'A little learning': knowledge and health in the 18th century.
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Biomedical subjects
Publications and source records attributed to R Porter.
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Changes in myosin light chain phosphorylation were measured during histamine-induced rhythmic contractions of hog carotid artery smooth muscle strips. Histamine made the muscle strips contract spontaneously every 1-5 min, and this allowed measurement of the time course of phosphorylation in relation to force development under conditions where diffusion of the agonist through tissue would not complicate the interpretation of the data. In the absence of histamine, phosphorylation was low [0.12 +/- 0.04 mol P/mol of the 20,000-Da light chain (LC 20)]. Phosphorylation was slightly (but not significantly) higher in the presence of 10 microM histamine in the relaxed state between contractions (0.20 +/- 0.03 mol P/mol LC 20). In muscle strips frozen during force development, when force had reached half of its peak value, phosphorylation was 0.38 +/- 0.06 mol P/mol LC 20. The highest levels of phosphorylation (0.49 +/- 0.04 mol P/mol LC 20) were found in strips frozen at the peak of the rhythmic contractions. Strips frozen when force had declined to half of the peak force showed low levels of phosphorylation (0.17 +/- 0.07 mol P/mol LC 20), indicating that the myosin light chain phosphatase activity was quite high. Mathematical modeling of the kinase and phosphatase reactions suggested that the apparent first-order phosphatase rate constant was at least 0.08 s-1 under these conditions. To obtain a better estimate of this rate constant, a second series of phosphorylation measurements were made early in the relaxation phase of the rhythmic contractions. The highest phosphatase rate constant obtained from these measurements was 0.23 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Neurons in laminae II, III, V, and VI of area 4 gamma of the cat motor cortex were studied following intracellular penetration with an HRP-filled micro-electrode. Antidromic and synaptic responses produced by stimulation of the cerebral peduncles and/or of the ventrolateral nucleus of the thalamus were investigated. Horseradish peroxidase was then iontophoresed into the same neurons to allow examination of their detailed morphology. The morphology of pyramidal neurons whose somata were located in a particular lamina was similar but differed from that of pyramidal neurons in other laminae. The modified pyramidal neurons of lamina II had a truncated apical dendrite or did not possess an obvious apical dendrite, even though the ascending dendritic branches were longer and more extensive than the "basal" branches. As was the case for the pyramidal cells in other laminae, the axons of these lamina II modified pyramidal cells descended toward the white matter; their somata were generally pyramidal in shape, and their dendrites were spiny. All pyramidal neurons except some of lamina VI had ascending dendrites which terminated in a tuft in lamina I, subpially. No intracortical collaterals were seen originating from the axons of lamina II or of lamina VI pyramidal neurons. Lamina III pyramidal neurons had extensive short and long axon collaterals which contributed synaptic boutons to all laminae of the cortex. Pyramidal neurons of lamina V had fewer axon collaterals whose synaptic boutons were restricted to laminae V and VI. All somata of pyramidal tract neurons (PRNs), identified by antidromic responses from peduncular stimulation, were located in lamina V, except for one which was located in lamina VI. Recurrent collaterals of pyramidal neurons were activated by peduncular stimulation. Recurrent excitatory postsynaptic potentials (epsps) could be evoked in fast PTNs, slow PTNs, other pyramidal neurons of lamina V, and pyramidal neurons of lamina VI at latencies between 1.3 and 6.25 msec. In some slow PTNs, a recurrent inhibitory postsynaptic potential of long duration was the predominant response. Stimulation of the ventrolateral nucleus of the thalamus resulted in epsps in pyramidal neurons of lamina III, V, and VI at latencies between 1.0 and 5.0 msec.
