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Biomedical subjects

J F Morrison

Publications and source records attributed to J F Morrison.

At least 109 records · Page 6Linked to original sources
PubMed1987

The effects of beta-adrenoceptor blockade on breathing during progressive exercise in normal man.

1 We have studied the effects of single oral doses of 80 mg propranolol and 100 mg atenolol on breathing during progressive exercise in nine healthy men in a double-blind, placebo-controlled experiment. As judged by their effects on exercise heart rate significant levels of beta-adrenoceptor blockade were achieved. 2 At the two lower levels of work rate (50 watts and 100 watts) minute ventilation on atenolol was lower than on placebo while at the highest level of work (200 watts) minute ventilation was higher on atenolol than on placebo. The regression of VE atenolol on VE placebo was 1.28 which is significantly different from unity (P less than 0.001). The results with propranolol were more scattered and failed to reach the 5% level of significance. 3 Effects on the pattern of breathing are small but when minute ventilation is matched with placebo, atenolol results in larger tidal volumes and prolonged inspiratory and expiratory time. 4 These observations are discussed in relation to other work in the literature.

Adrenergic beta-Antagonists↗
PubMed1987

Pressure and prolapse--the cause of solitary rectal ulceration.

The cause of solitary rectal ulceration has been investigated using a method that radiologically visualises rectal voiding whilst simultaneously measuring intrarectal pressure and external anal sphincter electromyographic activity. Control subjects and patients with the solitary rectal ulcer syndrome, both with and without mucosal ulceration, have been studied. A high incidence of rectal prolapse (94%) was present in the patients who voided. Overactivity of the anal sphincter during evacuation contributed to the fact that patients with mucosal ulceration required higher intrarectal pressures to void than the controls and the patients without mucosal ulceration. The results indicate that a combination of rectal prolapse and a high voiding pressure may act to cause the mucosal ulceration in this syndrome by exposing the rectal wall to a high transmural pressure gradient.

Adult↗
PubMed1986

Electrophysiological evidence for an excitatory projection from ventromedial forebrain structures on to raphe- and reticulo-spinal neurones in the rat.

Spinally projecting neurones in nucleus raphe magnus (NRM) and the adjacent reticular formation of the medulla were identified by their antidromic responses to electrical stimulation in the lumbosacral spinal cord. Identified raphe-spinal and reticulo-spinal neurones were then tested for the effects of electrical stimulation at sites in the ventromedial forebrain, including the anterior hypothalamus and preoptic area (AH/POA). The results of these experiments have demonstrated that a considerable proportion of raphe- and reticulo-spinal neurones receive an excitatory input from the AH/POA. It is suggested that activity in this descending pathway might contribute to the inhibitory effects of AH/POA stimulation on the nociceptor-evoked activities of spinal dorsal horn neurones.

Animals↗
PubMed1986

Mechanism of inhibition of dihydrofolate reductases from bacterial and vertebrate sources by various classes of folate analogues.

Different classes of folate analogues have been examined with respect to the mechanism of their inhibition of dihydrofolate reductases from Escherichia coli and chicken liver. In addition, the degree of synergism between the binding of these compounds and NADPH has been investigated. Methotrexate acts as a slow, tight-binding inhibitor of both enzymes whereas trimethoprim is a slow, tight-binding inhibitor of the enzyme from E. coli and a classical inhibitor of the chicken-liver enzyme. Pyrimethamine, 2,4-diamino-6,7-dimethylpteridine, a phenyltriazine, folate and folinate exhibit classical inhibition. The degree of synergism between the binding of NADPH and the inhibitor varied from low for pyrimethamine and folate to very large for the phenyltriazine which binds to the chicken-liver enzyme almost 50 000-times more tightly in the presence of NADPH. The degree of synergism is reflected in the type of inhibition that the folate analogues yield with respect to NADPH. Compounds which exhibit slight synergism give noncompetitive inhibition whereas those with a high degree of synergism yield uncompetitive inhibition. With the exception of folinate, all compounds that act as classical inhibitors give rise to competitive inhibition with respect to dihydrofolate. Folinate exhibits competitive inhibition against NADPH and noncompetitive inhibition against dihydrofolate. These results are consistent with the formation of an enzyme-dihydrofolate-folinate complex. The (6S, alphaS)-diastereoisomer of folinate was bound at least 1000-times more tightly than the (6R, alphaS)-diastereoisomer. Consideration has been given to the possible interactions that occur between residues on the enzyme and groups on the inhibitor that give rise to slow-binding inhibition.

