Genetic analyses of gustation in the fowl

Preferences towards quinine sulfate (QS) and dextrose (DEX) were tested in purelines and reciprocal crosses of two lines of chickens that had undergone 22 generations of selection for high and low juvenile body weight. Parental line-F₁ comparisons provided evidence for non-additive genetic variation for hedonic sensitivity towards QS and DEX, though in opposite directions. Additive genetic variation appeared to influence the preference ratios for both stimuli at super-threshold concentrations. These results are discussed with regard to their evolutionary implications.     

Cephalic-phase insulin secretion in normal and pancreatic islet-transplanted rats

The ability of saccharin, in comparison with glucose and tap water, to elicit glycemia-independent neurally mediated insulin secretion was investigated in chronically catheterized, freely moving rats. Plasma glucose and insulin concentrations were measured continuously from venous blood with a sampling resolution of one per minute. In normal rats, 1 ml of 0.15% saccharin caused a significant rapid rise in peripheral plasma insulin levels lasting up to 5 min, without significant changes in glycemia. Tap water alone also induced a transient elevation in insulinemia but was much smaller than the saccharin-induced response. In streptozotocin diabetic rats bearing intrahepatic, presumably denervated islet isografts, these rapid insulin responses to oral saccharin and tap water stimulation were completely abolished, whereas the early insulin response to intravenous glucose was decreased by only about 30%. These results are consistent with the concept of gustatory and other oral sensory signals acting as triggers for neurally mediated insulin release.     

The interaction of lymphocytes with autologous red cells

There is a relatively large degree of adherence of rabbit thymocytes to autologous or homologous mature and nucleated red cells, but not to heterologous red cells. The adherence is augmented by sera and a variety of protein solutions. It is inhibited by 4 × 10⁻³M iodoacetate or pretreatment of red cells by 0.01 to 0.5 per cent trypsin solution. Thymocytes obtained from one- to 7-day-old rabbits adhere to rabbit red cells to a larger extent than do thymocytes of adult rabbits. Significant autologous or homologous thymocyte-red cell adherence also occurred in the rat but not in the mouse or guinea pig. Heterologous adherence was not evident except in mixtures containing guinea pig thymocytes and rabbit red cells or mouse thymocytes and rat red cells. It is postulated that the adherence of thymocytes to the red cells occurs through nonimmune mechanisms and that it is likely to affect the homing patterns of the lymphocytes.     

In vivo release of neurotransmitters in the medial basal hypothalamus of the monkey

Summary In vivo release rates of norepinephrine (NE), epinephrine (E), dopamine (DA), gammaaminobutyric acid (GABA), glutamate (GLU) and beta-endorphin (E) in the medial basal hypothalamus (MBH) of unanaesthetized female macaca fascicularis monkey, and the effects thereon of estrogen (E2) treatment, have been estimated using pushpull perfusion methodology. DA, NE, E, GABA, GLU and E were all detectable in 30 min perfusate fractions. No direct correlation between their release rates and those of LH and PRL could be observed. E2 induced an initial decrease, then an increase, in LH and PRL secretion, and concomitant changes in the release patterns of DA, NE, E. GABA and GLU were apparent. This study demonstrates that in vivo push-pull perfusion methodology may be applied to the unanaesthetized monkey, and when combined with venous catheterization for serial blood sampling may prove to be a powerful tool in the investigation of the central molecular events governing neuroendocrine functions.     

Expression of high-affinity IL-4 receptors on murine tumour infiltrating lymphocytes and their up-regulation by IL-2.

