Heterosynaptic expression of depolarization-induced suppression of inhibition (DSI) in rat hippocampal cultures

Depolarization-induced suppression of inhibition (DSI) is a transient suppression of the inhibitory synaptic transmission, observed in the hippocampus and the cerebellum, upon postsynaptic depolarization. Using rat hippocampal cultures, we examined whether DSI is confined to the inhibitory synapses on the depolarized neuron or, if DSI can spread to those on neighboring non-depolarized neurons. Whole-cell recordings were performed in 108 neuronal pairs with the following synaptic responses. Stimulation of one neuron evoked the inhibitory autaptic currents (IACs) recurrently in that neuron and also elicited the inhibitory postsynaptic currents (IPSCs) orthodromically in the other neuron. In 38 of 108 pairs, the postsynaptic depolarization caused transient suppression of IPSCs (homosynaptic DSI). In 11 of the 38 pairs exhibiting the homosynaptic DSI, the depolarization also induced suppression of IACs (heterosynaptic DSI). The heterosynaptic DSI, like the homosynaptic DSI, depended on depolarizing pulse duration and was blocked by a phorbol ester. These results suggest that DSI can spread to the synapses on a neighboring non-depolarized neuron in rat hippocampal cultures.     

Phosphorylcholine antibodies in pulmonary infection

Phosphorylcholine (PC) antibodies in serum from patients with pulmonary infection, and from normal individuals, were studied. Anti-PC antibodies were detectable in the serum from normal individuals at mean concentrations of 320 g/ ml for the IgG class and 110 g/ml for the IgM class. Concentrations of anti-PC antibodies which were higher than normal for both the IgG and IgM classes were observed in the serum in pulmonary infection (1,440 g/ml and 210 g/ml, respectively). Despite the significant difference in the concentration of anti-PC antibodies, the PC-specific B cell precursor frequency in the peripheral blood lymphocytes showed no difference between normal individuals and the patients with pulmonary infection, or between the acute phase and the chronic phase in a single patient with chronic pulmonary infection. Serologically, the purified IgG anti-PC antibody did not share the cross-reactive idiotype of TEPC 15, which is the most common idiotype of the murine anti-PC antibodies. However, the purified IgM anti-PC antibody expressed a very weak cross-reactive idiotype of TEPC 15. It appears from these studies that human anti-PC antibodies may play an important biological role in pulmonary infection by microorganisms which possess a PC determinant.     

Effects of FK506 on rat thymic epithelial cells; immunohistochemical study.

The effects of FK506, a new immunosuppressive agent, on the rat thymus were investigated using the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies. Flow cytometric analysis of the thymus revealed that the proportion of cells labelled positively with OX7 (Thy-1 antigen), OX8 (CD8, T cytotoxic/suppressor cells) and W3/25 (CD4, T helper cells and macrophages) increased following treatment, with FK506, 1 mg/kg body weight for 14 days. A marked reduction of the thymic medulla following treatment was clearly demonstrated by staining with OX18 (MHC class I) and OX6 (MHC class II). Changes produced by FK506 were also observed in the cortical area of the thymus, being especially marked in the subcapsular area and around the blood vessels by staining with OX6, PKK-1 (alpha-cytokeratin), AB-1040 (type IV collagen), and AB-1220 (laminin). Eventually FK506 treatment resulted in patchy reduction of OX-6, PKK-1, AB-1040 and AB-1220 positive area in the cortex. This evidence suggests that FK506 may impair the thymic microenvironment and subsequently disturb the thymocyte maturation.     

Early stage of human adenovirus type 12-inoculated retinal tissue of F344 newborn rat

To elucidate the pathogenesis of adenovlrus type 12 (Ad12)-induced rat retinal tumor, an experimental animal model of human retinobiastoma (RB), DNA analysis, in situ hybridizatlon and immunohistochemlstry were performed. The adenovirus oncogene EIA was detected in the host genome by Southern blot hybridization. Examined retinal tlssues did not show any histological changes, but the number of retinal cells lmmunoreactive with an antibody to proliferating cell nuclear antigen (PCNA) increased with the course of study. In in situ hybridization, E1A gene expression was recognized at the Inner granular layer of the retina at an early stage arer virus inoculation, and subsequently, N-myc gene expression was recognized at the same region. No alteration was found in the retinoblastoma susceptibility gene ( Rb gene) expression. The product of the virus oncogene integrated into the host genome could induce an Increase in N-myc expression, without any abnormality of the Rb gene itself. Results from the present study could be useful in clarifying the tumorige-nesis of this experimental model.     

