PubMed Health⌕ Search

Biomedical subjects

M K Horne

Publications and source records attributed to M K Horne.

18 recordsLinked to original sources
PubMed1992

The effect of suramin on laboratory tests of coagulation.

The antitrypanosomal drug suramin, which has recently been under investigation as a cancer chemotherapeutic agent, has previously been found to induce heparin-like anticoagulants in treated patients. In the currently reported work suramin is shown to have an additional anticoagulant activity that is due to direct effects of the drug on procoagulant proteins. The studies were conducted with pooled normal plasma treated in vitro with suramin and with plasma samples obtained from patients who had received the drug intravenously for 2 weeks. It is demonstrated that in plasma suramin inhibits factors V, VIII, IX, X, XI, and XII, while thrombin, prothrombin, and factor VII are unaffected. The inhibition of factor V is virtually irreversible, although the effect of suramin on the other factors is readily reversed by dilution.

Blood Coagulation↗
PubMed1992

Sensory characteristics of monkey thalamic and motor cortex neurones.

1. Extracellular single-cell recordings were made from the cerebellar thalamus, the ventro-posterior lateralis par caudalis (VPLc) and motor cortex of three conscious monkeys. Recordings were made from the thalamus as well as the cortex in two monkeys. In all, recordings were made from the thalamus in four hemispheres and from the motor cortex in four hemispheres. The animals were trained to permit a detailed examination when relaxed. Unexpected perturbations were applied to the wrist. Seventy-seven wrist-related neurones were recorded in the cerebellar thalamus, forty-two neurones from the VPLc and eighty-four neurones in motor cortex. 2. Cerebellar nuclear stimulation was used to physiologically identify thalamic neurones receiving input from the cerebellum. The location of all neurones was verified histologically. 3. The majority of cerebellar thalamic neurones had deep sensory receptive fields related to a single muscle, a group of synergists or a single joint. There was a distinct topographical organization. These fields were similar to sensory fields in motor cortical neurones, but had higher thresholds. 4. VPLc neurones had discrete deep or cutaneous sensory fields, or a combination of these fields, which suggests convergence. VPLc neurones had fields with lower thresholds than cerebellar thalamic neurones. The somatotopically located forelimb area in the VPLc was posterior to and continuous with the forelimb area in the cerebellar thalamus. 5. VPLc neurones responded with a shorter latency to wrist perturbations than did cerebellar thalamic neurones. VPLc neurones with deep sensory fields changed firing significantly earlier than those with cutaneous fields. The VPLc is likely to be the major source of sensory input to the motor cortex, and based on the results of this study we suggest that the VPLc is the thalamic nucleus best placed to transmit short-latency afferent input from the forelimb. 6. The timing of the neuronal discharge of cerebellar thalamic and VPLc cells, which resulted from perturbations of the wrist, was best linked to the duration of movement rather than its amplitude. The cells began firing as soon as the velocity changed sign and continued firing until the sign of the velocity changed again. In subsequent corrective movements neuronal discharge in the VPLc appeared to also encode movement acceleration.

Animals↗
PubMed1992

The activity of monkey thalamic and motor cortical neurones in a skilled, ballistic movement.

