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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 451 records · Page 25Linked to original sources
PubMed1984

Acute increases in blood pressure cause arousal from sleep in lambs.

We did experiments to determine whether or not acute increases in blood pressure would cause arousal from sleep. Nine lambs were studied 3-4 days after a balloon-tipped catheter was inserted via the femoral artery into the descending aorta and electrodes for the following recordings were implanted: electrocorticogram, electro-oculogram, electrocardiogram and diaphragm electromyogram. Balloon inflation increased mean arterial blood pressure 27.9 +/- 6.3 mm Hg (mean +/- 1 S.D.) during quiet sleep (QS) and 24.4 +/- 8.9 mm Hg during active sleep (AS). Behavioral arousal occurred from both sleep states but was significantly (P less than 0.05) delayed during active sleep (21.3 +/- 6.7 s) compared to quiet sleep (10.0 +/- 3.3 s). This occurred despite there being a greater percent change in R-R interval for a percent change in mean blood pressure during active sleep (2.68 +/- 1.08) than during quiet sleep (1.55 +/- 0.62). The increases in blood pressure did not produce any significant changes in respiratory rate of integrated diaphragm activity. Thus, acute increases in blood pressure are capable of causing arousal from sleep. This finding should be considered when one discusses the possible mechanisms of arousal from sleep during rapidly developing hypoxemia.

Aging↗
PubMed1984

Modification of Lys-237 on actin by 2,4-pentanedione. Alteration of the interaction of actin with tropomyosin.

It has been possible to specifically label rabbit skeletal muscle actin at Lys-237 with 2,4-pentanedione, producing an enamine. This reaction can be reversed with hydroxylamine. The modification can be carried out with actin in either the G- or F-forms and does not affect polymerization-depolymerization. The modification does affect, however, the interaction of tropomyosin (Tm) with the modified F-actin. In the absence of Ca2+ and Mg2+ (mu = 0.12), Tm failed to bind to the modified F-actin whereas it did bind to unmodified F-actin (1 Tm:7 actins). Tm binding could be restored under these conditions by the addition of either troponin (Tn), Mg2+, or Mg2+ and Ca2+. Under certain conditions, Tm alone has been shown to inhibit actin-activated heavy meromyosin (HMM)-Mg2+-ATPase. This inhibition did not occur with the modified F-actin even though Tm was bound (approximately 1 Tm:7 actins). Even when Tn was added to this system (in the absence of Ca2+), no inhibition of ATPase could be observed. Thus, this modification appears to prevent F-actin X Tm from assuming the "blocking" inhibitory position (conformation). In addition, Tn appears to enhance the activation of heavy meromyosin-Mg2+-ATPase by the modified F-actin X Tm complex whether Ca2+ is present or not. This state may be analogous to the potentiated state (Murray, J. M., Knox, M. K., Trueblood, C. E., and Weber, A. (1982) Biochemistry 27, 906-915) seen with myosin subfragment 1-saturated actin at low ATP levels. Thus, using modified and unmodified F-actin, it is possible to produce three Tm X actin states: off (F-actin X Tm), on (modified F-actin X Tm), and "potentiated" (modified F-actin X Tm X Tn).

Actins↗
PubMed1984

Quasi-elastic light scattering studies on dormant and germinating Bacillus subtilis spores.

Spores of Bacillus subtilis in suspension, both dormant and germinating, have been examined by light-scattering methods, both integrated intensity and correlation versions. When intensity of scatter at constant volume was plotted against angle, curves possessing a maximum at about 20 degrees were regularly obtained but without any noticeable features at higher angles. This indicated polydispersity and/or asymmetry among the population. Curves of the intensity correlation function for both dormant and germinating spores at different angles, theta, did not superimpose at the lower angles when plotted appropriately, but did so for theta greater than 35 degrees. This was considered to arise from asymmetry of the spores. By using the high-angle data the apparent diffusion coefficient was determined for both dormant spores and for germinating spores from 1 min after germinant addition. No appreciable difference was observed, from which volume changes greater than 6% during germination could be excluded. The occurrence of germination was confirmed by both absorbance and phase-contrast-microscopy observations.

Alanine↗
PubMed1984

Two individuals with elliptocytic red cells apparently lack three minor erythrocyte membrane sialoglycoproteins.

