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Biomedical subjects

R G Williams

Publications and source records attributed to R G Williams.

At least 127 records · Page 7Linked to original sources
PubMed1984

Immunoreactive Met-enkephalin Arg6 in rat brain, and bovine brain, gut, and adrenal.

Antibodies directed against the Met-enkephalin-related hexapeptide, Met-enk Arg6, have been used in radioimmunoassays in the characterization of material in rat brain, and bovine striatum, colon, and adrenal medulla. Met-enk Lys6 reacted 0.27 relative to Met-enk Arg6, but Leu-enk Arg6 and C-terminal extensions or deletions of Met-enk Arg6 showed less than 0.02 immunoreactivity. In rat brain, the concentration of Met-enk Arg6-like immunoreactivity was less than 20 pmol X g-1 in all regions, but after trypsinization of tissue extracts there were up to 80-fold increases in immunoreactivity as a result of cleavage of C-terminally extended forms. The tryptic product eluted as Met-enk Arg6 on gel filtration. In control extracts of rat brain there were at least three immunoreactive forms of Met-enk Arg6; one eluted in the position of the hexapeptide standard on gel filtration and HPLC while the others had properties of N-terminally extended forms. In bovine striatum and colon the hexapeptide-like material predominated; but in bovine adrenal extracts, there were relatively low concentrations of the hexapeptide and, instead, the dominant immunoreactive forms corresponded to two components that were probably N-terminally extended variants. Trypsin again produced marked increases in immunoreactivity. HPLC studies indicated that Met-enk Arg6Phe7- and Met-enk Arg6Gly7Leu8-like immunoreactive peptides were important substrates in bovine brain for the production of hexapeptide immunoreactivity after trypsin. The differences in the patterns of immunoreactive forms in bovine adrenal, colon, and brain are consistent with tissue variations in the pathways of posttranslational processing of the precursor molecules.

Adrenal Glands↗
PubMed1984

Systemic venous and pulmonary arterial flow patterns after Fontan's procedure for tricuspid atresia or single ventricle.

Despite increasing use of Fontan or modified Fontan repairs, the comparative hemodynamic efficacy of different types of connections are unresolved. Accordingly, we undertook a prospective study designed to determine postoperative flow patterns after Fontan's operation. Seven subjects had tricuspid atresia and eight had single ventricle. Ages ranged from 5 to 38 years (mean 16.4). Ten subjects had nonvalved right atrial-to-pulmonary arterial connection, and four had nonvalved right atrial-to-right ventricular communication. A valved conduit established continuity between the right atrium and right ventricle in one subject. Doppler flow profiles were recorded in the pulmonary artery and in the superior and inferior venae cavae of each. A reference electrocardiogram was used for timing purposes. In 14 patients, forward flow in the pulmonary artery was biphasic. Flow began at the end of the T wave (early ventricular diastole), peaked at or before the P wave (atrial systole), and returned to baseline by the peak of the R wave. Forward flow recommenced at the peak of the R wave (ventricular systole) and returned to baseline at the end of the T wave. Flow in the superior vena cava varied, and could not be recorded in three subjects. Between the end of the P wave and peak of the R wave (atrial systole) flow was reversed in eight, absent in three, and forward in one patient. Forward flow occurred between the peak of the R wave and the end of the T wave and was either continuous or biphasic. Fourteen patients had adequate studies of inferior vena cava flow; reversed flow during atrial systole occurred in 10 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Mechanisms of cardiac supersensitivity to sympathomimetic amines.

Supersensitivity of the beta-adrenoceptor-mediated positive inotropic and chronotropic responses of the heart to sympathomimetic amines is considered. The various types of supersensitivity of both pre- and post-synaptic origins are described and the possible mechanisms involved are discussed. Emphasis is given to the supersensitivity that arises from depletion of sympathetic catecholamine stores by reserpine and 6-hydroxydopamine. Results are presented which indicate that in both cases the supersensitivity develops slowly, is specific for the beta-adrenoceptor and is not associated with an increase in affinity of agonists for the receptor. Radioligand binding data is presented to show that there is no increase in the total number of beta-adrenoceptor binding sites in membrane fractions from ventricular homogenates of animals receiving reserpine. A review of the literature on binding studies indicates two opposing views with respect to the effects of reserpine on beta-adrenoceptor binding sites, one showing no change and the other showing an increase in total binding sites. Limited studies in the literature show that 6-hydroxydopamine may increase the number of sites. Binding data therefore remains inconclusive and must be interpreted with caution. The relationship between the development of depletion-induced supersensitivity and the innervation of the tissue and its receptor type is discussed.

