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Biomedical subjects

H Gibson

Publications and source records attributed to H Gibson.

At least 37 records · Page 2Linked to original sources

Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei.

The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2j mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2j mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.

Animals↗

Mechanisms resisting fatigue in isometrically contracting human skeletal muscle.

Human adductor pollicis was fatigued during circulatory occlusion by supramaximal stimulation via the ulnar nerve using intermittent trains of stimuli in ascending (1, 10, 20, 50 and 100 Hz) and descending (100, 50, 20, 10 and 1 Hz) frequencies to investigate the contribution of relaxation rate slowing and post-tetanic potentiation (PTP) to fatigue resistance. At 50 and 100 Hz force was initially well maintained despite a marked loss of excitation as indicated by EMG, demonstrating the operation of a high-frequency 'safety factor' which appeared independent of the pattern of stimulation. At 10 Hz, force was initially potentiated before declining during both activity series. Potentiation was greater during the descending frequency series and the rate of decline of force, or fatigability, was reduced. The 'extra' low-frequency potentiation at 10 Hz was not simply the result of PTP of twitch force, since this declined more during the descending than during the ascending series, nor the result of maximal relaxation rate changes which were identical for both fatiguing series. It is hypothesized that the extra potentiation and reduced fatigability at low stimulation frequencies, when preceded by high frequency, is the result of increased myofibrillar Ca2+ availability and/or sensitivity. These findings may have important practical implications in relation to functional electrical stimulation techniques as used in paraplegia and in other areas of muscle research where fatigue is to be minimized.

Action Potentials↗

Human muscle fatigue: frequency dependence of excitation and force generation.

1. Human adductor pollicis was fatigued using intermittent trains of programmed stimulation at 1, 10, 20, 50, 100 and 1 Hz, during activity with and without circulatory occlusion, to investigate the relationships between force generation, excitation and maximal relaxation rate (MRR). 2. The relationship between force generation and excitation was markedly dependent on stimulation frequency. Force loss was greatest at low frequencies, with little reduction in excitation, but as frequency increased force was well maintained despite marked loss of excitation. 3. Changes in MRR during activity and recovery were independent of stimulation frequency. 4. Marked increases of force at 1 Hz (pre-tetanic) and 10 Hz occurred, with little reduction in excitation, during activity with and without circulatory occlusion. This may be due to post-tetanic potentiation in addition to slowing of relaxation (MRR). 5. At high frequency a 'safety factor' may thus operate to maintain force, despite obvious loss of excitation, while at low frequencies there may be marked potentiation of force, despite unchanged excitation. These mechanisms could permit resistance to fatigue with muscle function remaining optimal over a range of conditions.

Action Potentials↗

Cardiogenic shock in right ventricular infarction managed with a combined thermodilution and pacing pulmonary artery flotation catheter.

When cardiogenic shock complicates right ventricular infarction it is widely appreciated that rational therapy can only be achieved by use of plasma volume expansion and inotropic agents guided by invasive monitoring (Cohn et al., 1974). In these cases, there is a high incidence of symptomatic heart block and serious atrial and ventricular dysrhythmias (Cohn, 1979). Thus, venous access may be required for monitoring, pacing, infusion of fluid, and vasoactive or antiarrhythmic drugs. A case of right ventricular infarction complicated by cardiogenic shock, heart block, multiple arrhythmias and severe hypoxaemic respiratory failure is described. Technical problems in venous access were encountered and overcome by the use of a single multi-purpose catheter for haemodynamic monitoring, infusion of drugs and fluids and passage of a pacing wire. We believe that this is the first description of the use of such a catheter in the United Kingdom, although the use of a multi-purpose pulmonary artery flotation catheter with fixed pacing electrodes has been described before (Zaidan & Freniere, 1983).

Aged↗

A new static sampler for airborne total dust in workplaces.

This paper describes the development and laboratory testing of a new static dust sampler for airborne total dust in workplaces. Particular attention is paid to designing the sampling head and entry consistent with the concept of inspirability which in turn defines a biologically-relevant aspiration efficiency. The sampling head has a small cylindrical body and a transverse entry slot with thin protruding lips forming an integral part of a weighable capsule containing a 37 mm filter which collects all of the sampled dust (without introducing errors due to external particle blow-off or internal wall losses). A battery-powered sampling pump provides both air suction at 3 L/min and rigid mounting for the sampling head. The sampling head is rotated continuously through 360 degrees at approximately 1.5 rpm by a simple electric drive, connected to the stationary pump through a rotating seal. Wind tunnel testing of the instrument showed it to display an entry efficiency very close to the inspirability curve of Vincent and Armbruster (now recommended by the ACGIH Technical Committee on Air Sampling Procedures for defining inspirable particulate matter (IPM] for particles of aerodynamic diameter up to 90 micron and for windspeeds in the range of one to three m/sec.

Aerosols↗

Concentrating ability of lymphatic vessels.

The fluid from implanted capsules was analyzed for plasma proteins and compared with fluid sampled from small lymphatics which drained the region of the implanted capsules. The plasma protein concentration of capsular and lymphatic fluids were not found to be statistically different, for capsules implanted for greater than one month. Capsules implanted for less than one month demonstrate a much higher total protein than lymphatic fluid. This difference is thought to be due to several factors: (1) length of time that capsule has been implanted, (2) inflammation surrounding capsule, (3) time lag between sampling of lymphatic and tissue fluids. If capsules were used that had been implanted for greater than 1-1/2 months, then capsular and lymphatic fluids are not statistically different. A model is presented which predicts that the small initial lymphatics could or could not concentrate plasma proteins depending on the fate of the leaked fluid. The concentrating ability of the initial lymphatics will depend on whether or not the fluid leaked from the initial lymphatic is large relative to the surrounding volume, the time course of protein diffusion to the vicinity of the lymphatic and the rate of fluid removal from the space immediately surrounding the lymphatic. While there is a distinct possibility, since the forces exist, for a concentrating mechanism in larger lymphatic vessels, the data from implanted capsules indicate that we can assume that lymphatic vessels, especially in the subcutaneous region, contain plasma protein concentrations that are fairly representative of the tissue fluids of that region.

Animals↗