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Biomedical subjects

D A Taylor

Publications and source records attributed to D A Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1992

Effects of dexamethasone on late radiation injury following partial-body and local organ exposures.

Dexamethasone was evaluated as a treatment for radiation-induced lung, kidney, liver, and spinal cord injuries in rats. One experimental group was partial-body-irradiated (22.5 Gy) with the head, femur, and exteriorized intestine shielded to prevent acute mortality. Other animals received local irradiation to the kidney (20 Gy), liver (25 Gy), or a 1-cm segment of cervical spinal cord (18 to 40 Gy). Following irradiation half of the animals in each radiation group were given drinking water containing 188 micrograms/liter of dexamethasone. Tests were done to assess kidney function (hematocrit, plasma urea nitrogen, ethylenediaminetetraacetic acid clearance), liver function (rose bengal clearance, plasma glutamic oxaloacetic acid transaminase), or spinal cord injury (paralysis). The effectiveness of dexamethasone in preventing radiation injury was tissue specific. Dexamethasone eliminated lethal pleural fluid accumulation after partial-body irradiation and delayed development of kidney dysfunction after local kidney irradiation. As a result, dexamethasone increased the median survival time from 63 to 150 days after partial-body irradiation and from 126 to 175 days after local kidney irradiation. After whole-liver irradiation, development of hepatic functional injury was retarded by dexamethasone treatment but without significantly changing survival time. Dexamethasone had no effect on spinal cord tolerance but significantly shortened the latent period between radiation and paralysis.

Animals↗
PubMed1991

Structure of a recombinant calmodulin from Drosophila melanogaster refined at 2.2-A resolution.

The crystal structure of calmodulin (Mr 16,700, 148 residues) from Drosophila melanogaster as expressed in a bacterial system has been determined and refined at 2.2-A resolution. Starting with the structure of mammalian calmodulin, we produced an extensively refitted and refined model with a conventional crystallographic R value of 0.197 for the 5,239 reflections (F greater than or equal to 2 sigma (F)) within the 10.0-2.2-A resolution range. The model includes 1,164 protein atoms, 4 calcium ions, and 78 water molecules and has root mean square deviations from standard values of 0.018 A for bond lengths and 0.043 A for angle distances. The overall structure is similar to mammalian calmodulin, with a seven-turn central helix connecting the two calcium-binding domains. The "dumb-bell" shaped molecule contains seven alpha-helices and four "EF hand" calcium-binding sites. Although the amino acid sequences of mammalian and Drosophila calmodulins differ by only three conservative amino acid changes, the refined model reveals a number of significant differences between the two structures. Superimposition of the structures yields a root mean square deviation of 1.22 A for the 1,120 equivalent atoms. The calcium-binding domains have a root mean square deviation of 0.85 A for the 353 equivalent atoms. There are also differences in the amino terminus, the bend of the central alpha-helix, and the orientations of some of the side chains.

Amino Acid Sequence↗
PubMed1991

Mesenteric vascular responses of young spontaneously hypertensive rats.

Frequency-responses curves for nerve stimulation and dose-response curve for norepinephrine, 5-hydroxytryptamine potassium chloride, vasopressin and acetylcholine (ACh) were determined in isolated, perfused mesenteric vascular beds from young (approximately 5 weeks) spontanelouly hypertensive (SHR) and Wistar Kyoto rats. Although mean systolic blood pressure (measured by tail cuff plethysmography) was slightly higher in the SHR, this difference was not significant. Slopes and maximum responses were increased significantly for nerve stimulation and all agonists. The basal perfusion pressure was also significantly elevated in the SHR. These differences are consistent with existing evidence that structural changes occur in blood vessels of SHR at an early stage and probably precede development of hypertension. Such structural changes could therefore contribute to development of the hypertension. Cocaine (1 microM) markedly increased responses to nerve stimulation and bolus injections of norepinephrine in preparations from SHR with little or no effect on such responses in Wistar Kyoto preparations, a result consistent with the known greater density of noradrenergic nerves in SHR vasculature. In the presence of cocaine, there was unmasked a selective super-sensitivity (significantly lower ED50) to norepinephrine in the SHR. Thus SHR mesenteric vessels may possess an alteration in adrenoreceptors or their coupling to other cellular mechanisms. Responses to ACh revealed no indication of a deficient endothelial mediated relaxation. An altered media:lumen ratio of small arteries, hypernoradrenergic innervation and supersensitivity to the transmitter may contribute to development of hypertension.