Animals↗
PubMed1984

Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin-sensitive sensory neurons in the rat by combined immunohistochemistry and retrograde tracing.

The sensory innervation of the stomach and pancreas has been identified by retrograde tracing using the fluorescent dye True Blue (Illing, Gross-Umstadt, Federal Republic of Germany), coupled with the immunohistochemical localization of substance P. Labeled cells were visualized in spinal ganglia, nodose ganglia, celiac ganglion, and dorsal motor nucleus of the vagus after injection of True Blue into both stomach and pancreas. Substance P immunoreactivity was found in 35%-50% of gastric spinal afferent neurons and in approximately 15% of pancreatic spinal afferents. In rats treated at birth with the sensory neurotoxin capsaicin there was a reduction of about 70% in True Blue-labeled cells in the spinal and nodose ganglia, and virtually complete loss of substance P in these ganglia. There was also a marked depletion of substance P-immunoreactive fibers in the pancreas, and in the submucosa of the stomach. The results suggest that the substance P-containing spinal afferents that project to the gastric submucosa are an important component of the gastric sensory innervation.

Animals↗
PubMed1984

Experience with the Fontan procedure.

From 1975 to the present, 45 patients have undergone modifications of the Fontan procedure for complex congenital heart disease. There were 30 males and 15 females ranging in age from 2 to 38 years (mean 13 years). Primary diagnoses were tricuspid atresia in 19, univentricular heart in 24, and pulmonary atresia with intact ventricular septum in two. Right atrial-pulmonary arterial connections were performed in 32 patients, 11 with conduits (seven with valves and four without) and 21 by direct anastomosis with patch augmentation. Right atrial-right ventricular connections were made in 13 patients, six with valved conduits and seven without conduits. Follow-up ranged from 0.1 to 9 years, with a mean of 2.3 years. There were three early deaths (less than 30 days) (7%) and two late deaths (5%) in this series, all in patients with a univentricular heart. The late deaths were both related to venous hypertension. A venous assist device was used in eight patients in the immediate postoperative period and was effective in improving cardiac output and reducing fluid accumulation. Postoperative Doppler flow studies in 15 patients revealed biphasic pulmonary artery flow in all without distinction between the type of connection or the presence of a valve. Cardiac catheterization was performed in 16 patients a mean of 14 months postoperatively (range 1 to 42 months) and revealed a reduced cardiac index at rest. Exercise testing in eight patients demonstrated a marked rise in right atrial pressure with a reduced rise in the cardiac index, even in those without functional limitations. With a mean follow-up of 2.3 years, 78% of patients were in New York Heart Association Class I, 17% in Class II, and 5% in Class III. We conclude that the Fontan procedure is an excellent operation in carefully selected patients with tricuspid atresia and other forms of complex congenital heart disease.

Adolescent↗
PubMed1983

Extrinsic innervation of the rat pancreas: demonstration of vagal sensory neurones in the rat by retrograde tracing.

The extrinsic innervation of the rat pancreas was examined using retrograde tracing with the fluorescent dye True Blue. Retrogradely-labelled cell bodies were seen bilaterally in the nodose ganglia, and in the spinal ganglia at levels T6-L2. Labelled cells were also seen in the dorsal motor nucleus of the vagus, the nucleus ambiguus and the coeliac ganglion. Our results provide new and direct evidence for a vagal sensory innervation of the pancreas.

Animals↗
PubMed1983

Immunohistochemical studies of FMRF-amide-like immunoreactivity in rat brain.

The anatomical distribution of neuronal perikarya and nerve fibres containing FMRF-amide-like immunoreactivity in the brain, spinal cord and pituitary of the rat has been studied by immunohistochemistry. In animals pretreated with colchicine, the highest concentration of nerve cell bodies occurred in hypothalamic nuclei. Cells were also present in the cortex, striatum, septum, thalamus and in the brainstem. Beaded nerve fibres were abundant in the septum, nucleus of the striae terminalis, hypothalamus, medial regions of the thalamus, the parabrachial nucleus, the ventrolateral medulla, the substantia gelatinosa of the spinal trigeminal nucleus and the dorsal horn of the spinal cord. Fibres were also present in the cortex, striatum, amygdala, pons, ventral spinal cord and the neural lobe of the pituitary. The localization was specific in that preabsorbtion of the antisera with FMRF-amide, but not structurally related molecules such as Met-Enk-Arg6Phe7, APP or BPP, completely abolished the localization. The mammalian counterparts of FMRF-amide may have a neurotransmitter or neuromodulatory role.

