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S Rees

Publications and source records attributed to S Rees.

At least 91 records · Page 5Linked to original sources
PubMed1994

The development of cutaneous afferent pathways in fetal sheep: a structural and functional study.

In this study we have examined the functional and structural development of cutaneous afferent pathways in the fetal sheep hindlimb from 67 to 143 days of gestation. The earliest age at which extracellular discharges could be evoked in dorsal root ganglia and in dorsal horn cells by natural cutaneous stimulation was 75 days. The majority of cells responded to light stroking or indentation of the skin (low threshold) although some cells responded to intense squeezing (high threshold). With increasing gestational age, the majority of cells continued to respond to low threshold stimuli with cells responding to intense mechanical stimuli being recorded less frequently. Dorsal root ganglion cells responding to the cutaneous application of noxious heat (> 45 degrees C) were first observed at 107 days. We have also shown that fibres projecting from dorsal horn cells and presumably entering the spinothalamic tract carry signals at least as far as the mid thoracic spinal cord by 104 days. Ultrastructural studies of the skin revealed bundles of unmyelinated axons located to blood vessels throughout the dermis at 68 days. Innervation of the skin was first observed by silver staining at 75 days when fibres could be seen running along blood vessels in the dermis. With increasing gestational age fibres were seen traversing the dermis to innervate the epidermis as free nerve endings. Wool/hair follicle innervation was first evident at about 100-106 days with only a few follicles being innervated at this age. By 115 days, nerve endings had begun to form circumferential wrappings around follicles and by 134 days lanceolate terminals were observed around the base of the follicles. Biocytin-labelled afferent fibres entered the dorsal horn at 56 days. This initial innervation was sparse but by 76 days there was a marked increase in both the number of afferent fibres entering the dorsal horn and in the extent of their arborisation. Ultrastructural studies revealed that terminals immunoreactive for calcitonin gene-related peptide were present in lamina I as early as 61 days. The period of maximal synaptogenesis and synaptic maturation of this group of terminals appeared to occur between 87-128 days. Therefore the commencement of activation of dorsal horn cells by natural cutaneous stimulation occurs by mid gestation (75 days) in the fetal sheep. This is at the same time or just after peripheral nerves first innervate the skin and about 2 weeks after primary afferent terminals can be identified in the dorsal horn.

Afferent Pathways↗
PubMed1994

The structural and functional development of muscle spindles and their connections in fetal sheep.

In this paper we have studied the structural and functional development of hindlimb muscle receptors and the connections of their afferent fibres in fetal sheep (n = 26) from 67-143 days of gestation (term = 146 days). By recording extracellular discharges in dorsal root ganglia (L7, S1) we have shown that muscle spindle afferents first respond to a ramp-and-hold stretch at mid-gestation (approximately 75 days). Silver-stained preparations of muscle spindles revealed that afferent fibres are just beginning to form annulospiral windings at this age. It therefore appears that the annulospiral formation is not a necessary requirement for the generation of the response. By 87-92 days some receptors had developed a discharge at resting muscle length. Discharges were generally more robust and easier to elicit and static and dynamic components could be identified in the response to stretch. Although static sensitivity was generally low it was more evident than dynamic sensitivity. By 107-115 days it was possible to clearly distinguish between muscle and tendon afferents and to tentatively classify muscle responses as originating from primary or secondary afferent spindle endings. With increasing gestational age there was a progressive increase in the length and complexity of the spindle innervation in parallel with the maturation of functional activity. Biocytin injections into the dorsal root ganglia revealed afferent projections to the motoneuron pools by 67 days. Silver-staining of muscles showed that innervation of extrafusal fibres was also present by this age. We therefore conclude that the neural pathways necessary for reflex activity involving muscle spindles are present and functional from early in gestation and could contribute to early fetal movements.

Afferent Pathways↗
PubMed1994

Morphology of parallel fibres in the cerebellar cortex of the rat: an experimental light and electron microscopic study with biocytin.