Animals↗
PubMed1986

The role of pelvic floor denervation in the aetiology of idiopathic faecal incontinence.

Weakness of the muscles of the pelvic floor and external anal sphincter may in theory be caused by a traction injury to the pelvic nerves incurred as a result of the excessive perineal descent that accompanies straining in the descending perineum syndrome (DPS). To investigate the role of this weakness in the aetiology of idiopathic faecal incontinence (IFI), measurements of perineal position, puborectalis mean fibre density (MFD), anal canal pressures, rectal sensation, capacity, and compliance were made in continent (DPS alone, n = 20) and incontinent (DPS + I, n = 19) patients with DPS, and a group of age and sex matched control subjects (n = 20). Perineal descent on straining was greater in DPS alone than in DPS + I. Puborectalis MFD was raised by similar degree in both DPS groups compared with the control subjects, and external anal sphincter function, assessed as voluntary squeeze pressure, was impaired by similar degree in DPS + I and DPS alone compared with the control subjects. Maximal basal anal canal pressure and rectal compliance were significantly reduced in DPS + I compared with DPS alone and the control subjects. Thus IFI did not result from progression of neurogenic muscle weakness, but occurred when there was also diminished internal anal sphincter tone and reduced rectal compliance.

Aged↗
PubMed1986

A VIP/PHI-containing pathway links urinary bladder and sacral spinal cord.

Nerve fibres containing VIP and the co-produced PHI are found in the dorsal horn and autonomic centres of the sacral spinal cord and in pelvic organs. We have investigated the origin of these nerve fibres and a possible peptide-containing pathway linking pelvic viscera with the spinal cord of the cat and rat using neurochemical and neurosurgical procedures, retrograde tracing and immunocytochemistry. Cell bodies were located in the dorsal root ganglia (after colchicine injection), pelvic ganglia and bladder wall. Capsaicin treatment induced a loss of VIP/PHI from the dorsal horn. Retrograde tracing from the bladder revealed True Blue labelled cells in the dorsal root ganglia (L6, S1), parasympathetic nuclei and pelvic ganglia. Labelled cells were sequentially immunostained for VIP/PHI which were numerous in pelvic ganglia and scattered and weak in dorsal root ganglia. Pelvic nerve section induced a decrease of VIP/PHI immunoreactivity from the spinal cord and no change or a minimal increase in immunoreactive nerve fibers of the bladder. Thus pelvic visceral afferents with cell bodies in the dorsal root ganglia are a significant source of VIP/PHI-containing fibres in the sacral dorsal horn.

Afferent Pathways↗
PubMed1986

Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry.

The innervation of rat and guinea pig urinary tract was examined using immunohistochemistry, radioimmunoassay and True Blue retrograde tracing techniques and was further assessed following both surgical and chemical denervation experiments. Substantial amounts of calcitonin gene-related peptide-like immunoreactivity (range 20-150 pmol/g) were detected in tissue extracts and localised to nerve fibres distributed throughout the urinary tract of both species, these being concentrated in the ureter and base of the bladder. In the guinea pig, the number and distribution pattern of calcitonin gene-related peptide-like immunoreactive nerves appeared to be identical to that of substance P-containing nerves, whereas in the rat the former predominated. Seven days after injection of the fluorescent dye True Blue into tissues of the urinary tract, retrogradely labelled cells were found in the dorsal root ganglia. These cells had a segmental distribution pattern which was specific for each of the injection sites. Thus, after injection of True Blue into the left kidney hilum a single group of labelled cells were found in the ipsilateral T10-L2 dorsal root ganglia. In contrast, injection into the left ureter produced labelled cells in two separate groups of ipsilateral ganglia (T11-L3 and L6-S1). Injection into the wall of the bladder and upper urethra resulted in bilateral labelling, with most labelled cells occurring in L6 and S1 ganglia. Approximately 90% of labelled cells in T10-L3 dorsal root ganglia displayed calcitonin gene-related peptide-like immunoreactivity, but only 60% of retrogradely labelled bladder neurons in L6-S1 ganglia were immunoreactive for this peptide. Adult guinea pigs and neonatal rats injected systemically with capsaicin subsequently exhibited a marked reduction both in the amount of calcitonin gene-related peptide immunostaining and the concentration of immunoreactive material in the urinary tract, dorsal root ganglia and spinal cord. In rats treated neonatally with capsaicin, there was a significant reduction in the number of retrogradely labelled cells and a hypertrophy of the bladder. Sectioning of the pelvic and hypogastric nerves in the rat also resulted in a depletion of calcitonin gene-related peptide-like immunoreactive nerves in the bladder, whereas chemical sympathectomy appeared to have no effect. The results indicate that calcitonin gene-related peptide immunoreactivity occurs in a major proportion of afferent neurons supplying the urinary tract of the rat and guinea pig.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Chorismate mutase-prephenate dehydrogenase from Escherichia coli: positive cooperativity with substrates and inhibitors.

