PubMed Health⌕ Search

Biomedical subjects

C Knott

Publications and source records attributed to C Knott.

At least 37 records · Page 2Linked to original sources
PubMed1993

Regional effects of pertussis toxin in vivo and in vitro on GABAB receptor binding in rat brain.

Agonist binding to GABAB receptors modulates the activity of the guanine nucleotide binding proteins, Go and Gi. These G proteins are ADP-ribosylated by pertussis toxin and this prevents them from coupling to the GABAB receptor resulting in a reduction in high-affinity GABAB binding. GTP, which binds to a different site on the G protein alpha subunit, also reduces the affinity of the receptor for the G protein, and this can be used as a "marker" for G protein-GABAB receptor linkage. We have examined GABAB binding site distribution in rat brain after unilateral intrahippocampal pertussis toxin injection in vivo, and after incubating brain slices in pertussis toxin in vitro, using the technique of receptor autoradiography. The effect of pertussis toxin was compared with that of GTP gamma S on GABAB binding. Intrahippocampal pertussis toxin administration reduced GABAB but not GABAA receptor binding and the effects appeared to be limited by pertussis toxin diffusion. More widespread reductions in GABAB binding were seen after incubation of brain slices in vitro but the extent varied in different brain regions. No reduction was detected in the corpus striatum. GABAB binding was also reduced in membranes prepared from cerebral cortex, hippocampus and cerebellum but there was no significant reduction in the corpus striatum after pertussis toxin treatment. GTP gamma S reduced GABAB binding to a similar extent in all areas studied irrespective of their sensitivity to pertussis toxin suggesting that while GABAB binding sites are linked to G proteins throughout the rat brain, those in the corpus striatum may be predominantly pertussis toxin insensitive.

Animals↗
PubMed1992

Vigabatrin in the treatment of complex partial seizures.

We report the effect of vigabatrin on seizure frequency in 13 severely drug-resistant patients with intractable complex partial seizures (CPS) with or without secondary generalization. Patients were followed for a 3-month period before vigabatrin administration to establish a 'baseline'. Six patients became seizure free for 2-3 weeks immediately after starting vigabatrin. In seven patients a transient (4-6 weeks) increase in seizures above baseline occurred, which was attenuated by vigabatrin dose increments. After 3 months, the mean baseline CPS frequency was reduced from 7.75 +/- 1.18 (median 8, range 2.6-16) to 2.77 +/- 0.7 (median 1, range 0-7). At 6 months a > 50% improvement remained in seven patients. After 12 or more months CPS frequency returned to baseline in four patients, improved (by 25-62.5%) in four and deteriorated in three. One patient who was seizure free lost control at 16 months. Other effects were drowsiness (3), weight increase (3), diarrhoea (1), depression (2) and mood elevation (2). Four patients discontinued vigabatrin; one because of severe depression, three owing to lack of efficacy. Three patients have undergone and two are awaiting neurosurgery for their epilepsy. Thus, CPS frequency progressively deteriorated toward baseline in all patients, however, secondary generalizations were abolished in four and reduced in two.

Adolescent↗
PubMed1991

Isolation of hybridoma forming cells from immune spleens by unit gravity sedimentation.

In 1975 a method for the production of hybridomas that secrete monoclonal antibodies was first described (1). Since that time, surprisingly little information has emerged on the identity of the fusible spleen cell. In this report we describe the isolation of hybridoma forming cells from immune spleens and the enrichment of B cell populations in different states of activation. The B cells that reside in immune spleens are comprised of heterogeneous populations that differ in their states of activation. These populations have been difficult to separate and, therefore, difficult to characterize. Two factors that discriminate B cells in different states of activation are cell size and density. Unit gravity sedimentation is a simple, reliable and reproducible method for separating cells based on their size and density. Immune B cells were fractionated on a 10 to 25% serum gradient at unit gravity. Cells were collected and pooled, when necessary, to perform functional assays. Fractionated B cells were assayed for hybridoma formation, PFC response, Ig secretion and proliferation. The cells that exhibited hybridoma formation, PFC activity and Ig secretion were all found in the large cell fractions that comprised less than 10% of the cells recovered from the gradient. Proliferating B cells were found primarily in smaller cell fractions compared to antibody forming cells. Resting B cells were located in the smallest cell fractions recovered from the gradient. Data show that separation of immune B cells by unit gravity sedimentation is an effective means to isolate hybridoma forming cells and enrich for B cell subpopulations in different states of activation.