Since interleukin-2 (IL-2) and IL-4 act in concert to support the development of cytotoxic T lymphocytes (CTL) and the generation of antigen-specific tumour infiltrating lymphocytes (TIL), we investigated the interaction of these cytokines with an established TIL line. TIL proliferated in an additive fashion in response to suboptimal concentrations of IL-2 and various concentrations of IL-4. TIL possessed high-affinity IL-4 receptors whether cultured in recombinant IL-2 (rIL-2) or rIL-4, but cells cultured in rIL-2 had higher numbers of IL-4 receptors than cells cultured in rIL-4. When TIL were cultured in increasing concentrations of rIL-2, a dose-dependent enhancement in IL-4 receptor number was observed. The maximum induction of IL-4 receptor expression was achieved by 4 hr of incubation with rIL-2 and was completely blocked by cycloheximide. Other cytokines, such as rIL-1, recombinant tumour necrosis factor (rTNF), recombinant interferon-alpha (rIFN-alpha) and rIFN-gamma, had no effect on IL-4 receptor number. rIL-2 also up-regulated IL-4 receptors on CTLL-2, a murine CTL line. These data indicate that high-affinity IL-4 receptors exist on murine TIL and they can be up-regulated by IL-2. Our observation that IL-2 up-regulates IL-4 receptor may help explain the additive effects of these lymphokines on the proliferation of TIL and other cell lines. It may also help explain their co-operative effects on the generation of antigen-specific TIL and the differentiation of CTL.     

An appraisal of polystyrene-(ELISA) and nitrocellulose-based (ELIFA) enzyme immunoassay systems using monoclonal antibodies reactive toward antigenically distinct forms of human C-reactive protein

The purpose of this study was to compare and contrast two enzyme immunoassay systems: the enzyme-linked immunosorbent assay (ELISA), which utilizes polystyrene microtiter plates as the adsorptive surface and the enzyme-linked immunoflow assay (ELIFA), which utilizes nitrocellulose membranes. The principal parameter under scrutiny was the denaturing or unfolding effects caused by the interaction of the protein with the adsorptive surfaces in each assay system. These effects were monitored by utilizing two conformationally distinct forms of human C-reactive protein (CRP), the native form of CRP and a denatured form (M-CRP), with a corresponding panel of monoclonal antibodies (MAbs) specific to either CRP or M-CRP. The results show that the ELIFA system was less sensitive than the ELISA system but that the ELIFA assay can be completed in less time than the ELISA. Also, adsorption of native CRP to the polystyrene surface in the ELISA system resulted in conformational changes of the adsorbed native CRP protein such that M-CRP reactive determinants were available for binding with anti-M-CRP MAbs, whereas native CRP adsorbed to the nitrocellulose membrane in the ELIFA system resulted in very limited conversion of CRP to M-CRP reactive epitopes. These results have important implications for development of immunoassays and screening of MAbs for proteins whose conformations may be affected by adsorption to various surfaces.     

Immunohistochemical localization of apolipoproteins A-I and B in human carotid arteries

Decreased plasma levels of apolipoprotein A-I (apo A-I) and increased plasma levels of apolipoprotein B (apo B) have been shown to correlate with increased risk of atherosclerosis. While many studies have investigated the plasma levels of these apolipoproteins with regard to their value as predictors of cardiovascular disease, comparatively little is known about their precise tissue localization in atherosclerotic plaques. The purpose of this study was to determine the tissue localization of apo A-I and apo B in atherosclerotic segments of human carotid arteries through the use of immunohistochemical techniques. With tissue samples obtained from surgery and autopsy, apo A-I and apo B were found to be present in atherosclerotic plaques and absent in normal arterial tissue. In the plaques, both apo A-I and apo B were found extracellularly, primarily in the lipid core, but also in connective tissue. In addition, both apo A-I and apo B were found intracellularly in foam cells. This similar intracellular and extracellular distribution of apo A-I and apo B was unexpected, in view of their differing associations with atherosclerosis.     