Microinjections of biocytin have been made in the granular layer of the rat cerebellar cortex in order to label the axonal projections of a localised population of granule cells. Light microscopic techniques were used to determine the lengths of the parallel fibres and to measure the spacing and size of the fibre varicosities. Fibres were longest in the superficial one-third of the molecular layer, where mean overall length was 4.7 mm, and mean length decreased to 4.2 mm in the lower one-third of the molecular layer. We found no very short fibres but a small population deep in the molecular layer had a branch length of about one-half the average. Mean intervaricosity interval and varicosity size varied with distance from proximal to distal along the fibres. Mean intervaricosity interval was 3.7 microns within 250 microns of the fibre bifurcation points and progressively increased towards the distal ends, where the mean interval was 7.4 microns. Mean varicosity size was 0.82 microns 2 in this proximal region and decreased to 0.47 microns 2 about 1.2 mm distally. Mean intervaricosity interval on the ascending axons of the granule cells was 4.0 microns. Electron microscopy revealed that a high proportion (89%) of the parallel fibre varicosities formed synaptic junctions. The majority of the synapses (91%) were formed on Purkinje cell dendritic spines. Some varicosities also formed simultaneous synaptic contacts or double synapses with two spines. These double synapses occurred more frequently in the proximal region of the fibres (11%) than on the distal ends (2%). The length of the postsynaptic density also differed according to the location of the varicosities and the mean length at the proximal parallel fibre synapses was 0.59 microns compared with 0.38 microns at the distal synapses. It is concluded that a beam or bundle of parallel fibres originating from cells in a focal region of the granular layer will exert a graded synaptic influence on its target Purkinje cells, with the most powerful influence occurring on cells located around the proximal region of the fibres where they bifurcate and the weakest action being exerted on cells located at the distal end of the fibres.

Animals↗
PubMed1994

The ontogeny of [125I]rat-alpha-CGRP binding sites in the spinal cord of sheep: a prenatal and postnatal study.

In this study we describe the ontogeny of [125I]rat-alpha-calcitonin gene-related peptide binding sites in the spinal cord of fetal and postnatal sheep. The density and distribution of binding sites has been compared with the localization of calcitonin gene-related peptide like-immunoreactivity at corresponding stages of development [Nitsos I. and Rees S. (1993) Neuroscience 54, 239-252]. At 68 days of gestation (term = 146 days), the earliest fetal tissue examined, there was no evidence of binding sites in lamina I or the outer regions of lamina II (lamina IIo), although there was a sparse distribution of binding sites in the inner region of lamina II (lamina IIi). By comparison, binding appeared to be more marked in laminae III-V and more concentrated again in laminae VI-X. This distribution essentially remained constant until 124 days, when there appeared to be a marked increase in the density of binding sites throughout the gray matter, particularly in the dorsal horn in the lateral extent of both lamina IIo and IIi as well as in laminae III, V and VI. This increase was also observed in the intermediate zone (lamina VII) and in lamina X. Binding in the ventral horn, which was diffuse until this stage, now became particularly dense in the medial and lateral regions of the horn. From 124 days to one month postnatal, there was no marked change in the density or distribution of binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Magnetic resonance volume flow and jet velocity mapping in aortic coarctation.

OBJECTIVES: Nuclear magnetic resonance (MRI) velocity mapping was used to characterize flow waveforms and to measure volume flow in the ascending and descending thoracic aorta in patients with aortic coarctation and in healthy volunteers. We present the method and discuss the relation between these measurements and aortic narrowing assessed by MRI. Finally, we compare coarctation jet velocity measured by MRI velocity mapping with that obtained from continuous wave Doppler echocardiography. BACKGROUND: The development of a noninvasive imaging method for morphologic visualization of aortic coarctation and for measurement of its impact on blood flow is highly desirable in the preoperative and postoperative management of patients. METHODS: Magnetic resonance imaging phase-shift velocity mapping was used to measure ascending and descending aortic volume flow in 39 patients with aortic coarctation and in 12 healthy volunteers. Magnetic resonance imaging was also used for anatomic and peak jet velocity measurements. The latter were compared with those available from continuous wave Doppler study in 40% of the patients. RESULTS: Whereas ascending aortic volume flow measurement did not show significant differences between the patient and healthy control groups, volume flow curves in the descending aorta did show significant differences between the two groups. Peak volume flow (mean +/- SD) was 10.6 +/- 5.3 liters/min in patients and 19.6 +/- 4.7 liters/min in control subjects (p < 0.001). Time-averaged flow was 2.5 +/- 0.9 liters/min in patients and 3.9 +/- 1.1 liters/min in control subjects (p < 0.05). The descending/ascending aorta flow ratio was 0.47 +/- 0.19 in patients and 0.64 +/- 0.08 in control subjects (p < 0.05). These variables correlate well with the degree of aortic narrowing. Peak coarctation jet velocity measured by MRI velocity mapping is comparable to that obtained from continuous wave Doppler study (r = 0.95). CONCLUSIONS: We established normal ranges for volume flow in the descending aorta and demonstrated abnormalities in patients with aortic coarctation. These abnormalities are likely to be related to resistance to flow imposed by the coarctation and could represent an additional index for monitoring patients before and after intervention.

