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Biomedical subjects

B Matthews

Publications and source records attributed to B Matthews.

At least 73 records · Page 4Linked to original sources

N-acetylation and serotonergic measures in a group of psychiatric patients.

Serotonin is N-acetylated to melatonin. The purpose of this study was to explore the possibility of N-acetylation of dapsone reflecting serotonergic activity. The ratio of monoacetyldapsone/dapsone (MAD/DDS) in plasma, 5-HIAA in CSF, and imipramine-binding to platelets were investigated in a group of psychiatric patients, diagnosed according to the DSM-III as affective disorders, schizophrenia, and personality disorders. There was no significant correlation between either of the serotonergic estimates and N-acetylation in the whole patient group or in diagnostic subgroups of patients. Sixty-four percent of the patients were slow N-acetylators (MAD/DDS less than 0.4), which is a ratio in line with several other studies of psychiatric patients. Among patients with affective disorders, all unipolar patients were slow N-acetylators, while five out of six bipolar patients were fast N-acetylators. The N-acetylation of patients with a history of suicide attempt did not differ from those without. The discrepancy in N-acetylation between uni- and bipolar patients might again address the issue of them representing two different biochemical and genetic disorders.

Acetylation↗

A computer-based method of measuring facial asymmetry. Results from an assessment of the repair of cleft lip deformities.

The appearance of the nose, mouth and nostrils was analysed in two series of unilateral, complete cleft lip patients. A programme was written for use on a BBC microcomputer to measure the symmetry of facial features traced from photographs. Symmetry was measured using one of two methods: determining the area of non-overlap when one side was reflected on the other (area method) or calculating the distance from regularly spaced points on the outline of one side to the nearest point on the reflection of the opposite side (curve method). The rankings of the photographs based on these results were compared with the subjective rankings given by a lay panel. The results based on the curve method agreed well with the subjective rankings (P for Spearman Rank Correlation Coefficients = less than 0.02). The technique provides a cheap, simple and quick method of comparing symmetry in groups of patients.

Adolescent↗

Intrapulpal nerve stimulation in the rat.

Electrical stimulation of the rat incisor pulp has been frequently used as a method to study the mechanisms of pain. However, several of the techniques used to stimulate nociceptive nerves in these teeth also tend to excite non-nociceptive nerves in adjacent tissues. This report deals with the development and verification of a procedure which selectively stimulates pulpal nerves over a wide range of stimulus intensities. The methods consisted of placing electrodes in labial cavities of each of the two lower rat incisors, 1 mm distal to the level of the crest of the interdental papilla. Each cavity had a diameter of 0.5 mm and a depth of about three-quarters fo the crown diameter. Each electrode consisted of a Ag/AgCl filling compacted onto the end of a 0.1 mm silver wire. Constant current stimuli were passed between the two electrodes. EMG was monitored to detect reflex activation of the digastric muscle in response to intradental or extradental afferent excitation. The response consisted of two components. One was a long latency potential (LLP) (37 ms latency) (89 microA ave TH); the other was a short latency potential (SLP) (12 ms latency) (650 microA min TH). In all animals that LLP was abolished by bilateral sectioning of the tooth pulp 7 mm below the level of the labial gingival margin. The SLP was not abolished. This would indicate that the LLP was due to stimulation of pulpal fibers, and the SLP to excitation of extrapulpal fibers. This may prove to be a helpful method for nociceptive researchers to easily verify that they are actually stimulating pulpal afferents.

Animals↗

An electrophysiological and morphological study of the innervation and reinnervation of cat dentine.

1. Experiments were carried out to determine which, if any, of the cellular processes in cat dentine are nerves. This was done by examining in the electron microscope the contents of the dentinal tubules in control teeth and in teeth that had been denervated 56 h previously. The extent of any reinnervation, and associated return of neural responses to dentine stimulation were investigated 12 weeks after denervation. 2. In five cats, the inferior alveolar nerve was sectioned on one side and the cut ends reapposed. 3. Each of the tubules in the predentine of control teeth contained one process with a cross-sectional area of 0.21-1.14 micron2 and up to eight other, secondary processes which were generally smaller. The proportion which contained secondary processes was highest (83%) near the tip of the pulp and decreased further down the side of the crown of the tooth. 4. 56 h after denervation, almost all the secondary processes had disappeared, leaving just one of the larger processes in each tubule. It is concluded that these larger processes are odontoblast processes and that all the secondary processes are nerve terminals. 5. 12 weeks after denervation, small processes were again present in some tubules. Recordings in three cats showed that inferior alveolar nerve fibres had regenerated into the canine pulp and that some of these had re-established receptor properties similar to those in normal teeth.

