Murine Trophoblast Failure and Spontaneous Abortion

PROBLEM: Infection has been proposed to initiate abortion, and the role of viruses in spontaneous resorption in mice has not been tested. METHOD: The anti-viral drug ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was fed to CBA/J and C3H/HeJ female mice beginning on the morning after mating with DBA/2J males. RESULTS: Ribavirin treatment increased the rate of abortion (resorption) on day 13.5, and this was associated with retardation of the rate of embryo development and hypoplasia of the trophoblast. There was a reduction in trophoblast-dependent decidua-associated soluble suppressor activity, but there was no maternal mononuclear cell infiltrate of the type reported in association with resorption of semiallogeneic and xenogeneic mouse embryos. This may be due to an immunosuppressive effect of ribavirin. Ribavirin was able to potently suppress proliferation of mouse trophoblast and mastocytoma cell lines in vitro. CONCLUSIONS: There are several drug-induced murine abortion models that provide useful insights into potential mechanisms underlying spontaneous pregnancy failure, but in the ribavirin model, a direct impairment of trophoblast development appears to be responsible.     

Local blood flow and metabolism of the tongue before and during panting in the dog

Summary The effects of hyperthermia on blood flow and oxygen consumption of the tongue were investigated in anesthetized dogs. For comparison, blood flow through the skin and deep muscle of the hind leg was also measured in some animals. Increasing blood temperature revealed a biphasic response of lingual blood flow. At 41°C blood temperature respiratory frequency was twice that of control and there was a reduction of lingual blood flow, while resistance of the lingual bed was increased significantly. The arterio-venous oxygen difference (AVDO₂) of lingual blood was markedly increased at this level and the of the tongue was like-wise significantly greater than control. At 41.9°C, the steep increase of respiratory frequency was accompanied by a marked fall in lingual resistance as evidenced by a four-fold increase of lingual blood flow. The systemic AVDO₂ rose at this temperature, while the lingual AVDO₂ fell dramatically. There was no further increase of lingual . At both temperature levels the blood flow through the skin did not change substantially, while the deep muscle blood flow slightly increased. The mean arterial pressure showed a progressive fall during hyperthermia. It is assumed that the decrease of lingual blood flow at elevated blood temperature without panting is due to a redistribution of cardiac output to areas other than the tongue. The increase of lingual blood flow without an additional increase of lingual during panting may be explained solely as a mechanism for heat dissipation. The fact that the decrease of lingual resistance was demonstrated in immobilized animals concomitant with high frequency phrenic burst activity suggests that the decrease of lingual resistance and panting may be induced by a common central integrating mechanism.     

Mechanisms of respiration and phosphorylation in Ascaris muscle mitochondria

In Ascaris muscle mitochondria the major respiratory chain-linked phosphorylation activity is accomplished by a NADH-linked reduction of fumarate to succinate. Oxygen can also be employed as a terminal electron acceptor via a cyanide- and salicyl-hydroxamate-resistant terminal oxidase. As in fumarate-dependent electron transport this process appears to be coupled to energy conservation at phosphorylation site I. The branchpoint from which electrons are taken from the main respiratory chain to either the alternative oxidase or fumarate reductase is likely to be on the oxygen side of the NADH dehydrogenase segment.Malate and succinate are the only substrates which appreciably support respiration in the mitochondrion of the nematode. Regardless of the presence or absence of oxygen malate is utilized by an oxidation-reduction reaction resulting in the formation of pyruvate, acetate, succinate, propionate and CO₂. In addition, aerobically, hydrogen peroxide is formed as the product of oxygen reduction. Succinate accumulation was found to be significantly higher in the anaerobic as compared to the aerobic incubation mixtures. This effect was accompanied by an increase in anaerobic malate consumption. ATP generation and the formation of pyruvate, acetate and propionate were found to be similar in the presence and absence of oxygen.In malate-supported respiration of intact Ascaris mitochondria reducing equivalents (NADH) are produced exclusively through pyruvate and acetate formation. These enzymatic reactions are functionally coupled to the electron transport-linked reductions of fumarate to succinate and oxygen to hydrogen peroxide, respectively. In accordance with the position of the redox potentials of the fumarate/succinate and O₂/H₂O₂ couples, anaerobic and aerobic respiration was found to be associated with relatively low energy conservation efficiencies. Thus one molecule of ATP was conserved per 2e^? transferred to fumarate or oxygen, respectively. No evidence could be obtained for a significant activity of energy conservation sites II and III and electron transfer through the alternative oxidase pathway was shown not to be coupled to phosphorylation.     