A placebo-controlled trial of procaterol: A new long-acting oral beta2-agonist in bronchial asthma

Procaterol hydrochloride, a potent beta 2-adrenergic bronchodilator developed in Japan, was evaluated in a double-blind, placebo-controlled study for efficacy and safety in 45 patients (ages 18 to 55 yr) with chronic documented reversible airway disease. After a 1-week placebo washout period, patients were administered either 0.05 mg or 0.10 mg of procaterol or placebo twice daily for 2 wk. Spirometric determinations, vital signs, and ECGs were obtained at 1/2, 1, 2, 4, 6, and 8 hr after the first dose and at the same time intervals after 1 and 2 wk of treatment. Patients recorded on a daily basis peak flow rates, asthma symptoms, need for supplemental aerosol, concurrent medications, and side effects. Spirometry results indicated significant improvement in pulmonary function with both doses of procaterol compared with placebo (P less than 0.05). The larger dose was generally more effective. Bronchodilatation was evident 1/2 hr after dosing and peaked at 2 hr. At 8 hr after 0.10 mg of procaterol, FEV1 was still above predose values. Daily peak flow rates were significantly higher with 0.10 mg than with 0.05 mg (P less than 0.05) and placebo (P less than 0.001). Tremor and nervousness were the most frequent side effects. They occurred in a dose-related frequency, were mild and transient, and occurred early in treatment. No significant drug-related changes were noted in ECGs, heart rate, blood pressure, or clinical laboratory data. Procaterol was found to be an effective, well-tolerated oral bronchodilator with a long duration of action, especially at 0.10 mg twice daily.     

Estrogen-induced maternal behavior in hysterectomized-overiectomized virgin rats.

A single injection of 100 μg/kg estradiol benzoate (EB) either alone or in combination with 0.5 mg progesterone resulted in a significant reduction in the latency for the onset of maternal behavior in hysterectomized-ovariectomized virgin rats as compared to the latencies of groups which either remained intact or were hysterectomized, hysterectomized-ovariectomized, hysterectomized-ovariectomized and treated with 20 μg/kg EB, or ovariectomized-sham hysterectomized and injected with 100 μg/kg EB. In contrast to recent research, there was no shortening of the maternal latencies when ovariectomy or combined hysterectomy-ovariectomy was performed 8 weeks prior to testing while the administration of EB 8 weeks postoperatively was still effective in stimulating short-latency maternal care in hysterectomized-ovariectomized females and increased the percentage of ovariectomized sham hysterectomized animals responding maternally. It was concluded that estrogen is capable of inducing, not suppressing, maternal behavior in virgin rats and that the uterus may play an important but as yet undetermined role.     

Spinal neuronal inhibition and EEG synchrony by electrical stimulation in subcortical forebrain regions of the cat

Summary In cats anaesthetized with sodium pentobarbital and 70% N₂O, single lumbar dorsal horn neurons were excited by controlled noxious radiant heating of glabrous hindpaw skin. The EEG was recorded from the pericruciate cortex and posterior lateral gyrus. Subcortical forebrain sites where electrical stimulation inhibited dorsal horn neuronal heat-evoked responses contralaterally were identified by mapping the caudate nucleus, internal capsule, septum, nucleus accumbens and basal forebrain regions. Inhibitory sites were mainly located in the ventral forebrain (ventral septum, diagonal band, basal forebrain). The caudate nucleus and internal capsule had a low incidence and effectiveness of inhibitory sites. In the basal forebrain, the incidence and effectiveness of inhibitory sites decreased from caudal to rostral regions. There was a rostral limit of inhibitory sites, both medially and laterally. The magnitude of inhibition increased with graded increases in brain stimulation intensity. The mean incremental increase in inhibition was greater for caudal than for rostral basal forebrain sites. Mean stimulus currents for threshold of inhibition and for inhibition to 50% of control heat responses were lower for caudal than for rostral sites. Responses of the dorsal horn neurons to increasing temperatures of noxious skin heating were monotonic linear functions over the temperature range studied (48–53° C). Stimulation in both rostral and caudal basal forebrain decreased the slope of this stimulus-response function, with a greater decrease for caudal sites. Cortical EEG synchronization was evoked by stimulation in the caudate nucleus and rostral basal forebrain. For both regions, most synchronogenic sites did not produce descending inhibition of dorsal horn neurons. The significance of these findings in relation to descending inhibition from other brain regions and stimulation-produced analgesia is discussed.