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Biomedical subjects

J W Moore

Publications and source records attributed to J W Moore.

At least 19 recordsLinked to original sources

Study of thromboxane and prostacyclin metabolism in an in vitro model of first-trimester human trophoblast.

OBJECTIVES: The purpose of our study was to establish an in vitro tissue culture system to study eicosanoid metabolism in first-trimester trophoblastic tissue. Thromboxane A2, a potent vasoconstrictor, and prostacyclin, a potent vasodilator, were analyzed to evaluate their production in early pregnancy. STUDY DESIGN: Trophoblastic tissue was obtained via transabdominal chorionic villous sampling from 33 pregnancies at 9 to 12 weeks' gestation for cytogenetic diagnosis. Initially, tissue obtained from the cytogenetics lab was morphologically consistent with villous core cells. Through altering cell density and passage, the cells became morphologically consistent with cytotrophoblasts. The cell lines were exposed to arachidonic acid (50 mumol/L) and aspirin (1 to 100 mumol/L) for 24 hours. Thromboxane B2 and 6-keto prostaglandin F2 alpha were measured by radioimmunoassay. RESULTS: Villous core cells and cytotrophoblasts increased production of thromboxane A2 and prostacyclin in the presence of arachidonic acid (p < 0.002). The villous core cells produced more thromboxane A2 and prostacyclin than cytotrophoblasts (p < 0.02). A significant inhibition of both thromboxane A2 and prostacyclin production was seen in the presence of 100 mumol/L aspirin in both cell types (p < 0.05). CONCLUSIONS: This model may be useful for studying placental function in the first trimester because individual placental compartments can be evaluated in tissue culture. At the cellular level we were not able to detect a preferential decrease in thromboxane A2 production in the presence of aspirin (1 to 100 mumol/L).

6-Ketoprostaglandin F1 alpha

Endogenous plasma sex hormones in pre- and postmenopausal women with breast cancer: results from a case-control study in Moscow.

Plasma sex hormone-binding globulin (SHBG), testosterone, total oestradiol (E2) and proportion of E2 not bound to blood proteins (percentage free E2) have been measured in a case-control study to test whether any of these factors are related to the risk of breast cancer. The cases studied were 27 premenopausal and 34 postmenopausal women with newly diagnosed localized breast cancer who were admitted to the All-Union Cancer Research Centre, Moscow. The controls were an equivalent number of women from the same neighbourhood. These were matched for age (within 2 years) and menopausal status. The average levels of E2 in cases were significantly higher than controls (p = 0.004 and p < 0.001 for pre- and postmenopausal groups, respectively). Percentage free E2 was significantly raised only in premenopausal cases (p = 0.019). The plasma concentrations of testosterone and SHBG were similar for both pre- and postmenopausal groups. Raised E2 or percentage free E2 was associated with an increased relative risk of breast cancer. However, only E2 levels (crude or adjusted for body build) were significantly related to risk in the two menopausal sets (p = 0.022 and p = 0.002, respectively). High percentage free E2 was associated with almost a threefold increase in the risk of breast cancer in premenopausal women; however, this increase was not statistically significant (p = 0.083). The levels of SHBG or testosterone, crude or adjusted for body build and E2 concentration, were not related to risk of breast cancer.

Adult

Verbal fluency: a NART-based equation for the estimation of premorbid performance.

A sample of 142 subjects free of neurological or psychiatric disorder were administered the National Adult Reading Test (NART) and a verbal fluency (VF) test. A highly significant correlation between the NART and VF was obtained indicating that premorbid ability should be taken into account when interpreting VF performance. A regression equation was built to estimate premorbid performance on VF from the NART. A highly significant difference between predicted and obtained VF was obtained in a sample of neurological patients (N = 38). For ease of use, a table converting NART errors to predicted VF scores is presented.

Adolescent

Conditioned inhibition of the nictitating membrane response in rabbits following hypothalamic and mesencephalic lesions.

