Thyroid-vitamin A interactions in chicks exposed to 3,4,3',4'-tetrachlorobiphenyl: influence of low dietary vitamin A and iodine

Poultry chicks receiving a low vitamin A semipurified diet and exposed to 3,4,3',4'-tetrachlorobiphenyl became hypothyroid in comparison with unexposed controls. Metabolic rate, total serum thyroxine, total serum triiodothyronine, and food intake decreased significantly while thyroid weight increased. Unexpectedly, growth rate was not affected on this diet. In the case of chicks receiving a low vitamin A--low iodine semipurified diet and exposed to the PCB congener, the hypothyroid response was apparently antagonized. Comparing exposed chicks with unexposed controls, metabolic rate and the proportion of free T3 (i.e., %T3 resin uptake) increased while total serum thyroxine and thyroid weight were unchanged. In addition, growth rate, food consumption, and serum retinol decreased on this diet. These results are interpreted to mean that growth rate may have been altered by circulating levels of retinol, and vitamin A insufficiency may predispose birds to the hypothyroid effects of PCBs.     

Prenatal cocaine exposure disrupts the development of the serotonergic system.

Prenatal cocaine exposure has been found to result in a number of neurobehavioral abnormalities in both clinical and laboratory studies. We have previously shown that cocaine inhibits the growth of developing serotonin neurons in culture. This study examines the effects of cocaine on the developing serotonin system in vivo. Pregnant rats were injected with cocaine (40 mg/kg s.c.) from gestational day 13 to parturition. One group of rats was additionally injected on postnatal days 1-5 with cocaine (10 mg/kg s.c.). [3H]Paroxetine, a selective ligand for the serotonin uptake carrier, was used to quantify serotonin terminal fiber density at one day, one week, and four weeks postnatal. Cocaine exposure was found to significantly decrease [3H]paroxetine-labelled sites and thus the density of serotonin fibers in the cortex and hippocampus at one day and one week postnatal. By four weeks postnatal, no significant effect was observed, indicating that a recovery had occurred. Serotonin immunocytochemistry performed at one month revealed normal fiber distribution in the cortex but a loss of fibers in the CA1 and CA2 hippocampal fields. Postnatal treatment alleviated the effects of prenatal cocaine exposure, resulting in [3H]paroxetine binding levels at one week which were comparable to and, in the cortex, even higher than those of saline controls. We conclude that cocaine delays the maturation of the serotonin system when administered prenatally but may accelerate maturation when administered both pre- and postnatally.     

Receptive-field characteristics of single neurons in lateral suprasylvian visual area of the cat.

The visual receptive fields of 213 cells in the lateral suprasylvian visual cortex (LS, or Clare-Bishop area) were studied in cats anesthetized with nitrous oxide. Eighty-one percent of the cells were directionally selective. They responded poorly to stationary stimuli flashed on or off, but gave a directionally selective response to stimuli moving through the receptive field. Most of these had a single preferred direction and an opposite null direction. They typically responded to a range of directions of stimulus movement from 45 to 90 degrees to either side of the preferred direction. Small stimuli (1-2 degrees or smaller) typically were effective and 87% of the directionally selective cells showed spatial summation. About 32% had inhibitory mechanisms which decreased the response of the cell if the stimulus exceeded a maximum size. There was little or no evidence that LS area cells were orientation selective or sensitive to variations in stimulus shape independent of size.     

Binocular interactions in the cat's dorsal lateral geniculate nucleus. I. Spatial-frequency analysis of responses of X, Y, and W cells to nondominant-eye stimulation

1. X, Y, and W cells in the A and C layers of the cat's dorsal lateral geniculate nucleus (LGN) were tested for responses to stimulation of the nondominant eye. The main purpose was to determine the incidence of nondominant-eye excitation and inhibition among different classes of cells and to examine the spatial-frequency tuning of responses to the nondominant eye. 2. Of 198 cells that were tested with drifting sine-wave gratings presented to the nondominant eye, 109 (55%) showed statistically significant responses. Four types of responses were observed: an increase in the mean discharge rate (F0 excitation), a decrease in the mean discharge rate (F0 inhibition), an increased modulation at the fundamental frequency of the grating (F1 excitation), and a decreased modulation at the fundamental frequency of the grating (F1 inhibition). Overall, 29% of the cells responded with inhibition, 24% responded with excitation, and 2% showed both excitation and inhibition, depending upon the spatial frequency and/or the harmonic response component. The relative incidence of excitation and inhibition was similar for X, Y, and W cells, for cells with on-center and off-center receptive fields, for cells with different receptive-field eccentricities, and for cells in each LGN layer. In addition, within layers A and A1, responses were similar for cells at different distances from the laminar borders. 3. Spatial-frequency response functions indicated that cells could have band-pass or low-pass spatial-frequency tuning through the nondominant eye. Band-pass cells tended to be narrowly tuned (less than or equal to 1 octave), and low-pass cells responded to a broader range of spatial frequencies. These properties were similar for X, Y, and W cells. Spatial resolution tended to be low (less than or equal to 0.8 c/deg for most cells), although a few cells responded to the highest spatial frequency tested (5.4 c/deg). Likewise, optimal spatial frequency was low (less than or equal to 0.2 c/deg) for most cells. These properties were similar for X and Y cells, and there was a weak tendency for X and Y cells to have higher optimal spatial frequencies and spatial resolutions than W cells. 4. In terms of absolute change in activity, responses to drifting gratings were weak. However, cells that were inhibited generally showed 20-60% decreases in activity to the optimal spatial frequency, and cells that were excited generally showed 40-100% increases. Response amplitudes were similar for X, Y, and W cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones

Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4⁺ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H₂-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H₁- and H₃-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H₂-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma.     

Efficacy of HIV-specific and 'antibody-independent' mechanisms for complement activation by HIV-infected cells.

Previous studies in this laboratory have shown that efficient activation of complement (C) on HIV isolates and HIV-infected cells requires the binding of specific anti-HIV antibodies, while other investigators have observed 'antibody-independent' C activation. In an attempt to clarify these disparate findings, we investigated the effect of several variables on C activation by HIV-infected cells using flow cytometric analysis of C3 deposition. Antibody-mediated C activation using pooled sera from infected persons or human MoAbs directed against the V3 region of gp120 was always substantially higher than activation without antibody. Normal human serum (NHS) from a subset of HIV antibody-negative donors did, however, induce low levels of C3 deposition. Differences in C3 activation between the various NHS did not correlate with total haemolytic C levels or mannose-binding protein (MBP) levels. IgM isolated from NHS that induced high levels of C activation was at least partly responsible for the 'antibody-independent' C activation. Although there appeared to be a correlation between NHS that induced C activation and the presence of anti-blood type B IgM, absorption of anti-B did not abrogate the C3 deposition. Additionally, MoAb to the B antigen did not induce C3 deposition. These studies show that IgM in sera from HIV-uninfected donors can induce C3 deposition on HIV-infected cells, but that specific antibody-dependent C activation is substantially more efficient. Therefore, 'antibody-independent' C activation on HIV-infected cells may, in some cases, be more accurately described as HIV-cross-reactive antibody-dependent C activation.