Animals↗
PubMed1983

FMRFamide-like immunoreactivity in rat brain: development of a radioimmunoassay and its application in studies of distribution and chromatographic properties.

A radioimmunoassay is described for the molluscan neuropeptide, Phe-Met-Arg-Phe-NH2 (FMRFamide). The antibody used is C-terminal-specific and shows slight but significant (1-2%) cross-reactivity with chicken pancreatic polypeptide (APP). The assay has been used to identify in rat brain extracts a pair of molecules that may represent mammalian counterparts of FMRFamide. Their concentrations were highest in spinal cord and hypothalamus (greater than 10 pmol . g-1) and lowest in cerebellum and striatum (less than 3.5 pmol . g-1). The two immunoreactive peptides were separated on CM ion-exchange chromatography where they appeared to be less basic than FMRFamide. On Sephadex G50 gel filtration one eluted in a similar position of FMRFamide and the other slightly earlier suggesting it may be of higher molecular weight. The rat immunoreactive components do not correspond to previously described neuropeptides or hormones, and may be members of a new group of mammalian neuropeptides with transmitter or modulatory functions.

Animals↗
PubMed1983

Measurement of systemic and pulmonary blood flow and QP/QS ratio using Doppler and two-dimensional echocardiography.

A noninvasive method for measuring systemic and pulmonary blood flow using Doppler velocimetry combined with 2-dimensional (2-D) echocardiography has been developed. High correlations were found between Fick- and Doppler-derived indexed measurements of systemic and pulmonary flow as well as the pulmonary to systemic flow ratio in 33 patients undergoing cardiac catheterization (systemic flow [n = 28], r = 0.78; pulmonary flow [n = 21], r = 0.88; Qp/Qs ratio [n = 24], r = 0.85). The random errors of the 2 methods were not significantly different. Outflow tract obstruction, semilunar valve regurgitation, and patent ductus arteriosus were the only lesions in which limitations to the use of this method were encountered. We anticipate that this method will be of use in initial and serial evaluations of adult and pediatric patients with low cardiac output or intracardiac shunts.

Adolescent↗
PubMed1983

Determination of agonist affinity for cardiac beta-adrenoceptors during reserpine-induced supersensitivity.

The positive inotropic responses to orciprenaline of paced left atria and papillary muscles and the positive chronotropic responses of spontaneously beating right atria of guinea-pigs were recorded. Tissues from guinea-pigs pretreated with reserpine exhibited supersensitivity to beta-adrenoceptor stimulation as demonstrated by the significantly lower EC50 values to orciprenaline. The antagonism of these responses by Ro 03-7894 was characteristic of irreversible beta-adrenoceptor blockade--depression of maximum response and resistant to washout. The dissociation constants (KA) of orciprenaline were determined from the concentration-response curves obtained before and after Ro 03-7894, and no difference was found between tissues from untreated and reserpine-pretreated animals. KA values were also determined from the functional antagonism of the responses by carbachol. The degree of antagonism was less after reserpine pretreatment, but there was no increase in KA value. The reserpine-induced supersensitivity does not therefore appear to be due to an increase in agonist affinity for the cardiac beta-adrenoceptor.

Adrenergic beta-Agonists↗
PubMed1983

Noninvasive tests in the initial evaluation of heart murmurs in children.

We prospectively examined the usefulness of electrocardiography, chest radiography, and M-mode echocardiography in discriminating between the presence and absence of heart disease in 280 children older than one month and newly referred for evaluation of a heart murmur. After taking a history and performing a physical examination but before reviewing diagnostic tests, we categorized the children as having "no heart disease" (142), "possible heart disease" (34), or "definite heart disease" (104). Among the children initially thought to have no heart disease, the diagnosis was changed after a review of diagnostic tests in eight--three with mitral-valve prolapse, two with possible cardiomyopathy, and three with no heart disease on follow-up. Among those initially thought to have possible heart disease, the tests changed the diagnosis to definite heart disease in four, of whom only one had heart disease (mitral-valve prolapse) on follow-up. In no case did a review of tests change the diagnosis of definite heart disease. We conclude that the results of diagnostic tests are unlikely to change the clinical diagnosis of no heart disease or definite heart disease, when made by a qualified pediatric cardiologist in children newly referred for evaluation of a heart murmur.