Investigations have been made at pH 6.0 of the effect of chorismate and adamantane derivatives on the mutase and dehydrogenase activities of hydroxyphenylpyruvate synthase from Escherichia coli. When used over a wide range of concentrations, chorismate 5,6-epoxide, chorismate 5,6-diol, adamantane-1,3-diacetate, adamantane-1-acetate, adamantane-1-carboxylate, and adamantane-1-phosphonate give rise to nonlinear plots of the reciprocal of the initial velocity of each reaction as a function of the inhibitor concentration. The inhibitors do not induce the enzyme to undergo polymerization and have only a small effect on the S20,w value of the enzyme as determined by using sucrose density gradient centrifugation. At low substrate concentration, low concentrations of adamantane-1-acetate cause activation of both the mutase and dehydrogenase activities while at higher concentrations this compound functions as an inhibitor. When chorismate and prephenate are varied over a wide range of concentrations, double-reciprocal plots of the data indicate that the reactions exhibit positive cooperativity. The addition of albumin eliminates the cooperative interactions associated with substrates but has little effect on those associated with inhibitors.

Adamantane↗
PubMed1985

Electrically evoked activity in the human external anal sphincter.

Following electrical stimulation of perianal skin, short latency evoked electromyographic (EMG) responses from the external and sphincter have been interpreted as the electrophysiological correlate of the anal reflex. Delayed responses in patients with idiopathic faecal incontinence have been interpreted as evidence for denervation of the external anal sphincter. Electrically evoked responses were studied in normal subjects, either before and during spinal anaesthesia (n = 8), or before and during competitive neuromuscular blockade (n = 4), instituted for operative purposes. Short latency responses persisted unchanged in either latency or duration during spinal anaesthesia whereas long latency responses were completely abolished. Both short and long latency responses were abolished during competitive neuromuscular blockade. Short latency responses are not spinal reflex in nature, but due to stimulus activation of alpha-motoneuronal terminal branches. Delayed responses in incontinent patients cannot be interpreted as evidence for pudendal neuropathy. Long latency (i.e. greater than 40 ms) responses demand a functional sacral spinal cord and represent the true anal reflex. Their wide range of latency in normal subjects suggests this measurement will be of little use in confirming the presence or absence of pudendal neuropathy, and that other measures of neuropathy may be more appropriate.

Adolescent↗
PubMed1985

New method for the dynamic assessment of anorectal function in constipation.

A new dynamic technique for the investigation of anorectal function has been developed. This involves radiological visualization of the rectum during voiding of a semisolid radio-opaque contrast medium, and simultaneous measurement of the intrarectal pressure and electrical activity of the external anal sphincter. The method has been used to study patients (n = 16) with profound difficulty passing formed stool. It has demonstrated an abnormal increase in the activity of the puborectalis and superficial and sphincter muscles during voiding in these patients, compared with normal subjects (n = 6). The inability to void was associated with failure to widen the anorectal angle on straining.

Adult↗
PubMed1985

Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury.

Radioimmunoassay and immunocytochemistry were used to study the distribution of galanin, a novel 29 amino acid porcine intestinal peptide, in the central nervous system of the rat and pig. The pattern of distribution was similar in the two species, with the highest concentrations of galanin-like immunoreactivity found in the neurohypophysis, hypothalamus and sacral spinal cord. Immunocytochemical studies of these regions localized galanin-like immunoreactivity to cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus, to fibres in the pars nervosa and to numerous cell bodies and fibres in the dorsal horn of the spinal cord. On both gel and high pressure liquid chromatography, galanin-like immunoreactivity in rat and pig nervous tissue eluted as a single peak in a position similar to purified procine intestinal galanin standard. Surgical and pharmacological manipulations in the rat suggest the presence of galanin in afferent fibres. An increase of galanin-like immunoreactivity was observed in the sacral spinal cord of the rat following thoracic spinal cord transection. Thus galanin-like immunoreactivity in the brain is mainly localized in the hypothalamopituitary region. The decrease of galanin-like immunoreactivity in the dorsal horn of the spinal cord, following dorsal rhizotomy and pre-treatment of rats with capsaicin, indicates that many of the fibres, which are of small diameter, may well be derived from spinal sensory neurones.