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1. Pyramidal neurones in the precentral motor area of the monkey were studied using intracellular techniques. Pyramidal tract neurones (PTNs) were identified by antidromic activation from the cerebral peduncles or medullary pyramids. Orthodromic responses were recorded in PTNs and in other pyramidal neurones when antidromic volleys were set up by stimulation of the peduncles or pyramids. The neurones were then labelled by intracellular ionophoresis of horseradish peroxidase and their morphology examined. All neurones studied were identified as pyramidal cells according to their morphology. 2. Six pyramidal neurones located in lamina V were well stained; they included two fast PTNs and two slow PTNs. The morphology of all pyramidal neurones in this lamina (fast PTNs, slow PTNs and those pyramidal cells that were not antidromically characterized) was essentially similar. A single apical dendrite branched as it ascended and its terminals arborized subpially. Numerous lateral and oblique dendrites branched from the apical dendrites in lamina V and near its border with lamina III: short basal dendrites arborized in the vicinity of the soma in lamina V. Long basal dendrites had a wider field of arborization in lamina V and sometimes extended into lamina VI. 3. Three to five collaterals arose from the axon of lamina V cells in the cortex and arborized in laminae V and VI. Short collateral branches arborized in the vicinity of the soma in the region of the basal and lateral dendrites. Long collateral branches could be traced over long distances (often more than 1 mm). One pyramidal neurone in this lamina (a fast PTN) lacked short collateral branches from the axon. 4. Four pyramidal neurones in lamina III were stained well. The dendritic morphology of all these neurones was similar. Apical dendrites branched as they ascended and terminated subpially. Lateral and basal dendrites formed a column of dendritic branches around the soma. No long basal dendrites were seen. 5. The number and arborization of intracortical collaterals from the axon of lamina III cells varied widely; from three to twelve collaterals arose from the axon. The biggest arbor of collateral branches involved all the cortical laminae and was about 3 mm wide mediolaterally, while the smallest arbor was restricted mainly to lamina III in the vicinity of the soma. One neurone in this lamina also lacked short collateral branches from the axon. 6. Antidromic volleys from the pyramidal tract evoked excitatory responses in fast PTNs, predominantly inhibitory responses in slow PTNs and either excitatory or inhibitory responses in other pyramidal neurones in lamina V.(ABSTRACT TRUNCATED AT 400 WORDS)
1. Corticocortical synaptic influences on pyramidal neurones in the precentral motor cortex of monkeys were examined using intracellular recordings. Corticocortical afferents from the postarcuate premotor area and the somatic sensory cortical areas were activated by bifocal stimulation of the cortical surface. Neurones that were found to respond orthodromically to such stimuli were labelled by intracellular ionophoresis of horseradish peroxidase. 2. Almost all neurones that were penetrated satisfactorily and labelled successfully were found to be pyramidal neurones located in lamina III or lamina V. Some labelled neurones in lamina V were also characterized as pyramidal tract neurones (PTNs) by antidromic activation from the cerebral peduncles or medullary pyramids. 3. Pyramidal neurones located in lamina III and lamina V (including PTNs) were excited at short latency by stimulation of the premotor cortex (1.1-4.0 ms) and somatosensory cortex (1.1-6.5 ms). There were no statistical differences in the distributions of latencies of corticocortical EPSPs between those evoked in lamina III neurones and those recorded in lamina V neurones, or between corticocortical EPSPs evoked from the premotor cortex in comparison with those from the somatosensory cortex. Excitatory responses to stimulation of the premotor area were usually more difficult to evoke and smaller in amplitude than those produced by stimulation of the somatosensory areas. 4. Corticocortical EPSPs were often followed by IPSPs. The amplitudes of the EPSPs and IPSPs could be increased by increasing the stimulus intensity. In a few neurones IPSPs that were not preceded by EPSPs were recorded.
From December 1985 to April 1986, 458 patients underwent 600 transvaginal ultrasound-directed oocyte pickups (TVOPU) in preparation for in vitro fertilization and embryo transfer at The Royal North Shore Hospital of Sydney. Collections (552) were performed under light general anesthetic and, more recently, 48 were performed with light sedation. At least one oocyte was collected in 98.7% of all TVOPUs. A total of 3117 follicles (greater than 12 mm) were aspirated and 2576 oocytes were collected. Ninety-two clinical pregnancies were established after embryo transfer in 474 cycles. Major operative morbidity was low, with three pelvic abscesses and three pelvic hematomas reported. The procedure was well accepted by patients, with only one expressing a preference for the laparoscopic method. TVOPU is now the preferred method of oocyte pickup in our unit.