Animals↗
PubMed1990

Tetanus toxin produces neuronal loss and a reduction in GABAA but not GABAB binding sites in rat hippocampus.

The neuropathological effects of tetanus toxin, microinjected in the rat CA1 hippocampal area, were studied by using a microscopical and autoradiographical approach. Tetanus toxin produced a dose- and time-dependent neuronal loss in the CA1 area accompanied by a reduction in the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to GABAA but not GABAB sites in the pyramidal cell layer.

Animals↗
PubMed1989

Pharmacokinetics in pregnancy and placental drug transfer.

Total body water increases in pregnancy and while the uterus, placenta, fetus, and amniotic fluid constitute part of this increase, the largest component is in the extracellular water. Fat stores also increase and thus the distribution volumes of all drugs expand, but the major effect is seen in polar drugs which are confined to the extracellular space. Cardiac output and renal function also increase and elimination of polar drugs is accelerated. In contrast, the elimination of lipophilic drugs may be retarded, and the effect on intermediate drugs is variable. Polar drugs cross the placenta slowly and accumulate in amniotic fluid and therefore in the fetal gut lumen. Lipophilic drugs cross the placenta rapidly and their transplacental distribution is dependent on relative maternal and fetal affinity: this is determined largely by protein binding on either side of the placenta. The fetus and neonate dispose of all drugs less rapidly than adults, the most efficient elimination processes being sulphate conjugation and renal excretion.

Adrenergic beta-Agonists↗
PubMed1987

Signal processing technique to extract neuronal activity from noise.

A method of extracting extracellularly recorded action potentials from background electronic noise is described. Segments of traces containing stimulus-induced activity are Fourier transformed and the increase in the total power density over that of control noise segments is used as a measure of stimulus-induced neuronal activity. We show first, with observations from the amphibian visual system and mammalian auditory system, that our technique yields similar quantitative information to that obtained from the conventional spike counting method when the recording arrangement is optimal. Moreover, the size and centre of a visual receptive field can be determined even when the evoked action potentials are buried in the background noise. To investigate the potential of this technique further, we have used it to study the auditory responses in the amphibian midbrain. The power spectral density, we demonstrate here, is proportional to the stimulus intensity over a wide range, and varies systematically with stimulus frequency and the direction of sound source. Other possible applications of this technique, together with the theoretical basis for it, are discussed.

Action Potentials↗
PubMed1986

Transfer of fentanyl across the rabbit placenta. Effect of umbilical flow and concurrent drug administration.

The transfer of fentanyl has been studied in the perfused in situ rabbit placenta. Does were infused with fentanyl and, subsequently, with fentanyl plus bupivacaine and pethidine. Antipyrine was infused throughout as an index of materno-fetal exchange. The fetal side of one placenta was perfused artificially with Krebs buffer containing dextran, and the effluent collected from the umbilical vein (uv). Drug concentrations were measured in maternal arterial blood (ma) and uv. Maternal plasma protein binding was also measured. Transfer of fentanyl was intermediate between that of pethidine and bupivacaine (Cuv:Cma for fentanyl was 0.25, for bupivacaine, 0.11 and for pethidine was 0.44), while placental clearance (Cuv X umbilical flow/Cma) increased with umbilical flow between 0.5 and 4.0 ml min-1 for all drugs. When clearances of unbound drugs were calculated, those of bupivacaine, pethidine and antipyrine were similar, but that of fentanyl was higher. The clearance of fentanyl was not affected by the presence of bupivacaine and pethidine.

Analgesics↗
PubMed1986

Extracorporeal circuit sequestration of fentanyl and alfentanil.

Fentanyl or alfentanil, in doses approximating to those used in clinical practice, was added to the priming fluid of an extracorporeal circuit before the institution of cardiopulmonary bypass (CPB). The concentrations of both drugs in the priming fluid were measured over a 20-min period. The concentration of fentanyl decreased at neutral or high pH values, suggesting drug adsorption to the circuit. The concentration of alfentanil was unaffected. The administration of fentanyl to the priming fluid may produce lower anaesthetic concentrations than anticipated.

Adsorption↗
PubMed1986

Phenytoin kinetics during pregnancy and the puerperium.