In vivo electrical characteristics of human skin, including at biological active points

The aim is to compare the mean values of the in vivo electrical characteristics of bioiogical active points (BAPs) with those of the surrounding human skin. The impedance measurements at BAPs and on the surrounding skin are carried out in vivo on ten young, healthy people. The results of the measurements show that the BAP resistance R_P is smaller, and the capacitance C_P is higher, than the corresponding values for skin, R_S and C_S, respectively, these differences are larger at low frequencies (at f=3 Hz, R_S/R_P=3.19 and C_P/C_S=3.2). The mean values of the impedance measurements at the BAPs are different from those measured on the skin. The dependence of R_P and C_P on the pressing force, in the range of about 1–5 N, for the BAPs, has a smaller slope than that observed for the surrounding skin. An equivalent circuit for the BAPs is proposed that describes sufficiently well the experimental results obtained. These results show that the large dispersion in the observed impedance characteristics of the human body measurements in different body regions can be related to the influence of the BAPs present under the electrodes.     

Synaptic responses of neurons in the parietal associative cortex of the cat to stimulation of the red nucleus

Acute experiments on anesthetized and immobilized cats using intracellular recording were used to study the responses of neurons in the parietal associative cortex to stimulation of the red nucleus. Efferent neurons of the parietal cortex were identified by antidromal activation on stimulation of the intrinsic nuclei of the pons and motor cortex. Oligo- and polysynaptic EPSP in response to stimulation of the red nucleus were seen. The results are discussed in the light of the morphological organization of the rubrothalamic and cerebellothalamocortical tracts. Laboratory for Central Nervous System Physiology (Director V. V. Fanardzhyan), L. A. Orbel' Institute of Physiology, Armenian National Academy of Sciences, Erevan. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 81, No. 12, pp. 64–69, December, 1995.     

Effects of melanotan II,a melanocortin agonist,on grooming and exploration in rats after repeated restraint/immobilization

2 mg/kg melanotan II (MTII, administered i.p.), a cyclic peptide analog of α-melanocyte stimulating hormone, at a single dose increased grooming in naive rats placed in an unfamiliar open-field device without changing locomotion or rearing. Male rats exposed to restraint/immobilization stress (IS) for 1 h on three consecutive days displayed increased grooming after the second stressor exposure, compared to pre-stress levels. MTII, administered to the rats after IS, enhanced the grooming response compared both to the pre- and post-stress values. The increase was greatest after the first dose and declined over the following two applications. As to the locomotion of rats in the entire experimental space, IS reduced the distance moved only after the first two stressor exposures; MTII did not influence these alterations. Locomotion in the central part of arena was not reduced by the stressor or by MTII, on the contrary, there was an increase in both groups after the third intervention. The only observed change in rearing was an increase in the MTII group after the third restraint exposure. Thus, MTII selectively increased grooming without markedly affecting the spatio-temporal structure of locomotor behavior in the open-field. The decline of MTII enhanced grooming over the three test days may be interpreted in terms of adaptation to the stressor and of the developing tolerance to the peptide.     