1. Three monkeys were trained to perform a reaction-time task of the wrist and single-cell recordings were made from the motor cortex (eighty-four cells), ventro-posterior lateralis par caudalis (VPLc) (forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. The majority (43/77, 56%) of cerebellar thalamic neurones fired phasically during movement, whereas in the motor cortex most neurones (53/84, 64%) had a phasic-tonic discharge pattern. Most neurones in both locations discharged in relation to the direction of movement (reciprocal pattern). 3. The cerebellar thalamus is unlike the motor cortex in that it does not usually encode a signal for force or joint position in its discharge. 4. Twenty-two per cent (17/77) of cerebellar thalamic neurones had a period of reduced discharge rate before the phasic burst of activity, and represent a pattern of discharge not seen in motor cortex or VPLc neurones. 5. The onset of phasic activity in the cerebellar thalamus was significantly later (average 94 ms) than in the motor cortex but occurred just before electromyogram (EMG) activity. The phasic activity in the cerebellar thalamus usually ended before the phasic component of motor cortex discharge was completed. 6. Phasic activity in VPLc neurones commenced after the onset of EMG discharge and on average 26 ms after the commencement of movement. Most neurones with deep sensory receptive fields fired with a reciprocal pattern, while neurones with cutaneous fields usually fixed bidirectionally in relation to the task. Almost one-third of neurones signalled force and a similar number had discharge levels that encoded characteristics of the joint position. 7. The duration of discharge of VPLc neurones during the voluntary movement was marginally less than the duration of the movement velocity peak and the VPLc may therefore be signalling the duration of the velocity. Phasic activity in cerebellar thalamic neurones fired for a duration similar to the VPLc neurones, but commenced before the movement. Therefore, if the cerebellar thalamus is carrying information about the duration of the velocity, it does so before the movement starts. 8. The phasic burst of activity in cells of the cerebellar thalamus is timed so that it can contribute to the later component of the phasic burst of motor cortical discharge. Thus we speculate that in skilled, ballistic movements, the cerebellum may provide a response which travels via the cerebellar thalamus and helps to determine the magnitude and duration of the phasic part of cortical discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

A frequency analysis of neuronal activity in monkey thalamus, motor cortex and electromyograms in wrist oscillations.

1. Extracellular recordings were made in three monkeys while recording from neurones in the motor cortex (eighty-four cells), ventro-posterior lateralis pars caudalis (VPLc, forty-two cells) and cerebellar thalamus (seventy-seven cells). 2. This experiment was designed to produce active and reflex movements of varying velocities in order to study the relationship between amplitude of velocity and magnitude of neuronal discharge of thalamic neurones. The active movements were voluntary rapid alternating movements (RAMs) of the wrist and the reflex movements were produced by forcibly oscillating the wrist joint between frequencies of 1 and 7 Hz (forced oscillations). 3. This study was also designed to examine cerebellar influences on a reflex path, namely the transcortical reflex loop. Forced oscillations were predicted to provide circumstances where active damping was required to prevent excessive oscillations in the reflex path. Rapid alternating movements of the wrist were predicted to provide circumstances where oscillations at the natural frequency in that reflex path would support and propagate the movements. 4. Forced oscillations from 1 to 7 Hz produced movements of different velocities. VPLc and cerebellar thalamic neurones discharged in relation to the duration of movement in a particular direction, but their discharge levels were unrelated to the magnitude of the velocity. Motor cortex neurones fired in a pattern which was related to the timing but not the magnitude of the acceleration. 5. In forced oscillations of the wrist the resonant frequency was between 3 and 7 Hz. They may be controlled in part by a transcortical reflex. The cerebellar thalamic neurones did not fire before motor cortex neurones. Therefore, it is unlikely that the cerebello-thalamo-cortical pathway is necessary to damp these potentially unstable oscillations by an effect on antagonist-related cortical neurones. 6. Rapid alternating movements (RAMs) of monkeys' wrists were performed in a stereotyped fashion over a narrow range of frequencies with the greatest displacement in joint angle and peak velocity at the natural frequency of 3-5 Hz. 7. During the performance of RAMs, neuronal discharge modulated sinusoidally in the VPLc, cerebellar thalamus and motor cortex. There was no relationship between velocity and neuronal discharge of the cerebellar thalamic and motor cortical neurones but there did appear to be a relationship between velocity and VPLc neuronal discharge. 8. The onset of electromyogram (EMG) discharge changed earlier than neuronal discharge in the motor cortex and thalamus during the performance of RAMs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Motor function of the monkey globus pallidus. 1. Neuronal discharge and parameters of movement.