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During infancy, children develop an expanding repertoire of movement skills in parallel with the maturation in their brains of direct nerve-fibre connections between the cerebral cortex and motoneurons in the spinal cord. These corticomotoneuronal connections are characteristic of primates and can be studied in monkeys; in these animals, refinement in the control of movements of the hand is also associated with increasing development of corticomotoneuronal connections. In monkeys, motoneurons innervating distally acting muscles are preferentially excited by convergent activities in corticomotoneuronal fibres. This excitation has been demonstrated to be effective in natural functional states when a conscious monkey is performing learned movement tasks. Extensive intraspinal arborizations of individual corticomotoneuronal fibres could permit the engagement of large numbers of local motoneurons and related interneurons by each of these fibres. Abolition of corticomotoneuronal influences, after section of the pyramidal tracts, causes a permanent deficit in fractionation of use of muscles of the forelimb and an inability to carry out independent movements of the fingers.
A monkey was noted to have an intermittent startle response to tendon tapping and vibration of proximal arm muscles. The latency of the first phase of this response, averaging 34 ms in triceps (and of average duration 49 ms), was similar to that described for the long-latency reflex response to muscle stretch in the same muscles. Unrecognised startle responses could explain some of the reported differences in long-latency reflexes in proximal and distal muscles.
The relative numbers and locations of neurons projecting to the "forelimb" region of the precentral motor cortex were studied in three monkeys by using the retrograde transport of horseradish peroxidase. Within the forelimb area of the motor cortex itself, there are extensive and profuse interconnections. However, regions within this area receive afferents from very few neurons in other parts of the motor cortex representing hindlimb or head movements. Most of the motor cortical representation of the forelimb in the anterior bank of the central sulcus is devoid of callosal connections. In both the ipsilateral and contralateral hemispheres, the premotor (lateral area 6) and supplementary motor (medial area 6) areas dominate quantitatively the inputs to the motor cortical representation of the forelimb. The afferents from the premotor area are restricted and come from a region immediately behind the arcuate spur and adjacent parts of the superior and inferior limbs of the arcuate sulcus in the floor, caudal bank, and caudal lip of that sulcus. From the supplementary motor area (SMA), afferents originate from its whole rostrocaudal extent. Thalamic nuclear regions projecting to a restricted zone in the anterior bank of the central sulcus are recipients of cerebellar and somatosensory outputs. Involvement of more anterior parts of the motor cortex by the tracer labels thalamocortical cells, which are targets of pallidal output also. Within the first somatosensory cortex, cytoarchitectonic areas 1, 2, and 3a project to area 4. The projection from area 3a may provide one pathway by which short-latency peripheral inputs, especially from muscles, reach the motor cortex.
Defining functions for neural elements becomes more difficult the more remote they are, in synaptic linkages, from motor neurons. The precentral motor cortex contains a corticomotoneuronal projection system, only one synapse removed from motor neurons. Corticomotoneuronal fibres produce monosynaptic excitation of spinal motor neurons, which is more powerful for those acting distally, innervating extensor muscles of the fingers and intrinsic hand muscles. Latencies and time-course of corticomotoneuronal excitation are defined. Amplitudes of unitary corticomotoneuronal excitatory postsynaptic potentials are very small. Many corticomotoneuronal cells converge on a given motor neuron. Some motor neurons innervating proximally acting muscles appear to receive no corticomotoneuronal excitation. Disynaptic inhibitory actions are produced by corticospinal volleys via the common Ia inhibitory interneuron--possibly reciprocal actions produced over collaterals of corticomotoneuronal fibres. Anatomical divergence of projections of collaterals of an identified corticomotoneuronal fibre is extensive enough to provide both for delivery of synapses to a large number of motor neurons and for the dispersion of specific projections to inhibitory interneurons, to fusimotor neurons and to other interneurons. Functions of corticomotoneuronal elements in motor cortex whose targets have been identified and whose excitatory or inhibitory actions have been specified by cross-correlation have been studied by Fetz & Cheney (J Neurophysiol 1980; 44:751-772).