Action Potentials↗

Effect of acute hypercapnia on PTH-stimulated phosphaturia in dietary Pi-deprived rat.

The effects of respiratory acidosis on renal inorganic phosphate (Pi) handling are controversial. Clearance experiments, therefore, were performed in fasted, chronically parathyroidectomized (PTX), dietary Pi-deprived rats. The objectives were twofold: to study the effects of compensated and uncompensated hypercapnia per se on renal Pi excretion and to examine the interaction between acute hypercapnia, dietary Pi, and parathyroid hormone (PTH) on the renal handling of Pi. Acute hypercapnia increased the plasma Pi (delta 2.82 +/- 0.65 mg/dl, P less than 0.05) without altering the glomerular filtration rate (GFR). The FEPi increased (delta 7.26 +/- 0.48%, P less than 0.001) but the TRPi/GFR also increased. PTH (3 U X kg-1 X h-1) superimposed on hypercapnia resulted in a plasma Pi comparable to hypercapnia alone. The FEPi (7.56 +/- 0.78 vs. 24.43 +/- 2.20%; P less than 0.001) was higher and the TRPi/GFR (117 +/- 4 vs. 80 +/- 2 micrograms/min, P less than 0.01) lower, in the former group. PTH infusion during normocapnia resulted in a lower FEPi (0.20 +/- 0.10 vs. 24.43 +/- 2.20%, P less than 0.001) and a higher TRPi/GFR (106 +/- 2 vs. 80 +/- 2 micrograms/min, P less than 0.01) compared with PTH infusion during hypercapnia. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion was similar between the groups. During hypercapnia, when the extracellular acidemia was neutralized, the phosphaturic action of PTH persisted. These studies offer direct evidence that in chronically PTX, dietary Pi-deprived rats, the phosphaturic action of PTH is restored by hypercapnia per se. This effect appears to be independent of extracellular acidemia, changes in the plasma Pi and calcium, urinary pH and Na and cAMP excretion.

Acidosis, Respiratory↗

The course of postganglionic sympathetic fibres distributed with the facial nerve in the cat.

Electrophysiological techniques have been used to determine whether sympathetic fibres are present in branches of the facial nerve. Compound action potentials could be recorded from all branches of the facial nerve during stimulation of the cervical sympathetic trunk. The course taken by the sympathetic fibres was determined by observing whether nerve sections at different sites blocked these responses. Two pathways were found: one group of fibres leaves the superior cervical ganglion in the internal carotid nerve, joins the auricular branch of the vagus nerve at the jugular foramen and passes via this nerve to the facial nerve, which it joins in the facial canal just central to the stylomastoid foramen. A second, apparently smaller group of fibres travels in the internal carotid nerve, crosses the roof of the tympanic bulla in the tympanic plexus, enters the middle cranial cavity through the foramen lacerum and passes with the greater superficial petrosal nerve to join the facial nerve at the geniculate ganglion.

Action Potentials↗

Kinetic studies of 6-phosphogluconate dehydrogenase from sheep liver.

