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Biomedical subjects

K Foster

Publications and source records attributed to K Foster.

33 records · Page 2Linked to original sources

Cloning and expression of a cDNA encoding a catalytically active fragment of calf thymus DNA polymerase alpha.

A calf thymus cDNA expression library was constructed in the EcoRI site of lambda gt11 and probed with an antibody raised against calf thymus DNA polymerase alpha. Three classes of antibody-reactive clones were isolated. The largest class carried a 1.9 kilobase calf cDNA insert and expressed a 165-175 kilodalton beta-galactosidase:calf fusion protein which displayed DNA polymerase activity. The characteristic responses of the polymerase activity to alpha-specific inhibitors and antibodies identified the 1.9 kilobase cDNA as a sequence specifically derived from the structural gene encoding the pol alpha catalytic core.

Base Sequence

Effects of acipimox, a nicotinic acid derivative, on lipolysis in human adipose tissue and on cholesterol synthesis in human jejunal mucosa.

The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10(-5) mol/l) fell by 40 and 25% respectively (P less than 0.025 and P less than 0.025) in the presence of acipimox (10(-5) mol/l). In submaximally stimulated adipose tissue (isoprenaline 10(-7) mol/l) acipimox (10(-4) mol/l) fully inhibited release of fatty acids (P less than 0.05) and glycerol (P less than 0.025) to basal rates. In unstimulated adipose tissue acipimox (10(-3) mol/l) reduced the rate of glycerol release (P less than 0.05), but not the rate of fatty acid release. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2-14C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2-14C]acetate incorporation into sterols from 8.7 +/- 2.1 (mean +/- standard error) to 3.7 +/- 1.0 pmol h-1 mg-1 of tissue (P less than 0.01). Acipimox at 10(-4)-10(-2) mmol/l had no consistent effect on cholesterol synthesis. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.

Adipose Tissue

Arachidonate synthesis and uptake in isolated guinea-pig megakaryocytes and platelets.

Arachidonic acid (20:4) synthesis and uptake were studied in guinea-pig megakaryocytes and platelets. Isolated megakaryocytes and platelets were incubated with [3H]20:4, 8,11,14-[14C]eicosatrienoic acid (gamma-20:3) and [14C]linoleic acid (18:2) and their lipids were analyzed for radioactivity. The study showed that there was 0.153 microM of unesterified 20:3 and 0.237 microM of 20:4 in guinea-pig plasma in nonfasting animals. At these concentrations, 42.6 pmol of gamma-20:3 and 53.3 pmol of 20:4 were taken up per h per 10(5) megakaryocytes in vitro. Megakaryocytes desaturated 27% of the gamma-20:3 to 20:4 but could not desaturate 18:2. Platelets could not desaturate gamma-20:3 or 18:2. In megakaryocytes, the distribution of 20:4 synthesized by the desaturation of gamma-20:3 and 20:4 taken up reflected the endogenous distribution of 20:4 in megakaryocyte phospholipids and 20:4 was predominantly incorporated into phosphatidylethanolamine (PE). In contrast, the distribution of [3H]20:4 taken up into platelets did not reflect the endogenous distribution. 20:4 was primarily incorporated into platelet phosphatidylcholine and phosphatidylinositol. The study showed that megakaryocytes but not platelets possess a delta 5 desaturase and can synthesize 20:4 from gamma-20:3. Neither cell was shown to have a delta 6 desaturase. Megakaryocytes appear to have the capacity to determine the composition of all pools of platelet 20:4 either by uptake or synthesis of 20:4. Platelets, most likely, have a limited capacity to alter structural pools of 20:4 contained primarily in PE and phosphatidylserine (PS).

8,11,14-Eicosatrienoic Acid

Absence of age-related ploidy changes in a fish with indeterminate growth.

We considered the problem of age-related increase in ploidy of liver cells in the oyster toadfish Opsanus tau using a cytofluorometer. Over 90% of toadfish liver cells are diploid, and the ratio of diploid to tetraploid to octaploid cells remains constant in 3- to 11-year-old fish. The absence of ontogenetic increases in ploidy in toadfish, as opposed to mammals, correlates with fish patterns of indeterminate growth and plasticity.

Aging

Anterior thalamic lesions and neuronal activity in the cingulate and retrosplenial cortices during discriminative avoidance behavior in rabbits.