Animals↗
PubMed1984

Mechanisms of enzymatic and acid-catalyzed decarboxylations of prephenate.

The prephenate dehydrogenase activity of the bifunctional enzyme chorismate mutase-prephenate dehydrogenase from Escherichia coli catalyzes the oxidative decarboxylation of both prephenate and deoxoprephenate, which lacks the keto group in the side chain (V 78% and V/K 18% those of prephenate). Hydride transfer is to the B side of NAD, and the acetylpyridine and pyridinecarboxaldehyde analogues of NAD have V/K values 40 and 9% and V values 107 and 13% those of NAD. Since the 13C isotope effect on the decarboxylation is 1.0103 with deuterated and 1.0033 with unlabeled deoxoprephenate (the deuterium isotope effect on V/K is 2.34), the mechanism is concerted, and if CO2 has no reverse commitment, the intrinsic 13C and deuterium isotope effects are 1.0155 (corresponding to a very early transition state for C-C bond cleavage) and 7.3, and the forward commitment is 3.7. With deoxodihydroprephenate (lacking one double bond in the ring), oxidation occurs without decarboxylation, and one enantiomer has a V/K value 23-fold higher than the other (deuterium isotope effects are 3.6 and 4.1 for fast and slow isomers; V for the fast isomer is 5% and V/K 0.7% those of prephenate). The fully saturated analogue of deoxoprephenate is a very slow substrate (V 0.07% and V/K approximately 10(-5%) those of prephenate). pH profiles show a group with pK = 8.3 that must be protonated for substrate binding and a catalytic group with pK = 6.5 that is a cationic acid (likely histidine). This group facilitates hydride transfer by beginning to accept the proton from the 4-hydroxyl group of prephenate prior to the beginning of C-C cleavage (or fully accepting it in the oxidation of the analogues with only one double bond or none in the ring). In contrast with the enzymatic reaction, the acid-catalyzed decarboxylation of prephenate and deoxoprephenate (t1/2 of 3.7 min at low pH) is a stepwise reaction with a carbonium ion intermediate, since 18O is incorporated into substrate and its epi isomer during reaction in H218O. pH profiles show that the hydroxyl group must be protonated and the carboxyl (pK approximately 4.2) ionized for carbonium ion formation. The carbonium ion formed from prephenate decarboxylates 1.75 times faster than it reacts with water (giving 1.8 times as much prephenate as epi isomer). The observed 13C isotope effect of 1.0082 thus corresponds to an intrinsic isotope effect of 1.023, indicating an early transition state for the decarboxylation step. epi-Prephenate is at least 20 times more stable to acid than prephenate because it exists largely as an internal hemiketal.(ABSTRACT TRUNCATED AT 400 WORDS)

Carbon Isotopes↗
PubMed1984

Demonstration of paracervical ganglion origin for the vasoactive intestinal peptide-containing nerves of the rat uterus using retrograde tracing techniques combined with immunocytochemistry and denervation procedures.

The origin of the abundant vasoactive intestinal peptide (VIP)-immunoreactive nerves in the uterus has not been fully determined. In this study, a fluorescent dye, True Blue was injected into the uterus of rat and 6 days later, neuronal cell bodies of the paracervical ganglion were found to be labelled by this dye. Some of these labelled ganglion cells were also found to contain VIP immunoreactivity by immunocytochemistry. When the preganglionic pelvic and/or hypogastric nerves of rats were sectioned, the VIP-immunoreactive nerves in the uteri were not depleted, indicating that these nerves did not originate from the splanchnic ganglion, dorsal root ganglion or the spinal cord. Therefore it is concluded that VIP-immunoreactive nerves in the uterus originate from the paracervical ganglion.

Animals↗
PubMed1984

Catalytic mechanism of the dihydrofolate reductase reaction as determined by pH studies.

