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Biomedical subjects

C Watt

Publications and source records attributed to C Watt.

36 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

Morphological differences in the response of mouse small intestine to radiobiologically equivalent doses of X and neutron irradiation.

A scale has been developed to describe the effects of radiation on small intestinal villi. The scale has been used to compare the damage done to the villi in the period 0-5 days after irradiation by X-irradiation or neutron irradiation, using 10 Gy X-rays and 5 Gy neutrons, doses which are radiobiologically equivalent when assessed by the microcolony assay method. Use of the scale indicates that the damage done to the villi by neutrons is greater than that produced by X-rays. This has implications for the interpretation of radiobiological equivalent doses (R.B.E.). Resin light microscopy and transmission electron microscopy (T.E.M.) have also been used to examine small intestinal damage after 10 Gy X-irradiation and 5 Gy neutron irradiation. Differences include variations in crypt shape, mitotic activity and the proportion of crypts which are heavily parasitised. As well as the differences in villous shape which have been reflected in the different values on the scoring system, there are also variations in the response of the constituent cells of the epithelial compartment of the villi. In general, the effect of the neutron irradiation is more severe than that of the X-rays, particularly as would be suggested by a simple quantitation of crypt regeneration.

Animals↗

Damage to the surface of the small intestinal villus: an objective scale of assessment of the effects of single and fractionated radiation doses.

Scanning electron microscopy has been used to compare damage to mouse small intestinal mucosa after irradiation with different doses of photons and neutrons. Various stages of the collapse of villous structure seen after radiation include the production of conical and rudimentary villi and a flattened mucosa. A scale is proposed to relate radiation to villous damage. Points from this scale are taken to produce comparative ratios for equivalent damage produced by different radiation conditions. RBE values are quoted for neutron. X and gamma radiation given as single or fractionated irradiation doses and as whole or partial body irradiation. The relationship between the stroma in intravillous pegs and that of the pericryptal compartment is explored.

Animals↗

Scanning electron microscopy, autolysis, and irradiation as techniques for studying small intestinal morphology.

Examination of autolysed control mouse small intestine using scanning electron microscopy has revealed details of the connective tissue components of the mucosa. The cores of the villi are seen collapsed across the intervillous basin. Crypts of Lieberkuhn are seen as tubular channels stretching down from the intervillous basin. Sometimes the crypts are split in two by a connective tissue septum. The mouths of the crypts of Lieberkuhn are, in general, arranged in double rows between the single rows of villi. The ratio of number of crypts to numbers of villi was calculated as 5.01:1. This is close to the figure of 4.53:1, as quoted by Smith & Jarvis (1980) who used differential interference contrast microscopy to investigate the crypt to villus ratio. After radiation, the severe drop in the number of crypt mouths can be clearly seen by the combination of autolysis and scanning electron microscopy: the rows of crypt mouths between the villi have been lost, and many crypt mouths have been occluded by stromal tissue. The arrangement of the crypt mouths and the observation of mucosal abnormalities after irradiation have led to the postulation that cells leaving the crypt mouths move in a spiral manner towards and then up the villous surface: this postulated movement might imply an asymmetry in some properties of enterocytes. The use of scanning electron microscopy in conjugation with autolysis and irradiation has thus forced a critical re-examination of the relationships between crypts and villi.

Animals↗

Multinucleate giant enterocytes in small intestinal villi after irradiation.

Scanning electron microscopy of the small intestine of the mouse 5 days after X- or neutron irradiation has revealed the formation of giant cells on the villus surface. Correlative light microscopy and transmission electron microscopy have shown that these giant cells are syncytial in nature. Characteristic features of lipid inclusions and apical microvilli suggest tha these syncytia are giant enterocytes. It has also been shown that these giant cells are in contact with the connective tissue core of the villus and have a close contact with the normal enterocytes, thus maintaining mucosal integrity. It is postulated that radiation damage has caused incomplete separation during mitosis and that attempted division occurs outside the crypts of Lieberkuhn.

Animals↗

Surface damage in the small intestine of the mouse after X - or neutron irradiation.

Damage after X-irradiation includes lateral villous collapse, progressing after 3 - 5 days to villi which sometimes show signs of vertical collapse. After neutron irradiation vertical villous collapse is established earlier, with less swelling of villous tips. It seems, therefore, that at radiobiologically equivalent doses, neutron and X-irradiation produce different levels of surface damage, with neutron irradiation being the more destructive. Early villous tip damage may perhaps be due to disruption of susceptible cells already at the extrusion zone, or to stromal damage.

Animals↗

Lack of correlation between villus and crypt damage in irradiated mouse intestine.

It has been observed that scanning electron microscopy is a more sensitive indicator of mucosal damage at low radiation dose levels than conventional quantitative crypt counting techniques. Three different fractionation schedules were subjected to investigation by both of these methods to try to elucidate some features of irradiation damage to the whole of the intestinal mucosa, at dose levels commonly used in clinical practice. Despite variations in the qualitative observations, there was a marked difference in two of the schedules between damage expressed as crypt counts and that described by the qualitative techniques. In the first case high crypt numbers were associated with severe mucosal damage, whereas the second schedule produced a reduced crypt count in association with low damage to the surface mucosa. A third schedule produced results in which there was a general agreement between low crypt numbers and considerable surface mucosal damage. However, observations were made of mucosal formations not previously seen on damaged mucosal surfaces. These resembled the appearance normally associated with the gut of patients suffering from coeliac disease. Variations in the qualitative observations were seen in all the schedules so that their interpretation in terms of perturbation of cellular kinetics is difficult.

Animals↗

A preliminary study of scanning electron microscopic changes of the duodenum during healing of duodenal ulcers.

Using the scanning electron microscope, changes in the rat duodenum have been studied during the healing of gastric secretagogue-induced duodenal ulcers on the 1st, 3rd, 7th and 10th days post-infustion. A montage technique with fine resolution has allowed both the entire area of the duodenum and the cellular organization in individual villi in proximity to the ulcers to be investigated. There was a considerable range of appearances noted at any one time point due to the variations in the size and depth of the original area of ulceration. On day 1, there was acute destruction of the mucosal surface with distortion of the villi at the ulcer margin. By the 3rd day, some specimens already showed full epithelialization over the defects whereas others up to day 10 revealed persistent areas of ulceration. Occasional specimens showed areas suggestive of gastric surface metaplasia on the villous surface adjacent to these ulcers.

Animals↗

Hypersensitivity reactions in the small intestine. IV. Influence of allograft rejection on small intestinal mucosal architecture: a scanning and transmission electron microscope study.

The effect of a local delayed hypersensitivity reaction (allograft rejection) on small intestinal architecture has been examined by using scanning electron microscopy of the mucosal surface. In isografts, regarded as a morphological basis for normality of the system, the villi appeared normal and finger like. In allografts the appearances ranged from fairly normal areas to others with stunted and ridged villi, and flat areas in which crypt mouths opened on to the flat mucosal surface. The fine structure of epithelial cells was studied further by transmission electron microscopy. There was an apparent reduction in the size of the microvillous border in allografts but no other consistent abnormality. The similarities between this model of allograft rejection, and untreated coeliac disease in man, are highlighted and contrasted with the effects of acute radiation injury on the intestine.

Animals↗