Animals↗
PubMed1991

Cyclic AMP and adaptive supersensitivity in guinea pig atria.

Supersensitivity was induced by injection of guinea pigs with reserpine, 0.1 mg/kg/day for 7 days. This treatment induced chronotropic supersensitivity of isolated right atria to isoproterenol but not to forskolin. The pretreatment induced supersensitivity to the cyclic AMP-generating effects of isoproterenol or forskolin in left, but not right, atria. These results are discussed in reference to the extensive literature describing supersensitivity in the guinea-pig heart, including the possible role of the adenylyl cyclase system.

Animals↗
PubMed1991

Primary oesophageal rhabdomyosarcoma.

A case is presented of a rhabdomyosarcoma of the oesophagus with a description of the cytology, light microscopy, and immunocytochemical findings and a discussion of spindle cell tumours occurring at this site. Cytologically, large bizarre shaped pleomorphic cells were seen in which desmin was demonstrated in order to confirm the diagnosis after destaining a Papanicolaou stained slide and restaining it with antibody to desmin.

Carcinoma↗
PubMed1991

Catecholamine and neuropeptide Y levels in tissues from young Dahl rats following 5 days low- or high-salt diet.

The mesenteric vasculature of Dahl salt-sensitive (DS) rats on high-salt diet is supersensitive to nerve stimulation and to norepinephrine. The current experiments were undertaken to examine whether the enhanced sensitivity to nerve stimulation is due solely to the postsynaptic supersensitivity to norepinephrine, to increased sympathetic innervation, to altered transmitter release or to the presence of another transmitter acting as a potentiator. Catecholamine content and neuropeptide Y (NPY) presence were determined in tissues from young (approximately 5 weeks old) male Dahl rats exposed to 5 days of high (7%) or low (0.45%) salt diet. Catecholamine content from mesenteric artery, renal artery, caudal artery, right atrium, aorta, vas deferens and adrenal gland was quantified by high-pressure liquid chromatography with an electrochemical detector. A strain difference, independent of diet, between young DS and Dahl salt-resistant (DR) rats was seen only in adrenal epinephrine content. DS high-salt (+) rats displayed reduced norepinephrine content relative to DR+ in the mesenteric artery and right atrium. The release of norepinephrine from isolated mesenteric vasculature into the perfusate in response to transmural stimulation showed no significant differences between DS+ and DR+ preparations under basal, or deoxycorticosterone acetate (DOCA; 30 microM) perfusion conditions. The addition of 5 microM cocaine to the DOCA perfusion, while increasing total norepinephrine outflow in all preparations, failed to differentiate between DS+ and DR+. NPY immunofluorescence along mesenteric artery sections of DS+ and DR+ rats was not significantly different. Thus, in the tissues examined, enhanced responsiveness of vascular smooth muscle may not be explained by hypernoradrenergic innervation, elevated NPY innervation or altered release of transmitter.

Animals↗
PubMed1991

Specific supersensitivity of the mesenteric vascular bed of Dahl salt-sensitive rats.

Dahl salt-sensitive (DS) and salt-resistant (DR) rats were maintained on a diet containing normal (0.45%) or high (7%) salt for 5 days. The DS rats had slightly higher systolic blood pressures than DR rats, although a high salt diet failed to significantly elevate pressure in either group when compared with their appropriate (low salt diet) controls. The sensitivity of the isolated, perfused mesenteric vasculature from DS rats fed a high salt diet to nerve stimulation was greater when compared with all other groups in the presence or absence of cocaine (1 microM). A similar difference in sensitivity between high salt DS rats and high salt DR rats to bolus injections of norepinephrine was observed only in the presence of cocaine. The change in sensitivity was characterized by a leftward shift of the dose-response curve without a change in maximum response. No difference in sensitivity between the high salt DS group and any other treatment group was observed in response to the pressor agents KCl, angiotensin II, 5-hydroxytryptamine or the depressor agent acetylcholine. These data indicate that DS rats on a short-term, high salt diet possess a significant and specific elevation in sensitivity to nerve stimulation and norepinephrine in the absence of an increase in blood pressure. Differences in the effectiveness of cocaine among the groups suggest that differences may exist in neuronal uptake (uptake 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Involvement of mu, delta and kappa receptors in morphine-induced tolerance in the guinea pig myenteric plexus.