Rabbits were trained on a Pavlovian conditioned inhibition (CI) task using light as the reinforced conditioned stimulus (CS+) and the same light compounded with a tone as the nonreinforced CS-. The conditioned response was the nictitating membrane response. After attaining a criterion of CI performance, animals received radio-frequency lesions of the hypothalamus (n = 11) or midbrain (n = 14). For the hypothalamic lesion cases, primary damage extended from the optic chiasm to the pretectal region. For the mesencephalic lesion cases, primary damage ranged from the most rostral portions of the periaqueductal grey (PAG) caudally to the tegmental reticular formation at the level of the third nerve. Prior research suggested that the hypothalamic lesions would disrupt retention of CI by increasing responding to the CS-. Except where a lesion impinged upon the zona incerta, no CI disruption was observed. In accordance with previous studies (Berthier, N.E. and Moore, J.W., Physiol. Behav., 25 (1980) 667-673; Mis, F.W., J. Comp. Physiol. Psychol., 91 (1977) 975-988), post-lesioning CI disruption was observed in some of the mesencephalic lesion cases involving the posterior commissure, PAG and/or accessory oculomotor nuclei. However, CI performance recovered over the course of retraining.

Animals

Activity of spinal trigeminal pars oralis and adjacent reticular formation units during differential conditioning of the rabbit nictitating membrane response.

Spinal trigeminal nucleus pars oralis (SpoV) is anatomically linked to brain circuitry thought to subserve unconditioned and conditioned nictitating membrane responses in rabbit. Single-unit recording from SpoV and adjacent reticular formation obtained during conditioning from awake, behaving animals revealed modulation of unit firing related to CS, US, and CR occurrence. SpoV participates directly in the unconditioned response and probably relays US information to other brain areas subserving conditioning. The presence of CR-related activity suggests that SpoV may participate in the CR motor output pathway, and may also provide CR-related information to cerebellum. Sensory convergence and CR-related activity in reticular formation mark this structure as a candidate locus of primary neuronal plasticity in this example of conditioning.

Acoustic Stimulation

Conditioned stimulus duration in classical trace conditioning: test of a real-time neural network model.

In classical trace conditioning, the interstimulus interval (ISI) is equal to the conditioned stimulus (CS) duration plus the trace interval (TI), the interval between CS offset and unconditioned stimulus (US) onset. The Sutton-Barto-Desmond neural-network model of classical conditioning predicts that, with a sufficiently long TI, conditioning will be faster with a CS of relatively long duration than with one of shorter duration. This prediction is illustrated with simulations and tested with the rabbit nictitating membrane response. Animals were trained with a tone CS of 350- or 700-ms duration. The TI was fixed at 300 ms, so that the ISI for the two durations was 650 or 1000 ms, respectively. Another factor in the experimental design was tone intensity (63 or 83 dB). Consistent with the model's prediction, conditioning was faster with the longer ISI, but only with the louder tone. The results have implications for computational models of classical conditioning.

Acoustic Stimulation

Single-unit activity in red nucleus during the classically conditioned rabbit nictitating membrane response.

Previous investigations have suggested that the cerebellum and associated brainstem structures, including the red nucleus, are essential for the expression of the classically conditioned nictitating membrane (NM) response. The present study examined the firing patterns of extracellularly-recorded single units in the red nucleus of the awake rabbit during differential conditioning. Tones were used as conditioned stimulus (CS+ and CS-) and periocular electrostimulation was used as the unconditioned stimulus (US). Most units exhibited one or more changes in firing rate during the presentation of the CS, and increases in firing were much more common than decreases. The onset of some of these changes appeared to be time-locked to the onset of the CS ('CS-locked' responses), while other changes were time-locked to the onset of the CR ('CR-locked' responses). About one-third of all CS-locked changes were CR-dependent, meaning that the neuronal response was reduced when the CR did not occur. About two-thirds of all CR-locked responses preceded the onset of the CR, and lead times varied considerably across units. Many CR-locked units were located in what has been described as a dorsal face region of the red nucleus. Most units responded to the US, and some of the US responses were CR-dependent: i.e., a smaller US response was evoked when a CR preceded the US than when the CR was absent. Our results support the notion that cerebellum-brainstem circuits are involved in generating NM CRs.