We have studied the erythrocytes of two individuals (P. L. and K. W.) who lack the Gerbich (Ge) blood-group antigen. The erythrocytes of P. L. and K. W. were not reactive with two monoclonal antibodies (NBTS/BRIC 4 and NBTS/BRIC 10) which reacted with normal erythrocytes. The membranes of P. L. and K. W. erythrocytes appeared to lack three minor sialoglycoproteins (beta, beta 1 and gamma). These three minor sialoglycoproteins were found to be associated with the cytoskeletons of normal erythrocytes. Approx. 10% of the erythrocytes of P. L. and K. W. were frankly elliptocytic. We suggest that one or more of the minor sialoglycoproteins may play a part in maintaining the discoid shape of the human erythrocyte.

Blood Group Antigens↗
PubMed1984

Calorimetric studies on monomeric and polymeric actin.

Differential scanning calorimetry of polymeric F-actin at pH 8.0 showed that the polymer had a concentration-independent thermal profile with a single transition temperature of 81 degrees C. In contrast, the thermal profile of G-actin was concentration-dependent, and although it resembled the F-actin profile at lower concentrations, it was found to have a more complex profile at higher protein concentrations.

Actins↗
PubMed1984

High affinity epidermal growth factor receptors on the surface of A431 cells have restricted lateral diffusion.

Rhodamine-labelled epidermal growth factor (Rh-EGF) was shown to bind to A431 cells grown at low density both to a small number of high affinity receptors (KD = 2.8 X 10(-10) M; fraction of total binding sites approximately 0.12) and also to a large number of low affinity receptors (KD = 4 X 10(-9) M; fraction of total binding sites approximately 0.88). Measurements of the lateral diffusion of EGF receptors on the cell surface were made using Rh-EGF and the technique of fluorescence photobleaching recovery. The high affinity receptors (labelled with 1.6 X 10(-10) M Rh-EGF, 5% of EGF binding sites occupied) did not show lateral mobility over the temperature range 3 degrees-37 degrees C. The low affinity receptors (labelled with 2.4 X 10(-7) M Rh-EGF, 90% of EGF sites occupied) showed at least 75% fluorescence recovery after photobleaching, and lateral diffusion coefficients of approximately 2 X 10(-10) cm2/s. These results show that the two populations of EGF receptors defined by binding studies differ in their freedom to diffuse laterally. The observation that the high affinity receptors are immobile indicates that lateral diffusion of receptors, at least over a distance of a few hundred nanometres or more, may not be required for the action of low concentrations of EGF.

Carcinoma, Squamous Cell↗
PubMed1984

The fatty acid composition of serum lecithin after pregnancy complicated by pre-eclampsia.

Using gas-liquid chromatography the relative fatty acid composition of serum lecithin was measured in 22 women, during and after pregnancies complicated by pre-eclampsia, and the results were compared with those in 21 "normal" puerperal women. The increased values of 22:6 in the linolenic acid series found during pregnancy in women who had pre-eclampsia were also noted in the puerperium and the 22:6 value fell to normal more slowly. This might be due to an enhanced activity of the deacylation-reacylation cycle in this group of patients. All other fatty acids showed a rapid return to normal with values comparable to those of "normal" puerperal women 1 week after delivery. The differences in essential fatty acid distribution between normal and pre-eclamptic women did not seem to have a dietary cause. The prostaglandin precursors (arachidonic and dihomo-gamma-linolenic acids) were not reduced during pre-eclampsia or in the puerperium. Neither breast-feeding nor treatment of hypertension with hydralazine seemed to influence the fatty composition of serum lecithin.

Adult↗
PubMed1984

Systematic comparison of apomorphine-induced behavioral changes in two mouse strains with inherited differences in brain dopamine receptors.

Dosage and time dependencies of apomorphine-induced changes in stereotyped behaviors (climbing, gnawing and sniffing), locomotor activity and rearing activity were compared in young adult male mice of two inbred strains, DBA/2 and C57BL/6. These two strains are known to differ in their genetically specified brain dopamine receptor number. Apomorphine administered intraperitoneally at dosages of 0.5-20 mg/kg failed to induced stereotyped climbing in DBA/2 at any of the doses tested but markedly increased climbing in C57BL/6 at higher dosages. Apomorphine-induced stereotyped gnawing occurred in both strains at higher dosages although the latency was shorter and maximal effect greater in C57BL/6. Stereotyped sniffing was induced in both strains to a comparable degree at doses greater than or equal to 2.0 mg/kg, and the duration of this stereotypy was indistinguishable between strains. Locomotor activity was inhibited maximally in DBA/2 at an apomorphine dosage of 2 mg/kg and was inhibited to a greater extent than was C57BL/6. Rearing was inhibited in both strains by doses of apomorphine greater than or equal to 0.5 mg/kg; however the duration of the effect was considerably greater in DBA/2 than in C57BL/6. These data suggest that genetically determined differences in central dopamine receptors may have profound and selective effects on behaviors mediated by dopamine pathways; that complex behavioral patterns, e.g., apomorphine-induced stereotypy, may be dissected in to individual components by identifying neuropharmaco genetic differences between strains; that marked strain-specific, inherited differences in dopamine agonist-induced behavioral changes do occur among inbred, non-mutant mouse strains and that their occurrence in other mammalian species including man should be considered.