In order to examine the role of the basal ganglia (BG) in the regulation of basic movement parameters, we recorded extracellularly from pallidal neurons in conscious monkeys during the performance of a sequential wrist movement task which was composed of a series of holds and ballistic jumps. The movement sequence was predictable and had to be performed within specified time restraints. We recorded the activity of 297 neurons whose discharges were related to the movement task. We included only neurons whose discharges were related to movements at or about the wrist joint by prior examination outside the behavioural paradigm. Each neuron discharged preferentially to one direction of movement at or about the wrist joint. No consistent correlation was found between neuronal discharge and initial joint position, static load application, amplitude of movement or velocity of movement. The mean onset of neuronal discharge was 2 ms after the onset of EMG activity. The findings implied little contribution from the pallidal neurons in the execution of the current movement or to the movement's parameters. The implications are that the basal ganglia are likely to be concerned with other aspects of movement control.

Animals↗
PubMed1991

Motor function of the monkey globus pallidus. 2. Cognitive aspects of movement and phasic neuronal activity.

In order to study the role of the basal ganglia (BG) in cognitive aspects of movement, we recorded extracellularly from pallidal neurons in conscious monkeys while they performed a sequential wrist movement task consisting of a series of holds and ballistic jumps. The movement sequence had to be performed within specified time restraints and was predictable. We recorded the activity of 297 neurons whose discharges were related to the movement task. The movement-related response was found to be influenced by the contextual setting and by the degree of difficulty of the task in a subgroup of 82 neurons with a clear response to the first ballistic movement. Predictable and easy movements were usually represented by more prominent movement-related responses in 46% of these neurons; 35% of neurons from a different subset of 105 neurons also demonstrated a second phasic response just before the end of the final hold period of the task. This response was also found to be influenced by the predictability of the final hold period, both in its time duration and also by the direction of the following ballistic movement in double jump tasks. These findings were in keeping with a cognitive role for the BG in movement performance. In particular we suggest that the phasic neuronal activity was an internal cue generated by the BG for predictable movements of a subconscious nature which signals the end of a component of movement in a movement sequence. This cue is appropriately timed to terminate sustained neuronal activity in the SMA and to allow the next movement in the sequence to be executed.

Animals↗
PubMed1991

A heparin-like anticoagulant as part of global abnormalities of plasma glycosaminoglycans in a patient with transitional cell carcinoma.

A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples.

Aged↗
PubMed1990

Heparin-like anticoagulant associated with systemic candidiasis.

A 15 year old girl with aplastic anemia developed a heparin-like anticoagulant during the course of systemic candidiasis. This was initially detected in the laboratory by an elevation of the thrombin clotting time which corrected with toluidine blue but not by mixing with normal plasma. In vivo and in vitro the anticoagulant was remarkably resistant to neutralization by protamine sulfate. Nevertheless, its heparin-like nature was confirmed by its sensitivity to heparinase and its dependence on antithrombin III.

Adolescent↗
PubMed1990

The effect of molecular weight on heparin binding to platelets.

Low molecular weight heparin is reported to be less reactive with platelets than larger heparins. We probed the molecular basis for this pattern of reactivity by characterizing the saturable platelet binding of [3H]heparin in plasma using heparins of different molecular weights (Mr approximately 3000, approximately 5000, approximately 10,000, approximately 15,000). Binding affinity increased with increasing molecular weight, as expressed by decreasing apparent dissociation constants (Kdapp approximately 1.3 microM for Mr approximately 3000, to Kdapp approximately 0.31 microM for Mr approximately 15,000). After adjusting for the effect of antithrombin III in the plasma, true dissociation constants (Kd) could be calculated and these showed the same trend with molecular weight (Kd approximately 1.1 microM for Mr approximately 3000 to Kd approximately 0.096 microM for Mr approximately 15,000). Platelet binding capacity for the different heparin fractions also increased with molecular weight, although this correlation appeared to lessen with the largest species. Heparin antithrombin III affinity was shown not to affect heparin binding to platelets. We propose a model in which heparin binding to platelets is mediated by charge interaction. Larger molecules with more charge bind with greater affinity and to sites with a broader range of electronegativity than do smaller, less

Antithrombin III↗
PubMed1989

Intraventricular infusion of Dopamine in Parkinson's disease.