Acoustic Stimulation

The mRNAs encoding acidic FGF, basic FGF and FGF receptor are coordinately downregulated during myogenic differentiation.

Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that exert pleiotropic effects in a range of cell types including skeletal myocytes. Previous studies demonstrate that exogenously supplied FGFs stimulate proliferation of myoblasts and inhibit their differentiation in culture, but little information is available concerning endogenous expression of FGFs by skeletal myocytes. In this study acidic and basic FGF mRNAs were found to be expressed in murine and rat skeletal muscle, and expression was demonstrated to vary with the tissue and species examined. Myogenic cell lines were then analyzed to determine if FGFs are expressed in myoblasts, and if so, whether expression is regulated during myogenic differentiation. Murine Sol 8 and rat L6 myoblasts were found to express acidic and basic FGF mRNAs, and the expression of both growth factors was downregulated at the transcriptional level during myogenic differentiation. A decrease in expression of the mouse homologue of the human FGF receptor paralleled the decrease in acidic and basic FGF mRNAs in Sol 8 cells, indicating that the decrease in FGF receptor abundance previously observed during myogenic differentiation is regulated at the mRNA level. The results of this study suggest that a coordinate decrease in endogenously produced acidic and basic FGFs and their cognate receptor may participate in the regulation of myogenic differentiation. Furthermore, the observation that expression of a myogenic determination gene, myogenin, increases as FGF transcripts decline, together with previous data demonstrating suppression of myogenin expression by FGF, suggest a mechanism whereby endogenously produced FGFs may exert their effect on differentiation.

Animals

Propagation of action potentials in squid giant axons. Repetitive firing at regions of membrane inhomogeneities.

Effects of reduction in potassium conductance on impulse conduction were studied in squid giant axons. Internal perfusion of axons with tetraethylammonium (TEA) ions reduces G K and causes the duration of action potential to be increased up to 300 ms. This prolongation of action potentials does not change their conduction velocity. The shape of these propagating action potentials is similar to membrane action potentials in TEA. Axons with regions of differing membrane potassium conductances are obtained by perfusing the axon trunk and one of its two main branches with TEA after the second branch has been filled with normal perfusing solution. Although the latter is initially free of TEA, this ion diffuses in slowly. Up until a large amount of TEA has diffused into the second branch, action potentials in the two branches have very different durations. During this period, membrane regions with prolonged action potentials are a source of depolarizing current for the other, and repetitive activity may be initiated at transitional regions. After a single stimulus in either axon region, interactions between action potentials of different durations usually led to rebound, or a short burst, of action potentials. Complex interactions between two axon regions whose action potentials have different durations resembles electric activity recorded during some cardiac arrhythmias.

Action Potentials

Nonlinear cable equations for axons. I. Computations and experiments with internal current injection.

Steady-state potential and current distributions resulting from internal injection of current in the squid giant axon have been measured experimentally and also computed from nonlinear membrane cable equation models by numerical methods, using the Hodgkin-Huxley equations to give the membrane current density. The solutions obtained by this method satisfactorily reproduce experimental measurements of the steady-state distribution of membrane potential. Computations of the input current-voltage characteristic for a nonlinear cable were in excellent agreement with measurements on axons. Our results demonstrate the power of Cole's equation to extract the nonlinear membrane characteristics simply from measurement of the input resistance.

Animals

Nonlinear cable equations for axons. II. Computations and experiments with external current electrodes.

We have investigated the steady-state potential and current distributions resulting from current injection into a close-fitting channel into which a squid axon is placed. Hybrid computer solutions of the cable equations, using the Hodgkin-Huxley equations to give the membrane current density, were in good agreement with experimental observations. A much better fit was obtained when the Hodgkin-Huxley leakage conductance was reduced fivefold.

Animals