Tolerance in the longitudinal muscle-myenteric plexus (LM-MP) preparation to opioids appears to represent two separate phenomena. One phenomenon is characterized by marked subsensitivity to mu-selective opioid substances and a very short half-life. The other is characterized by moderate subsensitivity to morphine and to several nonopioid inhibitory substances and has a long half-life. The present investigation was to determine if the long half-life type of tolerance involves cross-tolerance between mu-selective opioids, such as morphine, and opioids selective for delta or kappa receptors. Tolerance was induced by s.c. implantation of morphine pellets for 7 days. Control guinea pigs received placebo pellets. Isolated LM-MP preparations were tolerant to the mu-selective agonists morphine and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin as well as to [D-Ala,2D-Leu5]enkephalin and [D-Ser2]leucine enkephalin-Thr, agonists only slightly selective for delta receptors over mu. The delta-selective agonist, [D-Pen2,D-Pen3]enkephalin, produced a biphasic concentration-response curve. The first phase, which included only very weak effects, presumably represented delta-mediated effects. The second phase reached virtually 100% inhibition of the twitch. Significant subsensitivity (tolerance) was demonstrated only for the second phase, presumably representing mu-mediated effects. There was no significant tolerance to the kappa-selective agonist, U50,488H. Consistent with the literature, the results indicate effective twitch inhibition mediated by mu and kappa receptors, but not delta receptors. Among opioids, tolerance induced by morphine pellets in the LM-MP is limited to mu receptor-mediated inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Sensitivity of cerebellar Purkinje neurons to neurotransmitters in genetically epileptic rats.

Epilepsy is a state of neuronal hyperactivity which may be caused by an altered relationship between inhibitory and excitatory influences on neurons. We have conducted experiments using microiontophoresis with in situ extracellular recording of anesthetized rat cerebellar Purkinje neuron activity to determine the sensitivity of these neurons to neurotransmitters in a genetic model of epilepsy. Quantitative evaluations of agonist-induced changes in activity were carried out by using poststimulus time histograms. Current-response curves were generated and linear regression analysis was performed to evaluate changes in responsiveness and sensitivity between control and genetically epilepsy-prone-9 rats. The current required to produce 50% inhibition of activity by GABA was 2.6-fold higher in the genetically epilepsy-prone-9 rats compared to control. In contrast, the amount of current required to produce 50% inhibition by norepinephrine was not significantly different between groups. There also was no significant change in cerebellar neuron sensitivity to the excitatory transmitter, glutamate. The lack of an alteration in sensitivity and responsiveness to norepinephrine or glutamate suggests that the hyperexcitability of neurons may be associated with a specific subsensitivity of the GABAergic system. Such a specific subsensitivity to gamma-aminobutyric acid would, therefore, yield a more excitable state of the neuron and may contribute to the development of the hyperactivity observed in epilepsy.

Animals↗
PubMed1991

Effects of GABA in the morphine-tolerant longitudinal muscle, myenteric plexus preparation of the guinea pig.

The effect of chronic treatment with morphine via pellet implantation on the sensitivity of the longitudinal smooth muscle-myenteric plexus of the guinea pig ileum to the contractile effects of gamma-aminobutyric acid (GABAA)-receptor agonists was assessed. GABA and muscimol elicited concentration-dependent contractions of the longitudinal smooth muscle which were due to the release of acetylcholine because the contractile effects were markedly attenuated by atropine (10 nM). The contractile action of GABA agonists does not involve an intermediate step mediated by nicotinic receptors because the concentration-response curves for GABA were unaffected by hexamethonium (1 mM). Bicuculline (10 microM) produced nearly equivalent rightward shifts of the concentration-response curves for both GABA and muscimol, indicating mediation of the contractile effects of these agents by GABAA receptors. Chronic exposure to morphine via pellet implantation did not alter the sensitivity of this preparation to either GABA or muscimol. This is in contrast to the development of supersensitivity of the longitudinal smooth muscle-myenteric plexus to other excitatory agonists (nicotine, 5-hydroxytryptamine and potassium), which accompanies the development of tolerance to opioids. GABA induces depolarization of myenteric neurons that is observed most prominently in AH neurons and rarely in S neurons. The stimulatory effects of nicotine and of GABA were inhibited by morphine (a predominantly mu opioid agonist) and by U50,488H (a predominantly kappa opioid agonist). The results are discussed within the context that supersensitivity to neuronal stimulants of the myenteric plexus in morphine-tolerant preparations is limited to substances which depolarize S neurons.

Animals↗
PubMed1991

Antagonism of norepinephrine by clonidine in the isolated rat mesenteric vascular bed.