Animals↗
PubMed1984

Interstrain variation in acute toxic response to caffeine among inbred mice.

Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, SWR/J). C57BL/6J, chosen as a "prototypic" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals.

Animals↗
PubMed1984

Effects of carnosine and anserine on muscle and non-muscle phosphorylases.

Rabbit muscle phosphorylases a and b are activated by carnosine, whereas potato and yeast phosphorylases are inhibited at the same concentration of dipeptide. Rabbit muscle phosphorylase a is activated by anserine whereas the b form enzyme and the potato and yeast enzymes are inhibited by the dipeptide. The dipeptides affect the Vmax values for the enzymes rather than the substrate Km values. Kinetic analysis suggested that, for rabbit muscle phosphorylase, both dipeptides compete for occupancy of the same binding site(s) on the enzyme.

Animals↗
PubMed1984

High resolution bone mineral densitometry with a gamma camera.

A technique is described by which the regional distribution of bone mineral can be determined in bone samples from small animals. The technique employs an Anger camera interfaced to a medical computer. High resolution (less than 1 mm) imaging is possible by producing magnified images of the bone samples. Regional densitometry of femurs from oophorectomised and bone grafted rats demonstrated significant heterogenity of bone mineral loss.

Animals↗
PubMed1984

Erythromycin uptake and accumulation by human polymorphonuclear leukocytes and efficacy of erythromycin in killing ingested Legionella pneumophila.

Studies were undertaken to demonstrate the efficacy of erythromycin in killing Legionella pneumophila organisms that have been ingested by human polymorphonuclear leukocytes. With use of an electron microscope-autoradiography method in conjunction with an antibiotic-uptake assay, it was shown that [3H]-labeled erythromycin A base penetrated into the cytoplasm of human polymorphonuclear leukocytes in concentrations up to 24 times higher than the extracellular drug level. Similar studies using [14C]benzyl penicillin revealed that this antibiotic penetrated human polymorphonuclear leukocytes very poorly. Removal of erythromycin from the extracellular environment resulted in rapid leakage of radioactivity from the cells; an assay for bioactivity showed that this material was unaltered drug. Human polymorphonuclear leukocytes were permitted to ingest L. pneumophila and were then treated with erythromycin A base. The erythromycin killed the ingested legionellae, as evidenced by bacterial plate counts and morphological destruction of ingested organisms. These data clearly demonstrate the efficacy of erythromycin in killing susceptible intracellular pathogens.

Erythromycin↗
PubMed1984

5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice.

The effects of repeated administration of antidepressant drugs or electroconvulsive shock on the binding of [3H]-spiperone to the 5-hydroxytryptamine 2 (5-HT2) receptor in mouse frontal cortex and the 5-HT-mediated head-twitch response have been examined. Repeated electroconvulsive shock increased both the head-twitch response and the number of 5-HT2 binding sites (Bmax). After 35 d but not 24 h or 14 d oral tranylcypromine (5.6 mg kg-1 per day) there was a marked decrease in both the behavioural response and the number of 5-HT2 receptors. Repeated oral doses of zimeldine (20 mg kg-1 per day, 14 days) also decreased the head-twitch response and the number of 5-HT2 binding sites and these effects persisted after 48 h withdrawal. Oral mianserin (2.1 mg kg-1 per day, 14 days) decreased both the behaviour and the number of 5-HT2 binding sites, but this change was also seen after acute (1 day) administration. After 48 h withdrawal from chronic treatment the head-twitch response was still decreased but the Bmax had returned to control values. Desipramine given orally (27 mg kg-1 per day, 14 days) decreased both the behaviour and number of 5-HT2 binding sites. After 48 h withdrawal, binding was still decreased but the head-twitch response was enhanced above control values. In contrast to repeated electroconvulsive shock (ECS), all drugs decreased both 5-HT2 binding and the head-twitch response, while the mice were still on treatment. Binding and behaviour did not correlate after withdrawal. It is concluded that antidepressant treatments do not produce a common alteration in 5-HT2 receptor number and function.

5-Hydroxytryptophan↗