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C Watt

Publications and source records attributed to C Watt.

At least 19 recordsLinked to original sources
PubMed1996

Colocalization of GABA, glycine, and their receptors at synapses in the rat spinal cord.

To determine whether GABA and glycine can act as cotransmitters at synapses in the rat spinal cord, we have compared the ultrastructural distribution of GABAA-receptor beta 3 subunit with that of the glycine receptor-associated protein gephyrin and combined this with postembedding detection of GABA and glycine. We also used a dual-immunofluorescence method to confirm that gephyrin was associated with the glycine-receptor alpha 1 subunit throughout the cord. GABAA beta 3-subunit immunoreactivity was restricted primarily to synapses, and at a majority of these synapses the presynaptic axon was GABA-immunoreactive. Many synapses showed both GABAA beta 3 and gephyrin immunoreactivity, and at most of these synapses GABA and glycine were enriched in the presynaptic axon. These results strongly support the idea that cotransmission by GABA and glycine occurs in the spinal cord.

Animals↗
PubMed1996

The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord.

The mu-opioid receptor MOR1 is present on primary afferent axons and a population of neurons in the superficial dorsal horn of the rat spinal cord. In order to determine which types of neuron possess the receptor we carried out pre-embedding immunocytochemistry with antibody to MOR1 and combined this with a post-embedding method to detect GABA and glycine in the rat. MOR1 immunoreactivity was seen on many small neurons in lamina II and a few in the dorsal part of lamina III. Although immunostaining was mainly restricted to the cell bodies and dendrites of these neurons, in some cases it was possible to see their axons, and a few of these entered lamina III. One hundred and thirty-nine MOR1-immunoreactive cells were tested with GABA and glycine antibodies, and the great majority of these (131 of 139; 94%) were not GABA or glycine immunoreactive, while the remainder showed GABA but not glycine immunoreactivity. These results suggest that most of the cells in the superficial dorsal horn which possess MOR1 are excitatory interneurons. They support the hypothesis that part of the action of mu-opioid agonists, such as morphine, involves the inhibition of excitatory interneurons which convey input from nociceptors to neurons in the deep dorsal horn, thus interrupting the flow of nociceptive information through polysynaptic pathways in the spinal cord.

Animals↗
PubMed1995

The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors.

In order to provide further information about the types of spinal neuron which possess neurokinin-1 receptors, we have carried out pre-embedding immunocytochemistry on sections of rat lumbar spinal cord with an antiserum raised against a synthetic peptide corresponding to part of the sequence of the receptor, and combined this with post-embedding immunocytochemistry to detect GABA and glycine. Numerous neuronal cell bodies showing neurokinin-1 receptor-immunoreactivity were seen in lamina I, laminae III-VI, the lateral spinal nucleus and the area around the central canal. Most of the cells observed in lamina III were small and had relatively restricted dendritic trees which could often not be followed into lamina II, however some larger cells in laminae III and IV had dendrites which extended through lamina II and into lamina I. Cells of the latter type are likely to represent a major target of substance P released from small-diameter primary afferents in the superficial dorsal horn. The great majority (255 out of 283) of spinal neurons which possessed neurokinin-1 receptor-immunoreactivity, including all of those in lamina I, were not GABA- or glycine-immunoreactive, however a few cells in the deep part of the dorsal horn and the lateral spinal nucleus and several cells near the central canal were GABA-immunoreactive, and some of these were also glycine-immunoreactive. These results suggest that substance P acts through neurokinin-1 receptors mainly on excitatory neurons within the spinal cord.

Afferent Pathways↗
PubMed1993

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates.

The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where perturbation of the axon results in axonal swelling and disconnection at a minimum of 2 h after injury.

Acceleration↗
PubMed1993

Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects.

In the present study, a comparison was made of the fatty acid composition of the grey and white matter of the frontal, parietal and parahippocampal regions of post-mortem brains of patients who had died with Alzheimer's disease (n = 15) and control postmortem subjects (n = 10). Diagnosis of Alzheimer-type disease was based on the presence of senile plaques and neurofibrillary tangles in post-mortem sections. Several highly significant and specific differences were observed between the two groups. Adrenic acid (22:4 n-6) was three to four times higher in the grey matter but lower in the white matter in each of the three regions in the Alzheimer brains than in the control group. These alterations were compensated by reciprocal changes in 18:0 in the grey matter and 16:1 fatty acids in the white matter. There was no significant difference in the proportion of other fatty acids, including those of the n-6 and n-3 series, in either the grey or the white matter of any of the three regions of the two groups, except for a higher proportion of 22:6 n-3 in the parietal white matter in the Alzheimer patients. There was no significant relationship between the levels of the individual fatty acids and age at death. It is suggested that the alterations in the fatty acid composition observed in the brains of Alzheimer patients may be caused by an aberration in the system by which essential fatty acids are transported into the brain.