Experiments were done in isolated, perfused mesenteric vascular beds from Sprague-Dawley rats. Bolus injections of norepinephrine (3-100 nmol) induced dose-dependent increases in perfusion pressure with a maximum increase greater than 100 mm Hg. In the same dose range, clonidine had no effect on perfusion pressure. In the presence of an elevated pressure caused by constant infusions of norepinephrine (6-20 microM), bolus injections of clonidine (0.1-10 nmol) or acetylcholine (0.007-7 nmol) caused dose-related decreases in perfusion pressure. Procedures which damage endothelium (brief exposure to methylene blue or reactive oxygen radicals) abolished the depressor action of acetylcholine but only moderately reduced the depressor action of clonidine. The depressor action of clonidine was not antagonized by the alpha-2 adrenoceptor antagonist, idazoxan. Acetylcholine produced depressor responses in the presence of 5-hydroxy-tryptamine or vasopressin, but clonidine did not. Dose-response curves to bolus doses of norepinephrine were shifted markedly to the right by an alpha-1 selective concentration of prazosin (1 nM) and were shifted to the right with depression of maximum by infusions of clonidine (0.3 and 1.0 microM). It is concluded that, in the mesenteric vasculature of the rat: 1) the role of alpha-2 adrenoceptors, in responses to clonidine, is minimal; 2) endothelial factors play little role, if any, in the depressor effects of clonidine and 3) clonidine has a potent ability to interfere with the alpha-1 adrenoceptor-mediated vasoconstriction induced by norepinephrine. This antagonistic action may be at the level of the receptor but could involve postreceptor steps.

Acetylcholine↗
PubMed1990

Giant cell hepatocellular carcinoma.

A terminal case of giant cell hepatocellular carcinoma, subsequent to Hepatitis B-associated macronodular cirrhosis is presented, illustrated and discussed. The uncommon finding of malignant ascites, in itself atypical of hepatocellular carcinoma, with an almost exclusive content of giant cells as the cellular component, was a feature of this unusual variant of hepatocellular carcinoma.

Adult↗
PubMed1990

Adaptations of synaptic form in an aberrant projection to the avian cochlear nucleus.

Surgical removal of the otocyst in chick embryos induces axons from the contralateral cochlear nucleus (nucleus magnocellularis, NM) to form, in addition to their normal endings in nucleus laminaris (NL), anomalous and persistent functional contacts in the ipsilateral NM (Jackson and Parks, 1988). We have examined how interaction between the abnormal synaptic partners during development influences the form of the axon terminal and its relation to the target neuron. In the light microscope, aberrant axon terminals labeled in vitro with HRP appear to form boutons quite unlike the large calycine endbulbs made by the normal cochlear nerve (CN) endings in NM. In the electron microscope, however, the anomalous endings appear embedded in the NM cells, something never seen normally in NM or NL. Morphometric analyses were performed on electron micrographs from NM and NL in animals aged embryonic day (E) 19 to posthatching day (P) 2 from which the right otocyst had been removed on E3 and in normal control animals. Aberrant endings appose 18% of the circumference of operated NM cells, versus 45% for CN axons in the normal NM at this age. The mean length of membrane apposition for the anomalous NM-to-NM endings was 215% greater than for normal NM-to-NL endings but 54% smaller than that in normal CN endings. These results support the idea that developmental interactions between synaptic partners can influence the form of the contact between the 2 neurons. The results also demonstrate, however, that formation of persistent and functional synapses with NM neurons throughout development is not sufficient to induce any axon to assume the calycine form of a cochlear nerve endbulb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1989

Full-length rat alpha and beta cardiac myosin heavy chain sequences. Comparisons suggest a molecular basis for functional differences.

The two cardiac myosin heavy chain isoforms, alpha and beta, differ functionally, alpha Myosin exhibits higher actin-activated ATPase than does beta myosin, and hearts expressing alpha myosin exhibit increased contractility relative to hearts expressing beta myosin. To understand the molecular basis for this functional difference, we determined the complete nucleotide sequence of full-length rat alpha and beta myosin heavy chain cDNAs. This study represents the first opportunity to compare full-length fast ATPase and slow ATPase muscle myosin sequences. The alpha and beta myosin heavy chain amino acid sequences are more related to each other than to other sarcomeric myosin heavy chain sequences. Of the 1938 amino acid residues in alpha and beta myosin heavy chain, 131 are non-identical with 37 non-conservative changes. Two-thirds of these non-identical residues are clustered, and several of these clusters map to regions that have been implicated as functionally important. Some of the regions identified by the clusters of non-identical amino acid residues may affect actin binding, ATP hydrolysis and force production.

Amino Acid Sequence↗