Bilateral electrolytic lesions of the anteroventral (AV) nucleus of the thalamus given after training impaired retention performance (extinction and reacquisition) of rabbits in a differential avoidance conditioning task. In addition, the lesions abolished the excitatory, discriminative multiple-unit discharges that had developed in the cingulate and retrosplenial cortices to the auditory conditional stimuli (CSs) during the course of behavioral acquisition, prior to the induction of the lesions. The excitatory discharges were supplanted in the subjects with lesions by CS-elicited reduction of neuronal firing to levels below the prestimulus baseline. Lesions given before training did not disrupt behavioral acquisition, but they did eliminate the excitatory tone-elicited neuronal discharges that normally occur in the cortex before and during training. The CS-elicited reduction of neuronal firing did not occur at the beginning of training in the subjects given lesions before training, but it developed during the course of training. The lesions did not eliminate the excitatory and discriminative neuronal activity of the prefrontal cortex. These results demonstrate that excitatory and discriminative neuronal discharges in the cingulate and retrosplenial cortices are critically dependent on the connections of these areas with the anterior thalamic nuclei. Also the lesion-induced disruption of performance during extinction and reacquisition but not during original learning confirms a prediction from past electrophysiological studies, that the AV thalamic nucleus is involved in the mediation of the maintenance and retention of the conditioned avoidance behavior, but not in its original acquisition.

Animals

Cingulate cortical and anterior thalamic neuronal correlates of the overtraining reversal effect in rabbits.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training, following differential conditioning of a locomotory (wheel rotation) avoidance response. The CS+ and CS- were pure tones (1 or 8 kHz) and the UCS was a footshock delivered through the grid floor of the wheel. One group of the rabbits received original training to a criterion followed immediately by reversal training. A second group received training to criterion followed by additional training sessions (overtraining), prior to reversal training. The results indicated that the overtraining reversal effect (ORE) occurred. That is, the overtrained subjects acquired the reverse discrimination in significantly fewer sessions than the non-overtrained subjects. The overall (non-discriminative) neuronal reactivity in all cingulate cortical laminae was reduced by overtraining, whereas the overall reactivity of the AV thalamus was enhanced. In addition, the non-overtrained subjects manifested a discriminative neuronal response appropriate to the original task (i.e. a greater response to the CS- than to the CS+ for reversal training), throughout the precriterial sessions of reversal training. This persistent 'original habit effect' occurred only at brief latencies (20-30 msec) after CS onset, and only in the deep cortical laminae (V-VI). The neuronal activity of the superficial laminae (I-IV) in non-overtrained subjects underwent a transition, in parallel with the behavior, from a discriminative response appropriate to the original task to one appropriate to the reversal task. No significant training-related changes were seen at any cortical depth in the overtrained subjects. Presentation of non-contingent footshocks during two sessions of reversal training following criterion re-enhanced the overall reactivity and the brief-latency discriminative neuronal response appropriate to the original task, which had undergone decline during reversal training, in the deep cortical laminae of the non-overtrained subjects. The enhanced overall reactivity and the discriminative activity in the superficial laminae of non-overtrained subjects had not declined during reversal training and were not altered by the non-contingent footshocks. The implications of these data are discussed in regard to the neural causation of the ORE.

Animals

Red cell size and the clinical and haematological features of homozygous sickle cell disease.

The contribution of red cell size (mean cell volume) to the clinical and haematological manifestations of homozygous sickle cell (SS) disease has been investigated by comparing the features of two groups of patients with low (less than or equal to 80 fl) and high (greater than 95 fl) MCV values after matching for age, sex and fetal haemoglobin level. The microcytic group manifested significantly higher Hb, PCV, RBC and HbA2 levels and significantly lower reticulocyte and irreversibly sickled-cell counts. Clinical features were not less severe in the microcytic group, splenomegaly persisting for longer and painful crises were more common although the latter difference did not reach significance. The milder haematological picture associated with decreased intravascular sickling was not reflected in a more mild clinical course. It is postulated that the higher viscosity accompanying the higher haemoglobin levels in microcytic patients may offset the rheological advantages of decreased intravascular sickling.

Adolescent

Early and late acquisition of discriminative neuronal activity during differential conditioning in rabbits: specificity within the laminae of cingulate cortex and the anteroventral thalamus.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus was recorded during discriminative conditioning of an avoidance response (locomotion) in rabbits. The results indicated a greater unit response in cingulate cortex to the positive conditional stimulus (CS+; a tone paired with a footshock unconditional stimulus [UCS]) relative to the negative conditional stimulus (CS-; a tone randomly interspersed with the positive stimuli but never paired with the UCS). The majority of neuronal records obtained from the deep laminae (V and VI) of cingulate cortex manifested first neuronal discrimination in the session of first exposure to conditioning. However, the majority of neuronal records of the superficial laminae (I-IV) showed first discrimination at a late stage of training, during the session in which the criterion of behavioral discrimination was met. The late developing discriminative activity of the superficial laminae was coincident with the late developing discriminative activity of the AV thalamus. Once acquired, neuronal discrimination in cortex persisted throughout 600 msec after CS onset, and during six sessions of training (overtraining) beyond criterion. Analysis of individual neuronal records suggested that the persistence during overtraining resulted from replacement of early fading neuronal discriminations by late neuronal discriminations.