During pregnancy changes in maternal physiology and plasma composition may alter drug binding and dose requirements. We have measured plasma unbound and total phenytoin, and saliva concentrations at intervals in 11 pregnant epileptics. Plasma albumin concentrations were also measured in pregnant and non-pregnant women. Saliva phenytoin correlated closely with the plasma unbound concentrations (r = 0.98). The saliva:plasma (S:P) ratio, reflecting the free fraction, was variable during pregnancy but tended to increase to maximal values at delivery and return to non-pregnant values within 2-8 weeks thereafter. Plasma albumin concentrations correlated poorly with phenytoin binding. Binding in umbilical cord plasma appeared higher than that in maternal plasma and total fetal concentrations correlated closely with maternal plasma concentrations at delivery. No ill effects of phenytoin were detected in the newborn infant. During the third trimester phenytoin dose increments were necessary to maintain therapeutic concentrations. After delivery maternal saliva phenytoin concentrations rose, and dose reductions were necessary to avoid clinical symptoms of toxicity. It is therefore appropriate to monitor saliva phenytoin concentrations regularly both during pregnancy and the puerperium.

Adult↗
PubMed1986

[Connective tissue reinforcing structures of the digital tendon sheaths of the human hand].

At a greater number of humid preparated human hands, all the ligamentous supports of the digital tendon sheath were exposed and their dimensions were determined. The osteofibrous channels, which contain the long flexor tendons of the digits, were bounded on the one hand by transversely concave shaft areas of the phalanges and the palmar ligaments and on the other side by the fibrous parts of the tendon sheath. From the second to the 5th finger, it has a regular extension of length, which begins proximal at the heads of the metacarpal bones and runs distal to the base of the nail phalanx. In some cases, there is a continuous communication between the digital tendon sheath of the little finger and the carpal synovial sheath. The tendon sheath of the flexor pollicis longus muscle in comparison with it is always in an open communication with the radial synovial sac of the wrist. At the fibrous supports of the digital tendon sheath, one can find constant and inconstant ligamentous structures. Regular shaped ligaments consist of annular fibers (A1 to A5). The proximal complex of fiber supports is a formation of the A1 and A2 ligaments. The band A1 can be divided into 2 ligaments both of roughly equal length, which lay between the head of the metacarpal bone and the base of the proximal phalanx. The strongest fibrous support of the whole digital tendon sheath represents the band A2. It is attached to the midth of the proximal phalanx and increases in strength from proximal to distal. The middle length varies between 6.7 mm at the thumb and 18.7 mm at the middle finger. The distal margin is strengthened by fibrocartilage tissue to be in accordance with the important function as a pulley. The annular band A4 forms the distal supporting complex height above the shaft of the middle phalanx. At the 2nd to the 5th finger it is, with a middle length of 6 to 7 mm, very much shorter than A2 and restrains first of all the tendon of the flexor digitorum profundus muscle. In the area of the interphalangeal joints, we can find the annular bands A3 and A5, which fiber texture is formed variable. Both ligaments are attached on either both sides with the joint capsule and the palmar plate. The other inconstant supports of the digital sheaths are systematically recorded indeed (C1 to C3), but only in exceptional cases they exist of cruciform fibers (Lig. cruciatum).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1985

The effect of airway anaesthesia on the control of breathing and the sensation of breathlessness in man.

The effect on ventilation of airway anaesthesia, produced by the inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter = 4.77 micron), was studied in 12 normal subjects. The dose and distribution of the aerosol were determined from lung scans after the addition to bupivacaine of 99mTc. Bupivacaine labelled in this way was deposited primarily in the central airways. The effectiveness and duration of airway anaesthesia were assessed by the absence of the cough reflex to the inhalation of three breaths of a 5% citric acid aerosol. Airway anaesthesia always lasted more than 20 min. Resting ventilation was measured, by respiratory inductance plethysmography, before and after inhalation of saline and bupivacaine aerosols. The ventilatory response to maximal incremental exercise and, separately, to CO2 inhalation was studied after the inhalation of saline and bupivacaine aerosols. Breathlessness was quantified by using a visual analogue scale (VAS) during a study and by questioning on its completion. At rest, airway anaesthesia had no effect on mean tidal volume (VT), inspiratory time (Ti), expiratory time (Te) or end-tidal PCO2, although the variability of tidal volume was increased. On exercise, slower deeper breathing was produced and breathlessness was reduced. The ventilatory response to CO2 was increased. The results suggest that stretch receptors in the airways modulate the pattern of breathing in normal man when ventilation is stimulated by exercise; their activation may also be involved in the genesis of the associated breathlessness. A hypothesis in terms of a differential airway/alveolar receptor block, is proposed to explain the exaggerated ventilatory response to CO2.

Adult↗