The steady-state kinetics of the oxidative decarboxylation of 6-phosphogluconate catalysed by 6-phosphogluconate dehydrogenase from sheep liver in triethanolamine and phosphate buffers (pH 7.0) have been reinvestigated. In triethanolamine buffer the enzyme is inhibited by high NADP+ concentrations in the presence of low fixed concentrations of 6-phosphogluconate. Data are consistent with an asymmetric sequential mechanism in which NADP+ and 6-phosphogluconate bind randomly and product release is ordered. The pathway through the enzyme--6-phosphogluconate complex appears to be preferred in triethanolamine buffer. Pre-steady-state studies of the oxidative decarboxylation reaction at pH 6.0-8.0 show that hydride transfer is greater than 900 s-1. After the fast formation of NADPH in amounts equivalent to about half of the enzyme-active-centre concentration, the rate of NADPH formation is equal to the steady-state rate. Two possible interpretations are considered. Rapid fluorescence measurements of the displacement of NADPH from its complex with the enzyme at pH 6.0 and 7.0 indicate that the dissociation of NADPH is fast (greater than 800 s-1) and cannot be the rate-limiting step in oxidative decarboxylation. Coenzyme binding studies at equilibrium have been extended to include the determination of the dissociation constants for the binary complexes of enzyme with NADPH and NADP+ at pH 6.0-8.0 and the dissociation constant for NADPH in the ternary enzyme--6-phosphogluconate--NADPH complex in triethanolamine buffer, pH 7.0.

Animals↗

Peripheral and central aspects of trigeminal nociceptive systems.

Three aspects of trigeminal pain are considered: the peripheral mechanisms of pain from teeth and from the cornea, and the role of the trigeminal brainstem nuclei in pain. Pain is probably the only sensation that can be evoked by stimulation of dentin or dental pulp in man. Five nerve-endings enter dentinal tubules from the pulp but do not extend into the outer dentine, which is nevertheless sensitive. In teeth of limited growth in experimental animals, the dental pulp is supplied by A beta, A delta and C fibres and these are associated with two categories of receptor: one responds to cooling and to other stimuli that cause displacement of the contents of the dentinal tubules such as probing and drying the dentine, and the other group responds most vigorously to heating. Some cold sensitive units have A beta fibres and the evidence suggests that stimulation of these is capable of evoking both muscle reflexes and pain and, near threshold, 'pre-pain' sensations. Thermal stimulation of the cornea produces sensations of pain and, with less intense stimuli, irritation, Mechanical stimulation also produces pain but it is not clear whether, below the pain threshold, such stimuli produce touch sensation or some other sensation related to pain. Histologically, the nerve-endings in the corneal epithelium consist of fine, bare processes closely associated with the surface of the epithelial cells. Recordings in experimental animals have shown that many of the receptors respond to several different forms of stimulus and their properties correlate well with those predicted from psychophysical experiments in man. The results of trigeminal tractotomy in man and recordings from the trigeminal brainstem nuclei in anaesthetized animals, have generally indicated that nucleus caudalis is the main relay in the pain pathway from the face and associated structures. Recent observations have, however, shown that tractotomy does not produce complete analgesia of this region and responses to thermal stimulation of teeth and noxious stimulation of other oro-facial tissues have been recorded from the more rostral parts of the brainstem nuclear complex. The surgical procedures employed to set up an animal for stereotaxic recording may induce long-lasting depression in the excitability of neurons in these nuclei, which masks some of their properties. The mechanism of this depression has not been established.

Animals↗

The effects of anaesthetics and remote noxious stimuli on the jaw-opening reflex evoked by tooth-pulp stimulation in the cat.

Previous studies indicate that the threshold of the jaw opening reflex (JOR) evoked by tooth-pulp stimulation is much lower in cats subjected to minimal surgical trauma and a short period of anaesthesia than in animals prepared for stereotaxic recording from the brainstem. Experiments have been carried out to determine whether the higher JOR thresholds observed in the latter group of cats could be attributed to the duration of the anaesthesia or the greater surgical trauma to which they were subjected. The effects on the JOR evoked by tooth-pulp stimulation of brief episodes of noxious and high intensity electrical stimulation of other tissues have been studied in anaesthetized cats. In lightly anaesthetized, control animals, the reflex threshold was usually below 100 microA, 0.1 ms and maintained anaesthesia did not affect this. Alphaxalone/alphadolone, methohexitone and alpha-chloralose produced similar results. Noxious or high intensity electrical stimuli applied to a paw, a pinna or the scalp caused either no change or a decrease in the JOR threshold of cats lightly anaesthetized with alphaxalone/alphadolone. With deeper anaesthesia, these same conditioning stimuli caused a maintained increase in JOR threshold which could be reversed by decreasing the anaesthetic dose. The results suggest that the high threshold of the JOR observed in earlier experiments was not due to anaesthesia but may have been caused by trauma.