Aged↗
PubMed1993

Awake patient monitoring to determine the need for shunting during carotid endarterectomy.

BACKGROUND: The indications for shunt placement to prevent cerebral ischemia during carotid endarterectomy have been controversial. Some investigators have recommended empiric shunting for patients presumed to be at higher risk for cerebral ischemia with a recent stroke or severe stenosis or occlusion of the contralateral internal carotid artery. METHODS: Carotid endarterectomy was performed in 81 cases with cervical block anesthetic, monitoring the awake patient for the development of cerebral ischemia (unresponsiveness or paralysis) during carotid clamping. The need for shunting (based on awake response) was compared in patients with the arbitrarily defined empiric indications for shunting (n = 29) versus those who did not have such clinical or anatomic findings (n = 52). RESULTS: Cerebral ischemia requiring shunting was observed in five (17.2%) of 29 cases with the defined indications for empiric shunting. This was not different than the need for shunting in the control group where cerebral ischemia was seen in eight (15.4%) of 52 cases. No intraoperative neurologic events occurred in any case, but one (1.2%) patient suffered a postoperative transient ischemia attack and another (1.2%) had a postoperative stroke. CONCLUSIONS: Empiric clinical or anatomic indications for shunting were not reliable predictors of cerebral ischemia that developed during carotid clamping in this study. Awake patient monitoring during carotid endarterectomy with regional anesthetic allowed prompt, accurate identification of patients with cerebral ischemia who would clearly benefit from placement of a shunt.

Aged↗
PubMed1992

The isolation and characterization of high-density-lipoprotein subfractions containing apolipoprotein E from human plasma.

1. Plasma high-density lipoprotein (HDL) was separated by heparin-Sepharose affinity chromatography into a non-bound, apolipoprotein E-poor, and a bound, apolipoprotein E-rich, fraction through the binding effect of Mn2+ in the column buffer. 2. The application of a series of elution buffers in which the concentration of Mn2+ was progressively replaced by Mg2+ resulted in the separation of the bound HDL into five subfractions. 3. Each subfraction migrated a different distance on gradient-gel electrophoresis. Three of the subfractions had RF (relative migration compared with BSA) values within the range of HDL2b. One subfraction contained largely HDL2a, with some material in the regions of HDL2b and HDL3a, and one subfraction spanned the RF regions of HDL2a, HDL3a and HDL3b. 4. The number of molecules, per HDL particle, of cholesteryl ester, non-esterified cholesterol and phospholipid increased with particle size, whereas triacylglycerol passed through a maximum and the number of amino acid residues remained approximately the same. 5. Apolipoprotein (apo) A-I was the major apoprotein in all five subfractions, but the latter differed appreciably in their contents of apo A-II and apo E. 6. The major fatty acid component of each subfraction was linoleic acid, with moderate amounts of C16:0 and C18:1 fatty acids and a smaller content of C18:0, C20:4,n-6 and C22:6,n-3, with no significant difference in composition between the subfractions. 7. This paper provides the first description of a method for the isolation of three subfractions of HDL2b together with other subfractions in quantities that are sufficient for further analytical or metabolic studies.

Adult↗
PubMed1992

The cerebrovascular response to experimental lateral head acceleration.