A patient with severe end-stage Parkinson's disease and troublesome fluctuations in motor function was treated with a long-term intraventricular infusion of dopamine. There was modest improvement in speech and mentation and there was smoother control of motor symptoms that was superior to that achieved by conventional oral medications.

Adult↗
PubMed1979

The afferents and projections of the ventroposterolateral thalamus in the monkey.

In seven monkeys (M. fascicularis), recordings were made from neurones in subnuclei VPLo and VPLc of the thalamus. The peripheral inputs to these cells from the forelimb were established by stimulating muscle, skin and joint nerves, and cutaneous receptive fields were examined by natural stimulation of the skin. The projection of the same cells to motor and sensory cortex was examined by stimulation of the cortex to demonstrate antidromic responses and by retrograde axonal transport of horseradish peroxidase injected into these regions of cortex. Of the 139 neurones which were driven by stimulation of peripheral nerves, 73 were located in VPLo. This suggests that there is a significant projection of forelimb afferents to VPLo in the monkey. Of the 73 neurones located in VPLo, 60 responsed to stimualtion of muscle or joint nerves. The projection to VPLo is therefore predominantly from deep receptors. Twenty-one of these 73 neurones had convergent inputs. The latencies of activation of units in VPLo were short (4--8 ms) and consistent with a lemniscal pathway via the dorsal column nuclei. Injection of horseradish peroxidase into the arm area of the motor cortex labelled cells in VPLo and not in VPLc. The neurones from which recordings were made in VPLo were located within the population of cells labelled with horseradish peroxidase after injections into the primary motor area. This suggests that this subnucleus is the thalamic relay for the sensory input from peripheral receptors to cells of the motor cortex.

Afferent Pathways↗
PubMed1979

Prolonged survival in chronic lymphocytic leukemia: a case report.

A patient with long-standing chronic lymphocytic leukemia with both humoral and cellular immunodeficiency had lymph node receptor evidence of a B lymphocyte disorder. He was also found to secrete the Epstein--Barr virus and, late in his illness, developed a markedly positive antinuclear antibody. Interrelationship of these findings may be important in the ultimate determination of the etiology and functional mechanisms in lymphocyte malignancies.

Adult↗
PubMed1978

Haemoglobin H disease in 2 Filipino families.

Haemoglobin H disease is described in successive generations of 2 Filipino families. The condition was asymptomatic. The inheritance pattern of haemoglobin H disease in these families appeared to be like that described for Thais.

Adolescent↗
PubMed1977

Hemoglobin S Travis: a sickling hemoglobin with two amino acid substitutions [beta6(A3)glutamic acid leads to valine and beta142 (h20) alanine leads to valine).

Hb S Travis is a previously undescribed sickling hemoglobin with two amino acid substitutions in the beta chain: beta6 Glu leads to Val and beta142 Ala leads to Val. The beta6 Glu leads to Val mutation imparts to Hb S Travis the characteristic properties of sickling hemoglobin, namely its association with erythrocyte sickling, the insolubility of the hemoglobin in the reduced form, and a minimum gelling concentration value identical to Hb S. Unlike Hb S, Hb S Travis exhibits an increased oxygen affinity and a decreased affinity for 2,3-bisphosphoglycerate and inositol hexakisphosphate. In addition, the variant hemoglobin's tendency to autoxidize and its mechanical precipitability suggest that there are conformational differences between Hb S and Hb S Travis.

Alanine↗
PubMed1975

"Early-peak" carbon monoxide production in certain erythropoietic disorders.

The "early-labeled" peak (ELP) of 14CO excretion following injection of glycine-2-14C was used to study erythropoiesis in a patient with sideroblastic anemia and in four subjects with myeloproliferative disorders. The ELP was greatly enlarged in all patients, as compared with a normal volunteer. The contour of the peaks from the hematologically abnormal subjects suggested the presence of increased erythroid heme degradation. In the patient with sideroblastic anemia, all hours of the early peak were significantly reduced after transfusion. This was interpreted to mean that even the earliest or "nonerythroid" phase of the peak is influenced by erythropoietic activity, at least under conditions of erythropoietic stress.

Anemia, Sideroblastic↗