Anesthetics↗

Kinetics of dissociation of reduced nicotinamide adenine dinucleotide phosphate from its complexes with malic enzyme in relation to substrate inhibition and half-of-the-sites reactivity.

Malic enzyme of pigeon liver binds NADPH at four equivalent enzyme sites and binds Mn2+ and malate each at two sets of "tight" and "weak" sites with negative cooperativity [Pry, T. A., & Hsu, R. Y. (1980) Biochemistry 19, 951-962]. Stopped-flow studies on the displacement of NADPH from the malate-enzyme complexes E4-NADPH4, E4-Mn2(2+)-NADPH4, E4-Mn2(2+)-NADPH4-dimalate, and E4-Mn2(2+)-NADPH4-tetramalate by large excess NADP+ or its analogue phosphoadenosine(2')diphospho(5')ribose show that NADPH dissociates from the binary complex rapidly with a first-order rate constant of 427 s-1. Dissociation from the ternary E4-Mn2(2+)-NADPH4 complex containing two tightly bound Mn2+ ions can be described by a single first-order process with a rate constant of 135 s-1, or more satisfactorily by two simultaneous first-order processes attributable to the reactions of Mn2+-deficient (k congruent to 427 s-1) and Mn2+-liganded (k = 96 s-1) subunits. The latter equals twice the maximum steady-state turnover rate of 53.2 + 3.0 s-1 assigned to dissociation of the reduced nucleotide from transient E-Mn2+-NADPH, and this 2:1 ratio strongly supports our proposed "half-of-the-sites" model [Hsu, R. Y., & Pry, T. A. (1980) Biochemistry 19, 962-968]. Dissociation from the E4-Mn2(2+)-NADPH4-dimalate complex (k = 100 s-1) follows only the slower process, suggesting that occupancy of malate at two sites tightens enzyme-bound NADPH on the adjacent sites. Binding of malate at two additional weak sites yields E4-Mn2(2+)-NADPH4-tetramalate and a NADPH dissociation rate constant of 2.69 s-1. The 97% decrease in NADPH dissociation parallels the observed 93% maximal inhibition by malate and is the cause of substrate inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Thresholds to electrical stimulation of nerves in cat canine tooth-pulp with A beta-, A delta- and C-fibre conduction velocities.

The thresholds to electrical stimulation and the conduction velocities of nerve fibres supplying the pulp of cat canine teeth have been determined. Compound action potentials and the responses of 80 single units were recorded from the inferior alveolar nerve. The properties of 4 types of coronal stimulating electrode were compared. In the single unit studies separate estimates of intradental and extradental conduction velocity of the fibres were obtained by stimulating the pulp in the crown and in the root of the tooth. The units had extradental conduction velocities ranging from 57.7 to 0.9 m . s-1 and therefore included A beta-, A delta- and C-fibres. The thresholds of the units to coronal stimulation ranged from 7 microA, 0.1 ms to 805 microA, 1.0 ms.

Afferent Pathways↗

Multiple simultaneous tumors in patients with head and neck cancer: a prospective, sequential panendoscopic study.

A prospective panendoscopic study (bronchoscopy, laryngoscopy, esophagoscopy) was carried out in 81 consecutively seen, untreated patients newly diagnosed as having a mucosal neoplasm in the upper aerodigestive tract, to determine how many had a synchronous second primary lesion of the aerodigestive tract. Fourteen patients (17%) proved to have multiple primary lesions (14 second-primary and two third-primary lesions). Three lesions were hypopharyngeal, six esophageal, three pulmonary, two laryngeal, and two oropharyngeal. Two of the additional lesions were found during routine head and neck examination, nine lesions would have been found with a single routine symptom- or roentgenogram-directed endoscopic examination; five, because of their location or small size, would not have been found without panendoscopy, even after chest roentgenography, indirect laryngoscopy, and barium esophagography had been done. The most productive endoscopic examinations for detecting second primary lesions were esophagoscopy and laryngoscopy, the former detecting six lesions, the latter five lesions. The yield of chest roentgenograms was low (1/79). No complications resulted from this prospective panendoscopic protocol study. THese findings should reinforce the belief that head and neck cancer is a panmucosal disease of the aerodigestive tract, that silent second synchronous primary lesions are not uncommon, and that every effort should be made to find all primary sites before treatment of the index tumor is begun.