Adolescent↗
PubMed1983

Two-dimensional echocardiographic assessment of caval and pulmonary venous pathways after the senning operation.

This study reports the 2-dimensional echocardiographic appearance of the caval and pulmonary venous pathways after the Senning procedure in 28 patients and establishes normal values for the caval and pulmonary venous pathway dimensions. Eighteen patients had no caval or pulmonary venous obstruction or tricuspid regurgitation at catheterization; 2 had isolated superior vena caval obstruction, 3 had isolated pulmonary venous obstruction, 4 patients had severe tricuspid regurgitation, and 1 had a large residual ventricular septal defect. The caval and pulmonary venous pathways were imaged in modified 4-chamber and transverse views, and the narrowest dimension of each pathway in each view was measured by 2 independent observers. Dimension measurements were then normalized to the cube root of body surface area. Caval and pulmonary venous pathway "dimension products" were obtained by multiplying the normalized dimension in the 4-chamber view by the normalized dimension in the transverse view. All patients with catheterization-proven caval or pulmonary venous obstruction or tricuspid regurgitation had caval or pulmonary venous pathway dimension products outside the normal range, defined by our measurements in the 18 patients with no caval or pulmonary venous obstruction or tricuspid regurgitation. Thus, 2-dimensional echocardiography can provide both quantitative and qualitative information about the caval and pulmonary venous pathways after the Senning procedure.

Child↗
PubMed1983

2-dimensional echocardiographic appearance of complete left-sided juxtaposition of the atrial appendages.

This report describes the 2-dimensional (2-D) echocardiographic appearance of left-sided juxtaposition of the atrial appendages (JAA). From January 1, 1978, to June 30, 1979, 2 infants had the diagnosis of left-sided JAA at autopsy. Both patients had previously been examined by subxiphoid 2-D echocardiography. On review of these studies, the septum secundum was found to be oriented posteriorly in the transverse view of the atria. From July 1979 to June 1981, prospective evaluation of all infants for the presence of this finding revealed 2 more patients. Left-sided JAA was confirmed at surgery in 1 case and by selective right atrial angiography in the other. The diagnosis of left-sided JAA has important implications for both atrial baffle operations and for the Fontan procedure.

Echocardiography↗
PubMed1983

Subxyphoid 2-dimensional echocardiographic identification of left ventricular papillary muscle anomalies in complete common atrioventricular canal.

Mitral valve dysfunction is probably the major cause of operative mortality from total repair of complete common atrioventricular (AV) canal in infancy. The presence of a solitary left ventricular (LV) papillary muscle appears to be 1 anatomic factor influencing the success of mitral reconstruction because suturing of the cleft between the superior and inferior components of the anterior mitral leaflet creates a parachute mitral valve deformity, which may result in stenosis or in unduly high tension on the components of the repair. This study reports on (1) the 2-dimensional (2-D) echocardiographic appearance of the LV papillary muscle architecture in patients with complete common AV canal compared with that in normal subjects, and (2) the incidence of solitary LV papillary muscle in patients with complete common AV canal. Two-dimensional echocardiography was performed in 31 infants with complete common AV canal, 14 normal infants, and 9 infants with a large ventricular septal defect not involving the AV canal region. Of 31 infants with complete common AV canal, 26 (80%) had 2 LV papillary muscles on 2-D echocardiography, 3 (10%) had 3 LV papillary muscles, and 3 (10%) had 1 LV papillary muscle. In patients with 2 LV papillary muscles, the anterolateral papillary muscle was displaced posteriorly compared with that in normal subjects and in patients with ventricular septal defect, whereas the posteromedial papillary muscle was in its normal location. Among the 25 patients with complete common AV canal with 2 LV papillary muscles, there was 1 operative death. Among the 6 infants with complete common AV canal with LV papillary muscle anomalies, 5 underwent surgical repair with 4 early deaths. Subxyphoid 2-D echocardiography is a useful technique for evaluating LV papillary muscle architecture in complete common AV canal and permits identification of patients who may be at higher risk for unsuccessful mitral reconstruction.

Echocardiography↗
PubMed1983

Regional differences in the development of cholecystokinin-like activity in rat brain.