Adolescent↗
PubMed1993

Development of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the spinal cord of fetal sheep.

In this study we have described the ontogeny of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the sacral spin cord, of fetal sheep (n = 37) from 56 to 140 days of gestation (term = 146 days). A few fine, varicose fibres immunoreactive for calcitonin gene-related peptide were present in Lissauer's tract, the dorsolateral funiculus and in laminae I and V in the dorsal horn of the spinal cord at 56-61 days of gestation. At this age, two groups of intensely staining immunoreactive cells were present in the motoneuron pool in laminae VIII and IX in the ventral horn of the spinal cord. By 77 days, immunoreactive fibres were also present in laminae II and X. With advancing gestational age, an increase in the intensity of staining was observed throughout the cord to term, with the exception of laminae VIII and IX, where a decrease was seen. Intense staining of cells in the motoneuron pool was evident until c. 128 days, after which time staining became very faint. Fine fibers immunoreactive for substance P were present in Lissauer's tract and lamina I of the spinal cord at 56-61 days of gestation. They were also present throughout laminae IV-VI and X as well as throughout the entire ventral horn. Immunoreactive fibres in lamina II were evident by 77 days. The staining increased in density but remained similar in distribution with increasing gestational age to term in the dorsal horn, but decreased markedly in the ventral horn. Cells immunoreactive for substance P were evident from 56 days, particularly on the border of laminae II and III, until late in gestation. Ultrastructural studies showed that axon terminals immunoreactive for calcitonin gene-related peptide and for substance P were present in lamina I by 61 days. Immunoreactivity for glutamate was evident at 83 days in dorsal root fibers and also in lamina I and II, where it was more prominent in cells than in fibres. At all ages examined, the dorsal horn stained more intensely than the ventral horn. Immunoreactivity for glutamate and neuropeptides appeared in the cells and fibres of dorsal root ganglia at 97-100 days. In the skin, immunoreactivity for calcitonin gene-related peptide and substance P was present at 85 days, some time after its appearance in the cord. Fibres immunoreactive for serotonin appeared in lamina I, at the neck of the dorsal horn and in the ventral horn at 83 days of gestation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Skeletal muscle blood flow in heart failure measured by ultrafast computed tomography: validation by comparison with plethysmography.

OBJECTIVES: Abnormalities of skeletal muscle perfusion and metabolism may be important in the symptomatic limitation of patients with chronic heart failure. A method for assessing both skeletal muscle blood flow and mass would be useful in clinical practice and research. Ultrafast computed tomography has the potential to make these measurements. The aim was to determine the accuracy with which skeletal muscle blood flow could be measured by ultrafast computed tomography in patients with chronic heart failure. METHODS: Leg blood flow measured by venous occlusion plethysmography was compared with skeletal muscle blood flow by ultrafast computed tomography. Fourteen patients with chronic heart failure (aged 51 to 76 years) were investigated. Plethysmography and ultrafast computed tomography measurements were performed at rest and during hyperaemic flow induced by symptom limited bicycle exercise followed by five minutes of leg ischaemia. The ultrafast computed tomography measurements were made by analysing the opacification of the blood pool and of the muscle after an intravenous bolus of non-ionic radio-opaque contrast. RESULTS: Flows assessed by plethysmography ranged from 1.5 to 38.1 ml x 100 ml-1 x min-1. The slope of the line relating the two methods was 1.1 (95% confidence interval 0.91 to 1.31), and the mean (95% limits of agreement) of the differences between the two methods was 2.5(10.6) ml x 100 ml-1 x min-1. CONCLUSIONS: Ultrafast computed tomography is a useful tool in the measurement of both skeletal muscle mass and perfusion in humans.

Aged↗
PubMed1992

Obstruction in extracardiac ventriculopulmonary conduits: value of nuclear magnetic resonance imaging with velocity mapping and Doppler echocardiography.