The results of a multicenter, double-blind, placebo-controlled clinical trial of the efficacy and safety of progabide (PGB) in the treatment of partial seizures are presented. This study was performed with a number of rigorous controls not usually present in clinical trials. These included uniform co-medication in which all patients received only phenytoin and carbamazepine; concentrations of these two drugs were maintained within narrow, predefined concentration ranges. There was no statistically significant difference between PGB and placebo in seizure frequency and seizure duration for most of the analyses performed. One patient was withdrawn from the study because of hepatotoxicity. PGB was associated with a significant inhibition of phenytoin but not carbamazepine clearance. The results of this study indicate that PGB was not a potent antiepileptic drug in this population of persons with intractable epilepsy.
Short latency responses were recorded from C5 phrenic roots and intracellularly from phrenic motoneurones following stimulation of the pericruciate cortex or medullary pyramids in cats anaesthetized with Nembutal or chloralose-urethane. Focal stimulation of the cortical surface (single pulses, 0.5-2 ms, 0.3-8 mA) during inspiration evoked EPSPs (latency 4.7 +/- 1.7 ms, rise time 1.9 +/- 1.1 ms, amplitude 0.22 to 3.94 mV) in 42% of motoneurones studied (n = 107). The EPSPs were absent, or on average 60% smaller, following stimulation during expiration. In all but two motoneurones, during both inspiration and expiration, hyperpolarizing potentials were observed either following the initial depolarization or alone. They could be reversed by hyperpolarizing current or chloride injection. Stimulation of the pyramidal tract at mid medullary level (1 to 3 pulses, 0.2 ms) evoked short latency excitation in phrenic motoneurones only with currents of more than 200 microA. Smaller stimuli applied to the medial reticular formation above the pyramidal tract evoked excitation (onset latency 1.5-3.2 ms) in which the earliest part was probably monosynaptic. These results show that the corticospinal responses in phrenic motoneurones are both excitatory and inhibitory. They are not transmitted through the pyramidal tract and are at least disynaptic. Excitation evoked from the medullary pyramidal tract can be explained by current spread beyond the pyramidal tract fibres.
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To analyze the function of proteoglycans (PG) in different types of leukocytes, both the relative amounts and specific types of proteoglycans produced by cultured human peripheral blood polymorphonuclear leukocytes (PMN) were were determined and compared to mononuclear leukocytes (PBMC). Media from 3-day cultured PMN contained significantly less (less than 10%) 35SO2-4-labeled PG than media from PBMC cultures. Incorporation of 35SO2-4 into cell-associated material was comparable for both types of white blood cells. In contrast to PBMC, PMN could not increase their synthesis or secretion of PG after exposure to concanavalin A or phorbol-12-myristate-13-acetate. Various inducers of leukocyte chemotaxis also failed to enhance PG production by PMNs. Release of prelabeled PG from PMNs could be induced by exposure to either opsonized or unopsonized zymosan (yeast) as well as the bacteria S. aureus, suggesting that particle ingestion may be accompanied by PG exocytosis. Both chondroitinase ABC and AC digested greater than 90% of PMN 35S-labeled material in media and 75% in cell lysates; HNO3 treatment removed less than 5% of N-linked 35SO4 from radiolabeled media and 25% from cells. Treatment with 0.5 N NaOH released shortened glycosaminoglycan chains from 35S-labeled PMN cell lysates. beta-D-xylosides did not stimulate an increase in polysaccharide chain production by cultured PMNs. These data suggest that PMNs can produce chondroitin 4-sulfate PG whose synthesis is not affected by treatments that alter PMN functions; in contrast to PBMCs, PMNs will actively release these molecules when exposed to micro-organisms that stimulate phagocytosis.
Goodwin Wharton (1653-1704) was a nobleman's son and a Whig MP who played no small part in English public life. His manuscript journal shows, however, that he also lived a bizarre secret life of the mind of a kind which, in later generations, would have led to his confinement as suffering from mental illness. Above all, through the offices of his medium and lover, Mary Parish, he entered into elaborate relations both with the fairy world and with God and His Angels. This paper examines our records of Wharton's consciousness.