Animals

Cingulate cortical and anterior thalamic neuronal correlates of reversal learning in rabbits.

Unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training following differential conditioning of a locomotory (wheel rotation) avoidance response. The positive and negative conditional stimuli (CS+ and CS-) were pure tones (1 kHz and 8 kHz), and the unconditional stimulus was footshock (1.5 mA). During the first session, activity appropriate to the original task (i.e., a greater neuronal response to the CS- than to the CS+) occurred in the deep cortical laminae (V and VI), but the superficial laminae (I-IV) manifested the original discrimination in certain records and the reverse discrimination in others. All discriminative effects diminished during subsequent sessions except the short-latency (25-msec) deep laminar original discrimination, which persisted throughout reversal training. Activity of the AV nucleus underwent gradual transition, in parallel with the behavior, from the original to the reverse discrimination. Arousal-producing footshocks given after behavioral reversal educed the original and reverse discriminations in the deep and superficial laminae, respectively. These data are interpreted to indicate the role of cingulate cortex and anterior thalamus for encoding the associative significance of the conditional stimuli.

Animals

Effects of distribution of the drug unconditioned stimulus on taste-aversion learning.

Rats injected with lithium chloride after exposure to a taste or olfactory stimulus learn stronger aversions to these cues if the drug is administered in two small injections 35 min apart than if all of the drug is given in a single injection. This facilitation of conditioning produced by distribution of the drug unconditioned stimulus occurs with both low and high lithium doses (Experiments 1 and 2), is more evident in male than in female rats (Experiment 1), and is directly related to the amount of the flavored solution consumed prior to drug treatment (Experiment 4). Increasing the interval between two small drug injections beyond an optimal value results in a progressive loss of the facilitation of conditioning (Experiments 2 and 3), and the optimal drug distribution interval may be shorter for olfactory cues (Experiment 3) than for taste stimuli (Experiments 1 and 2). Control observations (Experiments 5A and 5B) showed that the drug distribution effect is not due to handling or other non-drug factors involved in giving two rather than only one injection. The phenomenon is consistent with recently-proposed models of conditioning and suggests that the differential effectiveness of various drugs in taste aversion conditioning may be related to differences in the time course of the unconditioned drug effects.

Animals

Income of the population aged 55 and older, 1976.

This article inaugurates a biennial series of reports on the income of persons aged 55 and older. The survey on which it is based updates information on the broad economic picture for a cross-section of this population and forms the basis for an analysis of trends in the financial status of the group as a whole. In 1976, persons aged 55--61 were generally working full-time, not receiving income from pensions, and married. Those aged 73 and older were predominantly not working, mostly recipients of retirement pensions, and likely to be widows. Most persons aged 65 and older were receiving social security benefits; those with neither earnings nor a second pension constituted the largest subgroup and had the lowest median income. Married couples, as a group, were substantially better off financially than nonmarried persons because they were younger, two-person rather than one-person units, and had one member who was a man. Blacks were less likely than whites to receive pension income other than social security benefits, and their median benefits and earnings were both lower.

Black or African American

Skin burns from electrosurgical current.

At 34 skin sites on anesthetized pigs, graded levels of average electrosurgical current density, J (A/cm2), at 500 kHz were delivered for specified times (t sec) to cause thermal injury. The severity of cutaneous response was determined by gross and microscopic study 56 hours later. The product J2t has been defined as the relative energy density factor, and is proportional to the delivered energy that determines skin heating. Nine of 10 sites that received low energy density factor exposure (J2t = 0.20-0.70 A2/cm4.sec-1) exhibited maximum skin temperatures of 38-47 degrees C beneath the electrodes, and subsequently has either no damage or as mild second-degree burn lying just beyond the electrode contact zone. At 9 of 11 sites exposed to a medium energy density factor (J2t = 0.70-1.60), the maximum skin temperatures below the electrodes were between 49 and 55 degrees C, with single or multiple rings of second-degree burns located just inside or beyond the rim of the electrode. At all 13 sites exposed to high energy density (J2t = 1.60-7.50), the maximum skin temperatures beneath the electrodes were 55-81 degrees C, and severe burns were produced with white to brownish, dry, firm, third-degree burns surrounded by peripheral rings of second-degree burns. No significant skin damage was produced with skin temperatures less than 45 degrees C (an energy density factor of 0.75). These data identify the temperature and energy density factor necessary to produce lesions on porcine skin.

Animals