Bronchoscopy↗

On the mechanism of NADP+-linked isocitrate dehydrogenase from heart mitochondria. I. The kinetics of dissociation of NADPH from its enzyme complex.

The kinetics of dissociation of NADPH from its complex with isocitrate dehydrogenase, and from the abortive complex of enzyme, Mg2+, isocitrate and NADPH, have been studied in phosphate and triethanolamine buffers by means of rapid fluorescence measurements. The reactions are complex, and it is suggested that a conformational equilibrium of each of the complexes is involved, and that this conformational change is also responsible for a slow approach to the steady-state rate of oxidative decarboxylation observed previously in triethanolamine buffer under certain conditions (K. Dalziel, N. McFerran, B. Matthews & C.H. Reynolds, Biochem. J. 171, 743-750 (1978) ). It is concluded that release of free NADPH product is not the rate-limiting step in oxidative decarboxylation in the steady state. The validity of the ligand displacement method used to measure the dissociation kinetics of the enzyme-NADPH complex has been studied by computer simulation.

Animals↗

On the mechanism of NADP+-linked isocitrate dehydrogenase from heart mitochondria. II. The transient-state kinetics of the oxidative decarboxylation of isocitrate.

The kinetics of a single turnover of enzyme-catalysed oxidative decarboxylation have been studied by mixing a stoichiometric complex of enzyme, isocitrate and Mg2+ with large concentrations of NADP+ in a stopped-flow apparatus, and monitoring the formation of NADPH by fluorescence measurements. A transient is revealed that exhibits enhanced nucleotide fluorescence and is not detectable by light absorption measurements. The results obtained with the largest NADP+ concentrations, such that the product NADPH is largely displaced from its enzyme complex, show that a step that precedes the release of free NADPH is rate-limiting in the oxidative decarboxylation reaction under conditions of catalytic cycling. The rate constants for this step, tentatively identified as the formation of the complex of enzyme, Mg2+ and NADPH from a precursor NADPH-containing complex, and for the dissociation of NADPH from this complex have been estimated from the integrated rate equation for a simple model for the product phase of the reaction, by methods of nonlinear regression analysis. In line with the conclusions from the preceding paper, it is suggested that formation of an abortive complex of enzyme, Mg2+, isocitrate and NADPH under catalytic cycling conditions serves to by-pass the potentially rate-limiting dissociation of NADPH from the enzyme-Mg2+-NADPH complex.

Animals↗

Autoradiographic demonstration of ipsilateral and contralateral sensory nerve endings in cat dentin, pulp, and periodontium.

In order to determine the location of sensory nerve ending in cat teeth, 3H-proline and 3H-leucine were injected into the left trigeminal ganglion of eight cats aged 6.5-10 months; 24 hours was allowed for axonal transport of radioactive protein to dental nerve endings, and the endings were then detected by autoradiography. The pulps of most ipsilateral (left) teeth contained some labeled axons. These axons ended in the odontoblastic layer and predentin of roots and crown; at the tip of the pulp horn of each cusp, nerve endings also extended as far as 150 micrometer into dentinal tubules. Labeled nerve endings were extremely rare in contralateral (right) teeth; only one tooth of 83 studied (eight cats) contained heavily labeled axons, and one other had faintly labeled axons. Both labeled contralateral teeth were central maxillary incisors. Their labeled axons were unbranched in the root and arborized in the crown to end among odontoblasts and many adjacent dentinal tubules. Labeled periodontal nerve endings were most numerous in the apical one-third of the ligament, with some endings extending as far as the gingiva. The nerve endings in the periodontal ligament were often clustered and appeared to end freely between the collagen bundles; their radioactivity varied in the same way as that of pulp nerves in the adjacent root.

Animals↗