The variation with pH of the kinetic parameters of the reaction catalyzed by dihydrofolate reductase from Escherichia coli has been determined with the aim of elucidating the chemical mechanism of the reaction. The (V/K)DHF and V profiles indicated that protonation enhances the observed rate of interaction of dihydrofolate (DHF) with the enzyme-NADPH complex as well as the maximum velocity of the reaction. The pKa value of 8.09 observed in the (V/K)DHF profile is similar to that of 7.9 observed in the Ki profile for 2,4-diamino-6,7-dimethylpteridine while the pKa value of the V profile is displaced to 8.4. From the magnitude of the pH-independent value for (V/K)DHF, it is concluded that unprotonated dihydrofolate must react, at neutral pH, with the protonated form of the enzyme. The D(V/K)DHF value is independent of pH and equal to unity whereas the DV value varies as a wave function of pH with limiting values of 1.5 and 1.0 at low and high pH, respectively. It is proposed that dihydrofolate reacts with the unprotonated enzyme-NADPH complex to form a dead-end complex and with the protonated form of the same complex to form a productive complex. Further, it is considered that the protonated carboxyl of Asp-27 at the active site of the enzyme is responsible for the protonation of the N-5 nitrogen of dihydrofolate and that this protonation precedes and facilitates hydride transfer.

Escherichia coli↗
PubMed1984

Leisure-time physical activity levels, cardiovascular fitness and coronary risk factors in 1015 white Zimbabweans.

To determine a 'threshold' level of habitual physical activity for the reduction of coronary risk factors, a cross-sectional study of 646 male and 369 female White Zimbabweans aged 20 - 70 years was undertaken. Results showed that light exercise, even up to four times a week, was not associated with meaningful changes in maximum oxygen intake (VO2MAX) or reduction in body fat or the incidence of smoking, but such changes were seen in subjects involved in vigorous exercise. Ischaemic changes on exercise ECGs were less frequent among those participating in strenuous exercise more than twice a week than among those performing either mild exercise or strenuous exercise less than twice a week. These data show that a 'threshold' level of exercise might exist above which there is a reduction in the percentage of body fat, the incidence of smoking and abnormal ST-segment depression during exercise, increased VO2MAX values and a reduced rate of fall of VO2MAX with age. Whereas participation in only light exercises had little effect, more strenuous exercise was associated with beneficial alterations in all these parameters. This level of exercise is also the 'threshold' level for elevations in serum high-density lipoprotein cholesterol levels. The results suggest that future longitudinal studies should employ only more vigorous exercise, to be undertaken at least three or preferably more times a week.

Adult↗
PubMed1984

Inhibition of dihydrofolate reductase from bacterial and vertebrate sources by folate, aminopterin, methotrexate and their 5-deaza analogues.

The inhibition of dihydrofolate reductases from Escherichia coli and chicken liver by folate, methotrexate, aminopterin and their 5-deaza analogues was investigated to examine the importance of the N-5 nitrogen in slow-binding inhibition. Methotrexate, aminopterin and their 5-deaza analogues acted as slow, tight-binding inhibitors of both enzymes. Inhibition by methotrexate and 5-deazamethotrexate conformed to a mechanism in which there is an initial rapid formation of an enzyme-NADPH-inhibitor complex followed by a slow isomerization of this complex (Mechanism B). Aminopterin exhibited the same type of inhibition with the enzyme from E. coli. With the chicken-liver enzyme, however, the inhibition by aminopterin conformed to another type of slow-binding mechanism which involves only the slow interaction of the inhibitor with the enzyme to form an enzyme-NADPH-inhibitor complex (Mechanism A). The inhibition of both enzymes by 5-deazaaminopterin was also described by Mechanism A. Folate behaved as a classical, steady-state inhibitor of both enzymes, whereas 5-deazafolate exhibited slow-binding inhibition (Mechanism B) with the enzyme from E. coli and classical, steady-state inhibition with the enzyme from chicken liver. The substitution of a carbon for a nitrogen at the 5-position of methotrexate and aminopterin did not affect the tightness of binding of these compounds. By contrast, 5-deazafolate was bound about 4000 times more tightly than folate to the enzyme from E. coli and about 30 times more tightly than folate to the chicken-liver enzyme. Reasons for the differences in the binding of folate and 5-deazafolate are discussed.

Aminopterin↗
PubMed1984

Malignant melanoma of the choroid in a husband and wife.

A 52-year-old man was diagnosed as having a large malignant melanoma of the choroid in the right eye. Six years later his 58-year-old wife of almost 40 years was diagnosed as having a large malignant melanoma of the choroid in her left eye. In both patients the diagnosis was confirmed histologically following enucleation. Electron microscopy failed to reveal evidence of viral particles within the tumours. The implications of this unusual occurrence are discussed.

Choroid Neoplasms↗