OBJECTIVES: This study was designed to investigate the value of noninvasive imaging modalities for the detection of obstruction in extracardiac ventriculopulmonary conduits. BACKGROUND: the diagnosis of obstruction in a conduit by noninvasive methods can be difficult. Obstruction may be silent and its progression unnoticed. Nuclear magnetic resonance imaging (NMR) with velocity mapping is a new noninvasive technique that can provide high resolution images and has been shown to be a reliable method of measuring blood flow velocity. METHODS: Two-dimensional echocardiography, pulsed wave Doppler echocardiography and NMR spin echo imaging were used in 52 patients with an extracardiac ventriculopulmonary conduit. Continuous wave Doppler echocardiography was used in 30 of these, Doppler color flow mapping in 26 and NMR velocity mapping in 12. Cardiac catheterization data were available in 27 patients and operative or autopsy findings in 11. RESULTS: The conduit could be assessed by two-dimensional and pulsed wave Doppler echocardiography in only 17% of patients. Doppler color flow and continuous wave echocardiography provided technically satisfactory data in 19% and 83%, respectively. The anatomy of the conduit was adequately displayed by NMR imaging in 90%. A minimal diameter less than 18 mm indicated conduit obstruction, although failure to detect calcification resulted in obstruction being missed in some patients. Calculated gradients in obstructed conduits derived from NMR velocity mapping correlated well with results of continuous wave Doppler echocardiography and gave an accurate localization of the site of obstruction as well as a measure of its severity. CONCLUSION: NMR imaging with velocity mapping is the most effective noninvasive method of assessing obstruction in ventriculopulmonary conduits and can obviate the need for invasive investigation before an interventional procedure is performed.

Adult↗
PubMed1992

The structural and neurochemical development of the fetal guinea pig retina and optic nerve in experimental growth retardation.

In this study we have examined structural and neurochemical aspects of retinal and optic nerve development in experimentally growth-retarded fetal guinea pigs following maternal unilateral artery ligation. Eye weight (n = 4) and total retinal area (n = 6) at 62 days gestation (term approximately 66 days) were both relatively spared when expressed as a percentage of body weight but in absolute terms were significantly reduced by 18% (P less than 0.001) and 13% (P less than 0.05) respectively when compared with age-matched controls. The numerical density of neurons in the ganglion cell layer was significantly higher at both 52 days (n = 4) and 62 days (n = 4) in growth-retarded fetuses compared with controls. However, there was no difference between the groups in the total number of neurons in this retinal layer at either age, since retinal areas are reduced in growth retardation. The area of neuronal somata in the ganglion and inner nuclear layers was significantly reduced in growth-retarded fetuses compared with controls. There was a concomitant reduction in the width of the cellular layers in the retina and also in the plexiform (synaptic) and photoreceptor layers. The growth of the outer segments of the photoreceptor layer was particularly affected in peripheral retina. The higher packing density of cells and the reduced growth of the plexiform layers suggests a reduction in the growth of the neuropile in growth-retarded fetuses compared with controls. The radial bundling of ganglion cell axons coursing across the retina to enter the optic nerve head was poorly defined in growth retardation. In addition myelination was delayed in the optic nerve with the numerical density of myelinated axons being significantly reduced (P less than 0.005) in growth-retarded fetuses compared with controls. There was a significant reduction (P less than 0.01) in the number of amacrine cells in the inner plexiform layer expressing Substance P-like immunoreactivity in growth-retarded fetuses compared with controls. Glutamate-like immunoreactivity was most intense in the five laminae of the inner plexiform layer and in the outer plexiform layer and less pronounced in photoreceptors, ganglion cells and their axons. There was no qualitative difference in glutamate immunoreactivity between control and growth-retarded fetuses in any of these structures. Thus we have shown that intrauterine growth retardation has specific effects on the development of the fetal guinea pig retina, reducing the growth of several types of neurons and their processes and affecting the expression of the neuropeptide substance-P in amacrine cells.

Animals↗
PubMed1992

Expression of SV-40 T antigen in the small intestinal epithelium of transgenic mice results in proliferative changes in the crypt and reentry of villus-associated enterocytes into the cell cycle but has no apparent effect on cellular differentiation programs and does not cause neoplastic transformation.