A number of microvascular changes, such as the development of astrocyte lucency, increased endothelial pit/vesicle activity, development of crater like lesions, and endothelial microvilli have been reported after injury to the brain. Lateral head acceleration in the non-human primate, however, still provides the best experimental model for human diffuse axonal injury. No attempt has yet been made to document the spatial extent or time course of the microvascular response to acceleration injury to the head. We have examined the brains of baboons 1, 4, 6, and 12 h and 7 days after acceleration injury to the head to analyse the microvascular response. In the experimental animals there was a short-term rise in intracranial pressure followed by a long-term resolution, and a reduction in both mean arterial blood pressure and cerebral perfusion pressure which, however, never dropped below 75% of baseline for more than 5 min after injury in any animal. We found evidence for extravasation of blood in a small number of blood vessels in all parts of the brain. Interendothelial tight junctions are not disrupted. Pit/vesicle activity rises in the 1st h in the occipital cortex, but not until 4 h in the frontal cortex, and remains elevated for at least 7 days. There is little change in the thalamus. Development of microvilli is most rapid in the frontal cortex with peak values at 1 h, but slower in the thalamus and occipital cortex where peak values are only obtained at 6 h. Highest numbers of microvilli occur in parasagittal regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acceleration↗
PubMed1992

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Acceleration↗
PubMed1991

The microvascular response to stretch injury in the adult guinea pig visual system.

In a variety of brain injury models, both reactive axonal change and microvascular abnormalities occur. Development of a stretch injury model in the guinea pig optic nerve has allowed for the characterization of the early axonal response to injury. In this same model, we have now attempted to characterize those morphologic changes occurring in the visual system microvasculature after injury. Thirty adult guinea pigs were subjected to axonal stretch injury and killed at posttraumatic survival periods ranging from 10 minutes to 14 days. Twenty animals were examined by scanning electron microscopy (SEM) for the detection of posttraumatic changes in the surface morphology of the microvasculature, and 10 animals were processed for transmission electron microscopy (TEM) analysis. Through this approach, increased pit vesicle activity and formation of endothelial microvilli were recognized within 10 minutes of injury. Pit vesicle activity returned to control levels by 2 hours. The formation of endothelial microvilli was widespread, affecting the microvessels in both the stretched and unstretched optic nerves and in the chiasm. The greatest response developed most slowly in the stretched nerve, and it was faster but less marked in the unstretched nerve and chiasm. Microvilli were more numerous in larger vessels. Related astrocytic swelling/lucency was not apparent until 6 hours after injury. The astrocyte response was less marked than that documented after brain injury. The results of this investigation demonstrate a widespread microvascular response to stretch injury of the guinea pig optic nerve. Comparison with the documented responses to traumatic brain injury indicates different rates of response to different types of insult.

Animals↗
PubMed1991

Localisation of calcium ions and calcium-ATPase activity within myelinated nerve fibres of the adult guinea-pig optic nerve.

There is no published description of the distribution of free Ca2+, nor of the distribution of Ca(2+)-ATPase activity associated with the maintenance of low axoplasmic Ca2+ concentrations, in normal central myelinated nerve fibres. We have used the oxalate-pyroantimonate technique to localise free Ca2+, together with the lead-citrate technique to localise Ca(2+)-ATPase activity within myelinated fibres from the adult guinea-pig optic nerve. Pyroantimonate precipitate occurred within the axoplasm at nodes of Ranvier and the internode, at areas of myelin disruption, within Schmidt-Lanterman incisures (SLI) and glial paranodal loops. But precipitate was absent from the axoplasm beneath SLI and at the paranode. Ca(2+)-ATPase activity was localised in axonal smooth endoplasmic reticulum (SER), the outer membrane of mitochondria, the nodal axolemma, the glial membranes of the paranodal loops, the SLI and the external aspect of the myelin sheath. We have demonstrated large domains within the axons of CNS fibres where calcium is present or absent. Moreover, we have shown that, where calcium is absent, there is localisation of Ca(2+)-ATPase activity, which would serve to remove calcium from the adjacent axoplasm. Our results are compared with information obtained from PNS fibres and some differences of distribution discussed.

Animals↗
PubMed1990

Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity.

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.

Adult↗
PubMed1989

The effect of clomipramine treatment on plasma lipoproteins and high density lipoprotein subfractions in healthy subjects.

The effect of clomipramine on plasma lipoproteins, including high density lipoprotein (HDL) subfractions in five healthy males was investigated. The concentrations of total plasma cholesterol and low density lipoprotein cholesterol decreased slightly while that of total HDL-cholesterol showed a small increase, giving a decrease (p less than 0.05) in the ratio of total plasma cholesterol to HDL-cholesterol. The level of HDL2-cholesterol increased (p less than 0.01) with clomipramine treatment while there was no significant change in the concentration of HDL3-cholesterol. Gradient gel electrophoresis showed that administration of the drug was associated with an increase in the relative concentration of HDL2a as well as of HDL2b and a decrease in that of HDL3b/3c. The plasma concentration of apolipoprotein (Apo) A-I showed a small but insignificant increase. These changes in lipoprotein profile are characteristic of those associated with a decrease in coronary risk.