Responsiveness of the ANP providing system to volume load in conscious dogs

We examined in detail changes in arterial plasma ANP concentration in response to volume load in conscious dogs. In a 5-min volume load experiment, 18 ml/kg of isosmotic and isooncotic 3% Dextran 40 in saline was infused over a period of 5 min. Mean left atrial pressure (MLAP) increased transiently by 7.6±0.9 mm Hg. Plasma ANP level (P-ANP) did not significantly increase. Assayed P-ANP levels were corrected for hemodilution. Corrected P-ANP (C-ANP) significantly increased from 206±17 to 348±34 pg/ml. However, the level of C-ANP did not reach a steady state. No significant linear correlation was found between increases in MLAP and normalized C-ANP. In a 45-min volume load experiment, the elevated level of MLAP caused by the 5-min volume load was maintained for 40 min by supplemental infusion. C-ANP significantly increased from 196±18 pg/ml to 435±73 ng/ml. The level of C-ANP reached a steady state. A close linear correlation was observed between increases in MLAP and normalized C-ANP. However, the peak time of C-ANP lagged 10 min behind MLAP. These results indicate that it takes 10 min for P-ANP to reach a steady state in fully responding to a volume load, and that the long-term volume load is a prerequisite to the response of the ANP providing system.     

Effects of disulfide bond reduction on the excitatory and inhibitory postsynaptic responses of Aplysia ganglion cells.

Three kinds of the cholinoceptive neurons, nicotinic depolarizing (D)-, nicotinic hyperpolarizing (H)-, and muscarinic H-tyes, as well as two other kinds of neurons, GABA H- and dopamine H-types, were identified in Aplysia abdominal ganglion, and the effects of disulfide bond reduction and reoxidation on their postsynape acetylcholine-induced responses of both nicotinic types (D- and H-) were depressed by reducing the disulfide bonds with dithiothreitol (DTT) and restored by reoxidizing with 5, 5' -dithiobis-(2-nitrobenzoic acid): (DTNB), whereas the responses of the muscarinic H-, GABA H-, and dopamine H-cells were not affected at all by either DTT or DTNB. In contrast to the results obtained from the electroplax, the cholinergic receptors in our preparation showed neither the activation by hexamethonium nor the augmentation of decamethonium-induced responses after reduction of disulfide bonds. In addition, our preparation did not demonstrate the long-lasting responses to bromoaTT-induced depression of the nicotinic responses was studied on the dose-response curves; the mode of receptor inhibition was rather complexed, being neither type of competitive nor non-competitive. We concluded that the disulfide bond is a crucial element in both types of nicotinic receptors (D and H), and that this bond is related to the activation process of the receptors regardless of their ionic specificities.     

Calibration of Mg2SiO4(Tb) thermoluminescent dosimeters for use in determining diagnostic x-ray doses to adult health study participants

Characteristics of Mg2SiO4(Tb) thermoluminescent dosimeters (TLD) were ascertained preparatory to measuring doses from diagnostic x-ray examinations received by Adult Health Study participants. These detectors are small, relatively sensitive to low-dose x-rays, and are appropriate for precise dosimetry. Extensive calibration is necessary for precisely determining doses according to their thermoluminescent intensities. Their sensitivities were investigated by dose, according to x-ray tube voltage, and by exposure direction, to obtain directional dependence. Dosimeter sensitivity lessened due to the fading effect and diminution of the planchet. However, these adverse effects can be avoided by storing the dosimeters at least 1.5 h and by using fresh silver-plated planchets. Thus the TLDs, for which sensitivities were determined in this study, will be useful in subsequent diagnostic x-ray dosimetry.