glutamine synthetase. Also, free O-phosphotyrosine and numerous phosphate esters that serve as substrates for common phosphomonoesterases were not hydrolyzed. The molecular weight of the native enzyme, estimated by Sephacryl-S-200 gel chromatography, is 27,600. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis showed a single component with a molecular weight of 28,600. From the amino acid composition, a minimum molecular weight of 28,000 was calculated.

4-Nitrophenylphosphatase↗

PubMed1985

Cholinergic influences on hippocampal glucose metabolism.

2-Deoxy-D-[3H]glucose autoradiography was employed to investigate the effects of acute cholinergic manipulations on hippocampal glucose metabolism. In general, manipulations designed to reduce cholinergic activity (medial septal ablation, atropine treatment) reduced hippocampal glucose metabolism. Maximal decrements were found in the terminal fields of the septohippocampal projection after medial septal lesions, while maximal deficits after atropine treatment correlated with muscarinic receptor binding. Electrical stimulation of the medial septum resulted in increased glucose utilization in some terminal fields of the septohippocampal projection and decreased utilization in the terminal fields of the perforant pathway. Our data clearly indicate that acute alterations in cholinergic activity can affect hippocampal glucose metabolism but the distribution, direction and degree of these changes is dependent on the specific treatment.

Animals↗

PubMed1985

Postnatal development of brain alpha 1-adrenergic receptors: in vitro autoradiography with [125I]HEAT in normal rats and rats treated with alpha-difluoromethylornithine, a specific, irreversible inhibitor of ornithine decarboxylase.

The postnatal development of brain alpha 1-adrenergic receptors was studied in the rat brain using in vitro autoradiography. In some regions, such as the globus pallidus, receptor-binding sites were present at birth and increased during the first week but then decreased to very low levels by adulthood. In contrast, other regions such as the olfactory bulb and cerebral cortex exhibited little binding at birth, with a subsequent increase in receptors during the second week of life that persisted into the mature stage. Several regions had an intermediate pattern with significant labelling at birth, an increase in the first few weeks and a smaller decrement in binding sites as adulthood was approached. The data suggested that there were two archetypal development patterns, one of which was potentially related to the arrival of noradrenergic nerve projections (olfactory bulb) and the other of which was determined intrinsically by differentiation (globus pallidus). The two patterns could be distinguished by their sensitivity to alpha-difluoromethylornithine, a drug that inhibits ornithine decarboxylase, leading to a slowing of cellular replication, differentiation and migration. Drug treatment dramatically delayed the developmental fall-off of binding in the globus pallidus such that receptor sites remained in high concentration well past the point at which they disappeared in control animals. In the olfactory bulb, however, alpha-difluoromethylornithine had little or no effect on the ontogeny of receptor binding. These studies provide evidence that alpha 1-adrenergic receptors in various brain regions develop at different rates and with at least two characteristic patterns. Autoradiographic techniques provide important insights into receptor development that cannot be garnered from biochemical methods using isolated membrane preparations.

Adrenergic alpha-Antagonists↗