The postnatal development of cholecystokinin (CCK) in rat brain was studied by radioimmunoassay and bioassay of tissue extracts. Marked differences were found in the patterns of development in different regions of the brain. In the cerebellum and brainstem of newborn rats the concentrations of CCK8-like immunoreactivity were 40-100% those in adults, whereas in more rostral regions the concentrations were 1-10% of those in adults. Between 0 and 14 days in concentrations of CCK-like activity measured by radioimmunoassay increased up to 30-fold in hypothalamus, cortex and olfactory bulb; in the cortex there were further increases up to 42 days. Cortical CCK was also measured by bioassay on rabbit gall bladder in vitro; bioactivity was identified in foetuses, and after birth showed a similar pattern of increase to that measured by radioimmunoassay. Immunoreactive material in extracts of neonatal cerebellum, brainstem and cortex was identified as CCK8 on the basis of cross-reactivity with different antisera, and chromatographic properties on gel filtration. The results raise the possibility of different rates of maturation of central CCKergic systems.

Animals↗
PubMed1983

Distribution of enkephalin-related peptides in rat brain: immunohistochemical studies using antisera to met-enkephalin and met-enkephalin Arg6Phe7.

The enkephalin-related heptapeptide, Tyr-Gly-Gly-Phe-Met-Arg-Phe, forms the C-terminus of a biosynthetic precursor that contains both Met-enkephalin and Leu-enkephalin sequences. We have studied the distribution of heptapeptide-like immunoreactivity in rat brain by immunohistochemistry using a C-terminal specific antiserum. The results were compared with those obtained using an antiserum specific for the C-terminus of Met-enkephalin which does not react with C-terminally-extended variants. Both antisera specifically stained cell bodies and fibres in many regions of the rat central nervous system. Colchicine was needed for the demonstration of cell bodies with the Met-enkephalin antiserum, but not for the heptapeptide antiserum. In the nucleus of the solitary tract, in the commissural nucleus, the nucleus raphe obscurus and in the hypothalamus, studies of serial sections and re-staining experiments indicated that the two antisera stained the same cell bodies. However, in the olfactory bulb, the anterior olfactory nucleus, the olfactory tubercle, the nucleus accumbens, caudate-putamen, central nucleus of the amygdala, nucleus interstitialis striae terminalis, pre-lateral mamillary nuclei, ventral hypothalamus, hippocampus, peri-aqueductal grey and the granular layer of the cerebellum, cells were stained by the heptapeptide antiserum but not the Met-enkephalin antiserum. The two antisera revealed similar patterns of staining of nerve fibres in many regions including hypothalamus, central nucleus of the amygdala, lateral septum, thalamus, mid-brain and spinal cord. But in other areas notably, pallidum, caudate-putamen, substantia inominata, nucleus of the solitary tract and commissural nucleus, there were abundant fibres and terminals revealed by the Met-enkephalin antiserum but not by the heptapeptide antiserum. The results are discussed with respect to possible patterns of enkephalin biosynthesis; it is suggested that in some neurones immunoreactive enkephalin precursors terminating in the heptapeptide sequence are processed to produce the heptapeptide which is stored in terminals and is available for release as an endogenous opioid agonist in its own right. In other cases, however, it is suggested that the heptapeptide might be cleaved by removal of -Arg-Phe to yield Met-enkephalin which is the primary opioid product of this class of neurone.

Animals↗
PubMed1983

Sensory substance P-innervation of the urinary bladder: possible site of action of capsaicin in causing urine retention in rats.

In rats treated neonatally with capsaicin there is, in later life, a tendency tendency towards urine retention. Since capsaicin is known to cause irreversible loss of certain primary sensory neurons, notably those containing substance P, we have studied the sensory innervation of the bladder in capsaicin-treated and control rats using retrograde tracing methods and immunohistochemistry; in addition, the motor function of the bladder was assessed in in vitro experiments, using electrical field stimulation. Five days after injection of the fluorescent tracer True Blue into the wall of the bladder, numerous labelled cells were identified in dorsal root ganglia T13, L1, L2, L6, and S1 and smaller numbers of cells were found in T12 and L3. In capsaicin-treated rats the numbers of labelled cells were reduced by over 50% in L1, L6 and S1. In control rats, 10-16% of True Blue labelled cells also contained substance P as demonstrated by indirect immunofluorescence, but in capsaicin-treated rats substance P cells were virtually absent. In in vitro studies, contractions of the detrusor muscle to electrical field stimulation, both before and after atropine, were similar in control and capsaicin-treated rats. We suggest that capsaicin causes urine retention in rats due to an impairment of sensory transmission from the bladder (that could involve substance P) and a consequent failure in the normal micturition reflexes.

Animals↗