Murine interleukin 5 receptor isolated by immunoaffinity chromatography: comparison of determined N-terminal sequence and deduced primary sequence from cDNA and implication of a role of the intracytoplasmic domain

The murine interleukin 5 receptor (IL-5R) was identified by utilizing an immobilized IL-5 and an immobilized monoclonal antibody against the murein IL-5R (designated H7 mAb). The H7 mAb immunoaffinity-purified materials from the extract of cell-surface radioiodinated T88-M cells (an IL-5-dependent early B cell line) using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) were reacted with an immobilized IL-5 matrix. SDS-PAGE of the adsorbed fraction revealed a single band at approximately 60 kDa. The binding of the 60 kDa protein to the immobilized IL-5 matrix was inhibited by the excess IL-5. The CHAPS-extract depleted of the 60 kDa protein by the absorption with H7 mAb did not contain any IL-5 binding proteins. Immunoaffinity procedure provided a final 7400-fold purification, based on an estimation of the content of the 60 kDa protein (approximate purity: 20%) from the silver-stained pattern of SDS-PAGE. Actin was copurified with the 60 kDa protein at an approximate ratio of 1:1, suggesting that the intracytoplasmic domain of the IL-5R may interact with actin. Furthermore, soluble IL-5R (molecular mass: 50 kDa) was purified by the H7 mAb-immunoaffinity chromatography. The purified soluble IL-5R was capable of inhibiting the binding of IL-5 to T88-M cells. Preparative SDS-PAGE followed by electroblotting onto a membrane permitted the determination of the N-terminal sequence of the IL-5R. The determined N-terminal sequence of the IL-5R and the deduced primary sequence from recently isolated cDNA were compared.     

Micropuncture studies on the influence of antidiuretic hormone on tubular fluid reabsorption in rats with hereditary hypothalamic diabetes insipidus

Summary Micropuncture studies were carried out on rats with hereditary hypothalamic diabetes insipidus, in order to measure net sodium and water reabsorption in proximal convolutions and short loops of Henle during water diuresis and ADH-induced antidiuresis. Intravenous infusion of 0.15 mU ADH per minute reduced urine flow from 74.5 l per kidney per minute to 10.8 l, and increased urine osmolality from 117 to 605 mOsm/kg. These changes could be reversed by stopping ADH.ADH did not alter the fractional reabsorption of fluid or the reabsorptive capacity for sodium in the proximal tubules. Nor did it change glomerular filtration rates of single superficial nephrons or of the entire kidney.Fractional reabsorption of the glomerular filtrate up to the early distal convolution was significantly higher (82.0%) in water diuresis than in antidiuresis (74.4%). Since this reabsorption remained unchanged in the proximal convolutions, the decreased reabsorption during antidiuresis must have occurred in the short loops. Fractional reabsorption of sodium up to the early distal tubule was essentially identical during water diuresis and antidiuresis, indicating that ADH does not enhance urinary concentration by increasing the reabsorption of sodium from short loops.On leave of absence from the Department of Physiology, Dartmouth Medical School, Hannover, N. H., from January to June, 1967. Recipient of USPHS Research Career Program Award 5-K3-GM-21, 786.     

Dendritic spines in the visual cortex of the mouse: Introduction to a mathematical model

Summary The spines of apical dendrites of the layer V pyramidal cells of the area striata in the mouse represent a sequence of post-synaptic structures receiving a variety of contacts from terminal fibers derived fundamentally from short axon cells and superficial pyramidal cells. The study of Golgi preparations of mice 180 days old shows the existence of the most complicated terminal structures over portions of apical dendrites at the levels of layers III and IV. Observations on young mice reveals the terminations of the specific afferent fibers on the dendrites of short axon cells. A mathematical model which defines the distribution of spines along the apical dendrites is introduced. The principal equation of the model has been adjusted from the data processing of microscope countings through a series of programs written for an IBM 7070. The equation defines satisfactorily the different distributions of dendritic spines in mice 10–180 days old raised in normal conditions and in complete darkness. The equation defines also the distribution of dendritic spines in the visual cortex of mice enucleated at birth on one side, and the distribution along the apical dendrites of various cortical areas of the hamster, cat and man. The number of dendritic spines increases with the age of the subject and their distribution varies significantly according to the values of the parameters of the model.