The mouse intestinal epithelium represents a unique mammalian system for examining the relationship between cell division, commitment, and differentiation. Proliferation and differentiation are rapid, perpetual, and spatially well-organized processes that occur along the crypt-to-villus axis and involve clearly defined cell lineages derived from a common multipotent stem cell located near the base of each crypt. Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene were used to establish three pedigrees of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells situated in the uppermost portion of small intestinal crypts and in already committed, differentiating enterocytes as they exited these crypts and migrated up the villus. T antigen production was associated with increases in crypt cell proliferation but had no apparent effect on commitment to differentiate along enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel-immunocytochemical studies plus RNA blot hybridization analyses suggested that the differentiation programs of these lineages were similar in transgenic mice and their normal littermates. This included enterocytes which, based on the pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating nuclear antigen expression, had reentered the cell cycle during their migration up the villus. The state of cellular differentiation and/or TAg production appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase to M-phase cells (collected by metaphase arrest with vincristine) and of the intensities of labeling of nuclei by [3H]thymidine indicated that the duration of S phase was longer in differentiating, villus-associated enterocytes than in the less well-differentiated crypt epithelial cell population and that there may be a block at the G2/M boundary. Sustained increases in crypt and villus epithelial cell proliferation over a 9-mo period were not associated with the development of gut neoplasms--suggesting that tumorigenesis in the intestine may require that the initiated cell have many of the properties of the gut stem cell including functional anchorage.

Animals↗
PubMed1991

Prenatal development of cutaneous afferent connections in the spinal cord of fetal sheep. A physiological and neurochemical study.

In this study we have examined the physiological and neurochemical development of the cutaneous afferent pathways from the hindlimb to the spinal cord in fetal sheep. We have shown that somatosensory input from the hindlimb evokes activity in DRG neurons at 87d gestation and in cells in the dorsal horn at 92d (term, 146d). There is evidence of immunoreactivity for substance P, calcitonin gene-related peptide and glutamine several days prior to this at 77-80 days. The implication of these findings are discussed.

Afferent Pathways↗
PubMed1991

Growth retardation and the development of the respiratory system in fetal sheep.

In an experimental model of fetal growth retardation which involves the reduction of placental mass in ewes, we have investigated the effects of intrauterine deprivation on aspects of structural development of the trachea and lungs of fetal sheep (140 days gestation). We have also measured the volume of luminal liquid aspirated from the lungs and the phospholipid content of this liquid as an index of pulmonary surfactant production. The effects of growth retardation are evident in the trachea where the structural development of the mucosal and submucosal layers has been affected. Abnormal aspects of development include the frequent lack of a ciliated border on epithelial cells in the mucosal layer and the reduction in the extent of the folds usually characteristic of this layer in near term fetal sheep. Although the fetal lungs are smaller in growth retardation (P less than 0.01) they are appropriate for fetal weight and their structural development does not appear to have been retarded. In contrast, lung liquid volume is significantly reduced in relation to lung weight in growth retarded fetuses and the concentration of phospholipids in lung liquids is also reduced (P less than 0.01).

Animals↗
PubMed1991

Basic FGF and TGF-beta 1 influence commitment to melanogenesis in neural crest-derived cells of avian embryos.

In previous studies, we showed that neural crest (NC)-derived cells from embryonic quail dorsal root ganglia (DRG) and peripheral nerve (PN), which do not normally give rise to melanocytes, become committed to melanogenesis following treatment in culture with the phorbol ester drug 12-O-tetradecanoyl phorbol-13-acetate (TPA). These and other observations support the notion that melanocytes and Schwann cells are derived from a common bipotent intermediate in the neural crest lineage--the melanocyte/Schwann cell progenitor. In this study, we test the possibility that peptide growth factors found in the embryonic environment might act similarly to TPA to influence the fates of these cells. DRG and PN explants were cultured in medium supplemented with a variety of growth factors, and then the cultures were examined for the presence of pigment cells. We found that basic fibroblast growth factor (bFGF), but not various other growth factors, induced pigmentation in about 20% of these cultures. When low concentrations of TPA were included in the culture medium, bFGF augmented the TPA-induced pigmentation, significantly increasing the proportion of pigmented cultures. These effects of bFGF were age-dependent, and could be blocked by addition of a bFGF-neutralizing antibody to the culture medium. In contrast to these stimulatory effects of bFGF, transforming growth factor-beta 1 (TGF-beta 1) was found to inhibit the TPA- or bFGF-induced pigmentation of DRG cultures. These data suggest, therefore, that at least some NC-derived cells are responsive to bFGF and TGF-beta 1, and that these growth factors may play an important role in the control of NC cell fate.

Animals↗