Adult↗
PubMed1988

Calculating cardiac output from transmitral volume flow using Doppler and M-mode echocardiography.

To simplify transmitral volume flow determination by Doppler echocardiography, a formula for calculating mean mitral valve orifice area using M-mode echocardiography without any 2-dimensional measurements was developed and evaluated in this study. The maximal mitral orifice area was assumed to be circular and its diameter was calculated from the maximal M-mode mitral leaflet separation. The maximal area was multiplied by the mean to maximal anterior mitral leaflet excursion ratio to correct for phasic changes in flow orifice area during ventricular filling. This measurement had a high correlation (r = 0.97, standard error of the estimate + 0.26 cm2) with mean mitral valve orifice area calculated from frame-by-frame analysis of short-axis 2-dimensional echoes in a select group of 10 normal volunteers and 10 patients with cardiomyopathy who had very high quality images of the mitral valve leaflet tips. Cardiac output calculated using the new method for orifice area estimation combined with apex view mitral valve Doppler velocities was then validated in 48 consecutive patients undergoing thermodilution cardiac output determinations with a close correlation between Doppler and thermodilution cardiac output (2.3 to 6.1 liter/min, r = 0.93, standard error of the estimate = 362 ml). The correlation improved when 12 patients with mild mitral insufficiency were excluded (r = 0.95). The M-mode echocardiogram-derived mitral valve orifice method combined with Doppler mitral valve velocities is accurate, easy to perform, has a high success rate and should increase the applicability of Doppler echocardiography for estimation of cardiac output.

Adult↗
PubMed1987

The acute effect of marathon running on plasma lipoproteins in female subjects.

The acute effect of running a 42.2 km marathon race on plasma lipoproteins was investigated in 12 female subjects (aged 21 to 41 years). During the race there was a significant increase (P less than 0.01) in the concentration of total plasma cholesterol. The mean post-race concentration of high density lipoprotein cholesterol (HDL-C) was 64.0 +/- 16.2 (SD) mg 100 ml-1, compared with 52.1 +/- 14.0 mg 100 ml-1 before the race, representing a significant increase (P less than 0.002). There was no significant difference in the concentration of very low density lipoprotein (VLDL) or low density lipoprotein (LDL) before and after the exercise. The mean concentration of the cholesteryl ester moiety of the HDL increased from 43.7 +/- 12.3 to 54.3 +/- 15.7 mg 100 ml-1 (P less than 0.002), while there was no significant changes in the concentration of the unesterified cholesterol, phospholipid, triacylglycerol or protein moieties of the HDL. The relative proportions of apolipoproteins A-I, A-II, C and E remained unchanged during the exercise. The changes in the concentration of each of the lipoprotein fractions observed during the marathon varied considerably between subjects. The individual increases in the concentration of HDL-C ranged from 4.1 to 28.4 mg 100 ml-1, while both increases and decreases in individual concentrations of VLDL and LDL as well as of total plasma cholesterol were observed. These observations suggest that women undergo greater changes in HDL-C concentration that men during acute exercise, while considerable variation between individuals occurs.

Adult↗
PubMed1984

Drinking and creativity: objective and subjective effects.

A literature characterized by considerable speculation but a paucity of empirical studies prompted this experiment on the relation between drinking and creativity. After being queried about how they believed alcohol would affect their creative performance, 40 male undergraduate social drinkers were assigned to one of four treatments in a balanced placebo design. Those actually receiving alcohol consumed a mixture containing .6 g of ethanol per kg of body weight. All subjects then completed the entire Figural portion and the Unusual Uses subtest of the Verbal portion of the Torrance Tests of Creative Thinking. Posttesting explored subjects' own evaluations of their creative products and the kinds of attributions they made about factors contributing to the outcomes. Results showed minimal effects of beverage manipulations on measured creativity even when a priori belief and concurrent mood scores were covaried. However, those individuals who thought they had received alcohol gave significantly more positive evaluations of their creative performances than did subjects who believed they were in the non-alcohol treatments. Subjects did not attribute changes in creativity to drinking. Theoretical and practical implications of these findings were discussed.

Adolescent↗